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Sample records for testosterone treatment alters

  1. Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep

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    SERGIO E RECABARREN

    2007-01-01

    Full Text Available Although evidence is accumulating that prenatal testosterone (T compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 µg/kg, as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01. The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05. AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05. Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring

  2. Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome.

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    Recabarren, Monica; Carrasco, Albert; Sandoval, Daniel; Diaz, Felipe; Sir-Petermann, Teresa; Recabarren, Sergio E

    2017-09-07

    The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

  3. Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

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    Santosa, Sylvia; Bush, Nikki C; Jensen, Michael D

    2017-08-01

    Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. This was a prospective, randomized trial. Mayo Clinic Clinical Research Unit. Thirty-two male volunteers ages 18 to 50 participated in these studies. Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group. We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content. Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity. These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.

  4. Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone.

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    Beggs, Luke A; Yarrow, Joshua F; Conover, Christine F; Meuleman, John R; Beck, Darren T; Morrow, Matthew; Zou, Baiming; Shuster, Jonathan J; Borst, Stephen E

    2014-09-01

    Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men. Sixty men aged ≥60 yr with serum T <300 ng/dl or bioavailable T <70 ng/dl received treatment with TE (125 mg/wk) vs. vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all measurements). Most of the aforementioned changes occurred in the first 3 mo of treatment, and finasteride coadministration did not significantly alter any of these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation. We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5α-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.

  5. Treatment of Men for "Low Testosterone": A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Samantha Huo

    Full Text Available Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of "low testosterone" (low-T for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation did not show consistent benefit for cardiovascular risk, sexual function, mood and behavior, or cognition. Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo. Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido. Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function. Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality, psychological well-being, or mood. The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials.

  6. The marketing of testosterone treatments for age-related low testosterone or 'Low T'.

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    Mintzes, Barbara

    2018-03-22

    To summarize the research evidence on promotion of testosterone for 'Low T', or age-related hypogonadism. Marketing of testosterone for 'Low T' has relied on strategies that are inadequately regulated to prevent off-label promotion, such as unbranded 'disease-awareness' advertising campaigns targeting the general public, sponsored continuing medical education (CME) and ghostwriting. A recent US analysis of television advertising exposure levels versus insurance claims found that both unbranded 'disease-awareness' advertising and branded ads were associated with increased rates of testosterone testing, treatment initiation, and treatment without prior testing. Exposés of sponsored CME and ghostwriting indicate misrepresentation of the research evidence on the sequelae of untreated low testosterone and on treatment efficacy. In the United States, advertising to the general public ceased in 2014 after the Food and Drug Administration changed product labeling to clarify that testosterone is only indicated for pathological hypogonadism. Unbranded 'disease-awareness' advertising to the general public and 'Low T' messages for health professionals have continued elsewhere. The review of the experience of promotion of testosterone for 'Low T' and research evidence on effects of advertising targeting the public highlights the need for improved regulation of unbranded 'disease awareness' advertising to ensure adequate protection of public.

  7. Progressive Improvement of T-Scores in Men with Osteoporosis and Subnormal Serum Testosterone Levels upon Treatment with Testosterone over Six Years

    NARCIS (Netherlands)

    Haider, A.; Meergans, U.; Traish, A.; Saad, F.; Doros, G.; Lips, P.T.A.M.; Gooren, L.

    2014-01-01

    Testosterone deficiency leads to bone loss and testosterone treatment has a beneficial effect. This study investigated the effects of normalizing serum testosterone on bone mineral density in 45 men with osteoporosis, diagnosed with testosterone deficiency (serum testosterone levels <12.1 nmol/L,

  8. Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis.

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    Yurci, Alper; Yucesoy, Mehmet; Unluhizarci, Kursad; Torun, Edip; Gursoy, Sebnem; Baskol, Mevlut; Guven, Kadri; Ozbakir, Omer

    2011-12-01

    Hypogonadism characterized by low serum testosterone level, loss of libido, small testes, impotence and gynecomastia is a common clinical situation in male patients with advanced chronic liver disease. The aim of the study was to assess the efficacy and safety of testosterone replacement on muscle strength, bone mineral density (BMD), body composition and gynecomastia in hypogonadal men with liver cirrhosis. Sixteen hypogonadal male cirrhotic patients were included and twelve completed the study. Abdominal USG and/or MRI were performed to exclude hepatocellular cancer. Testogel 50mg/day was administered for 6 months. Liver enzymes, hormone profiles and muscle strength were evaluated monthly. Body composition parameters, BMD and gynecomastia were evaluated before and after 6 months. Serum free testosterone level was higher (20.13 ± 10.06 pmol/L; 57.26 ± 39.56 pmol/L, P=0.002) after treatment. Testosterone replacement resulted in an increase in muscle strength (34.03 ± 7.24 kg; 39.18 ± 5.99 kg, Pfat tissue (P=0.012) and the sum of the four regions (P=0.04). Subareolar breast tissue was lower (28.83 ± 17.18 mm; 15.00 ± 6.74 mm, P=0.007) after treatment. No significant adverse effects were detected. Testosterone gel 50mg/day raises free testosterone to values below supraphysiological levels in cirrhotic men. Transdermal testosterone replacement improves muscle strength, ameliorates gynecomastia, alters body fat distribution and causes upper body adiposity in hypogonadal men with cirrhosis. Application of testosterone gel, which undergoes no hepatic first-pass metabolism, seems as a safe and well-tolerated agent in liver cirrhosis as compared to other anabolic steroids, which may be associated with various adverse events. Copyright © 2011. Published by Elsevier Masson SAS.

  9. THE TESTOSTERONE TRIALS: THE DESIGN OF SEVEN COORDINATED TRIALS TO DETERMINE IF TESTOSTERONE TREATMENT BENEFITS ELDERLY MEN

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    Snyder, Peter J; Ellenberg, Susan S; Cunningham, Glenn R; Matsumoto, Alvin M; Bhasin, Shalender; Barrett-Connor, Elizabeth; Gill, Thomas M; Farrar, John T; Cella, David; Rosen, Raymond C; Resnick, Susan M; Swerdloff, Ronald S; Cauley, Jane A; Cifelli, Denise; Fluharty, Laura; Pahor, Marco; Ensrud, Kristine E; Lewis, Cora E; Molitch, Mark E; Crandall, Jill P; Wang, Christina; Budoff, Matthew J; Wenger, Nanette K; Mohler, Emile R; Bild, Diane E; Cook, Nakela L; Keaveny, Tony M; Kopperdahl, David L; Lee, David; Schwartz, Ann V; Storer, Thomas W; Ershler, William B; Roy, Cindy N; Raffel, Leslie J; Romashkan, Sergei; Hadley, Evan

    2014-01-01

    Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and determine definitively if testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this trial. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and also symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, treatment and monitoring and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data safety monitoring board (DSMB), the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in subject selection was setting the eligibility criterion

  10. Does exposure to testosterone significantly alter endogenous metabolism in the marine mussel Mytilus galloprovincialis?

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    Fernandes, Denise; Navarro, Juan Carlos; Riva, Consuelo; Bordonali, Silvia; Porte, Cinta

    2010-11-15

    Mussels (Mytilus galloprovincialis) were exposed to different concentrations of testosterone (T: 20, 200 and 2000ng/L) in a semi-static water regime (1-day dosing intervals) for up to 5 days in an attempt to see whether endogenous steroid levels and steroid metabolism were altered by exogenous exposure to testosterone. Whole tissue levels of total testosterone (free+esterified) sharply increased in a concentration-dependent manner, from 2ng/g in controls to 290ng/g in organisms exposed to the highest concentration. In contrast, levels of free testosterone were only significantly elevated at the high-exposure group (5-fold increase with respect to controls). Increased activity of palmitoyl-CoA:testosterone acyltransferase (ATAT) was detected in organisms exposed to the highest concentration of testosterone, while those exposed to low and medium concentrations showed significant alterations in their polyunsaturated fatty acid profiles. The obtained results suggest that esterification of the excess of T with fatty acids might act as a homeostatic mechanism to maintain endogenous levels of free T stable. Interestingly, a decrease in CYP3A-like activity was detected in T-exposed mussels together with a significant decrease in the metabolism of the androgen precursor androstenedione to dihydrotestosterone (5α-DHT). Overall, the work contributes to the better knowledge of androgen metabolism in mussels. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Effects of oral testosterone undecanoate treatment for severe hypospadias.

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    Chen, Chao; Gong, Chun-Xiu; Zhang, Wei-Ping

    2015-06-01

    We sought to evaluate the effects of oral testosterone undecanoate treatment based on the temporary growth of penis and the complications of surgery in children with microphallic hypospadias. A total of 72 randomized consecutive children with microphallic hypospadias were included in the study from March 2011 to September 2013. While 34 children were treated with oral testosterone undecanoate treatment prior to surgery on time (group 1), 36 children did not receive any treatment preoperatively (group 2). All children underwent hypospadias repair using transverse preputial island flap (Duckett technique) urethroplasty or combination of Duckett and Thiersch-Duplay techniques. Penile length, diameter, serum testosterone level, and secondary effects were recorded before and after therapy in group 1. Postoperative complications were assessed with respect to fistulas, urethral strictures, diverticula, meatal stenosis, and glanular dehiscence in both groups. Mean penile length and diameter increased significantly by 1.06 ± 0.53 cm (P testosterone group had this complication (P > 0.05). There were three patients (8.3 %) with diverticula in group 2 and three patients (8.9 %) with this complication in group 1 (P > 0.05). None of our patients had signs or symptoms of meatal stenosis, glanular dehiscence, or residual chordee in both groups. Finally, there was a significant difference between the overall reoperation rates of group 2 (14 patients, 38.9 %) and group 1 (five patients, 14.7 %, P testosterone undecanoate was effective in improving the temporary penile growth and decreasing the surgical complications in children with microphallic hypospadias.

  12. Clinical practice experience with testosterone treatment in men with testosterone deficiency syndrome.

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    McLaren, Drew; Siemens, D Robert; Izard, Jason; Black, Angela; Morales, Alvaro

    2008-11-01

    To report on a clinical practice series of testosterone-replacement therapy (TRT) in men with testosterone deficiency syndrome (TDS), examining clinical efficacy, biochemical parameters and effects on prostate health over a 2-year period. A retrospective review of 85 patients with symptoms of TDS and at least a 3-month trial of TRT was performed in this single-centre, clinical practice setting. Three domains of symptomatology were evaluated: libido, erectile function and energy levels. Symptoms were assessed by a combination of patient reporting, physician's assessment and validated symptom assessment scores. Total testosterone (TT), calculated bio-available testosterone (BT) and prostate-specific antigen (PSA) levels were continuously measured and effects on prostate health were examined. Only 38 (45%) patients in this cohort remained on TRT for >2 years. The most common reason for discontinuing treatment was lack of clinical response but those remaining on TRT had continued improvement in libido, erectile function and energy levels. During treatment, the average TT and calculated BT values significantly increased compared with the baseline values at most of the evaluated time points, with no significant change in average PSA values. In all, 15% of this cohort had some degree of progression of lower urinary tract symptoms. Seven patients had eight 'for-cause' prostate biopsies either during supplementation or at any date after completion, with an only three positive for cancer. Only 45% of men on TRT remained on treatment for >2 years in this clinical practice experience of men with TDS. Those remaining showed persistent improvement in their symptoms. The average TT and BT values increased significantly with no significant change in PSA levels.

  13. Strength training and testosterone treatment have opposing effects on migration inhibitor factor levels in ageing men

    DEFF Research Database (Denmark)

    Glintborg, D.; Christensen, L. L.; Kvorning, T.

    2013-01-01

    Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men......Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men...

  14. Effects of combined treatment of α-tocopherol, L-ascorbic acid, selenium and zinc on bleomycin, etoposide and cisplatin-induced alterations in testosterone synthesis pathway in rats.

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    Kilarkaje, Narayana

    2014-12-01

    To investigate the effects of therapeutically relevant dose levels of bleomycin, etoposide and cisplatin (BEP) on testicular steroidogenic enzymes, and possible protective effects of an antioxidant cocktail (AC). Adult Sprague-Dawley rats received BEP with or without the AC (α-tocopherol, L-ascorbic acid, selenium and zinc) for either (a) 4 days (short term; 1.5, 15 and 3 mg/kg), or (b) three cycles of 21 days each (0.75, 7.5 and 1.5 mg/kg), or (c) the three cycles with a 63-day recovery period. The expression of steroidogenic enzymes were measured in the testes by Western blotting and immunofluorescent labeling. The short-term BEP exposure resulted in a decrease in scavenger receptor class-B1 and an increase in luteinizing hormone receptor (LHR). The AC with or without BEP has increased the levels of LHR, 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD, but without significant changes in testosterone levels. The three cycles of BEP up-regulated the expression of steroidogenic acute regulatory protein (StAR) and down-regulated that of cholesterol side chain cleavage enzyme (P450scc), cytochrome p450 17A1 (Cyp17A1, recovered by the AC) and 17β-HSD, associated with significant reduction in testosterone levels. The three cycles with the recovery time led to decreases in LHR, StAR, P450scc and Cyp17A1 and increases in 3β-HSD and 17β-HSD. The AC did not enhance the recovery of the enzyme levels. The three cycles of BEP treatment inhibit the testosterone synthesis pathway even after the recovery time. The AC recovers the effects of BEP chemotherapy on a few steroidogenic enzymes.

  15. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment.

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    Resnick, Susan M; Matsumoto, Alvin M; Stephens-Shields, Alisa J; Ellenberg, Susan S; Gill, Thomas M; Shumaker, Sally A; Pleasants, Debbie D; Barrett-Connor, Elizabeth; Bhasin, Shalender; Cauley, Jane A; Cella, David; Crandall, Jill P; Cunningham, Glenn R; Ensrud, Kristine E; Farrar, John T; Lewis, Cora E; Molitch, Mark E; Pahor, Marco; Swerdloff, Ronald S; Cifelli, Denise; Anton, Stephen; Basaria, Shehzad; Diem, Susan J; Wang, Christina; Hou, Xiaoling; Snyder, Peter J

    2017-02-21

    Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to -26), executive function (Trail-Making Test B minus A; range, -290 to 290), and spatial ability (Card Rotation Test; score range, -80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean

  16. Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer.

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    Golla, Vishnukamal; Kaplan, Alan L

    2017-07-01

    Previously considered an absolute contraindication, the use of testosterone therapy in men with prostate cancer has undergone an important paradigm shift. Recent data has changed the way we approach the treatment of testosterone deficiency in men with prostate cancer. In the current review, we summarize and analyze the literature surrounding effects of testosterone therapy on patients being treated in an active surveillance protocol as well as following definitive treatment for prostate cancer. The conventional notion that defined the relationship between increasing testosterone and prostate cancer growth was based on limited studies and anecdotal case reports. Contemporary evidence suggests testosterone therapy in men with testosterone deficiency does not increase prostate cancer risk or the chances of more aggressive disease at prostate cancer diagnosis. Although the studies are limited, men who received testosterone therapy for localized disease did not have higher rates of recurrences or worse clinical outcomes. Current review of the literature has not identified adverse progression events for patients receiving testosterone therapy while on active surveillance/watchful waiting or definitive therapies. The importance of negative effects of testosterone deficiency on health and health-related quality of life measures has pushed urologists to re-evaluate the role testosterone plays in prostate cancer. This led to a paradigm shift that testosterone therapy might in fact be a viable option for a select group of men with testosterone deficiency and a concurrent diagnosis of prostate cancer.

  17. Testosterone enhances risk tolerance without altering motor impulsivity in male rats.

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    Cooper, Sarah E; Goings, Sydney P; Kim, Jessica Y; Wood, Ruth I

    2014-02-01

    Anabolic-androgenic steroids (AAS) increase impulsive and uncontrolled aggressive ('roid rage) in humans and enhance agonistic behavior in animals. However, the underlying mechanisms for AAS-induced aggression remain unclear. Potential contributing elements include an increase risk-taking and/or motor impulsivity due to AAS. This study addressed the effects of chronic high-dose testosterone on risk tolerance using a risky decision-making task (RDT) and motor impulsivity with a go/no-go task in operant chambers. Male Long-Evans rats were treated for at least 4 weeks with testosterone (7.5mg/kg) or vehicle beginning in late adolescence. Testosterone was used because it is popular among human AAS users. In RDT testing, one lever was paired with delivery of a small "safe" food reward, while the other was paired with a large "risky" reward associated with an increasing risk of footshock (0%, 25%, 50%, 75%, 100%) in successive test blocks. Three shock intensities were used: 1.0, 1.2, and 1.4mA/kg. As shock intensity and risk of shock increased, preference for the lever signifying a large reward significantly declined for both vehicle- and testosterone-treated rats (ptestosterone-treated rats showed greater preference for the large reward, compared to vehicle-treated controls. Increased preference for the large reward, despite risk of footshock, is consistent with increased risk tolerance. In go/no-go testing, rats were trained to press a single lever if the go cue was presented (stimulus light) or to refrain from pressing during the no-go cue (tone). There was no effect of testosterone on pre-cue responses, or performance in go and no-go trials. These results suggest that AAS may increase risk-tolerance without altering motor impulsivity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

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    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-05

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model.

    Science.gov (United States)

    Chaudhari, Nirja K; Nampoothiri, Laxmipriya P

    2017-02-01

    Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.

  20. Testosterone as Potential Effective Therapy in Treatment of Obesity in Men with Testosterone Deficiency: A Review

    Science.gov (United States)

    Saad, Farid; Aversa, Antonio; Isidori, Andrea M; Gooren, Louis J

    2012-01-01

    Objective: Obesity negatively affects human health. Limiting food intake, while producing some weight loss, results in reduction of lean body mass. Combined with moderate exercise it produces significant weight loss, maintains lean body mass and improves insulin sensitivity, but appears difficult to adhere to. Bariatric surgery is clinically effective for severely obese individuals compared with non-surgical interventions, but has limitations. Clinical and pre-clinical studies have implicated a role for testosterone (T) in the patho-physiology of obesity. Methods: Evidence Acquisition and Synthesis: A literature search in PubMed on the role of T in counteracting obesity and its complications. Results: Obesity per se impairs testicular T biosynthesis. Furthermore, lower-than-normal T levels increase accumulation of fat depots, particularly abdominal (visceral) fat. This fat distribution is associated with development of metabolic syndrome (MetS) and its sequels, namely type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T treatment reverses fat accumulation with significant improvement in lean body mass, insulin sensitivity and biochemical profiles of cardiovascular risk. The contribution of T to combating obesity in hypogonadal men remains largely unknown to medical professionals managing patients with obesity and metabolic syndrome. Many physicians associate T treatment in men with risks for prostate malignancy and CVD. These beliefs are not supported by recent insights. Conclusion: While overall treatment of obesity is unsuccessful, T treatment of hypogonadal men may be effective, also because it improves mood, energy, reduces fatigue and may motivate men to adhere to diet and exercise regimens designed to combat obesity. PMID:22268394

  1. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review.

    Science.gov (United States)

    Saad, Farid; Aversa, Antonio; Isidori, Andrea M; Gooren, Louis J

    2012-03-01

    Obesity negatively affects human health. Limiting food intake, while producing some weight loss, results in reduction of lean body mass. Combined with moderate exercise it produces significant weight loss, maintains lean body mass and improves insulin sensitivity, but appears difficult to adhere to. Bariatric surgery is clinically effective for severely obese individuals compared with non-surgical interventions, but has limitations. Clinical and pre-clinical studies have implicated a role for testosterone (T) in the patho-physiology of obesity. A literature search in PubMed on the role of T in counteracting obesity and its complications. Obesity per se impairs testicular T biosynthesis. Furthermore, lower-than-normal T levels increase accumulation of fat depots, particularly abdominal (visceral) fat. This fat distribution is associated with development of metabolic syndrome (MetS) and its sequels, namely type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T treatment reverses fat accumulation with significant improvement in lean body mass, insulin sensitivity and biochemical profiles of cardiovascular risk. The contribution of T to combating obesity in hypogonadal men remains largely unknown to medical professionals managing patients with obesity and metabolic syndrome. Many physicians associate T treatment in men with risks for prostate malignancy and CVD. These beliefs are not supported by recent insights. While overall treatment of obesity is unsuccessful, T treatment of hypogonadal men may be effective, also because it improves mood, energy, reduces fatigue and may motivate men to adhere to diet and exercise regimens designed to combat obesity. © 2012 Bentham Science Publishers

  2. Mercury correlates with altered corticosterone but not testosterone or estradiol concentrations in common loons.

    Science.gov (United States)

    Franceschini, Melinda D; Evers, David C; Kenow, Kevin P; Meyer, Michael W; Pokras, Mark; Romero, L Michael

    2017-08-01

    We investigated the relation between environmental mercury exposure and corticosterone concentrations in free-living adult common loons (Gavia immer). We determined blood and feather mercury concentrations and compared them to testosterone, estradiol, and stress-induced plasma corticosterone concentrations. Although neither testosterone nor estradiol correlated with Hg levels, there was a robust positive relation between blood Hg and stress-induced corticosterone concentrations in males, but not in females. The lack of an effect in females may have been due to overall less contamination in females. There were no significant correlations between feather Hg and stress-induced corticosterone in either sex. To help determine whether Hg had a causal effect on corticosterone, we investigated the impact of experimental Hg intake on the corticosterone stress response in captive juvenile loons. Juveniles were subjected to three different feeding regimes: 0, 0.4 and 1.2μg Hg (as MeHgCL)/g wet weight (ww) fish. We then measured baseline and 30min post-solitary confinement stressor corticosterone concentrations. The Hg fed chicks exhibited a decreased ability to mount a stress response. From these data, we conclude that Hg contamination does appear to alter the corticosterone response to stress, but not in a consistent predictable pattern. Regardless of the direction of change, however, exposure to mercury contamination and the resulting impact on the corticosterone stress response in common loons may substantially impact health, fitness and survival. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The effects of chronic testosterone administration on body weight, food intake, and adipose tissue are changed by estrogen treatment in female rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Yanagihara, Rie; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Mayila, Yiliyasi; Kuwahara, Akira; Irahara, Minoru

    2017-07-01

    In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats. In addition, chronic testosterone administration increased hypothalamic CYP19a1 mRNA levels in OVX rats, whereas it did not alter CYP19a1 mRNA levels in OVX with estradiol-administered rats, indicating that conversion of testosterone to estrogens in the hypothalamus may be activated in testosterone-administered OVX rats. Furthermore, chronic testosterone administration decreased hypothalamic TNF-α mRNA levels in OVX rats, whereas it increased hypothalamic IL-1β mRNA levels in OVX with estradiol-administered rats. On the other hand, IL-1β and TNF-α mRNA levels in visceral and subcutaneous WAT and liver were not changed by chronic testosterone administration in both groups. These data indicate that the effects of chronic testosterone administration on BW, FI, WAT weight, and adipocyte size were changed by estradiol treatment in female rats. Testosterone has facilitative effects on BW gain, FI, and adiposity under the estradiol-supplemented condition, whereas it has inhibitory effects in the non-supplemented condition. Differences in the responses of hypothalamic factors, such as aromatase and inflammatory cytokines, to testosterone might underlie these opposite effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue

    2015-01-01

    PURPOSE: We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. METHODS: Double-blinded, placebo-controlled study in 54 men aged 60-78 years...... central fat mass (r = 0.84). CONCLUSIONS: Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass....

  5. [Testosterone and erectile dysfunction].

    Science.gov (United States)

    Diemer, T

    2010-01-01

    Primary hypogonadism represents a classic but rare cause of erectile dysfunction (ED) in men. Therapy with testosterone as monotherapy is therefore unlikely to cure ED in the typical ED patient. However, recent developments indicate a much greater role of testosterone in erectile function than has been supposed in the past. Serum testosterone levels decline in men with increasing age. Aging men might develop late-onset hypogonadism (LOH) associated with characteristic symptoms. Typical symptoms of LOH are represented by decreased libido and sexual function, osteoporosis, altered distribution of body fat, overall reduction in physical strength, and alterations in the general mood. Experimental and clinical studies over the last few years have also pointed out that hypogonadism results in characteristic alterations of the erectile tissue of the penis. These alterations might be reversible in response to hormone therapy with testosterone. Particularly testosterone might be a helpful supportive therapy in cases where PDE-5 antagonists have tended to lose their effectiveness on the erectile tissue in the treatment of ED.

  6. Cardiovascular complications following chronic treatment with cocaine and testosterone in adolescent rats.

    Directory of Open Access Journals (Sweden)

    Sheila A Engi

    Full Text Available Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR, and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.

  7. Comparison of the pre-treatment testosterone levels in benign ...

    African Journals Online (AJOL)

    Objectives: To compare serum testosterone and prostate specific antigen (PSA) levels of patients diagnosed of prostate cancer to those with benign prostatic hyperplasia (BPH). Subjects and methods: One hundred and thirteen male patients with or without LUTS who had indication(s) for prostate biopsies were recruited.

  8. Comparison of the pre-treatment testosterone levels in benign ...

    African Journals Online (AJOL)

    D.E. Orakwe

    2017-01-26

    Jan 26, 2017 ... Abstract. Objectives: To compare serum testosterone and prostate specific antigen (PSA) levels of patients diagnosed of prostate cancer to those with benign prostatic hyperplasia (BPH). Subjects and methods: One hundred and thirteen male patients with or without LUTS who had indica- tion(s) for prostate ...

  9. Marketing and Testosterone Treatment in the USA: A Systematic Review.

    Science.gov (United States)

    Bandari, Jathin; Ayyash, Omar M; Emery, Sherry L; Wessel, Charles B; Davies, Benjamin J

    2017-10-01

    Testosterone replacement therapy (TRT) is currently approved by the Food and Drug Administration only for classic hypogonadism, although off-label indications have resulted in a dramatic expansion in prescriptions in the USA. Marketing may significantly affect prescriber behavior. To systematically review all available evidence on marketing and TRT in the USA. PubMed, Embase, and Scopus were searched up to July 2017 for all relevant publications reporting on assessments of the TRT market size, economic costs associated with hypogonadism, trends in TRT prescriptions, drug discontinuation rates, and advertising and sales efforts in the USA. Twenty retrospective studies were included in the final analysis. The market size for hypogonadism constitutes 5.6-76.8% of men in the USA, with the lower end of the range representing the strictest criteria for diagnosis. Men with a diagnosis of hypogonadism consume $14 118 in direct and indirect costs to the payer. Over the last 2 decades, TRT prescriptions have increased between 1.8- and 4-fold. After 1 yr, 80-85% of men discontinue TRT. There is an association between direct-to-consumer advertising and testosterone testing, TRT prescriptions, and TRT without testosterone testing. There is a high prevalence of misinformation on Internet advertising. Off-label indications have driven the dramatic expansion of TRT prescriptions over the last 2 decades. Direct-to-consumer advertising poses a unique challenge in the USA. Overtreatment can be avoided by applying strict diagnostic criteria for hypogonadism, which limits the addressable market for TRT. In this report, we reviewed the relationship between marketing and testosterone therapy in the USA. We found that many patients are prescribed testosterone without an appropriate diagnosis of hypogonadism, which may be related to the marketing efforts for off-label prescribing. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response.

    Science.gov (United States)

    White, Hillary D; Brown, Lin A J; Gyurik, Robert J; Manganiello, Paul D; Robinson, Thomas D; Hallock, Linda S; Lewis, Lionel D; Yeo, Kiang-Teck J

    2015-08-01

    To test our hypothesis that testosterone deficiency plays an important role in chronic pain, a Phase I/II pilot study was initiated with 12 fibromyalgia patients to verify that a daily dose for 28days with transdermal testosterone gel would 1) significantly and safely increase mean serum testosterone concentrations from low baseline levels to mid/high-normal levels, and 2) effectively treat the pain and fatigue symptoms of fibromyalgia. Pharmacokinetic data confirmed that serum free testosterone concentrations were raised significantly above baseline levels, by assessment of maximum hormone concentration (Cmax) and area under the curve (AUC) parameters: free testosterone Cmax was significantly raised from a mean of 2.64pg/mL to 3.91pg/mL (pfibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment. These results are consistent with the hypothesized ability of testosterone to relieve the symptoms of fibromyalgia. Symptoms not tightly related to fibromyalgia were not improved. Copyright © 2015. Published by Elsevier B.V.

  11. Effects of testosterone treatment on hypothalamic neuroplasticity in female-to-male transgender individuals.

    Science.gov (United States)

    Kranz, Georg S; Hahn, Andreas; Kaufmann, Ulrike; Tik, Martin; Ganger, Sebastian; Seiger, René; Hummer, Allan; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2018-01-01

    Diffusion-weighted imaging (DWI) is used to measure gray matter tissue density and white matter fiber organization/directionality. Recent studies show that DWI also allows for assessing neuroplastic adaptations in the human hypothalamus. To this end, we investigated a potential influence of testosterone replacement therapy on hypothalamic microstructure in female-to-male (FtM) transgender individuals. 25 FtMs were measured at baseline, 4 weeks, and 4 months past treatment start and compared to 25 female and male controls. Our results show androgenization-related reductions in mean diffusivity in the lateral hypothalamus. Significant reductions were observed unilaterally after 1 month and bilaterally after 4 months of testosterone treatment. Moreover, treatment induced increases in free androgen index and bioavailable testosterone were significantly associated with the magnitude of reductions in mean diffusivity. These findings imply microstructural plasticity and potentially related changes in neural activity by testosterone in the adult human hypothalamus and suggest that testosterone replacement therapy in FtMs changes hypothalamic microstructure towards male proportions.

  12. Evaluation of late-onset hypogonadism (andropause) treatment using three different formulations of injectable testosterone.

    Science.gov (United States)

    Hohl, Alexandre; Marques, Mario Octávio Thá; Coral, Marisa Helena César; Walz, Roger

    2009-11-01

    To compare the modalities of treatment for male hypogonadism available in Brazil. Thirty-two men with late-onset hypogonadism ('andropause') were followed-up in the Hospital de Guarnição de Florianópolis, in Florianópolis, south Brazil. Clinical diagnosis was established according to AMS questionnaire (positive if equal to or higher than 27 points), and laboratory diagnosis was made through low values of total testosterone (under 300 ng/dL) and/or free calculated testosterone (under 6.5 ng/dL). Patients were randomized to three non-enteral treatment groups (Deposteron--11 patients; Durateston--11 patients; and Nebido--10 patients). Clinically, Nebido seemed to be superior when compared to Deposteron (mean value of improvement percentage; p = 0.03) and when compared to Durateston (post-treatment average AMS score; p = 0.03). According to laboratory analysis, Nebido showed higher testosterone levels than Deposteron and Durateston (p < 0.001). All non-enteral testosterone formulas available in the Brazilian market are efficient in raising testosterone levels and in clinical improvement of hypogonadal patients. Nebido showed both a better clinical and laboratory effectiveness.

  13. Transplantation of CD51+Stem Leydig Cells: A New Strategy for the Treatment of Testosterone Deficiency.

    Science.gov (United States)

    Zang, Zhi Jun; Wang, Jiancheng; Chen, Zhihong; Zhang, Yan; Gao, Yong; Su, Zhijian; Tuo, Ying; Liao, Yan; Zhang, Min; Yuan, Qunfang; Deng, Chunhua; Jiang, Mei Hua; Xiang, Andy Peng

    2017-05-01

    Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51 + SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51 + SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51 + cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro. As a specific cytotoxin that eliminates Leydig cells (LCs) in adult rats, ethane dimethanesulfonate (EDS) was used to ablate LCs before the SLC transplantation. After being transplanted into the testes of EDS-treated rats, the CD51 + cells differentiated into mature LCs, and the recipient rats showed a partial recovery of testosterone production and spermatogenesis. Notably, a testosterone analysis revealed a circadian rhythm of testosterone secretion in cell-transplanted rats, and these testosterone secretions could be suppressed by decapeptyl (a luteinizing hormone-releasing hormone agonist), suggesting that the transplanted cells might be regulated by the HPG axis. This study is the first to demonstrate that CD51 + SLCs can restore the neuroendocrine regulation of testicular function by physiologically recovering the expected episodic changes in diurnal testosterone serum levels and that SLC transplantation may provide a new tool for the studies of testosterone deficiency treatment. Stem Cells 2017;35:1222-1232. © 2017 AlphaMed Press.

  14. Testosterone levels and sexual function disorders in depressive female patients: effects of antidepressant treatment.

    Science.gov (United States)

    Kumsar, Şükrü; Kumsar, Neslihan Akkişi; Sağlam, Hasan Salih; Köse, Osman; Budak, Salih; Adsan, Öztuğ

    2014-02-01

    Women suffer from depression more frequently than men, which indicates that sex hormones might be involved in the etiology of this disease. The purpose of this study was to assess the relationship between testosterone and depression pathophysiology in depressive women along with sexual function. We also investigated whether antidepressant treatment causes any change in levels of this hormone or in sexual function. Premenopausal female patients aged 25-46 years (n = 52) with diagnosed major depression were included in this study as the patient group, and 25- to 46-year-old premenopausal women without depression (n = 30) were included as the control group. Serum testosterone and sex hormone-binding globulin (SHBG) levels were measured twice, before and after the antidepressant treatment. Bioavailable testosterone (cBT) levels were calculated using the assay results for total testosterone (TT), SHBG, and albumin according to the formulas of Vermeulen et al. Depression severity was measured using the 17-item Hamilton Depression Rating Scale, and sexual function was evaluated with the Arizona Sexual Experience Scale. The mean TT and cBT levels significantly increased in the patient group after the antidepressant treatment (P treatment TT and cBT levels were significantly lower in the patient group than in the control group (P treatment serum TT and cBT levels in the patient and control groups (P > 0.05). There were no significant differences among the groups in terms of SHBG level. The low testosterone levels in depressed women compared with women in the control group and the elevated levels post-pharmacotherapy suggest that testosterone may be involved in depression. © 2013 International Society for Sexual Medicine.

  15. Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, Jens Henrik Sahl

    1987-01-01

    Liver haemodynamics and liver function were measured in 34 alcoholic cirrhotic men before entry and after 12 months (median) in a double-blind, placebo-controlled study on the effect of oral testosterone treatment (200 mg t.i.d.). Comparing data at entry with those at follow-up in the total patient......, testosterone-treated patients did not differ significantly from placebo-treated patients regarding any of the measured variables. No significant relationships could be demonstrated between ethanol consumption and liver haemodynamics and liver function, but the number of patients consuming more than 100 g...... ethanol per day decreased significantly (P less than 0.001) from 22 (65%) before entry to one (3%) during follow-up. In conclusion, oral testosterone treatment of men with alcoholic cirrhosis does not explain the significant improvement of liver haemodynamics and function observed in this study. However...

  16. Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels in a randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Ng Tang Fui, M; Hoermann, R; Prendergast, L A; Zajac, J D; Grossmann, M

    2017-03-01

    Obese men commonly have reductions in circulating testosterone and report symptoms consistent with androgen deficiency. We hypothesized that testosterone treatment improves constitutional and sexual symptoms over and above the effects of weight loss alone. We conducted a pre-specified analysis of a randomized double-blind, placebo-controlled trial at a tertiary referral center. About 100 obese men (body mass index (BMI)⩾30 kg m - 2 ) with a repeated total testosterone level ⩽12 nmol l -1 and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very-low-energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n=49, cases) or matching placebo (n=51, controls). Pre-specified outcomes were the between-group differences in Aging Male Symptoms scale (AMS) and international index of erectile function (IIEF-5) questionnaires. Eighty-two men completed the study. At study end, cases showed significant symptomatic improvement in AMS score, compared with controls, and improvement was more marked in men with more severe baseline symptoms (mean adjusted difference (MAD) per unit of change in AMS score -0.34 (95% confidence interval (CI) -0.65, -0.02), P=0.04). This corresponds to improvements of 11% and 20% from baseline scores of 40 and 60, respectively, with higher scores denoting more severe symptoms. Men with erectile dysfunction (IIEF-5⩽20) had improved erectile function with testosterone treatment. Cases and controls lost the same weight after VLED (testosterone -12.0 kg; placebo -13.5 kg, P=0.40) and maintained this at study end (testosterone -11.4 kg; placebo -10.9 kg, P=0.80). The improvement in AMS following VLED was not different between the groups (-0.05 (95% CI -0.28, 0.17), P=0.65). In otherwise healthy obese men with mild to moderate symptoms and modest reductions in testosterone levels, testosterone treatment improved

  17. Effects of testosterone administration on liver structure and function in aging rats.

    Science.gov (United States)

    Nucci, Ricardo Aparecido Baptista; Teodoro, Ana Caroline de Souza; Krause Neto, Walter; Silva, Wellington de Assis; de Souza, Romeu Rodrigues; Anaruma, Carlos Alberto; Gama, Eliane Florencio

    2017-06-01

    Aging males have a decrease in testosterone levels, by which the testosterone treatment may influence in a negatively fashion the liver. This study aimed to analyze the effects of aging with or without testosterone administration on the liver components of animals. Wistar rats were divided into three groups: 20 months' group (G20), 24 months' group (G24), group treated with testosterone for 16 weeks (GT). All groups were sacrificed at 24 months except for G20 that was sacrificed at 20 months. Aging and testosterone treatment alters the body weight (BW), liver weight (LW) and relative liver weight. Besides, testosterone increased the mitogen capacity of hepatocytes. Nonetheless, we reinforce the negative effects of testosterone on old animals' liver as chronic hepatic congestion and/or cholestasis. In addition, we observed that testosterone plays an important role on hepatic glycogen stores. Our study showed many implications for the knowledge about the effects of aging with or without testosterone administration on old animals' liver.

  18. Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, R. Charles, E-mail: rnichols@floridaproton.org [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Williams, Christopher R.; Costa, Joseph A. [Division of Urology, University of Florida Shands Hospital, Jacksonville, FL (United States); Mendenhall, Nancy P. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-03-01

    Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

  19. Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

    International Nuclear Information System (INIS)

    Nichols, R. Charles; Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng; Williams, Christopher R.; Costa, Joseph A.; Mendenhall, Nancy P.

    2012-01-01

    Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

  20. Prostate-specific antigen (PSA) concentrations in hypogonadal men during 6 years of transdermal testosterone treatment.

    Science.gov (United States)

    Raynaud, Jean-Pierre; Gardette, Jean; Rollet, Jacques; Legros, Jean-Jacques

    2013-05-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Hypogonadism affects an estimated 2-4 million men in the USA, but only 5% receive treatment. Testosterone replacement therapy reduces the effects of testosterone deficiency on sexual function, mood and energy in hypogonadal patients. Long-term hypogonadism management requires testosterone treatment to restore serum concentrations of testosterone and its active metabolites, within physiological ranges; a testosterone preparation that achieves physiological plasma concentrations without supra-physiological escape is a preferred option. A previous 1-year study European clinical study showed the efficacy and safety of a transdermal testosterone patch (Testopatch(®) ). The present study shows the long-term (6-year) safety and efficacy of Testopatch in patients with primary or secondary hypogonadism. We show that, over the long-term, Testopatch was associated with no relevant changes in PSA concentration and PSA velocity, or any significant prostate risks (there were no cases of prostate cancer). To assess the change in prostate-specific antigen (PSA) concentrations in patients with primary or secondary hypogonadism, receiving transdermal testosterone. This was an interventional, 6-year study, conducted in Urology and Endocrinology centres in Belgium, France, Germany, the Netherlands and Spain. Participants were primary (48%) or secondary (52%) hypogonadal patients who received two 60 cm(2) testosterone patches (Testopatch(®) ), delivering 4.8 mg of testosterone per day, applied every 2 days. During treatment, total testosterone (TT), dihydrotestosterone, oestradiol and, PSA concentrations were measured in a centralised laboratory every 3 months during the first year, and every 6 months thereafter. In all, 200 patients [mean (sd) age 41.0 (12.5) years, body weight 82.5 (13.7) kg, height 177.2 (9.3) cm, body mass index 26.2 (3.4) kg/m(2) ] were treated with transdermal testosterone patches. In all, 161 patients

  1. Effect of Voluntary Ethanol Consumption Combined with Testosterone Treatment on Cardiovascular Function in Rats: Influence of Exercise Training.

    Science.gov (United States)

    Engi, Sheila A; Planeta, Cleopatra S; Crestani, Carlos C

    2016-01-01

    This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6), animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α1-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances.

  2. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

    Science.gov (United States)

    Taylor, Frederick; Levine, Laurence

    2010-01-01

    The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1-2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim 1% (5 gm daily) is $270, Androgel 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

  3. Testosterone Modifies Alterations to Detrusor Muscle after Partial Bladder Outlet Obstruction in Juvenile Mice

    Directory of Open Access Journals (Sweden)

    Andrew S. Flum

    2017-06-01

    Full Text Available Lower urinary tract symptoms secondary to posterior urethral valves (PUV arise in boys during adolescence. The reasons for this have previously been attributed to increased urine output as boys experience increased growth. Additionally, there are few choices for clinicians to effectively treat these complications. We formed the new hypothesis that increased androgen levels at this time of childhood development could play a role at the cellular level in obstructed bladders. To test this hypothesis, we investigated the role of testosterone on bladder detrusor muscle following injury from partial bladder outlet obstruction (PO in mice. A PO model was surgically created in juvenile male mice. A group of mice were castrated by bilateral orchiectomy at time of obstruction (CPO. Testosterone cypionate was administered to a group of castrated, obstructed mice (CPOT. Bladder function was assessed by voiding stain on paper (VSOP. Bladders were analyzed at 7 and 28 days by weight and histology. Detrusor collagen to smooth muscle ratio (Col/SM was calculated using Masson’s trichrome stain. All obstructed groups had lower max voided volumes (MVV than sham mice at 1 day. Hormonally intact mice (PO continued to have lower MVV at 7 and 28 days while CPO mice improved to sham levels at both time points. In accordance, PO mice had higher bladder-to-body weight ratios than CPO and sham mice demonstrating greater bladder hypertrophy. Histologically, Col/SM was lower in sham and CPO mice. When testosterone was restored in CPOT mice, MVV remained low at 7 and 28 days compared to CPO and bladder-to-body weight ratios were also greater than CPO. Histologic changes were also seen in CPOT mice with higher Col/SM than sham and CPO mice. In conclusion, our findings support a role for testosterone in the fibrotic changes that occur after obstruction in male mice. This suggests that while other changes may occur in adolescent boys that cause complication in boys

  4. Testosterone Injection

    Science.gov (United States)

    ... typical male characteristics. Testosterone injection works by supplying synthetic testosterone to replace the testosterone that is normally ... as a pellet to be injected under the skin.Testosterone injection may control your symptoms but will ...

  5. Bilateral anorchia in infancy: occurence of micropenis and the effect of testosterone treatment.

    Science.gov (United States)

    Zenaty, D; Dijoud, F; Morel, Y; Cabrol, S; Mouriquand, P; Nicolino, M; Bouvatier, C; Pinto, G; Lecointre, C; Pienkowski, C; Soskin, S; Bost, M; Bertrand, A M; El-Ghoneimi, A; Nihoul-Fekete, C; Léger, J

    2006-11-01

    To analyze the clinical and histological findings in boys with bilateral anorchia and the response to testosterone treatment on penis length. Patients were divided into two groups according to the absence (group A, n = 29) or the presence (group B, n = 26) of palpable intrascrotal or inguinal mass at first clinical examination. A micropenis was found in 46% of patients (n = 24) with a similar proportion in both groups. Testosterone treatment induced a mean penis length gain of 1.9 +/- 1.3 SDS (standard deviation score). However, micropenis persisted in six patients. Histological examination (n = 18) confirmed the absence of any testicular structure with deferent ducts being present unilaterally or bilaterally in all but three patients. In these three patients, a hemorrhagic testis, probably as a result of a mechanical torsion, was found. The presence of isolated micropenis in almost half of patients with bilateral anorchia strongly suggests that the testicular damage frequently occurs during the second half of gestation after male sexual differentiation. In most cases, testosterone treatment stimulates the penile growth. Although the pathogenesis of bilateral anorchia may be heterogeneous, our study suggests that gonads may have been functionally abnormal before they disappeared, and suggests that some patients have an intrinsic endocrine disorder.

  6. Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters

    NARCIS (Netherlands)

    Bui, Hong N.; Schagen, Sebastian E. E.; Klink, Daniel T.; Delemarre-van de Waal, Henriette A.; Blankenstein, Marinus A.; Heijboer, Annemieke C.

    2013-01-01

    In our hospital, female-to-male (FtM) transgender adolescents from the age of 16 are treated with two- or four-weekly intra-muscular injections of testosterone-esters. Some patients treated with four-weekly injections have complaints of fatigue and experience mood swings towards the end of the

  7. Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters

    NARCIS (Netherlands)

    Bui, H.N.; Schagen, S.E.; Klink, D.T.; Delemarre-van de Waal, H.A.; Blankenstein, M.A.; Heijboer, A.C.

    2013-01-01

    Introduction: In our hospital, female-To-male (FtM) transgender adolescents from the age of 16 are treated with two- or four-weekly intra-muscular injections of testosterone-esters. Some patients treated with four-weekly injections have complaints of fatigue and experience mood swings towards the

  8. Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial.

    Science.gov (United States)

    Gianatti, Emily J; Dupuis, Philippe; Hoermann, Rudolf; Strauss, Boyd J; Wentworth, John M; Zajac, Jeffrey D; Grossmann, Mathis

    2014-08-01

    To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35-70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo -0.08 [95% CI -0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0-0.7]; P = 0.05), despite a decrease in fat mass (MAD -2.38 kg [-3.10 to -1.66]; P Testosterone therapy reduced subcutaneous (MAD -320 cm(3) [-477 to -163]; P Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. No effect of long-term oral testosterone treatment on liver morphology in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Christoffersen, Pernille Yde; Eriksen, J

    1987-01-01

    The effect of oral testosterone treatment (200 mg tid) on liver morphology was examined in a double-blind, placebo controlled study including men with alcoholic cirrhosis (n = 126). Liver biopsies obtained before randomization showed micronodular cirrhosis in 119 patients (94%), alcoholic hepatitis...... influence the prevalence of these changes. Further, testosterone treatment had no significant effect on the prevalence of other morphological changes, including vascular and malignant changes. However, in the testosterone-treated group one patient developed diffuse sinusoidal dilation and one patient showed...... not establish any indication or any contraindication in terms of hepatic histopathology with the possible exception of hepatic venous thrombosis for the use of oral testosterone treatment in men with alcoholic cirrhosis....

  10. [Testosterone and mortality].

    Science.gov (United States)

    Stárka, Luboslav

    Subnormal levels of testosterone are frequently found in men of higher age category. Hypogonadal men have lower life expectancy than men with full androgenization and cardiovascular disease, obesity or diabetes is often associated with hypotestosteronemia. Low testosterone level is risk factor for these diseases. However, until now it is not clear whether testosterone deficiency is a cause or consequence of atherosclerosis or metabolic syndrome. A handful of symptoms and metabolic risk markers in hypogonadal men can be ameliorated by testosterone supplementation. Testosterone treatment increased sexual activity and well-being and had a moderate benefit with respect to depressive symptoms but no significant benefit to vitality. Testosterone has a beneficial effect on cardiovascular risk factors, but there is not clear whether it reduces mortality.Key words: civilization diseases - late onset hypogonadism - morbidity - mortality - testosterone - testosterone supplementation.

  11. Effect of chronic cabergoline treatment and testosterone replacement on metabolism in male patients with prolactinomas.

    Science.gov (United States)

    Auriemma, Renata S; Galdiero, Mariano; Vitale, Pasquale; Granieri, Luciana; Lo Calzo, Fabio; Salzano, Ciro; Ferreri, Lucia; Pivonello, Claudia; Cariati, Federica; Coppola, Giorgio; de Angelis, Cristina; Colao, Annamaria; Pivonello, Rosario

    2015-01-01

    Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients. Thirty-two men with prolactinomas, including 22 with total testosterone (TT) 8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment. Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI0), homeostatic model assessment of insulin secretion (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-β. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI0, HOMA-β and HOMA-IR significantly improved compared to baseline, with FI, ISI0, HOMA-β and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC. In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB. © 2015 S. Karger AG, Basel.

  12. Modulation of catechol estrogen synthesis by rat liver microsomes: effects of treatment with growth hormone or testosterone

    International Nuclear Information System (INIS)

    Quail, J.A.; Jellinck, P.H.

    1987-01-01

    The ability of GH from various mammalian species, administered to normal mature male rats by constant infusion, to decrease the hepatic 2-hydroxylation of estradiol (E2) to female levels, as measured by the release of 3 H 2 O from [2-3H]E2, was determined. Rat and human GH (hGH) showed the highest activity while ovine GH was inactive. PRL (0.6 IU/h X kg) administered together with hGH (0.02 IU/h X kg) did not antagonize the feminizing action of GH. Infusion of hGH into male rats decreased the affinity of estradiol 2-hydroxylase for its steroid substrate and altered the linear Lineweaver-Burk plot towards a nonlinear hyperbolic plot characteristic of the female. The apparent Michaelis-Menten constant (Km) for the reaction was 1.69 microM for males and 2.75 microM for testosterone-treated ovariectomized females. An equal mixture of liver microsomes from male and female rats gave kinetic values similar to those observed with males alone. Neonatal imprinting with androgen did not alter the magnitude of the response of female rats to treatment with testosterone and/or GH at maturity and the androgen effect could only be shown in ovariectomized animals. The results with rats of different endocrine status were corroborated by the kinetic data and by the pattern of metabolites obtained with [4- 14 C]E2 when examined by TLC and autoradiography. The hormonal control of estradiol 2-hydroxylase, the key enzyme in catechol estrogen formation, and the contribution of sex-specific multiple forms of the enzyme to this reaction are discussed

  13. Fighting experience alters brain androgen receptor expression dependent on testosterone status

    Science.gov (United States)

    Li, Cheng-Yu; Earley, Ryan L.; Huang, Shu-Ping; Hsu, Yuying

    2014-01-01

    Contest decisions are influenced by the outcomes of recent fights (winner–loser effects). Steroid hormones and serotonin are closely associated with aggression and therefore probably also play important roles in mediating winner–loser effects. In mangrove rivulus fish, Kryptolebias marmoratus, individuals with higher testosterone (T), 11-ketotestosterone and cortisol levels are more capable of winning, but titres of these hormones do not directly mediate winner–loser effects. In this study, we investigated the effects of winning/losing experiences on brain expression levels of the receptor genes for androgen (AR), oestrogen α/β (ERα/β), glucocorticoid (GR) and serotonin (5-HT1AR). The effect of contest experience on AR gene expression depended on T levels: repeated losses decreased, whereas repeated wins increased AR gene expression in individuals with low T but not in individuals with medium or high T levels. These results lend strong support for AR being involved in mediating winner–loser effects, which, in previous studies, were more detectable in individuals with lower T. Furthermore, the expression levels of ERα/β, 5-HT1AR and GR genes were higher in individuals that initiated contests against larger opponents than in those that did not. Overall, contest experience, underlying endocrine state and hormone and serotonin receptor expression patterns interacted to modulate contest decisions jointly. PMID:25320171

  14. Effect of Voluntary Ethanol Consumption Combined with Testosterone Treatment on Cardiovascular Function in Rats: Influence of Exercise Training.

    Directory of Open Access Journals (Sweden)

    Sheila A Engi

    Full Text Available This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6, animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α1-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances.

  15. [Hypoplasia of the penis: etiologic diagnosis and results of treatment with delayed-action testosterone].

    Science.gov (United States)

    Velásquez-Urzola, A; Léger, J; Aigrain, Y; Czernichow, P

    1998-08-01

    Results of long-term testosterone treatment of congenital hypoplasia of the penis are sparse; the aim of this work was to evaluate these results according to age at onset of treatment, the presence or absence of hypospadias, and its eventual adverse effect upon growth and bone maturation. Sixty-six children with congenital hypoplasia of the penis, isolated (n = 31) or associated with a hypospadias (n = 35), were evaluated between 1 day and 16 years of age. The prevalence (40% of the cases) of the different malformations and/or syndromes associated with congenital hypoplasia and its severity were not different whether the penis was isolated or associated with hypospadias (male-pseudohermaphroditism). The effect of the testosterone heptylate (IM) was evaluated in 40 children treated before 10 years of age. The penis' increase in length was more important in the children with isolated micropenis (+2.1 +/- 0.8 SDS) than those with hypospadias (+1.3 +/- 1.2 SDS) but, in all cases, its increase was better when the treatment was started during the neonatal period, which corresponded to those with the most severe forms of micropenis. A mean regression of the penile volume of -0.7 +/- 0.8 SDS was noticed after the end of each stimulation. No long-term secondary effects related to treatment were seen on later growth and bone-maturation. Penile length at the last follow-up was not associated with total dose of testosterone but with its length at the first evaluation time (r = 0.52; P = 0.002).

  16. Current approaches to erectile dysfunction and testosterone deficiency.

    Science.gov (United States)

    Wespes, E

    2010-12-01

    Androgens are essential for the development of the penis and it is well known that testosterone play a critical role in the physiology of erectile function. From animal studies, testosterone insufficiency disrupts cellular-signaling pathways and induces pathologic alterations in penile tissues leading to erectile dysfunction. In human, the testosterone threshold for maintaining erection is low which explains the reason why some contracted men still have an erection due to the androgens produced by the adrenal gland. Testosterone alone can improve erectile function in hypogonadic patients. Associated with PDE5-I, testosterone supplementation is a treatment for the hypogonadic patients non responders to therapy. The article reviews the different aspects of the testosterone role in the pathophysiology of erection.

  17. Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

    OpenAIRE

    Wilson, V S; McLachlan, J B; Falls, J G; LeBlanc, G A

    1999-01-01

    Assessment of the impact of environmental chemicals on androgen homeostasis in rodent models is confounded by high intraindividual and interindividual variability in circulating testosterone levels. Our goal was to evaluate changes in testosterone biotransformation processes as a measure of androgen homeostasis and as a biomarker of exposure to androgen-disrupting chemicals. Sex-specific differences in hepatic testosterone biotransformation enzyme activities were identified in CD-1 mice. Gona...

  18. Effects of testosterone treatment on hypothalamic neuroplasticity in female-to-male transgender individuals

    OpenAIRE

    Kranz, Georg S.; Hahn, Andreas; Kaufmann, Ulrike; Tik, Martin; Ganger, Sebastian; Seiger, René; Hummer, Allan; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2017-01-01

    Diffusion-weighted imaging (DWI) is used to measure gray matter tissue density and white matter fiber organization/directionality. Recent studies show that DWI also allows for assessing neuroplastic adaptations in the human hypothalamus. To this end, we investigated a potential influence of testosterone replacement therapy on hypothalamic microstructure in female-to-male (FtM) transgender individuals. 25 FtMs were measured at baseline, 4 weeks, and 4 months past treatment start and compared t...

  19. Evaluation of late-onset hypogonadism (andropause) treatment using three different formulations of injectable testosterone

    OpenAIRE

    Hohl, Alexandre; Marques, Mario Octávio Thá; Coral, Marisa Helena César; Walz, Roger

    2009-01-01

    OBJECTIVE: To compare the modalities of treatment for male hypogonadism available in Brazil. METHODS: Thirty-two men with late-onset hypogonadism ("andropause") were followed-up in the Hospital de Guarnição de Florianópolis, in Florianópolis, south Brazil. Clinical diagnosis was established according to AMS questionnaire (positive if equal to or higher than 27 points), and laboratorial diagnosis was made through low values of total testosterone (under 300 ng/dL) and/or free calculated testost...

  20. Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance

    DEFF Research Database (Denmark)

    Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun

    2014-01-01

    is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved...... in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls....... Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin...

  1. Beneficial effect of testosterone in the treatment of chronic autoimmune thyroiditis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, S.A.; Young, P.R.; Penhale, W.J.

    1986-01-01

    Early thymectomy and sublethal irradiation of normal rats consistently induces a sex-dependent chronic autoimmune thyroiditis. Females are much more susceptible to this autoimmune disorder than are males. The possible therapeutic effects of testosterone (Te) on established autoimmune thyroiditis has been investigated in this model. The pathologic condition of the gland before treatment was monitored by a thyroid grafting and extirpation techniques. Te administration by either parenteral injection or implantation caused significant regression of established thyroiditis. Repeated doses of Te ester in oil were found to be more effective than powdered free-Te given by implantation, and frequently produced complete resolution of chronic lesions involving the entire gland. In these thyroids, there was reappearance of normal thyroid architecture and complete absence of mononuclear cellular infiltration. However, no inhibitory effect on serum autoantibody production to thyroglobulin was noted with any form of Te treatment. These observations strengthen the concept that cellular rather than humoral mechanisms are involved in the pathogenesis of thyroiditis.

  2. Plasma testosterone and androstenedione in insulin dependent patients at time of diagnosis and during the first year of insulin treatment

    DEFF Research Database (Denmark)

    Gluud, C; Madsbad, S; Krarup, T

    1982-01-01

    Ten male patients and 6 female patients with newly diagnosed insulin dependent diabetes mellitus and significant ketosis were studied before and during the first year of insulin treatment. At onset plasma concentrations of testosterone and androstenedione were significantly (P less than 0...

  3. Modulation of the pentose phosphate pathway alters phase I metabolism of testosterone and dextromethorphan in HepG2 cells.

    Science.gov (United States)

    Xiao, Wen-jing; Ma, Ting; Ge, Chun; Xia, Wen-juan; Mao, Yong; Sun, Run-bin; Yu, Xiao-yi; Aa, Ji-ye; Wang, Guang-ji

    2015-02-01

    The pentose phosphate pathway (PPP) is involved in the activity of glucose-6-phosphate dehydrogenase (G6PD) and generation of NADPH, which plays a key role in drug metabolism. The aim of this study was to investigate the effects of modulation of the PPP on drug metabolism capacity in vitro. A pair of hepatic cell lines, ie, the cancerous HepG2 cells and normal L02 cells, was used. The expression of CYP450 enzymes, p53 and G6PD in the cells were analyzed. The metabolism of testosterone (TEST, 10 μmol/L) and dextromethorphan (DEM, 1 μmol/L), the two typical substrates for CYP3A4 and CYP2D6, in the cells was examined in the presence of different agents. Both the expression and metabolic activities of CYP3A4 and CYP2D6 were considerably higher in HepG2 cells than in L02 cells. The metabolism of TEST and DEM in HepG2 cells was dose-dependently inhibited by the specific CYP3A4 inhibitor ketoconazole and CYP2D6 inhibitor quinidine. Addition of the p53 inhibitor cyclic PFT-α (5, 25 μmol/L) in HepG2 cells dose-dependently enhanced the metabolism of DEM and TEST, whereas addition of the p53 activator NSC 66811 (3, 10, 25 μmol/L) dose-dependently inhibited the metabolism. Furthermore, addition of the G6PD inhibitor 6-aminonicotinamide (5, 15 μmol/L) in HepG2 cells dose-dependently inhibited the metabolism of DEM and TEST, whereas addition of the PPP activity stimulator menadione (1, 5, 15 μmol/L) dose-dependently enhanced the metabolism. Modulation of p53 and the PPP alters the metabolism of DEM and TEST, suggesting that the metabolic flux pattern of PPP may be closely involved in drug metabolism and the individual variance.

  4. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study

    Directory of Open Access Journals (Sweden)

    Carlos Teodósio Da Ros

    2012-08-01

    Full Text Available INTRODUCTION: Male testosterone deficiency is associated with bad sexual function and quality of life (QoL. The aim of this study was to determine whether a daily dose of 25 mg clomiphene citrate (CC is effective in stimulating the endogenous testosterone production pathway and to address the applicability of this medication as a therapeutic option for symptomatic hypogonadism. MATERIALS AND METHODS: This was a prospective study. Men with low sexual desire and testosterone levels (T below 400 ng/dL were selected to receive CC. Blood samples were obtained to determine baseline measurements of serum T, estradiol, LH, lipid profile and fasting plasma glucose. Each patient was treated with a daily dose of 25 mg CC for at least 3 months. Patients were asked if they experienced any side effects related to the use of CC and if they experienced any improvement in their sexual profile. Paired samples T-test was utilized to analyze responses to therapy. RESULTS: Our cohort consisted of 125 men with hypogonadism and low libido. Mean age was 62 years (± 11.1 years. Serum T levels ranged from 309 ng/dL (baseline, mean value to 642 ng/dL (3 months after CC initiation, mean value (p < 0.001. Serum cholesterol levels ranged from 197 to 186 mg/dL (p = 0.003. There were no statistically significant differences when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting plasma glucose and prolactin. All men reported improvements in the post-treatment QoL scores. No serious adverse events were recorded. CONCLUSIONS: The CC was effective in stimulating the endogenous production of testosterone. A lower level of total cholesterol was verified after three months of treatment. This medication should be considered as a therapeutic option for some patients with symptomatic male testosterone deficiency.

  5. Testosterone reduces amygdala-orbitofrontal cortex coupling.

    NARCIS (Netherlands)

    Wingen, G.A. van; Mattern, C.; Verkes, R.J.; Buitelaar, J.K.; Fernandez, G.S.E.

    2010-01-01

    Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered

  6. Testosterone reduces amygdala-orbitofrontal cortex coupling

    NARCIS (Netherlands)

    van Wingen, Guido; Mattern, Claudia; Verkes, Robbert Jan; Buitelaar, Jan; Fernández, Guillén

    2010-01-01

    Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered

  7. Testosterone and obesity.

    Science.gov (United States)

    Kelly, D M; Jones, T H

    2015-07-01

    Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal-obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism. © 2015 World Obesity.

  8. Short- and long-term clinical skin effects of testosterone treatment in trans men.

    Science.gov (United States)

    Wierckx, Katrien; Van de Peer, Fleur; Verhaeghe, Evelien; Dedecker, David; Van Caenegem, Eva; Toye, Kaatje; Kaufman, Jean Marc; T'Sjoen, Guy

    2014-01-01

    Our knowledge concerning the effects of testosterone (T) therapy on the skin of trans men (female-to-male transsexuals) is scarce. The aim of this study was to evaluate the short- and long-term clinical effects of T treatment on the skin of trans men. We conducted a prospective intervention study in 20 hormone naive trans men and a cross-sectional study in 50 trans men with an average of 10 years on T therapy. Acne lesions were assessed using the Gradual Acne Grading Scale, hair patterns using the Ferriman and Gallwey classification (F&G), and androgenetic alopecia using the Norwood Hamilton Scale. T treatment increased facial and body hair growth. The F&G score increased progressively from a median value of 0.5 at baseline to a value of 12 after 12 months of T administration. After long-term T treatment, all but one trans man achieved an F&G score indicative of hirsutism in women, with a median value of 24. Only one trans man acquired mild frontotemporal hair loss during the first year of T treatment, whereas 32.7% of trans men had mild frontotemporal hair loss and 31% had moderate to severe androgenetic alopecia after long-term T therapy. The presence and severity of acne increased during the first year of T therapy, and peaked at 6 months. After long-term T treatment, most participants had no or mild acne lesions (93.9%). Dermatological outcome was not demonstrably related to individual serum T or dihydrotestosterone levels. T treatment increased facial and body hair in a time-dependent manner. The prevalence and severity of acne in the majority of trans men peaked 6 months after beginning T therapy. Severe skin problems were absent after short- and long-term T treatment. © 2013 International Society for Sexual Medicine.

  9. Presence of mother and unfamiliar female alters levels of testosterone, progesterone, cortisol, adrenocorticotropin, and behavior in maturing Guinea pigs.

    Science.gov (United States)

    Hennessy, Michael B; Maken, Deborah S; Graves, Franklynn C

    2002-08-01

    Although the guinea pig is characterized by precocial physical development and minimal active maternal care, studies suggest the presence of the mother can influence neuroendocrine and behavioral activity of offspring even well beyond weaning. Previous results may have been influenced by the procedure of housing weaned subjects with the mother to within 2 days of testing. The present study examined approximately 40-day-old guinea pigs housed apart from the mother for 0 (not rehoused), 2, or 10 days. Rehousing without the mother led to elevations in plasma testosterone (measured in males), progesterone (measured in females), cortisol, and adrenocorticotropin (ACTH) (both measured in males and females). Offspring housed without the mother for 10 days had the highest progesterone, cortisol, and ACTH levels. Testosterone elevations were observed in 2-day-, but not 10-day-, rehoused animals. Regardless of rehousing condition, 60 min isolation in a novel test cage elevated progesterone, cortisol, and ACTH, and reduced testosterone. These effects were all moderated if the subject was tested with the mother or another female. Sexual behavior toward the mother was observed frequently, but only in males housed apart from her prior to testing. Overall, males and females that had been housed apart from the mother interacted with her as they would an unfamiliar female. Our results corroborate previous findings, suggest the effect of housing apart from the mother on male testosterone is transitory, and indicate that continuous housing with the mother past weaning suppresses circulating progesterone in females and cortisol and ACTH in both sexes.

  10. Congenital hypogonadotropic hypogonadism and micropenis: effect of testosterone treatment on adult penile size why sex reversal is not indicated.

    Science.gov (United States)

    Bin-Abbas, B; Conte, F A; Grumbach, M M; Kaplan, S L

    1999-05-01

    Micropenis is commonly due to fetal testosterone deficiency. The clinical management of this form of micropenis has been contentious, with disagreement about the capacity of testosterone treatment to induce a functionally adequate adult penis. As a consequence, some clinicians recommend sex reversal of affected male infants. We studied 8 male subjects with micropenis secondary to congenital pituitary gonadotropin deficiency from infancy or childhood to maturity (ages 18 to 27 years). Four patients were treated with testosterone before 2 years of age (group I) and four between age 6 and 13 years (group II). At presentation, the mean penile length in group I was 1.1 cm (-4 SD; range, 0.5 to 1.5 cm) and in group II it was 2.7 cm (-3.4 SD; range, 1.5 to 3.5 cm). All patients received one or more courses of 3 intramuscular injections of testosterone enanthate (25 or 50 mg) at 4-week intervals in infancy or childhood. At the age of puberty the dose was gradually increased to 200 mg monthly and later to an adult replacement regimen. As adults, both group I and II had attained a mean final penile length of 10.3 cm 2.7 cm with a range of 8 to 14 cm (mean adult stretched penile length for Caucasians is 12.4 2.7 cm). Six of 8 men were sexually active, and all reported normal male gender identity and psychosocial behavior. We conclude that 1 or 2 short courses of testosterone therapy in infancy and childhood augment penile size into the normal range for age in boys with micropenis secondary to fetal testosterone deficiency; replacement therapy at the age of puberty results in an adult size penis within 2 SD of the mean. We found no clinical, psychologic, or physiologic indications to support conversion of affected male infants to girls. Further, the results of this study do not support the notion, derived from data in the rat, that testosterone treatment in infancy or childhood impairs penile growth in adolescence and compromises adult penile length.

  11. Effects of gonadectomy and testosterone treatment on aquaporin expression in the kidney of normotensive and hypertensive rats.

    Science.gov (United States)

    Loh, Su Yi; Giribabu, Nelli; Salleh, Naguib

    2017-07-01

    We tested the hypothesis that testosterone-induced increase in blood pressure was due to changes in aquaporin (AQP) expression in kidneys. In this study, expression level of kidney AQPs was investigated under testosterone influence. Adult normotensive Wistar Kyoto (WKY) and hypertensive SHR male and female rats underwent gonadectomy. For female rats, testosterone was given for six weeks duration, two weeks following ovariectomy via subcutaneous silastic implant. Mean arterial pressure (MAP) was measured in all the rats after eight weeks via carotid artery cannulation and the rats were then sacrificed and kidneys were harvested for analyses of AQP-1, 2, 3, 4, 6, and 7 mRNA and protein expressions by quantitative real-time PCR and Western blotting, respectively. Distribution of AQP subunits' protein in kidneys was observed by immunofluorescence. In male WKY rats, MAP, AQP-1, 2, 4, and 7 protein; and mRNA expression decreased however AQP-3 protein and mRNA expression increased following orchidectomy. The vice versa effects were observed in testosterone-treated ovariectomized female WKY rats. However, no changes in AQP-6 expression were observed. Meanwhile, in adult male SHR rats, MAP and expression level of all AQP subunits decreased following orchidectomy. The opposite effects were seen in ovariectomized female SHR rats following testosterone treatment. Immunofluorescence study showed AQP-1 and AQP-7 were distributed in the proximal convoluted tubules (PCT) while AQP-2, AQP-4, and AQP-6 were distributed in the collecting ducts (CDs). AQP-3 was distributed in the PCT and CD. In conclusion, changes in AQP subunit expression in kidneys could explain changes in blood pressure under testosterone influence. Impact statement This study provides fundamental understanding on the mechanisms underlying testosterone-induced increase in blood pressure which involve regulation of aquaporin channel subunits in the kidneys. A better understanding of this issue can help to explain

  12. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue

    2015-01-01

    Purpose. We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. Methods. Double-blinded, placebo-controlled study in 54 men aged 60-78 years...... central fat mass (r = 0.84). Conclusions. Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass....

  13. Roosters affected by epididymal lithiasis present local alteration in vitamin D3, testosterone and estradiol levels as well as estrogen receptor 2 (beta) expression.

    Science.gov (United States)

    Oliveira, André G; Dornas, Rubem A P; Praes, Lílian C; Hess, Rex A; Mahecha, Germán A B; Oliveira, Cleida A

    2011-09-01

    Epididymal lithiasis is a reproductive dysfunction of roosters that is associated with loss of fertility and is characterized by the formation of calcium stones in the lumen of the efferent ductules of the epididymal region. The efferent ductules of birds are responsible for the reabsorption of the fluid coming from the testis as well as luminal calcium. It has been hypothesized that the epididymal stone formation may be related to the impairment of local fluid or calcium homeostasis, which depends on hormones such as estradiol (E(2)). Therefore, this study aimed to investigate possible alterations in the expression of ERα (ESR1) and ERβ (ESR2) in the epididymal region of roosters affected by epididymal lithiasis. The study was performed by immunohistochemistry and western blotting assays. In addition, the concentrations of E(2), vitamin D3, and testosterone, which are also key hormones in maintenance of calcium homeostasis, were determined in the plasma and epididymal region, by ELISA. It was observed that ESR2 expression is increased in all segments of the epididymal region of affected roosters, whereas ESR1 levels are not altered. Moreover, the hormone concentration profiles were changed, as in the epididymal region of roosters with lithiasis the E(2) levels were increased and vitamin D3 as well as testosterone concentrations were significantly decreased. These results suggest that a hormonal imbalance may be involved with the origin and progression of the epididymal lithiasis, possibly by affecting the local fluid or calcium homeostasis.

  14. Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone.

    Science.gov (United States)

    La Vignera, Sandro; Condorelli, Rosita Angela; Cimino, Laura; Russo, Giorgio Ivan; Morgia, Giuseppe; Calogero, Aldo E

    2016-01-01

    The traditional pharmacological treatment of patients with late onset hypogonadism (LOH) is represented by different formulations of testosterone (T) or alternatively by the extractive human chorionic gonadotropin (HCG). The hormone replacement treatment (HRT) is associated with the potential increase of hematocrit, serum concentrations of prostate-specific antigen (PSA) and prostate volume. Moreover, the gynecomastia represent a condition frequently associated with HRT. Recent evidences showed the role of leydig cells in the 25-hydroxylation of vitamin D and the elevated frequency of hypovitaminosis D among LOH patients. Finally, another important aspect of LOH is represented by the frequency of secondary infertility due to age or to traditional HRT. This study evaluated 40 LOH patients treated for 6 months with extractive HCG (n = 10 patients) and three different formulations of T: transdermal (n = 10 patients), undecaonate (n = 10 patients) and enantate (n = 10 patients). Hormonal, anthropometric, metabolic and sperm parameters were evaluated and compared. Moreover, the main safety parameters and the results of the main questionnaires were evaluated. After treatment, HCG group showed serum concentrations of 25-OH-vitamin D significantly higher (p < 0.05) and serum concentrations of oestrogens significantly lower (p < 0.05) compared with other groups. Moreover, they showed a mean value of hematocrit, PSA and prostate volume significantly lower (p < 0.05) compared with other groups. Finally, all the groups treated with T showed a significant reduction (p < 0.05) of sperm density and of percentage of spermatozoa with progressive motility compared with HCG group.

  15. Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer.

    Science.gov (United States)

    Disciglio, Vittoria; Devecchi, Andrea; Palumbo, Orazio; Carella, Massimo; Penso, Donata; Milione, Massimo; Valle, Giorgio; Pierotti, Marco Alessandro; Vitellaro, Marco; Bertario, Lucio; Canevari, Silvana; Signoroni, Stefano; De Cecco, Loris

    2016-06-07

    Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described. Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers. By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

  16. Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Whoon Jong; Nichols, Romaine C. Jr. [Dept. of Radiation Oncology, Univ. of Florida, Gainesville (United States); Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: rnichols@floridaproton.org; And others

    2013-04-15

    Background: To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy. Material and methods: Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs. Results: The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant. Conclusion: Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy.

  17. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

    Directory of Open Access Journals (Sweden)

    Gary Golds

    2017-01-01

    Full Text Available It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed.

  18. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

    Science.gov (United States)

    Houdek, Devon

    2017-01-01

    It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed. PMID:28408926

  19. Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido.

    Science.gov (United States)

    Estienne, Mark J; Harper, Allen F; Speight, Susan M; Crawford, Russell J; Barb, C Richard

    2009-11-01

    The objective was to determine the effects of the opioid peptide receptor antagonist, naloxone on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n=8) or low libido (n=8) based on the willingness to mount an artificial sow and allow semen collection. On the day of the experiment, blood was sampled every 15 min for 4 h before and 4 h after i.v. injection of naloxone (1 mg/kg body weight). After naloxone treatment, a libido status by time interaction was detected and concentrations of LH within 15 min after treatment were greater (plibido boars than for Low-libido boars. Concentrations of testosterone were highly variable amongst boars and there were no effects of libido status (p=0.66) or libido status by time (p=0.66). There was, however, an effect of time (ptestosterone in samples collected between 0.5 and 1.25 h after naloxone were greater than concentrations in samples collected prior to injection. In summary, the responsiveness of the hypothalamic-gonadotropic-gonadal axis to opioid receptor antagonism was heightened in boars displaying a high level of sexual motivation.

  20. Early social instability affects plasma testosterone during adolescence but does not alter reproductive capacity or measures of stress later in life.

    Science.gov (United States)

    Siegeler, Katja; Wistuba, Joachim; Damm, Oliver S; von Engelhardt, Nikolaus; Sachser, Norbert; Kaiser, Sylvia

    2013-08-15

    The social environment plays an important role in modulating processes of the hormonal and behavioural profile of an animal in a variety of group-living species. In wild cavies for instance, unstable social environmental conditions during pregnancy and lactation lead to an infantilised biobehavioural profile of the male offspring. In the present study, the influence of the social environment during pregnancy and lactation on the male wild cavy offsprings' plasma testosterone development, reproductive capacity and stress system activity was investigated. To this purpose, 12 sons whose mothers had lived in an unstable social environment during pregnancy and lactation were compared with 12 sons whose mothers had lived in a stable social environment during the same time. Plasma testosterone (T) and plasma cortisol (C) concentrations were determined from days 20 to 107 of age. Adrenal tyrosine hydroxylase (TH) activity and different parameters of reproductive capacity (weights of testes, epididymides and accessory sex glands, cellular composition of the testes, DNA fragmentation indices and sperm motility parameters) were analysed at day 107 of age. TH activity and plasma C were unaffected by different social environmental conditions early in life. The developmental time course of T concentrations, however, was significantly different: Sons whose mothers had lived in an unstable social environment during pregnancy and lactation showed a delayed increase in T concentrations around adolescence compared to controls. In contrast, no reproduction-related parameters measured within this study differed significantly between the two groups. Thus, early social instability affects plasma testosterone development during adolescence in a significant way but does not alter reproductive capacity or measures of stress later in life. © 2013.

  1. Randomized controlled trial to evaluate transdermal testosterone in female cancer survivors with decreased libido; North Central Cancer Treatment Group protocol N02C3.

    Science.gov (United States)

    Barton, Debra L; Wender, Donald B; Sloan, Jeff A; Dalton, Robert J; Balcueva, Ernie P; Atherton, Pamela J; Bernath, Albert M; DeKrey, Wanda L; Larson, Tim; Bearden, James D; Carpenter, Paul C; Loprinzi, Charles L

    2007-05-02

    Decreased libido is one of several changes in sexual function that are often experienced by female cancer patients. Transdermal testosterone therapy has been associated with increased libido among estrogen-replete women who report low libido. In a phase III randomized, placebo-controlled crossover clinical trial, we evaluated whether transdermal testosterone would increase sexual desire in female cancer survivors. Postmenopausal women with a history of cancer and no current evidence of disease were eligible if they reported a decrease in sexual desire and had a sexual partner. Eligible women were randomly assigned to receive 2% testosterone in Vanicream for a testosterone dose of 10 mg daily or placebo Vanicream for 4 weeks and were then crossed over to the opposite treatment for an additional 4 weeks. The primary endpoint was sexual desire or libido, as measured using the desire subscales of the Changes in Sexual Functioning Questionnaire, as assessed at baseline and at the end of 4 and 8 weeks of treatment. Serum levels of bioavailable testosterone were measured at the same times. All statistical tests were two-sided. We enrolled 150 women. Women who were on active testosterone cream had higher serum levels of bioavailable testosterone than women on placebo (mean change from baseline, testosterone versus placebo, week 4, 11.57% versus 0%, difference = 11.57%, 95% confidence interval [CI] = 8.49% to 14.65%; week 8, 10.21% versus 0.28%, difference = 9.92%, 95% CI = 5.42% to 14.42%; Plibido change from baseline to weeks 4 and 8 was similar on both arms. Increased testosterone level did not translate into improved libido, possibly because women on this study were estrogen depleted.

  2. Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird

    Science.gov (United States)

    Peterson, Mark P.; Rosvall, Kimberly A.; Taylor, Charlene A.; Lopez, Jacqueline Ann; Choi, Jeong-Hyeon; Ziegenfus, Charles; Tang, Haixu; Colbourne, John K.; Ketterson, Ellen D.

    2014-01-01

    Males and females can be highly dimorphic in metabolism and physiology despite sharing nearly identical genomes, and both sexes respond phenotypically to elevated testosterone, a steroid hormone that alters gene expression. Only recently has it become possible to learn how a hormone such as testosterone affects global gene expression in non-model systems, and whether it affects the same genes in males and females. To investigate the transcriptional mechanisms by which testosterone exerts its metabolic and physiological effects on the periphery, we compared gene expression by sex and in response to experimentally elevated testosterone in a well-studied bird species, the dark-eyed junco (Junco hyemalis). We identified 291 genes in the liver and 658 in the pectoralis muscle that were differentially expressed between males and females. In addition, we identified 1727 genes that were differentially expressed between testosterone-treated and control individuals in at least one tissue and sex. Testosterone treatment altered the expression of only 128 genes in both males and females in the same tissue, and 847 genes were affected significantly differently by testosterone treatment in the two sexes. These substantial differences in transcriptional response to testosterone suggest that males and females may employ different pathways when responding to elevated testosterone, despite the fact that many phenotypic effects of experimentally elevated testosterone are similar in both sexes. In contrast, of the 121 genes that were affected by testosterone treatment in both sexes, 78% were regulated in the same direction (e.g. either higher or lower in testosterone-treated than control individuals) in both males and females. Thus, it appears that testosterone acts through both unique and shared transcriptional pathways in males and females, suggesting multiple mechanisms by which sexual conflict can be mediated. PMID:24198265

  3. No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Gluud, C; Wantzin, P; Eriksen, J

    1988-01-01

    . Furthermore, the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period (p less than 0.01). However, the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function...

  4. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  5. Hormonal, metabolic, and endometrial safety of testosterone vaginal cream versus estrogens for the treatment of vulvovaginal atrophy in postmenopausal women: a randomized, placebo-controlled study.

    Science.gov (United States)

    Fernandes, Tatiane; Pedro, Adriana O; Baccaro, Luiz F; Costa-Paiva, Lucia H

    2018-02-16

    The aim of the study was to evaluate the laboratory and endometrial safety of topical testosterone versus topical estrogen for the treatment of vaginal atrophy in postmenopausal women. This was a randomized, placebo-controlled trial of 60 postmenopausal women aged 40 to 70 years at the Menopause Clinic of CAISM UNICAMP. Women were randomized into three vaginal treatment groups: estrogen, testosterone, or placebo. The treatment was applied 3 times a week for 12 weeks. Hormonal laboratory values of follicle-stimulating hormone, luteinizing hormone, estradiol, estrone, androstenedione, total testosterone, free testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin were assessed at baseline and at 6 and 12 weeks. Metabolic laboratory values of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase were also assessed at baseline and at 6 and 12 weeks. Endometrial safety was assessed using ultrasonography at baseline and at 12 weeks. After 12 weeks of treatment, there were no significant differences in hormonal or metabolic laboratory values among all three groups. Two participants in the estrogen group had increased serum estradiol after 12 weeks of treatment. No change in endometrial thickening was reported in all three groups. Twelve weeks of treatment with topical testosterone or estrogen in postmenopausal women with symptoms of vaginal atrophy demonstrated laboratory and endometrial safety when compared with placebo.

  6. Changes of Serum Total and Free Testosterone Concentrations in Male Chronic Hemodialysis Patients with Secondary Hyperparathyroidism in Response to Cinacalcet Treatment

    Directory of Open Access Journals (Sweden)

    Piotr Kuczera

    2016-01-01

    Full Text Available Background/Aims: Calcium sensing receptor (CaSR is expressed, among others also in testis. Cinacalcet binds to the CaSR, increases sensitivity of CaSR to serum calcium and is used in the treatment of secondary hyperparathyroidism (sHPT in chronic hemodialysis patients (HDP. In most of male HDP, serum testosterone concentration is lower than in healthy males. The aim of this study was to assess the influence of six-month treatment with cinacalcet on the serum total and free testosterone concentration in male HDP with sHPT. Methods: 38 male, hemodialysed CKD patients with sHPT (PTH>300 pg/ml were enrolled into the study. In each patient serum PTH, total testosterone (TT and free testosterone (FT concentrations were assessed before the first dose of cinacalcet and then after 3 and 6 months of treatment. The results are presented as means with 95% confidence interval. Results: In 33 patients who completed the study cinacalcet treatment caused significant decrease of serum PTH from 1143 pg/ml (828 - 1458 pg/ml at the baseline, to 809 pg/ml (487 - 1132pg/ml after 3 month of treatment (p = 0.002, and to 607 pg/ml (281 - 934pg/ml; p Conclusion: Treatment with cinacalcet decreases serum total and free testosterone concentration in male hemodialysed patients with chronic kidney disease and secondary hyperparathyroidism.

  7. Developmental programming: Impact of prenatal testosterone treatment and postnatal obesity on ovarian follicular dynamics

    OpenAIRE

    Padmanabhan, V; Smith, P; Veiga-Lopez, A

    2012-01-01

    Prenatal testosterone (T) excess leads to reproductive dysfunctions in sheep with obesity exaggerating such defects. Developmental studies found ovarian reserve is similar in control and prenatal T sheep at fetal day 140, with prenatal T females showing increased follicular recruitment and persistence at 10 months of age (postpubertal). This study tested if prenatal T sheep show accelerated depletion prepubertally and if depletion of ovarian reserve would explain loss of cyclicity in prenatal...

  8. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

    OpenAIRE

    Golds, Gary; Houdek, Devon; Arnason, Terra

    2017-01-01

    It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testoster...

  9. Testosterone treatment in women : Aspects on sexuality, well-being and metabolism

    OpenAIRE

    Flöter Rådestad, Angelique

    2004-01-01

    The expected postmenopausal lifetime of women in the western world is about 30 years. Hormones, such as estrogen and progestogen, may affect the quality of postmenopausal life and have been well studied. Androgens act on numerous tissues in the body, however little is known about their biological function in women and the possible effects of androgen insufficiency on women s health. Oophorectomy reduces by half the levels of testosterone in serum and may be associated wit...

  10. The many faces of testosterone

    Directory of Open Access Journals (Sweden)

    Jerald Bain

    2008-01-01

    Full Text Available Jerald BainDepartment of Medicine, Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario, CanadaAbstract: Testosterone is more than a “male sex hormone”. It is an important contributor to the robust metabolic functioning of multiple bodily systems. The abuse of anabolic steroids by athletes over the years has been one of the major detractors from the investigation and treatment of clinical states that could be caused by or related to male hypogonadism. The unwarranted fear that testosterone therapy would induce prostate cancer has also deterred physicians form pursuing more aggressively the possibility of hypogonadism in symptomatic male patients. In addition to these two mythologies, many physicians believe that testosterone is bad for the male heart. The classical anabolic agents, 17-alkylated steroids, are, indeed, potentially harmful to the liver, to insulin action to lipid metabolism. These substances, however, are not testosterone, which has none of these adverse effects. The current evidence, in fact, strongly suggests that testosterone may be cardioprotective. There is virtually no evidence to implicate testosterone as a cause of prostate cancer. It may exacerbate an existing prostate cancer, although the evidence is flimsy, but it does not likely cause the cancer in the first place. Testosterone has stimulatory effects on bones, muscles, erythropoietin, libido, mood and cognition centres in the brain, penile erection. It is reduced in metabolic syndrome and diabetes and therapy with testosterone in these conditions may provide amelioration by lowering LDL cholesterol, blood sugar, glycated hemoglobin and insulin resistance. The best measure is bio-available testosterone which is the fraction of testosterone not bound to sex hormone binding globulin. Several forms of testosterone administration are available making compliance

  11. Possibilities оf use of testosterone undecanoate in treatment in stroke male patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    L. Yu. Morgunov

    2014-11-01

    Full Text Available We have studied 154 men with the first hemispheric ischemic stroke. Clinical and laboratory studies have revealed the androgen deficiency in 66.3 %, with its frequency higher in patients with diabetes mellitus type 2 (50 % and 26.3 %, respectively. Forty-two men with diabetes mellitus type 2 and acquired androgenic deficit received replacing treatment with testosterone undecanoate. After 2 years from the beginning of treatment, there were the decrease in clinical severity of androgenic deficit, the increase of total and free testosterone levels, and muscle power in the main group compared to the controls. Body mass index, glycated hemoglobin, cholesterol, triglycerides, low density lipoproteins have decreased as well. Secondary stroke has developed in 3 (7.1 % patients of the main group and in 5 (16.6 % controls. The treatment with androgens has a positive effect on risk factors of secondary ischemic stroke. It is an effective method for improvement of social adaptation of men survived after the stroke..

  12. RESTORATION OF FERTILITY IN A MAN WITH AZOOSPERMIA DEVELOPED IN RESPONSE TO TREATMENT WITH TESTOSTERONE GEL (A CASE REPORT

    Directory of Open Access Journals (Sweden)

    I. A. Korneev

    2017-01-01

    Full Text Available Testosterone replacement therapy (TRT allows to combat the symptoms of age-related androgen deficiency (AAD; however, it may have side effects, including the reduction in sperm count and even complete cessation of spermatogenesis and development of azoospermia. The fertility may not be restored even within 18 month after treatment completion. Russian researcher explored the impact of TRT with gel on the ejaculate parameters in men with hypogonadism and observed no negative effects on spermatogenesis within 3 months after treatment initiation. We describe a clinical case of reversible azoospermia induced by a relatively short course of TRT with gel. Fertilizing capacity of sperm was finally restored, which was confirmed by a clinical pregnancy obtained by in vitro fertilization. Physicians prescribing TRT should inform their patients that such treatment is contraindicated to those men who would like to preserve their fertility and explain that the restoration of fertility will take some time after treatment completion.

  13. Encapsulation of testosterone by chitosan nanoparticles.

    Science.gov (United States)

    Chanphai, P; Tajmir-Riahi, H A

    2017-05-01

    The loading of testosterone by chitosan nanoparticles was investigated, using multiple spectroscopic methods, thermodynamic analysis, TEM images and modeling. Thermodynamic parameters showed testosterone-chitosan bindings occur mainly via H-bonding and van der Waals contacts. As polymer size increased more stable steroid-chitosan conjugates formed and hydrophobic contact was also observed. The loading efficacy of testosterone-nanocarrier was 40-55% and increased as chitosan size increased. Testosterone encapsulation markedly alters chitosan morphology. Chitosan nanoparticles are capable of transporting testosterone in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Testosterone Replacement Therapy: The Emperor's New Clothes.

    Science.gov (United States)

    Sansone, Andrea; Sansone, Massimiliano; Lenzi, Andrea; Romanelli, Francesco

    2017-02-01

    The mean age of the world population has steadily increased in the last decades, as a result of increased life expectancy and reduced birth rate. Global aging has led to a greater worldwide cost for healthcare: hormonal alterations contribute to the pathogenesis of several conditions and might cause a significant reduction in the perceived sense of well-being. Menopause is archetypal of hormonal alterations occurring during aging: in males, sex hormones do not decrease abruptly, yet testosterone levels decrease steadily and continuously during aging, ultimately resulting in late-onset hypogonadism. Treatment of this condition might mitigate most symptoms; however, testosterone replacement therapy (TRT) should be prescribed only in selected patients and it should not be considered as an antiaging treatment. In recent years, different authors have questioned health risks associated with testosterone treatment; while position statements from many scientific societies seem to be reassuring, the Food and Drug Administration has issued a warning in regard to the possible side effects of this therapy. We aim to review recent controversies and discoveries in regard to TRT.

  15. Effect of oral testosterone treatment on serum concentrations of sex steroids gonadotrophins and prolactin in alcoholic cirrhotic men. Copenhagen Study Group for Liver Diseases

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick; Svenstrup, Bo

    1988-01-01

    The aim of this study was to examine the serum concentrations of sex steroids and pituitary hormones in a randomly selected group of alcoholic cirrhotic men participating in a randomized, placebo-controlled study on the efficacy of oral testosterone treatment on the liver. Before treatment...

  16. The many faces of testosterone

    Science.gov (United States)

    Bain, Jerald

    2007-01-01

    Testosterone is more than a “male sex hormone”. It is an important contributor to the robust metabolic functioning of multiple bodily systems. The abuse of anabolic steroids by athletes over the years has been one of the major detractors from the investigation and treatment of clinical states that could be caused by or related to male hypogonadism. The unwarranted fear that testosterone therapy would induce prostate cancer has also deterred physicians form pursuing more aggressively the possibility of hypogonadism in symptomatic male patients. In addition to these two mythologies, many physicians believe that testosterone is bad for the male heart. The classical anabolic agents, 17-alkylated steroids, are, indeed, potentially harmful to the liver, to insulin action to lipid metabolism. These substances, however, are not testosterone, which has none of these adverse effects. The current evidence, in fact, strongly suggests that testosterone may be cardioprotective. There is virtually no evidence to implicate testosterone as a cause of prostate cancer. It may exacerbate an existing prostate cancer, although the evidence is flimsy, but it does not likely cause the cancer in the first place. Testosterone has stimulatory effects on bones, muscles, erythropoietin, libido, mood and cognition centres in the brain, penile erection. It is reduced in metabolic syndrome and diabetes and therapy with testosterone in these conditions may provide amelioration by lowering LDL cholesterol, blood sugar, glycated hemoglobin and insulin resistance. The best measure is bio-available testosterone which is the fraction of testosterone not bound to sex hormone binding globulin. Several forms of testosterone administration are available making compliance much less of an issue with testosterone replacement therapy. PMID:18225457

  17. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition.

    Science.gov (United States)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue; Larsen, Rasmus; Højlund, Kurt; Brixen, Kim; Hougaard, David M; Handberg, Aase; Andersen, Marianne

    2015-01-01

    We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. Double-blinded, placebo-controlled study in 54 men aged 60-78 years with bioavailable testosterone 94 cm randomized to TT (gel, 50-100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. sCD36, total and regional fat mass were established by Dual X-ray absorptiometry and magnetic resonance imaging. Data are presented as median (quartiles). Kruskal-Wallis and Mann-Whitney tests were performed on delta values at 0, 3 and 6 months. ST + placebo decreased sCD36 levels by 21% [from 0.80 (0.68-1.22) to 0.63 (0.51-0.73) rel. units] vs. TT and vs. placebo (p testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta central fat mass (r = 0.84). Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass.

  18. Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols.

    Science.gov (United States)

    Sato, Naoko; Hasegawa, Tomonobu; Hasegawa, Yukihiro; Arisaka, Osamu; Ozono, Keiichi; Amemiya, Shin; Kikuchi, Toru; Tanaka, Hiroyuki; Harada, Shohei; Miyata, Ichiro; Tanaka, Toshiaki

    2015-04-01

    Male hypogonadotropic hypogonadism (MHH), a disorder associated with infertility, is treated with testosterone replacement therapy (TRT) and/or gonadotropins replacement therapy (GRT) (TRT and GRT, together with HRT hormone replacement therapy). In Japan, guidelines have been set for treatment during adolescence. Due to the risk of rapid maturation of bone age, low doses of testosterone or gonadotropins have been used. However, the optimal timing and methods of therapeutic intervention have not yet been established. The objective of this study was to investigate the current situation of treatment for children with MHH in Japan and to review a primary survey involving councilors of the Japanese Society for Pediatric Endocrinology and a secondary survey obtained from 26 facilities conducting HRT. The subjects were 55 patients with MHH who reached their adult height after HRT. The breakdown of the patients is as follows: 7 patients with Kallmann syndrome, 6 patients with isolated gonadotropin deficiency, 18 patients with acquired hypopituitarism due to intracranial and pituitary tumor, 22 patients with classical idiopathic hypopituitarism due to breech delivery, and 2 patients with CHARGE syndrome. The mean age at the start of HRT was 15.7 yrs and mean height was 157.2 cm. The mean age at reaching adult height was 19.4 yrs, and the mean adult height was 171.0 cm. The starting age of HRT was later than the normal pubertal age and showed a significant negative correlation with pubertal height gain, but it showed no correlation with adult height. As for spermatogenesis, 76% of the above patients treated with hCG-rFSH combined therapy showed positive results, though ranging in levels; impaired spermatogenesis was observed in some with congenital MHH, and favorable spermatogenesis was observed in all with acquired MHH. From the above, we propose the establishment of a treatment protocol for the start low-dose testosterone or low-dose gonadotropins by dividing subjects into

  19. Treatment with percutanous testosterone gel in postmenopausal women with decreased libido--effects on sexuality and psychological general well-being.

    Science.gov (United States)

    Nathorst-Böös, J; Flöter, A; Jarkander-Rolff, M; Carlström, K; Schoultz, B von

    2006-01-10

    To elucidate if percutanous treatment with 10mg testosterone per day could enhance sexuality and psychological well-being in postmenopausal women presenting problems with low libido. Secondary to study the influence on blood lipids, hemoglobin and erythropoietin levels. Fifty-three postmenopausal women participated. As a complement to their already on-going HRT, 10mg of a testosterone gel (Testogel, Besins-Iscovesco) or placebo was administered. Treatment continued for three plus three months in a double blind, randomized, crossover design. The scores concerning "frequency of sexual activity, orgasm and intercourse", "sexual arousal, fantasies and enjoyment", "satisfaction with orgasms", and "interest in sex" were all significally improved for testosterone addition as compared to placebo both before and after crossover. Testosterone levels increased more than 10-fold during treatment while DHT-levels were more than doubled. Estrogen levels were not affected during the addition of testosterone. Liver enzymes, total cholesterol, triglycerides, HDL and LDL revealed no significant differences between any of the periods or groups. Endometrial thickness did not change significantly during treatment. Hemoglobin and erythropoietin remained unchanged. No significant differences in the number of experienced side effects were found. Testosterone gel of 10mg had positive effects on several aspects of sexual life such as frequency of sexual activity, orgasm, arousal, fantasies and sexual interest in postmenopausal women on HRT. Several psychological variables were positively influenced. The given dose resulted in too high serum levels. Even if no negative effects were observed, monitoring of serum levels and a decreased dose should be considered in future studies.

  20. Effects on Voice Fundamental Frequency and Satisfaction with Voice in Trans Men during Testosterone Treatment-A Longitudinal Study.

    Science.gov (United States)

    Nygren, Ulrika; Nordenskjöld, Agneta; Arver, Stefan; Södersten, Maria

    2016-11-01

    To investigate effects of testosterone treatment regarding voice virilization, voice problems, and voice satisfaction in transsexual female-to-male individuals, referred to as trans men. Longitudinal. Fifty trans men, diagnosed with transsexualism, 18-64 years, met the inclusion criteria. Voice data before treatment and after 3, 6, or 12 months were available from 49 participants, and for 28 participants also after 18 and/or 24 months of treatment. Digital audio recordings of speech range profiles and voice range profiles were carried out in a sound-treated booth following clinical routines. Acoustic analyses of fundamental frequency (F0) and sound pressure level were made. Endocrine data and answers from questionnaires concerning voice function and voice problems were collected from medical records. Mean F0 and mode F0 of the habitual voice decreased significantly after 3 months, 6 months, and up to 12 months, when group data were congruent with reference data for males. Mean F0 was 125 Hz after 12 months with a large interindividual variation. Sound pressure level values did not change significantly. Voice satisfaction correlated with lower F0 values. Twenty-four percent of the participants reported voice symptoms, for example, vocal instability and fatigue, and had received voice therapy. F0 values did not correlate with androgen levels. Most trans men developed a male voice and were satisfied. However, it is important to detect the substantial group of trans men with voice problems and with insufficient voice virilization and who may need voice therapy. Therefore, we recommend systematic voice assessments during testosterone treatment. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  1. Testosterone and weight loss: the evidence.

    Science.gov (United States)

    Traish, Abdulmaged M

    2014-10-01

    The purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency. Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome. The aforementioned improvements are attributed to improved mitochondrial function, increased energy utilization, increased motivation and vigor resulting in improved cardio-metabolic function and enhanced physical activity. The implication of testosterone therapy in management of obesity in men with testosterone deficiency is of paramount clinical significance, as it produces sustained weight loss without recidivism. On the contrary, alternative therapeutic approaches other than bariatric surgery failed to produce significant and sustained outcome and exhibit a high rate of recidivism. These findings represent strong foundations for testosterone therapy in obese men with testosterone deficiency and should spur clinical research for better understanding of usefulness of testosterone therapy in treatment of underlying pathophysiological conditions of obesity.

  2. Testosterone and weight loss: the evidence

    Science.gov (United States)

    Traish, Abdulmaged M.

    2014-01-01

    Purpose of review The purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency. Recent findings Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome. The aforementioned improvements are attributed to improved mitochondrial function, increased energy utilization, increased motivation and vigor resulting in improved cardio-metabolic function and enhanced physical activity. Summary The implication of testosterone therapy in management of obesity in men with testosterone deficiency is of paramount clinical significance, as it produces sustained weight loss without recidivism. On the contrary, alternative therapeutic approaches other than bariatric surgery failed to produce significant and sustained outcome and exhibit a high rate of recidivism. These findings represent strong foundations for testosterone therapy in obese men with testosterone deficiency and should spur clinical research for better understanding of usefulness of testosterone therapy in treatment of underlying pathophysiological conditions of obesity. PMID:25105998

  3. Prenatal Testosterone Treatment Leads to Changes in the Morphology of KNDy Neurons, Their Inputs, and Projections to GnRH Cells in Female Sheep

    Science.gov (United States)

    Cernea, Maria; Padmanabhan, Vasantha; Goodman, Robert L.; Coolen, Lique M.

    2015-01-01

    Prenatal testosterone (T)-treated ewes display a constellation of reproductive defects that closely mirror those seen in PCOS women, including altered hormonal feedback control of GnRH. Kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in steroid feedback control of GnRH secretion, and prenatal T treatment in sheep causes an imbalance of KNDy peptide expression within the ARC. In the present study, we tested the hypothesis that prenatal T exposure, in addition to altering KNDy peptides, leads to changes in the morphology and synaptic inputs of this population, kisspeptin cells of the preoptic area (POA), and GnRH cells. Prenatal T treatment significantly increased the size of KNDy cell somas, whereas POA kisspeptin, GnRH, agouti-related peptide, and proopiomelanocortin neurons were each unchanged in size. Prenatal T treatment also significantly reduced the total number of synaptic inputs onto KNDy neurons and POA kisspeptin neurons; for KNDy neurons, the decrease was partly due to a decrease in KNDy-KNDy synapses, whereas KNDy inputs to POA kisspeptin cells were unaltered. Finally, prenatal T reduced the total number of inputs to GnRH cells in both the POA and medial basal hypothalamus, and this change was in part due to a decreased number of inputs from KNDy neurons. The hypertrophy of KNDy cells in prenatal T sheep resembles that seen in ARC kisspeptin cells of postmenopausal women, and together with changes in their synaptic inputs and projections to GnRH neurons, may contribute to defects in steroidal control of GnRH observed in this animal model. PMID:26061725

  4. Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men.

    Science.gov (United States)

    Saad, Farid; Yassin, Aksam; Haider, Ahmad; Doros, Gheorghe; Gooren, Louis

    2015-04-01

    To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. A total of 561 hypogonadal men from two registry studies were divided into age groups of ≤65 years (group Y, n=450; range, 32-65 years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH.

  5. Testosterone effect on the expression of genes that mediate testosterone metabolism and genes that mediate the effect of those metabolites on the prostate.

    Science.gov (United States)

    Shidaifat, Falah; Lin, Young C

    2012-09-04

    The aim of this study was to investigate the effect of testosterone treatment on the proliferation index and the mRNA expression levels of 5α-reductase, CYP7B1, androgen receptor (AR), and estrogen receptor β (ΕRβ) in the canine prostate. Immature dogs were treated with testosterone for one month, after which prostate gland growth was assessed by comparing the proliferation index in prostates from testosterone-treated dogs with that of untreated control dogs. The relative mRNA expression levels of the aforementioned genes in the prostate glands of testosterone-treated and untreated dogs were determined by real time PCR. Testosterone treatment induced a highly significant reduction in proliferation index in prostate gland. This inhibition of prostate gland growth was associated with differential mRNA expression of 5α-reductase, CYP7B1, AR, and ΕRβ by the prostate gland of testosterone-treated dogs, as compared to that of untreated dogs. While the expression levels of 5α-reductase and CYP7B1 mRNA were significantly down-regulated by testosterone treatment, the expression level of ER-β mRNA was highly up-regulated. In contrast, AR mRNA expression was not significantly altered. Prostate gland proliferation appeared to be associated with the expression levels of genes that encode proteins that control intra-prostatic levels of testosterone metabolites and their respective receptors. Testosterone treatment may regulate gene expression in the prostate to generate a phenotype that suppresses growth-promoting signaling through AR and enhances anti-proliferative signaling through ERβ. Therefore, targeting disturbances of this genetic machinery in benign prostate hyperplasia and prostate cancer is of a therapeutic potential. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Effect of oral testosterone treatment on serum concentrations of sex steroids gonadotrophins and prolactin in alcoholic cirrhotic men. Copenhagen Study Group for Liver Diseases

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick; Svenstrup, Bo

    1988-01-01

    than 0.01) higher median serum concentrations of oestrone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. The patients were randomized to treatment with either oral micronized testosterone (200 mg t.d.s.) or placebo for a median duration of 1 year. In the placebo group (n......, but no significant changes were observed regarding serum oestradiol and prolactin concentrations. Both LH and FSH concentrations decreased significantly (P less than 0.05) in the testosterone-treated group when compared with concentrations at entry and concentrations in the placebo group....

  7. Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients.

    Science.gov (United States)

    Rovira-Llopis, Susana; Bañuls, Celia; de Marañon, Aranzazu M; Diaz-Morales, Noelia; Jover, Ana; Garzon, Sandra; Rocha, Milagros; Victor, Victor M; Hernandez-Mijares, Antonio

    2017-07-01

    Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesion molecules and leukocyte-endothelium cell interactions were evaluated. Testosterone levels were lower in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFα, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabetic patients, while rolling velocity was reduced. Testosterone levels correlated negatively with glucose, HOMA-IR, HbA1c, triglycerides, nonHDL-c, ApoB, hs-CRP and AIP, and positively with HDL-c and ApoA1. The multivariable regression model showed that HDL-c, HOMA-IR and age were independently associated with testosterone. Furthermore, testosterone levels correlated positively with membrane potential and rolling velocity and negatively with ROS production, VCAM-1, rolling flux and adhesion. Our data highlight that low testosterone levels in diabetic men are related to impaired metabolic profile and mitochondrial function and enhanced inflammation and leukocyte-endothelium cell interaction, which leaves said patients at risk of cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Could you have low testosterone?

    Science.gov (United States)

    ... hypothalamus and pituitary) that control hormone production Low thyroid function Too much body fat ( obesity ) Other disorders, chronic diseases, medical treatments, or infection Symptoms Some men with low testosterone do not have ...

  9. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life.

    Science.gov (United States)

    Yassin, Dany-Jan; Doros, Gheorghe; Hammerer, Peter G; Yassin, Aksam A

    2014-06-01

    Late-onset hypogonadism (LOH) is diagnosed when declining testosterone concentrations in the aging male cause unwanted symptoms such as erectile dysfunction (ED), reduced bone density and muscle strength, and increased visceral obesity. Testosterone deficiency is also associated with insulin resistance and the metabolic syndrome (MetS). Restoring testosterone to physiological concentrations has beneficial effects on many of these symptoms; however, it is not known whether these effects can be sustained in the long term. To investigate whether treatment with testosterone undecanoate (TU) has a long-term and sustained effect on parameters affected by the MetS in men with LOH and ED, to determine whether long-term testosterone treatment can improve the overall health-related quality of life in these men, and to establish the safety of long-term testosterone treatment. Two hundred sixty-one patients (mean age 59.5 ± 8.4 years) diagnosed with LOH and ED were treated with long-acting TU in a prospective, observational, and longitudinal registry study. Men received intramuscular injections of 1,000 mg TU at day 1, at week 6, and every 3 months thereafter. Parameters affected by the MetS, including obesity parameters (body weight, waist circumference, and body mass index [BMI]), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, HbA1c (glycated hemoglobin), and blood pressure, as well as total testosterone levels and health-related quality of life, were assessed. We found TU significantly improved obesity parameters (body weight, waist circumference, and BMI) and lowered total cholesterol, LDL cholesterol, triglycerides, fasting blood glucose, HbA1c , and blood pressure over the 5-year study. HDL cholesterol was increased. TU treatment resulted in a sustained improvement in erectile function and muscle and joint pain, which contributed to an improvement in long-term health-related quality of life. Furthermore

  10. Postnatal exposure to flutamide affects CDH1 and CTNNB1 gene expression in adult pig epididymis and prostate and alters metabolism of testosterone.

    Science.gov (United States)

    Gorowska, E; Zarzycka, M; Chojnacka, K; Bilinska, B; Hejmej, A

    2014-03-01

    In both epididymis and prostate the dynamic cross-talk between the cells is hormonally regulated and, in part, through direct cell-to-cell interactions. Functionality of the male reproductive organs may be affected by exposure to specific chemicals, so-called 'reprotoxicants'. In this study we tested whether early postnatal and prepubertal exposure to anti-androgen flutamide altered the expression of adherens junction genes encoding E-cadherin (CDH1) and β-catenin (CTNNB1) in adult pig epididymis and prostate. In addition, the expression of mRNAs and proteins for 5α-reductase (ST5AR2) and aromatase (CYP19A1) were examined to show whether flutamide alters metabolism of testosterone. Thus, flutamide was injected into male piglets between Days 2 and 10 and between Days 90 and 98 postnatally (PD2 and PD90; 50 mg/kg bw), tissues that were obtained on postnatal Day 270. To assess the expression of the genes and proteins, real-time RT-PCR and Western blot were performed respectively. Moreover, adherens junction proteins were localized by immunohistochemistry. In response to flutamide, CDH1 and CTNNB1 expressions were down-regulated along the epididymis, mostly in PD2 group (p < 0.001, p < 0.01). In the prostate, CDH1 mRNA and protein expressions were significantly down-regulated (p < 0.01), whereas CTNNB1 mRNA was slightly up-regulated in both flutamide-treated groups. CTNNB1 protein level was markedly elevated in both PD2 (p < 0.001) and PD90 (p < 0.01) groups. In the epididymis, the expression of ST5AR2 and CYP19A1 was down- and up-regulated, respectively (p < 0.05), whereas in the prostate evident decrease in CYP19A1 expression (p < 0.001, p < 0.01, p < 0.05) was demonstrated. In both tissues, membranous immunolocalization of CTNNB1 suggests its involvement in cell-cell adhesion. Overall, flutamide administration resulted in suppression of androgen action in the epididymis and prostate leading to deregulation of CDH1 and CTNNB1 gene expressions which is probably

  11. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial.

    Science.gov (United States)

    Ng Tang Fui, Mark; Prendergast, Luke A; Dupuis, Philippe; Raval, Manjri; Strauss, Boyd J; Zajac, Jeffrey D; Grossmann, Mathis

    2016-10-07

    Whether testosterone treatment has benefits on body composition over and above caloric restriction in men is unknown. We hypothesised that testosterone treatment augments diet-induced loss of fat mass and prevents loss of muscle mass. We conducted a randomised double-blind, parallel, placebo controlled trial at a tertiary referral centre. A total of 100 obese men (body mass index ≥ 30 kg/m 2 ) with a total testosterone level of or below 12 nmol/L and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). The main outcome measures were the between-group difference in fat and lean mass by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography). A total of 82 men completed the study. At study end, compared to controls, cases had greater reductions in fat mass, with a mean adjusted between-group difference (MAD) of -2.9 kg (-5.7 to -0.2; P = 0.04), and in visceral fat (MAD -2678 mm 2 ; -5180 to -176; P = 0.04). Although both groups lost the same lean mass following VLED (cases -3.9 kg (-5.3 to -2.6); controls -4.8 kg (-6.2 to -3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P testosterone treatment was almost exclusively due to loss of body fat. clinicaltrials.gov, identifier NCT01616732 , registration date: June 8, 2012.

  12. Maternal treatment with dexamethasone during lactation alters ...

    African Journals Online (AJOL)

    Increased glucocorticoid levels may affect serum electrolyte levels and the architecture of the adrenal cortex. This study was designed to investigate the effects of maternal treatment with dexamethasone during lactation on serum electrolytes and structure of the adrenal gland. Methods: Twenty lactating dams were divided ...

  13. Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI).

    Science.gov (United States)

    Van Caenegem, E; Wierckx, K; Taes, Y; Schreiner, T; Vandewalle, S; Toye, K; Lapauw, B; Kaufman, J-M; T'Sjoen, G

    2015-02-01

    To assess the evolution of body composition and bone metabolism in trans men during the first year of cross-sex hormonal therapy. In a prospective controlled study, we included 23 trans men (female-to-male trans persons) and 23 age-matched control women. In both groups, we examined grip strength (hand dynamometer), biochemical markers of bone turnover (C-terminal telopeptides of type 1 collagen (CTX) and procollagen 1 aminoterminal propeptide (P1NP)), total body fat and lean mass, and areal bone mineral density (aBMD) by dual-X-ray absorptiometry (DXA) and fat and muscle area at the forearm and calf, bone geometry, and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), before treatment and after 1 year of treatment with undecanoate (1000 mg i.m./12 weeks). Before hormonal treatment, trans men had similar bone and body composition compared with control women. Testosterone treatment induced in trans men a gain in muscle mass (+10.4%) and strength and loss of fat mass (-9.7%) (all Ptrans men (P=0.036 and P=0.001 respectively). None of these changes were observed in the control group. Short-term testosterone treatment in trans men increased muscle mass and bone turnover. The latter may rather reflect an anabolic effect of testosterone treatment rather than bone loss. © 2015 European Society of Endocrinology.

  14. NIH-Supported Trials Test Hormonal Therapy in Older Men with Low Testosterone Levels

    Science.gov (United States)

    ... test hormonal therapy in older men with low testosterone levels Testosterone treatment improved sexual function, had smaller effect on walking, vitality. A preliminary study of testosterone therapy in older men with low levels of ...

  15. Hypoactive sexual desire disorder in women: treatment options beyond testosterone and approaches to communicating with patients on sexual health.

    Science.gov (United States)

    Lodise, Nicole M

    2013-04-01

    Hypoactive sexual desire disorder (HSDD) affects nearly 1 in 10 women. Thus, it is essential for pharmacists and other health care providers to be comfortable when discussing a patient's sexual health to ensure appropriate triage so that the specific causes of HSDD can be identified and potential recommendations provided. HSDD is defined as the absence or deficiency of sexual interest and/or desire, leading to significant distress and interpersonal difficulties. As health care providers, pharmacists have a critical role in assessing the presence of HSDD and providing education on available treatment options. This article will review the potential causes of HSDD and low sexual desire, the screening tools available, and the significant role of health care professionals in communicating with patients about their sexual health. An overview of the importance of behavioral modifications, the current pharmacologic options being investigated, and the use of complementary and alternative therapies will also be explored. Currently, buproprion is the primary pharmacologic agent that has shown positive results in treating patients with HSDD. The use of testosterone therapy will not be addressed in this article, as this therapy is described in greater detail elsewhere. © 2013 Pharmacotherapy Publications, Inc.

  16. Analysis of testosterone effects on sonic hedgehog signaling in juvenile, adolescent and adult sprague dawley rat penis.

    Science.gov (United States)

    Bond, Christopher W; Angeloni, Nicholas L; Podlasek, Carol A

    2010-03-01

    Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone. The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20). The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold. SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.

  17. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters.

    Science.gov (United States)

    Yassin, Aksam; Nettleship, Joanne E; Talib, Raidh A; Almehmadi, Yousef; Doros, Gheorge

    2016-01-01

    Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function - erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.

  18. Controversies in testosterone supplementation therapy

    Directory of Open Access Journals (Sweden)

    Mohit Khera

    2015-04-01

    Full Text Available Testosterone has now become one of the most widely used medications throughout the world. The rapid growth of the testosterone market in the past 10 years is due to many factors. We currently have a worldwide aging population. In the US, the number of men 65 years old or older is increasing 2-3 times faster than the number of men younger than 65 years. In addition, poor general health and certain medical conditions such as diabetes/metabolic syndrome (MetS, cardiovascular disease (CVD, and osteoporosis have been associated with low serum testosterone levels. [1],[2],[3] There are now fewer concerns regarding the development of prostate cancer (PCa after testosterone therapy, making it a more attractive treatment option. Finally, the introduction of different forms of testosterone supplementation therapy (TST with increased promotion, marketing, and direct-to-consumer advertising is also driving market growth. As the demand for TST continues to grow, it is becoming more important for clinicians to understand how to diagnose and treat patients with low testosterone.

  19. Negative regulation of glucose metabolism in human myotubes by supraphysiological doses of 17β-estradiol or testosterone.

    Science.gov (United States)

    Garrido, Pablo; Salehzadeh, Firoozeh; Duque-Guimaraes, Daniella E; Al-Khalili, Lubna

    2014-09-01

    Exposure of skeletal muscle to high levels of testosterone or estrogen induces insulin resistance, but evidence regarding the direct role of either sex hormone on metabolism is limited. Therefore, the aim of this study was to investigate the direct effect of acute sex hormone exposure on glucose metabolism in skeletal muscle. Differentiated human skeletal myotubes were exposed to either 17β-estradiol or testosterone and metabolic characteristics were assessed. Glucose incorporation into glycogen, glucose oxidation, palmitate oxidation, and phosphorylation of key signaling proteins were determined. Treatment of myotubes with either 17β-estradiol or testosterone decreased glucose incorporation into glycogen. Exposure of myotubes to 17β-estradiol reduced glucose oxidation under basal and insulin-stimulated conditions. However, testosterone treatment enhanced basal palmitate oxidation and prevented insulin action on glucose and palmitate oxidation. Acute stimulation of myotubes with testosterone reduced phosphorylation of S6K1 and p38 MAPK. Exposure of myotubes to either 17β-estradiol or testosterone augmented phosphorylation GSK3β(Ser9) and PKCδ(Thr505), two negative regulators of glycogen synthesis. Treatment of myotubes with a PKC specific inhibitor (GFX) restored the effect of either sex hormone on glycogen synthesis. PKCδ silencing restored glucose incorporation into glycogen to baseline in response to 17β-estradiol, but not testosterone treatment. An acute exposure to supraphysiological doses of either 17β-estradiol or testosterone regulates glucose metabolism, possibly via PKC signaling pathways. Furthermore, testosterone treatment elicits additional alterations in serine/threonine kinase signaling, including the ribosomal protein S6K1 and p38 MAPK. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taira, Al V. [Western Radiation Oncology, Mountain View, CA (United States); Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV (United States); Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A. [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV (United States); Wallner, Kent E. [Puget Sound Healthcare Corporation Group Health Cooperative, University of Washington, Seattle, WA (United States)

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

  1. Reduced total testosterone concentrations in young healthy South Asian men are partly explained by increased insulin resistance but not by altered adiposity.

    OpenAIRE

    2010-01-01

    Abstract Objective: To compare ethnic differences in total, free and bioavailable testosterone amongst young healthy South Asian and Caucasian men. Design and subjects: Cross-sectional study of 134 healthy males (age 20-40 years) of South Asian (n=67) or Caucasian (n=67) origin, recruited from hospital staff and students working in Newport, UK. Subjects were excluded if they had a fasting plasma glucose >5.9 mmol/l, central obesity (waist circumference ?94cm [Caucasian] or ?90cm...

  2. Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males

    Directory of Open Access Journals (Sweden)

    Lisa Wagels

    2018-03-01

    Full Text Available Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status–seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration. A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants’ choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se. In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone.

  3. Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males.

    Science.gov (United States)

    Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

    2018-01-01

    Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status-seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants' choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se . In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone.

  4. Detectability of testosterone esters and estradiol benzoate in bovine hair and plasma following pour-on treatment

    NARCIS (Netherlands)

    Stolker, A.A.M.; Groot, M.J.; Lasaroms, J.J.P.; Nijrolder, A.W.J.M.; Blokland, M.H.; Riedmaier, I.; Becker, C.; Meyer, H.H.D.; Nielen, M.W.F.

    2009-01-01

    The abuse of synthetic esters of natural steroids such as testosterone and estradiol in cattle fattening and sports is hard to detect via routine urine testing. The esters are rapidly hydrolysed in vivo into substances which are also endogenously present in urine. An interesting alternative can be

  5. Effects of intratesticular zinc gluconate treatment on testicular dimensions, echodensity, histology, sperm production, and testosterone secretion in American black bears (Ursus americanus).

    Science.gov (United States)

    Brito, Leonardo F C; Sertich, Patricia L; Rives, William; Knobbe, Marc; Del Piero, Fabio; Stull, Gordon B

    2011-05-01

    Eight adult American black bears were used to evaluate the effects of chemical castration by intratesticular zinc gluconate treatment on testicular dimensions, echodensity, histology, sperm production, and testosterone secretion. Treatment did not affect testicular dimensions and did not result in decreased resting or GnRH-stimulated testosterone secretion. Multifocal hyperchoic areas in the testicular parenchyma were observed on ultrasound examination, and white foci were observed on gross pathology examination after zinc gluconate treatment. Histologically, there were normal seminiferous tubules containing either round or elongated spermatids, along with abnormal tubules in all bears after treatment. Vacuolation of the seminiferous epithelium, sloughing of germ cells into the tubules' lumen, presence of multinuclear giant cells, and reduced height of the seminiferous epithelium with missing generations of germ cells were commonly observed. The most severe testicular changes were multifocal and included fibrosis, complete degeneration of the seminiferous epithelium with shrinkage of the tubule, and sperm stasis. Epididymal sperm reserve was 982.74 ± 654.16 × 10(6) sperm (mean ± SEM) and motile sperm were observed in the epididymis of all but one of the bears. In conclusion, although intratesticular zinc gluconate treatment in black bears resulted in testicular degenerative changes detected by ultrasound and histology examinations, sperm production was not completely ablated. We inferred that normal fertility might have been compromised, but treatment unlikely resulted in sterility. Copyright © 2011. Published by Elsevier Inc.

  6. Testosterone Therapy in Men With Prostate Cancer

    Science.gov (United States)

    Kaplan, Alan L.; Hu, Jim C.; Morgentaler, Abraham; Mulhall, John P.; Schulman, Claude C.; Montorsi, Francesco

    2016-01-01

    Context The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. Objective To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. Evidence acquisition We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. Evidence synthesis The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. Conclusions An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life—and the ability of testosterone therapy to mitigate these effects—has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone

  7. Testosterone and metabolic syndrome.

    Science.gov (United States)

    Cunningham, Glenn R

    2015-01-01

    Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  8. Testosterone and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Glenn R Cunningham

    2015-04-01

    Full Text Available Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS. Many of the components are accepted risk factors for cardiovascular disease (CVD. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT and sex hormone binding globulin (SHBG levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  9. [Testosterone replacement therapy for prostate cancer].

    Science.gov (United States)

    Kaminsky, A; Sperling, H

    2010-01-01

    During the male 40s total testosterone levels decrease continuously. If clinical symptoms like decreasing libido, erectile dysfunction, osteoporosis, altered distribution of body fat, reduction in physical strength, or alterations in psychological mood are combined with a decreased serum testosterone level late-onset hypogonadism (LOH) is obvious. Before the substitution of testosterone is initiated, it is essential to exclude prostate cancer because the progress of prostate cancer depends on androgens. The question is now how to treat patients who suffer from androgen deficiency but have cured prostate cancer in their history? Concerning this there are only a few studies with a small number of patients which show that testosterone substitution therapy is possible without an increased risk for recurrence of prostate cancer. As long as the patient was cured it does not matter if he underwent a radical prostatectomy or brachytherapy. Absolutely necessary is that the patient is well informed about the therapy and regularly controlled during the therapy.

  10. Prenatal Virilization Associated with Paternal Testosterone Gel Therapy

    OpenAIRE

    Rivkees ScottA; Patel Anisha

    2010-01-01

    Transdermal testosterone gels are used in the treatment of hypoandrogenism of males. Virilization due to exposure to testosterone gels has been reported in children resulting in a US Food and Drug Administration (FDA) warning about secondary exposure to these products. At present, we are unaware of prenatal virilization associated with unintentional testosterone gel exposure. We report prenatal virilization in a female infant due to secondary maternal exposure to the father's testosterone ge...

  11. Prenatal Virilization Associated with Paternal Testosterone Gel Therapy

    OpenAIRE

    Patel, Anisha; Rivkees, Scott A.

    2010-01-01

    Transdermal testosterone gels are used in the treatment of hypoandrogenism of males. Virilization due to exposure to testosterone gels has been reported in children resulting in a US Food and Drug Administration (FDA) warning about secondary exposure to these products. At present, we are unaware of prenatal virilization associated with unintentional testosterone gel exposure. We report prenatal virilization in a female infant due to secondary maternal exposure to the father's testosterone gel...

  12. Exposure to di(n-butyl)phthalate and benzo(a)pyrene alters IL-1β secretion and subset expression of testicular macrophages, resulting in decreased testosterone production in rats

    International Nuclear Information System (INIS)

    Zheng Shanjun; Tian Huaijun; Cao Jia; Gao Yuqi

    2010-01-01

    Di(n-butyl)phthalate (DBP) and benzo(a)pyrene (BaP) are environmental endocrine disruptors that are potentially hazardous to humans. These chemicals affect testicular macrophage immuno-endocrine function and testosterone production. However, the underlying mechanisms for these effects are not fully understood. It is well known that interleukin-1 beta (IL-1β), which is secreted by testicular macrophages, plays a trigger role in regulating Leydig cell steroidogenesis. The purpose of this study was to reveal the effects of co-exposure to DBP and BaP on testicular macrophage subset expression, IL-1β secretion and testosterone production. Adult male Sprague-Dawley rats were randomly divided into seven groups; two groups received DBP plus BaP (DBP + BaP: 50 + 1 or 250 + 5 mg/kg/day) four groups received DBP or BaP alone (DBP: 50 or 250 mg/kg/day; BaP: 1 or 5 mg/kg/day), and one group received vehicle alone (control). After co-exposure for 90 days, the relative expression of macrophage subsets and their functions changed. ED2 + testicular macrophages (reactive with a differentiation-related antigen present on the resident macrophages) were activated and IL-1β secretion was enhanced. DBP and BaP acted additively, as demonstrated by greater IL-1β secretion relative to each compound alone. These observations suggest that exposure to DBP plus BaP exerted greater suppression on testosterone production compared with each compound alone. The altered balance in the subsets of testicular macrophages and the enhanced ability of resident testicular macrophages to secrete IL-1β, resulted in enhanced production of IL-1β as a potent steroidogenesis repressor. This may represent an important mechanism by which DBP and BaP repress steroidogenesis.

  13. Effect of testosterone deficiency on cholesterol metabolism in pigs fed a high-fat and high-cholesterol diet.

    Science.gov (United States)

    Cai, Zhaowei; Xi, Haitao; Pan, Yongming; Jiang, Xiaoling; Chen, Liang; Cai, Yueqin; Zhu, Keyan; Chen, Cheng; Xu, Xiaoping; Chen, Minli

    2015-03-07

    Testosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet. Sexually mature male miniature pigs (6-7 months old) were randomly divided into 3 groups as follows: intact male pigs fed an HFC diet (IM+HFC), castrated male pigs fed an HFC diet (CM+HFC), and castrated pigs with testosterone replacement fed an HFC diet (CM+HFC+T). Serum testosterone levels and lipid profiles were measured, and gene expression levels associated with hepatic cholesterol metabolism were determined. Furthermore, total hepatic cholesterol contents and the activities of enzymes mediating hepatic cholesterol metabolism were measured. Serum testosterone levels were significantly decreased in CM+HFC pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. Castration significantly increased the serum levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as hepatic lipid contents in pigs fed an HFC diet. Compared with IM+HFC and CM+HFC+T pigs, low-density lipoprotein receptor (LDLR) mRNA expression and protein levels were significantly decreased in the livers of CM+HFC pigs. In contrast, we found that compared with IM+HFC pigs, hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and serum PCSK9 protein levels were significantly increased in CM+HFC pigs. Moreover, testosterone treatment reversed the increase in PCSK9 expression in CM+HFC pigs. However, neither castration nor testosterone replacement affected the expression of the other hepatic genes that were tested. This study demonstrated that castration-induced testosterone deficiency caused severe hypercholesterolemia in pigs fed an HFC diet; furthermore, these

  14. Testosterone therapy in microphallic hypospadias: topical or parenteral?

    Science.gov (United States)

    Chalapathi, G; Rao, K L N; Chowdhary, S K; Narasimhan, K L; Samujh, Ram; Mahajan, J K

    2003-02-01

    Local or systemic application of testosterone is reported to stimulate penile growth. Intramuscular testosterone has been found to be effective in 50% of patients; however, variable results have been reported with topical testosterone. The current study is an attempt to compare the efficacy of intramuscular versus topical testosterone application. A total of 26 consecutive patients with hypospadias and small penis (growth was accomplished by topical application of testosterone (Testoviron, oily solution containing testosterone propionate, 25 mg, and testosterone enanthate, 110 mg, equivalent to about 100 mg of testosterone, Schering, Germany) with a dose of 2 mg/kg/wk, for 3 weeks. While in group B, testosterone (same preparation as above) was administered by intramuscular injection weekly for 3 consecutive weeks. Penile length, diameter, and secondary effects were recorded before, during, and 3 weeks after the therapy by a single observer. Significant penile growth (P growth of at least 50% compared with the initial size. The basal serum testosterone was within the normal range in both the groups. During therapy the serum testosterone was elevated above the basal level in all patients, but within the normal range except in 2 patients of group A. In these 2 children the serum testosterone level crossed the normal range. Linear growth did not alter significantly for the chronological age. Two patients of group A went on to have pubic hair, one of them had elevated testosterone level above the normal range. There was a surge in serum testosterone in all children, although significant penile enlargement was observed in 60% children in group A and 75% in group B. Although the desired therapeutic effect of testosterone was achieved in both the groups, this study failed to show any significant difference between the 2 routes of administration. However, in group A, (topical) serum testosterone crossed the normal range in 15% of patients and was associated with significant

  15. Testosterone reduces conscious detection of signals serving social correction - Implications for antisocial behavior

    NARCIS (Netherlands)

    Honk, E.J. van; Schutter, D.J.L.G.

    2007-01-01

    Elevated levels of testosterone have repeatedly been associated with antisocial behavior, but the psychobiological mechanisms underlying this effect are unknown. However, testosterone is evidently capable of altering the processing of facial threat, and facial signals of fear and anger serve

  16. Testosterone and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Thomas R Jarvis

    2015-04-01

    Full Text Available The use of testosterone to treat the symptoms of late-onset hypogonadal men has increased recently due to patient and physician awareness. However, concerns regarding the effect of testosterone on the prostate, in particular any possible effect on the risk of prostate cancer have prompted further research in this regard. Surprisingly, numerous retrospective or small, randomized trials have pointed to a possible improvement in male lower urinary tract symptoms (LUTS in patients treated with testosterone. The exact mechanism of this improvement is still debated but may have a close relationship to metabolic syndrome. For the clinician, the results of these studies are promising but do not constitute high levels of evidence. A thorough clinical examination (including history, examination and laboratory testing of testosterone should be undertaken before considering the diagnosis of late-onset hypogonadism or instigating treatment for it. Warnings still remain on the testosterone supplement product labels regarding the risk of urinary retention and worsening LUTS, and these should be explained to patients.

  17. The Role of Testosterone in the Etiology and Treatment of Obesity, the Metabolic Syndrome, and Diabetes Mellitus Type 2

    OpenAIRE

    Saad, Farid; Gooren, Louis J.

    2010-01-01

    Obesity has become a major health problem. Testosterone plays a significant role in obesity, glucose homeostasis, and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein c...

  18. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial

    NARCIS (Netherlands)

    Davis, Susan R.; van der Mooren, M. J.; van Lunsen, Rik H. W.; Lopes, Patrice; Ribot, Claude; Ribot, Jean; Rees, Margaret; Moufarege, Alain; Rodenberg, Cynthia; Buch, Akshay; Purdie, David W.

    2006-01-01

    Evaluation of the use of testosterone therapy for hypoactive sexual desire disorder (HSDD) after oophorectomy has mostly involved women treated with oral estrogen preparations. We investigated the efficacy and safety of a testosterone patch in surgically menopausal women receiving concurrent

  19. Testosterone replacement alters the cell size in visceral fat but not in subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism animal model

    Directory of Open Access Journals (Sweden)

    Abdelhamed A

    2015-03-01

    Full Text Available Amr Abdelhamed,1,2 Shin-ichi Hisasue,1 Masato Shirai,3 Kazuhito Matsushita,1 Yoshiaki Wakumoto,1 Akira Tsujimura,1 Taiji Tsukamoto,4 Shigeo Horie1 1Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan; 2Department of Dermatology, Venereology and Andrology, Sohag University, Graduate School of Medicine, Sohag, Egypt; 3Department of Urology, Juntendo University Urayasu Hospital, Urayasu, Japan; 4Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Japan Background: Patients with late-onset hypogonadism (LOH benefit from testosterone replacement by improvement in the parameters of the metabolic syndrome, but fat cell morphology in these patients is still unclear. This study aims to determine the effect of testosterone replacement on the morphology of fat cells in subcutaneous and visceral adipose tissue and on erectile function in hypogonadal aged male rats as a model of LOH. Methods: Ten male Sprague-Dawley rats aged 20–22 months were randomly allocated to two groups, ie, aged male controls (control group, n=5 and aged males treated with testosterone replacement therapy (TRT group, n=5. Testosterone enanthate 25 mg was injected subcutaneously every 2 weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP and mean arterial blood pressure (MAP ratio was assessed. Visceral and subcutaneous adipose tissue specimens were collected and analyzed using Image-J software. Results: Body weight at 2, 4, and 6 weeks after TRT was 800.0±35.4 g, 767.5±46.3 g, and 780±40.4 g, respectively (not statistically significant. The ICP/MAP ratio was 0.341±0.015 in the TRT group and 0.274±0.049 in the control group (not statistically significant. The median subcutaneous fat cell size was 4.85×103 (range 0.85–12.53×103 µm2 in the control group and 4.93×103 (range 6.42–19.7×103 µm2 in the TRT group (not statistically significant. In contrast, median visceral fat cell size was significantly

  20. A comparative study of ethanolic extracts of Pedalium murex Linn. fruits and sildenafil citrate on sexual behaviors and serum testosterone level in male rats during and after treatment.

    Science.gov (United States)

    Sharma, Vikas; Thakur, Mayank; Dixit, V K

    2012-08-30

    Pedalium murex Linn. has been used as Vajikaran Rasayana (aphrodisiac) in traditional Indian medicine to treat male sexual dysfunction and impotency. The aim of this study was to investigate effects of P. murex fruits extract on sexual behaviors and testosterone level of male rats during and past withdrawal of treatment. The extract (50, 100,150mg/kg body weight/day) and sildenafil citrate (5mg/kg body weight/day) were administered orally by gavages for 28 days to male Wistar albino rats. Penile erection index (PEI), mount latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), post ejaculatory interval (PEjI) and serum testosterone levels were studied at day 0, 15, 28 during treatment. They were further evaluated after day 7 and 15 past discontinuation of the treatment. In-vitro nitric oxide release activity was also investigated in human corpus cavernosal cell line. The ethanolic extract significantly reduced the ML, IL, EL and PEjI (paphrodisiac property. Study lends growing support for the traditional use of P. murex as a sexual stimulating agent and offers a significant potential for studying the effect on male sexual response and its dysfunctions. The findings justify the concept of Rasayana as rejuvenative tonics and support their role in prevention or delay of the aging process. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Testosterone deficiency: a historical perspective

    Directory of Open Access Journals (Sweden)

    Eberhard Nieschlag

    2014-02-01

    Full Text Available The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial (and other oriental courts employed castrates as overseers in harems who often obtained high-ranking political positions. The era of testis transplantation and organotherapy was initiated by John Hunter in London who transplanted testes into capons in 1786. The intention of his experiments was to prove the 'vital principle' as the basis for modern transplantation medicine, but Hunter did not consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849 in Göttingen and is thus considered the father of endocrinology. Following his observations, testicular preparations were used for therapy, popularized by self-experiments by Charles-Edouard Brown-Séquard in Paris (1889, which can at best have placebo effects. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproved. Today testicular transplantation is being refined by stem cell research and germ cell transplantation. Modern androgen therapy started in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam. In the same year testosterone was chemically synthesized independently by Adolf Butenandt in Göttingen and Leopold Ruzicka in Basel. Since testosterone was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl testosterone, now obsolete because of liver toxicity. The early phases of testosterone treatment coincide with the first description of the most prominent syndromes of hypogonadism by Klinefelter, by

  2. Fetal programming: prenatal testosterone treatment leads to follicular persistence/luteal defects; partial restoration of ovarian function by cyclic progesterone treatment.

    Science.gov (United States)

    Manikkam, Mohan; Steckler, Teresa L; Welch, Kathleen B; Inskeep, E Keith; Padmanabhan, Vasantha

    2006-04-01

    Prenatal testosterone (T) excess during midgestation leads to estrous cycle defects and polycystic ovaries in sheep. We hypothesized that follicular persistence causes polycystic ovaries and that cyclic progesterone (P) treatment would overcome follicular persistence and restore cyclicity. Twice-weekly blood samples for P measurements were taken from control (C; n = 16) and prenatally T-treated (T60; n = 14; 100 mg T, im, twice weekly from d 30-90 of gestation) Suffolk sheep starting before the onset of puberty and continuing through the second breeding season. A subset of C and T60 sheep were treated cyclically with a modified controlled internal drug-releasing device for 13-14 d every 17 d during the first anestrus (CP, 7; TP, 6). Transrectal ovarian ultrasonography was performed for 8 d in the first and 21 d in the second breeding season. Prenatal T excess reduced the number, but increased the duration of progestogenic cycles, reduced the proportion of ewes with normal cycles, increased the proportion of ewes with subluteal cycles, decreased the proportion of ewes with ovulatory cycles, induced the occurrence of persistent follicles, and reduced the number of corpora lutea in those that cycled. Cyclic P treatment in anestrus, which produced one third the P concentration seen during luteal phase of cycle, did not reduce the number of persistent follicles, but increased the number of progestogenic cycles while reducing their duration. These findings suggested that follicular persistence might contribute to the polycystic ovarian morphology. Cyclic P treatment was able to only partially restore follicular dynamics, but this may be related to the low replacement concentrations of P achieved.

  3. Toxicological screening of Mikania glomerata Spreng., Asteraceae, extract in male Wistar rats reproductive system, sperm production and testosterone level after chronic treatment

    Directory of Open Access Journals (Sweden)

    Rita de Cássia da Silveira e Sá

    2010-07-01

    Full Text Available Some compounds present in therapeutic plants may be responsible for the occurrence of adverse side effects. Coumarin and flavonoids are substances found in many plant species that showed antifertility activity in female rats and dogs, respectively. Mikania glomerata Spreng., Asteraceae, known as guaco in Brazil, is a plant largely used in folk medicine and its leaves are reported to have coumarin and flavonoids. This work analyzes the effect of chronic administration of M. glomerata on the reproductive system of male rats. Thirty-day-old Wistar rats were treated with M. glomerata hydroalcoholic extract at a dose of 3.3 g/kg of body weight for ninety days. Body and organ weights, gamete concentration on the epididymis cauda, serum testosterone level and food consumption were evaluated. No significant alteration was observed in any of the variables analyzed, suggesting the absence of toxic action or antifertility activity of the M. glomerata hydroalcoholic extract.

  4. Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency.

    Science.gov (United States)

    Guerrieri, Gioia M; Martinez, Pedro E; Klug, Summer P; Haq, Nazli A; Vanderhoof, Vien H; Koziol, Deloris E; Popat, Vaishali B; Kalantaridou, Sophia N; Calis, Karim A; Rubinow, David R; Schmidt, Peter J; Nelson, Lawrence M

    2014-09-01

    Women with primary ovarian insufficiency (POI) display low androgen levels, which could contribute to mood and behavioral symptoms observed in this condition. We examined the effects of physiologic testosterone therapy added to standard estrogen/progestin therapy on quality of life, self-esteem, and mood in women with POI. One hundred twenty-eight women with 46,XX spontaneous POI participated in a 12-month randomized, placebo-controlled, parallel-design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy. Quality of life, self-esteem, and mood symptoms were evaluated with standardized rating scales and a structured clinical interview. Differences in outcome measures between the testosterone and placebo treatments were analyzed by Wilcoxon rank sum tests. No differences in baseline characteristics, including serum hormone levels (P > 0.05), were found. Baseline mean (SD) Center for Epidemiologic Studies Depression Scale scores were 10.7 (8.6) and 9.2 (7.8) for testosterone and placebo, respectively (P = 0.35). After 12 months of treatment, measures of quality of life, self-esteem, and mood symptoms did not differ between treatment groups. Serum testosterone levels achieved physiologic levels in the testosterone group and were significantly higher compared with placebo (P self-esteem and had minimal effects on mood. Other mechanisms might play a role in the altered mood accompanying this disorder.

  5. Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized rats.

    Science.gov (United States)

    Crestani, Carlos C; Tavares, Rodrigo F; Guimarães, Franscisco S; Correa, Fernando M A; Joca, Sâmia R L; Resstel, Leonardo B M

    2011-11-30

    In the present study, we investigated the effects induced by fluoxetine treatment (10 mg/kg) for either 1 or 21 consecutive days on arterial pressure and heart rate basal levels, baroreflex activity, hemodynamic responses to vasoactive agents and cardiovascular responses to acute restraint stress. Mild hypertension was observed after 21 days of treatment, but not after administration for 1 day. Moreover, chronic treatment affected the baroreflex control of heart rate, which was characterized by a reduced reflex tachycardia and an enhanced bradycardiac baroreflex response. The pressor responses to systemic administration of the selective α(1)-adrenoceptor agonist phenylephrine, as well as the depressor responses to systemic infusion of the nitric oxide donor sodium nitroprusside, were reduced after chronic fluoxetine treatment. Fluoxetine treatment for 21 days reduced both the pressor and tachycardiac responses evoked by acute restraint stress. In conclusion, the results indicate the development of mild hypertension after chronic fluoxetine treatment. This effect was followed by changes in the baroreflex control of heart rate and altered vascular responsiveness to pressor and depressor agents, which may explain, at least in part, the increase in arterial pressure. Chronic fluoxetine treatment also affected cardiovascular responses to restraint stress, thus indicating that fluoxetine may affect cardiovascular adaptation under conditions of stress. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone.

    Science.gov (United States)

    Machowska, A; Brzozowski, T; Sliwowski, Z; Pawlik, M; Konturek, P C; Pajdo, R; Szlachcic, A; Drozdowicz, D; Schwarz, M; Stachura, J; Konturek, S J; Pawlik, W W

    2008-02-01

    Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.

  7. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men

    Directory of Open Access Journals (Sweden)

    Gårevik N

    2014-12-01

    Full Text Available Nina Gårevik, Anders Rane, Linda Björkhem-Bergman, Lena Ekström Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Aims: To study the effect and time profile of different doses of testosterone enanthate on the blood lipid profile and gonadotropins. Experimental design: Twenty-five healthy male volunteers aged 27–43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses of Testoviron® Depot. Luteinizing hormone (LH, follicle-stimulating hormone (FSH, blood lipid profile (total cholesterol, plasma [p-] low-density lipoprotein, p-high-density lipoprotein [HDL], p-apolipoprotein A1 [ApoA1], p-apolipoprotein B, p-triglycerides, p-lipoprotein(a, serum [s-] testosterone, and 25-hydroxyvitamin D3 were analyzed prior to, and 4 and 14 days after dosing. Testosterone and epitestosterone in urine (testosterone/epitestosterone ratio were analyzed prior to each dose after a washout period of 6–8 weeks. Results and discussion: All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic–pituitary–gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg did not have any effect on the lipid profile. Conclusion: The single doses of testosterone produced a dose-dependent increase in serum testosterone concentrations together with suppression of s-LH and s-FSH. Alterations in ApoA1 and HDL were observed after the two highest single doses. It is possible that long-time abuse of anabolic androgenic steroids will lead to alteration in vitamin D status

  8. Immunodeficiency in the chicken. II. Production of monomeric IgM following testosterone treatment or infection with Gumboro disease.

    Science.gov (United States)

    Ivanyi, J

    1975-06-01

    Chickens were treated at an early embryonal age with testosterone propionate or infected neonatally with the virus producing Gumboro disease. Their sera were subsequently fractionated by Sephadex G-200 chromatography, and showed a complete deficiency of IgG and the presence of IgM which was eluted with the 7S protein fraction. Purified and 125-I-labelled monomeric IgM was examined by SDS-acrylamide gel electrophoresis and found to contain both mu and light chains, together with a chain of intermediary size, which was absent from the patterns of 19S IgM or IgG.

  9. Testosterone therapy decreases subcutaneous fat and adiponectin in aging men.

    Science.gov (United States)

    Frederiksen, L; Højlund, K; Hougaard, D M; Mosbech, T H; Larsen, R; Flyvbjerg, A; Frystyk, J; Brixen, K; Andersen, M

    2012-03-01

    Testosterone therapy increases lean body mass and decreases total fat mass in aging men with low normal testosterone levels. The major challenge is, however, to determine whether the metabolic consequences of testosterone therapy are overall positive. We have previously reported that 6-month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, placebo-controlled study on 6-month testosterone treatment (gel) in 38 men, aged 60-78 years, with bioavailable testosterone 94 cm. Central fat mass (CFM) and lower extremity fat mass (LEFM) were measured by dual X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAT), visceral adipose tissue (VAT), and thigh subcutaneous fat area (TFA) were measured by magnetic resonance imaging. Adiponectin levels were measured using an in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention. LEFM was decreased (b = -0.47 kg, P = 0.07) while CFM did not change significantly (b = -0.66 kg, P = 0.10) during testosterone therapy. SAT (b = -3.0%, P = 0.018) and TFA (b = -3.0%, P testosterone therapy (b = -1.3 mg/l, P = 0.001). Testosterone therapy decreased subcutaneous fat on the abdomen and lower extremities, but visceral fat was unchanged. Moreover, adiponectin levels were significantly decreased during testosterone therapy.

  10. Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

    Science.gov (United States)

    Goetz, Laura G; Mamillapalli, Ramanaiah; Devlin, Maureen J; Robbins, Amy E; Majidi-Zolbin, Masoumeh; Taylor, Hugh S

    2017-11-01

    Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency. Copyright © 2017 the American Physiological Society.

  11. Testosterone and Depression

    Directory of Open Access Journals (Sweden)

    Şükrü Kartalcı

    2010-12-01

    Full Text Available Androgens have various effects on human body and mood. Testosterone, a hormone mainly secreted from testes and adrenals, is one of the most potent androgens. Multiple studies have found that testosterone plays a role in regulating sexual activity, libido, social behaviors, aggression, cognitive functions, sleep control and well-being in men and women. Testosterone deficiency in hypogonadic or elderly men leads to neuropsychiatric problems, such as fatigue, loss of libido, irritability, insomnia and depressive mood. Testosterone replacement therapy consistently reverses these sequel in men. On the other hand, hyperandrogenic states in women are related to aggression and antisocial behavior, which might lead to depressive mood. Low testosterone levels may also result in depression among oophorectomized women. Because of such effects, a relationship between testosterone and depression has long been an issue of speculation, but yet very few studies have addressed this relation. Along with clinical studies, experimental and epidemiological studies show that testosterone is related to depression in men and women. But studies of testosterone concentrations in depression have yielded inconsistent results reporting low as well as high testosterone levels associated with depression. In this article, the physiological and psychological effects of testosterone and evidence regarding its relationship to depressive disorders and possible gender differences have been reviewed.

  12. Anthropometry in Klinefelter syndrome--multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism.

    Science.gov (United States)

    Chang, Simon; Skakkebæk, Anne; Trolle, Christian; Bojesen, Anders; Hertz, Jens Michael; Cohen, Arieh; Hougaard, David Michael; Wallentin, Mikkel; Pedersen, Anders Degn; Østergaard, John Rosendahl; Gravholt, Claus Højbjerg

    2015-03-01

    Klinefelter syndrome, 47, XXY (KS), is underdiagnosed partly due to few clinical signs complicating identification of affected individuals. Certain phenotypic traits are common in KS. However, not all aspects of the KS phenotype are well described. To describe anthropometry and body composition in KS and relate findings to biochemistry and X-chromosome related genetic markers. Seventy three KS males referred to our clinic and 73 age-matched controls underwent comprehensive measurements of anthropometry and body composition in a cross-sectional, case-controlled study. Furthermore, genetic analysis for parental origin of the supernumerary X-chromosome, skewed X-chromosome inactivation and androgen receptor (AR) CAG repeat length was done. Anthropometry and body composition in KS and the effect of genotype hereon. KS males were taller (absolute difference: 5.1 cm, P Anthropometry and body composition in KS is specific and dysmorphic and affected by AR CAG repeat length and decreased exposure to testosterone already during fetal life.

  13. Muscle specific miRNAs are induced by testosterone and independently upregulated by age

    DEFF Research Database (Denmark)

    Nielsen, Søren; Hvid, Thine; Kelly, Meghan

    2014-01-01

    Age dependent decline in skeletal muscle function leads to impaired metabolic flexibility in elderly individuals. Physical activity and testosterone treatment have proven efficient strategies for delaying this condition. However, a common molecular pathway has not been identified. Muscle specific...... of miR133a/b. In conclusion, alterations in fitness level and circulating testosterone seem to represent two independent regulatory events where testosterone is a specific regulator of miR-133a/b expression....... miRNAs (myomiRs) regulate metabolic pathways in skeletal muscle, are regulated by physical activity, and have response elements for testosterone in their promoter region. We therefore hypothesized that myomiRs would be regulated in skeletal muscle during aging. We further investigated any potential...... gender-dependent regulation of these miRNAs. We found that the myomiRs miR-1, miR-133a, and miR-133b were increased in skeletal muscle of elderly men compared to younger men. In addition, miR-133a/133b expression was markedly higher in women compared to men. Elimination of circulating testosterone in men...

  14. Diagnosis and management of testosterone deficiency

    Directory of Open Access Journals (Sweden)

    James A McBride

    2015-04-01

    Full Text Available Testosterone supplementation therapy (TST use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD. Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.

  15. Diagnosis and management of testosterone deficiency

    Science.gov (United States)

    McBride, James A; Carson, Culley C; Coward, Robert M

    2015-01-01

    Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD. PMID:25532575

  16. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.

    Science.gov (United States)

    Grossmann, Mathis; Hoermann, Rudolf; Wittert, Gary; Yeap, Bu B

    2015-09-01

    The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial. To perform a systematic review and meta-analysis of placebo-controlled double-blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome. A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature. Eligible studies were published placebo-controlled double-blind RCTs published in English. Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data. Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta-analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) -1·58 [-2·25, -0·91], P treatment effect was nonsignificant for RCTs using a more stringent computer-based equation (HOMA2), MD -0·19 [-0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD -0·15 [-0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD -2·49 [-5·81, 0·83], P = 0·14). This meta-analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome. © 2014 John Wiley & Sons Ltd.

  17. Effects of exogenous testosterone on isolated rabbit corpus cavernosum penis.

    Science.gov (United States)

    Yildirim, S; Utkan, T; Yildirim, K; Sarioglu, Y

    2000-02-01

    To study the effects of exogenous excess of testosterone on the constricting effect of phenylephrine and endothelium-dependent and -independent relaxing effects of different agonists in the corpus cavernosum penis (CCP). Specimens of the CCP were obtained from rabbits testosterone for 1 and 2 months and untreated for 2 months after testosterone-treatment for 2 months. Preparations were mounted between two parallel platinum electrodes in organ baths. Responses to phenylephrine, carbachol, and sodium nitroprusside were obtained by adding the reagent cumulatively to the bath. The phenylephrine-induced contractions were decreased with no change in agonist potency (pD2 value) after both 1 and 2 month testosterone-treatment and did not return to control values in corpus cavernosum obtained from rabbits untreated for 2 months after testosterone-treatment for 2 months. Testosterone treatment for 1 or 2 months increased the endothelium-dependent relaxations induced by carbachol and decreased the relaxations elicited by electric stimulation but did not affect the relaxations induced by sodium nitroprusside. These relaxant responses to carbachol and electric stimulation did not return to control values in corpus cavernosum obtained from rabbits untreated for 2 months after testosterone-treatment for 2 months. There were no significant changes in the pD2 values calculated by agonist-induced relaxation responses in all testosterone-treatment groups compared with control group. The exogenous excess of testosterone plays an important role in erectile function by a direct action on the relaxant and contractile responses of CCP.

  18. Testosterone Deficiency and Nocturia: A Review

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shigehara

    2017-04-01

    Full Text Available Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS, and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions.

  19. Altering surface characteristics of polypropylene mesh via sodium hydroxide treatment.

    Science.gov (United States)

    Regis, Shawn; Jassal, Manisha; Mukherjee, Nilay; Bayon, Yves; Scarborough, Nelson; Bhowmick, Sankha

    2012-05-01

    Incisional hernias represent a serious and common complication following laparotomy. The use of synthetic (e.g. polypropylene) meshes to aid repair of these hernias has considerably reduced recurrence rates. While polypropylene is biocompatible and has a long successful clinical history in treating hernias and preventing reherniation, this material may suffer some limitations, particularly in challenging patients at risk of wound failure due to, for example, an exaggerated inflammation reaction, delayed wound healing, and infection. Surface modification of the polypropylene mesh without sacrificing its mechanical properties, critical for hernia repair, represents one way to begin to address these clinical complications. Our hypothesis is treatment of a proprietary polypropylene mesh with sodium hydroxide (NaOH) will increase in vitro NIH/3T3 cell attachment, predictive of earlier and improved cell colonization and tissue integration of polypropylene materials. Our goal is to achieve this altered surface functionality via enhanced removal of chemicals/oils used during material synthesis without compromising the mechanical properties of the mesh. We found that NaOH treatment does not appear to compromise the mechanical strength of the material, despite roughly a 10% decrease in fiber diameter. The treatment increases in vitro NIH/3T3 cell attachment within the first 72 h and this effect is sustained up to 7 days in vitro. This research demonstrates that sodium hydroxide treatment is an efficient way to modify the surface of polypropylene hernia meshes without losing the mechanical integrity of the material. This simple procedure could also allow the attachment of a variety of biomolecules to the polypropylene mesh that may aid in reducing the complications associated with polypropylene meshes today. Copyright © 2012 Wiley Periodicals, Inc.

  20. Blood Test: Testosterone

    Science.gov (United States)

    ... For Parents / Blood Test: Testosterone What's in this article? What It Is Why It's Done Preparation The Procedure What to Expect Getting the Results Risks Helping Your Child If You Have Questions Print en español Análisis de sangre: testosterona What It Is A testosterone test measures ...

  1. Benefits and risks of testosterone treatment for hypoactive sexual desire disorder in women: a critical review of studies published in the decades preceding and succeeding the advent of phosphodiesterase type 5 inhibitors

    Directory of Open Access Journals (Sweden)

    Sandra Léa Bonfim Reis

    2014-04-01

    Full Text Available With advancing age, there is an increase in the complaints of a lack of a libido in women and erectile dysfunction in men. The efficacy of phosphodiesterase type 5 inhibitors, together with their minimal side effects and ease of administration, revolutionized the treatment of erectile dysfunction. For women, testosterone administration is the principal treatment for hypoactive sexual desire disorder. We sought to evaluate the use of androgens in the treatment of a lack of libido in women, comparing two periods, i.e., before and after the advent of the phosphodiesterase type 5 inhibitors. We also analyzed the risks and benefits of androgen administration. We searched the Latin-American and Caribbean Health Sciences Literature, Cochrane Library, Excerpta Medica, Scientific Electronic Library Online, and Medline (PubMed databases using the search terms disfunção sexual feminina/female sexual dysfunction, desejo sexual hipoativo/female hypoactive sexual desire disorder, testosterona/testosterone, terapia androgênica em mulheres/androgen therapy in women, and sexualidade/sexuality as well as combinations thereof. We selected articles written in English, Portuguese, or Spanish. After the advent of phosphodiesterase type 5 inhibitors, there was a significant increase in the number of studies aimed at evaluating the use of testosterone in women with hypoactive sexual desire disorder. However, the risks and benefits of testosterone administration have yet to be clarified.

  2. Mitochondria, glycogen and lipid droplets in skeletal muscle during testosterone treatment and strength training. A randomized, double blinded, placebo-controlled trial

    DEFF Research Database (Denmark)

    Jensen, Richard Christian; Lehman Christensen, Louise; Nielsen, Joachim

    2018-01-01

    testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six‐month ST or combined three‐month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD......Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double‐blinded, placebo‐controlled study, we investigated...... the effects of six‐month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were...

  3. Bare-Part Color in Female Budgerigars Changes from Brown to Structural Blue following Testosterone Treatment but Is Not Strongly Masculinized

    Science.gov (United States)

    Lahaye, Stefanie E. P.; Eens, Marcel; Darras, Veerle M.; Pinxten, Rianne

    2014-01-01

    Whereas several studies have shown that experimentally increased levels of the androgenic steroid testosterone can affect female behavior, fewer studies have focused on the activational effects of exogenous testosterone on female morphology. With respect to colorful displays in birds, almost exclusively the effects of testosterone manipulation on female carotenoid-based colorations have been studied. Other color types such as structural colors (i.e. UV, blue and violet colors that result from differential light reflection in the nanostructures of the tissue) remain largely unstudied. Here, we investigated the short- and long-term effects of exogenous testosterone on the expression of structural bare-part coloration in female budgerigars, Melopsittacus undulatus. In this parrot species, bare-part coloration is expressed in the cere, a structure over the beak which is brown in females and structural blue in males. We experimentally increased plasma testosterone levels in testosterone-treated females (T-females) compared to controls (C-females) and we performed weekly spectrophotometric measurements of the cere for five weeks after implantation and one measurement after ten weeks. We also estimated the extent to which testosterone masculinized female cere color by comparing the experimental females with untreated males. We found significant effects of testosterone on cere color from week four after implantation onwards. T-females expressed significantly bluer ceres than C-females with higher values for brightness and UV reflectance. T-female cere color, however, remained significantly less blue than in males, while values for brightness and UV reflectance were significantly higher in T-females than in males. Our quantitative results show that exogenous testosterone induces the expression of structural blue color in females but does not strongly masculinize female cere coloration. We provide several potential pathways for the action of testosterone on structural color

  4. Bare-part color in female budgerigars changes from brown to structural blue following testosterone treatment but is not strongly masculinized.

    Directory of Open Access Journals (Sweden)

    Stefanie E P Lahaye

    Full Text Available Whereas several studies have shown that experimentally increased levels of the androgenic steroid testosterone can affect female behavior, fewer studies have focused on the activational effects of exogenous testosterone on female morphology. With respect to colorful displays in birds, almost exclusively the effects of testosterone manipulation on female carotenoid-based colorations have been studied. Other color types such as structural colors (i.e. UV, blue and violet colors that result from differential light reflection in the nanostructures of the tissue remain largely unstudied. Here, we investigated the short- and long-term effects of exogenous testosterone on the expression of structural bare-part coloration in female budgerigars, Melopsittacus undulatus. In this parrot species, bare-part coloration is expressed in the cere, a structure over the beak which is brown in females and structural blue in males. We experimentally increased plasma testosterone levels in testosterone-treated females (T-females compared to controls (C-females and we performed weekly spectrophotometric measurements of the cere for five weeks after implantation and one measurement after ten weeks. We also estimated the extent to which testosterone masculinized female cere color by comparing the experimental females with untreated males. We found significant effects of testosterone on cere color from week four after implantation onwards. T-females expressed significantly bluer ceres than C-females with higher values for brightness and UV reflectance. T-female cere color, however, remained significantly less blue than in males, while values for brightness and UV reflectance were significantly higher in T-females than in males. Our quantitative results show that exogenous testosterone induces the expression of structural blue color in females but does not strongly masculinize female cere coloration. We provide several potential pathways for the action of testosterone on

  5. KAJIAN TERAPI AKUPUNKTUR TERHADAP KADAR HORMON TESTOSTERON PRIA USIA LANJUT

    Directory of Open Access Journals (Sweden)

    Bambang Wasito Tjipto

    2012-12-01

    Full Text Available Background: Testosterone was the most important androgen secreted into the blood in males. It was responsible for development of secondary male sex characteristics and its measurements are helpful in evaluating the hypogonadal states. Decreasing of testosterone in males started in middle age, about 45–59 years old. It is responsible of decreasing muscle mass and strength, increasing of body fat especially abdominal fat and gynecomastia, less of libido and sexual intercourse frequency, increase of erectile dysfunction. Objective: The objective of this study was conducted stimulation on acupuncture reproduction point to increase testosterone hormone level in elder’s men. Methods: The study used non randomized experiment pre- post test without control group design, the samples was 40 older men, about 50 – more than 70 years old. The stimulation on acupuncture point CV-4, Sp-6, LV-3, and ST-36, on older men were given five times per week, for ten treatments, before treatment each patient was determined the concentration of testosterone hormone and after ten times acupuncture treatment. Results: 15 old men, have increased testosterone level, 20 old men have decreased testosterone level, and 16 old men have no changes in libido after ten times acupuncture treatment. Not all responder after therapy acupuncture ten times at reproduction point have increased of hormone testosterone. Most of 50–69 year men have increased testosterone level. Men above 70 year have no changes testosterone level. There were 24 old men have changes in libido without increased testosterone level. Conclusion: acupuncture may used as alternative therapy to increased testosterone level and libido for elderly men. Key words: Acupuncture, testosterone hormone, old men

  6. Intrinsa: An Inquiry into Female Sexual Dysfunction and Testosterone

    OpenAIRE

    Quasha, Devon R.

    2006-01-01

    In December 2004, the Food & Drug Administration rejected Intrinsa, a testosterone transdermal system for the treatment of hypoactive sexual desire disorder in surgically menopausal women. Intrinsa, as well as the FDA's decision, sparked considerable controversy. Principally, it raised questions about the use of testosterone to treat sexual dysfunction in women. This paper examines the relationship between testosterone and female sexual dysfunction and explores, specifically, whether there is...

  7. Monitoring testosterone levels in testosterone-treated men.

    Science.gov (United States)

    Winters, Stephen J

    2016-01-01

    Dose adjustment with transdermal testosterone preparations should recognize the variability of serum total testosterone levels between applications and over the course of 24 h. Dose adjustments are also made difficult by between-laboratory assay variability. Low SHBG with obesity and diabetes lowers the total testosterone level, and free or bioavailable testosterone may prove to be a better choice for monitoring the progress and dosing of testosterone-treated men with adult onset hypogonadism.

  8. Sub-chronic testosterone treatment increases the levels of epithelial sodium channel (ENaC-α, β and γ in the kidney of orchidectomized adult male Sprague–Dawley rats

    Directory of Open Access Journals (Sweden)

    Su Yi Loh

    2016-06-01

    Full Text Available Testosterone has been reported to cause blood pressure to increase. However mechanisms that underlie the effect of this hormone on this physiological parameter are currently not well understood. The aims of this study were to investigate effects of testosterone on expression of α, β and γ-epithelial sodium channel (ENaC proteins and messenger RNAs (mRNAs in kidneys, the channel known to be involved in Na+ reabsorption, which subsequently can affect the blood pressure. Methods. Adult male Sprague–Dawley (SD rats were orchidectomized fourteen days prior to receiving seven days treatment with testosterone propionate (125 µg/kg/day or 250 µg/kg/day with or without flutamide (androgen receptor blocker or finasteride (5α-reductase inhibitor. Following sacrifice, the kidneys were removed and were subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR respectively. The distribution of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Results. The α, β and γ-ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. In these rats, α, β and γ-ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. Co-treatment with flutamide or finasteride resulted in the levels of α, β and γ-ENaC proteins and mRNAs in kidneys to decrease. In conclusions, increases in α, β and γ-ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na+ reabsorption which subsequently might cause an increase in blood pressure.

  9. DDT increases hepatic testosterone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sierra-Santoyo, Adolfo; Albores, Arnulfo; Cebrian, Mariano E. [Cinvestav-IPN, Seccion de Toxicologia, Mexico (Mexico); Hernandez, Manuel [Cinvestav-IPN, Departamento de Biologia Celular (Mexico)

    2005-01-01

    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-{sup 14}C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2{alpha}-hydroxytestosterone (OHT), and 16{alpha}-OHT but higher 6{beta}-OHT whereas treated females produced less 7{alpha}-OHT and AD but higher 6{beta}-OHT and 6{alpha}-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6{beta}-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6{alpha}-/15{alpha}-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6{alpha}-/16{alpha}-OHT and 6-dehydrotestosterone/16{alpha}-OHT ratios followed a similar tendency, with the ratio 6{alpha}-/16{alpha}-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats. (orig.)

  10. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

    Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

  11. Impact of testosterone on body fat composition.

    Science.gov (United States)

    De Maddalena, Chiara; Vodo, Stella; Petroni, Anna; Aloisi, Anna Maria

    2012-12-01

    An excessive food supply has resulted in an increasing prevalence of overweight and obesity, conditions accompanied by serious health problems. Several studies have confirmed the significant inverse correlation between testosterone and obesity. Indeed after decades of intense controversy, a consensus has emerged that androgens are important regulators of fat mass and distribution in mammals and that androgen status affects cellularity in vivo. The high correlation of testosterone levels with body composition and its contribution to the balance of lipid metabolism are also suggested by the fact that testosterone lowering is associated with important clinical disorders such as dyslipidemia, atherosclerosis, cardiovascular diseases, metabolic syndrome and diabetes. In contrast, testosterone supplementation therapy in hypogonadic men has been shown to improve the lipid profile by lowering cholesterol, blood sugar and insulin resistance. Leptin, ghrelin and adiponectin are some of the substances related to feeding as well as androgen regulation. Thus, complex and delicate mechanisms appear to link androgens with various tissues (liver, adipose tissue, muscles, coronary arteries and heart) and the subtle alteration of some of these interactions might be the cause of correlated diseases. This review underlines some aspects regarding the high correlations between testosterone physiology and body fat composition. Copyright © 2012 Wiley Periodicals, Inc.

  12. Sexual Health: Testosterone Therapy

    Science.gov (United States)

    ... Low testosterone may contribute to a decrease in motivation or self-confidence. You may feel sad or ... products about potential for venous blood clots. U.S. Food and Drug Administration. http://www.fda.gov/Drugs/ ...

  13. The relationship between sleep disorders and testosterone in men

    Directory of Open Access Journals (Sweden)

    Gary Wittert

    2014-04-01

    Full Text Available Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG, or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.

  14. Has testosterone passed the test in premenopausal women with low libido? A systematic review.

    Science.gov (United States)

    Reed, Beverly G; Bou Nemer, Laurice; Carr, Bruce R

    2016-01-01

    There are limited evaluation and treatment options for low libido in premenopausal women. This review sought to evaluate the available evidence supporting the evaluation of testosterone serum levels and testosterone treatment of premenopausal women with low libido. MEDLINE, PubMed, and ClinicalTrials.gov were searched for articles that referenced the evaluation of testosterone serum level and/or testosterone treatment on premenopausal women with low libido from 1995 to 2015. Additional references were obtained from the reference sections of other papers and from peer review. Studies that included only postmenopausal women were excluded. A total of 13 studies were reviewed in detail. Nine studies examined the relationship between testosterone serum levels and sexuality, an additional three studies examined the effect of testosterone treatment on premenopausal women with low libido, and one study examined both the topics. Six of the ten testosterone serum evaluation studies failed to show a significant association between testosterone serum level and libido. Only one out of four studies examining testosterone treatment in premenopausal women was able to show any clear improvement in libido; however, the effect was limited to only the intermediate dose of testosterone, with the low and high doses of testosterone not producing any effect. The currently available evidence does not support testosterone serum evaluation or treatment in premenopausal women with low libido. Hence, further studies are warranted.

  15. Plasma osteoprotegerin is associated with testosterone levels but unaffected by pioglitazone treatment in patients with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, D; Hermann, Pernille; Rasmussen, Lars Melholt

    2013-01-01

    Objective Increased osteoprotegerin (OPG) levels are associated with increased cardiovascular risk and decreased bone resorption. Pioglitazone treatment reduces the inflammatory state but may decrease bone mineral density. OPG levels during pioglitazone treatment have not previously been evaluated...

  16. DI(N-BUTYL) PHTHALATE AND DIETHYLHEXYL PHTHALATE IN COMBINATION ALTER SEXUAL DIFFERENTIATION IN A CUMULATIVE MANNER AS A RESULT OF DEPRESSED FETAL TESTOSTERONE PRODUCTION AND INSL3 GENE EXPRESSION IN MALE RATS

    Science.gov (United States)

    Plasticizers di(n-butyl) phthalate (DBP) and diehtylhexyl phthalate (DEHP) have similar modes of action: in utero exposure reduces testosterone (T) production in fetal male rats, inhibits reproductive tract differentiation, and induces reproductive organ malformations. In utero e...

  17. 21 CFR 862.1680 - Testosterone test system.

    Science.gov (United States)

    2010-04-01

    ... measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females...

  18. Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

    Directory of Open Access Journals (Sweden)

    Gårevik Nina

    2012-03-01

    Full Text Available Abstract Background Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR. There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR. Methods 39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2. Results The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007. This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively. Conclusion Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.

  19. Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats.

    Science.gov (United States)

    Wang, Yu-Rong; Xu, Yuan; Jiang, Zhen-Zhou; Zhang, Lu-Yong; Wang, Tao

    2017-05-01

    Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg -1 for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  20. [Hypoactive sexual desire and testosterone deficiency in men].

    Science.gov (United States)

    Lejeune, H; Huyghe, É; Droupy, S

    2013-07-01

    Relations between sexual desire and testosterone are more complex than previously thought particularly in ageing males. A Medline search of the existing literature utilizing terms testosterone, libido, sexual desire, hypogonadism, and andropause, was performed until January 2012. Testosterone is a physiological stimulator of sexual desire. In case of complete hypogonadism, libido is very low and testosterone treatment restores sexual desire. In epidemiological studies, the relationship between testosterone and sexual desire is statistically significant but less strict because of interactions with other factors which decrease both sexual desire and testosterone levels. It is especially the case in ageing males: in addition to a possible late-onset hypogonadism, other etiological factors (health, partnership, socioeconomical and psychological factors) and other sexual dysfunctions (such as erectile dysfunction) must be taken into account. The decrease of sexual desire is one of the symptoms seen in late-onset hypogonadism. The effect of testosterone replacement therapy is more obvious that testosterone is low and there are no other causes of impaired sexual desire. There is no evidence that testosterone therapy increases the risk of prostate cancer, benign prostatic hyperplasia or promotes the clinical expression of subclinical prostate cancer. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy.

    Science.gov (United States)

    Hsieh, Tung-Chin; Pastuszak, Alexander W; Hwang, Kathleen; Lipshultz, Larry I

    2013-02-01

    Testosterone replacement therapy results in decreased serum gonadotropins and intratesticular testosterone, and impairs spermatogenesis, leading to azoospermia in 40% of patients. However, intratesticular testosterone can be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which may support continued spermatogenesis in patients on testosterone replacement therapy. We retrospectively reviewed the records of hypogonadal men treated with testosterone replacement therapy and concomitant low dose human chorionic gonadotropin. Testosterone replacement consisted of daily topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every other day. Serum and free testosterone, estradiol, semen parameters and pregnancy rates were evaluated before and during therapy. A total of 26 men with a mean age of 35.9 years were included in the study. Mean followup was 6.2 months. Of the men 19 were treated with injectable testosterone and 7 were treated with transdermal gel. Mean serum hormone levels before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p human chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the partner during followup. Low dose human chorionic gonadotropin appears to maintain semen parameters in hypogonadal men on testosterone replacement therapy. Concurrent testosterone replacement and human chorionic gonadotropin use may preserve fertility in hypogonadal males who desire fertility preservation while on testosterone replacement therapy. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. [Plasma testosterone, obesity, metabolic syndrome and diabetes].

    Science.gov (United States)

    Prévost, Gaëtan; Eas, Florence; Kuhn, Jean-Marc

    2014-02-01

    The frequency of diabetes and/or metabolic syndrome rises concurrently with that of body mass index (BMI). In adult men, plasma testosterone level changes evolve inversely to that of BMI. Plasma total testosterone, sex hormone-binding globulin (SHBG) and free testosterone are significantly lower in adult men with a clinical and biological pattern of metabolic syndrome (MetS) than in those without such a pattern. After adjustment for confounding factors, diabetes type 2 (DT2) remains associated with a significant decrease of plasma testosterone level. The androgenic blockade, used as a treatment for disseminated prostate cancer, induces a metabolic pattern similar to MetS. In men older than 65 years, a decrease of plasma testosterone level is associated with an increased risk of stroke or of death linked to a cardiovascular event. After exclusion of contraindications, the substitution with androgens of a demonstrated hypogonadism in a obese patient, notably when obesity is associated with a pattern of MetS and/or a DT2, could have some metabolic and cardiovascular advantages. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Testosterone and glucose metabolism in men: current concepts and controversies.

    Science.gov (United States)

    Grossmann, Mathis

    2014-03-01

    A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic-pituitary-testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.

  4. Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized rats

    OpenAIRE

    Crestani, Carlos Cesar [UNESP; Tavares, Rodrigo F.; Guimaraes, Franscisco S.; Correa, Fernando M. A.; Joca, Samia R. L.; Resstel, Leonardo B. M.

    2011-01-01

    In the present study, we investigated the effects induced by fluoxetine treatment (10 mg/kg) for either 1 or 21 consecutive days on arterial pressure and heart rate basal levels, baroreflex activity, hemodynamic responses to vasoactive agents and cardiovascular responses to acute restraint stress. Mild hypertension was observed after 21 days of treatment, but not after administration for 1 day. Moreover, chronic treatment affected the baroreflex control of heart rate, which was characterized ...

  5. Testosterone: action, deficiency, substitution

    National Research Council Canada - National Science Library

    Nieschlag, E; Nieschlag, S. (Susan); Behre, H. M. (Hermann M.)

    2004-01-01

    ... reviews applications in male contraception, the role of 5 -reductase inhibitors and the controversial use of DHEA. For this book the editors have assembled the world leaders in testosterone research and clinical andrology and endocrinology. A special feature of the book is the fact that its 24 chapters were submitted simultaneously to ens...

  6. Methandrostenolone and testosterone RIA

    International Nuclear Information System (INIS)

    Bojadzsieva, M.; Mann, V.; Peter, F.; Blatniczky, L.; Pucsok, J.

    1979-01-01

    Some problems of the RIA method and its applications in pediatrics are treated. The intenstinal absorption and excretion of methandrostenolone and testosterone were investigated by RIA. Methandrostenolone RIA was proved to be an easy and sensitive method in the investigation of absorption and excretion. (H.E.)

  7. The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy.

    Science.gov (United States)

    Tryniszewski, Wieslaw; Kamiński, Grzegorz; Maziarz, Zbigniew; Nowak, Michal; Gadzicki, Mariusz; Radek, Maciej

    2018-01-10

    Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p Metabolism). We observed

  8. Lowered testosterone in male obesity: mechanisms, morbidity and management.

    Science.gov (United States)

    Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

    2014-01-01

    With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.

  9. Lowered testosterone in male obesity: mechanisms, morbidity and management

    Science.gov (United States)

    Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

    2014-01-01

    With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials. PMID:24407187

  10. Lowered testosterone in male obesity: Mechanisms, morbidity and management

    Directory of Open Access Journals (Sweden)

    Mark Ng Tang Fui

    2014-04-01

    Full Text Available With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.

  11. Medico-legal aspects of altered sensation following endodontic treatment: a retrospective case series

    DEFF Research Database (Denmark)

    Givol, Navot; Rosen, Eyal; Bjørndal, Lars

    2011-01-01

    The objective of this study was to analyze cases of liability claims related to persistent altered sensation following endodontic treatments so as to characterize the medico-legal aspects of this complication.......The objective of this study was to analyze cases of liability claims related to persistent altered sensation following endodontic treatments so as to characterize the medico-legal aspects of this complication....

  12. ALTERATIONS IN BARLEY PROTEOME UPON FUNGAL INFECTION AND TRICYCLAZOLE TREATMENT

    Directory of Open Access Journals (Sweden)

    Manoj Kumar a,b

    2017-04-01

    Full Text Available The barley proteome was investigated upon fungal infection and subsequent treatment by tricyclazole (TCZ, which is known to have applications in spot blotch disease management in barley.Significantly enhanced chlorophyll content was recorded in TCZ treated plants. The disease severity was significantly reduced after TCZ application in pathogen inoculated plants by reducing the appressoria formation at infection site in barley leaves. Two-dimensional gel electrophoresis (2-DE revealed the expression profile of proteins from (I control plants (healthy barley leaves; application with sterile water,(II plants after foliar application of TCZ (100 µg/ml, (III plants inoculated with B. sorokiniana and (IV plants treated with TCZ (72 h after B. sorokiniana inoculation. A set of 33 proteins expressed differentially after TCZ treatment. Out of this 19 had known functions, while others were unknown or hypothetical proteins. These differentially expressed proteins were related to redox-activity and gene expression, electron transfer,cell division and chromosome partitioning, cell envelop biogenesis, energy metabolism and conversion, respiration and pathogenesis related functions in the barley plants. The study provides a platform and documents the proteins that might be involved in disease management in barley following TCZ application. It is expected that the study will provide boost in understanding proteome regulation upon fungal infection and subsequent anti-fungal treatment and will attract researchers for further validation leading to better pest management.

  13. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement.

    Science.gov (United States)

    Kim, Edward D; McCullough, Andrew; Kaminetsky, Jed

    2016-04-01

    To determine the effects of daily oral doses of enclomiphene citrate compared with topical testosterone gel treatment on serum total testosterone (TT), luteinising hormone (LH), follicle-stimulating hormone (FSH), and sperm counts in men with secondary hypogonadism. Two parallel randomised, double-blind, double-dummy, placebo-controlled, multicentre, phase III studies were undertaken to evaluate two doses of enclomiphene citrate vs testosterone gel (AndroGel(®) 1.62%) on TT, LH, FSH, and sperm counts in overweight men aged 18-60 years with secondary hypogonadism. Men were screened and enrolled in the trials (ZA-304 and ZA-305). All enrolled men had early morning serum TT levels in the low or low normal range (≤300 ng/dL; ≤10.4 nmol/L) and had low or normal LH (testosterone gel group at 16 weeks. Enclomiphene citrate maintained sperm concentration in the normal range over the treatment period, while there was a marked reduction in spermatogenesis in the testosterone gel group. Enclomiphene citrate consistently increased serum TT, LH and FSH, restoring normal levels of serum TT. Enclomiphene citrate treatment maintained sperm concentrations in the normal range. The effects on TT were also seen with testosterone replacement via testosterone gel but sperm counts were not maintained. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  14. Prenatal testosterone and stuttering.

    Science.gov (United States)

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Ecstasy-Induced Caspase Expression Alters Following Ginger Treatment

    Directory of Open Access Journals (Sweden)

    Sara Soleimani Asl

    2013-11-01

    Full Text Available Introduction: Exposure to 3-4, methylenedioxymethamphetamine (MDMA leads to cell death. Herein, we studied the protective effects of ginger on MDMA- induced apoptosis. Methods: 15 Sprague dawley male rats were administrated with 0, 10 mg/kg MDMA, or MDMA along with 100mg/kg ginger, IP for 7 days. Brains were removed to study the caspase 3, 8, and 9 expressions in the hippocampus by RT-PCR. Data was analyzed by SPSS 16 software using the one-way ANOVA test. Results: MDMA treatment resulted in a significant increase in caspase 3, 8, and 9 as compared to the sham group (p<0.001. Ginger administration however, appeared to significantly decrease the same (p<0.001. Discussion: Our findings suggest that ginger consumption may lead to the improvement of MDMA-induced neurotoxicity.

  16. Prostate volume and growth during testosterone replacement therapy is related to visceral obesity in Klinefelter syndrome.

    Science.gov (United States)

    Selice, R; Caretta, N; Di Mambro, A; Torino, M; Palego, P; Ferlin, A; Foresta, C

    2013-12-01

    Klinefelter syndrome (KS) is a chromosomal alteration characterized by increased risk of metabolic syndrome, mainly caused by visceral obesity. In the last years, obesity has been studied as a potential risk factor for prostate disease and recently a link has been demonstrated between visceral adiposity with prostate volume. The aim of this study was to analyze the relationship between obesity and prostate volume and growth during testosterone therapy in KS subjects. We evaluated reproductive hormones, metabolic parameters, anthropometric measures, PSA, and prostate volume in 121 naïve non-mosaic KS patients and 60 age-matched healthy male controls. Fifty-six KS hypogonadic subjects were treated with testosterone-gel 2% and reevaluated after 18 months of treatment. Prostate volume in KS was positively related to waist circumference (WC). The KS group with WC ≥94 cm had significantly higher prostate volume, BMI, insulin plasma levels, homeostasis model assessment index, total cholesterol, triglycerides, and glycemia with respect to the KS group with WC testosterone replacement therapy, only hypogonadic KS men with WC ≥94 cm had a statistically significant increase in prostate volume. Furthermore, in untreated KS subjects, prostate volume showed a statistically significant increase after 18 months of follow-up only in subjects with WC ≥94 cm. This study showed that visceral obesity, insulin resistance, and lipid and glucose metabolism alterations are associated with prostate volume and growth during testosterone replacement therapy in KS, independently from androgen or estrogen levels. These latter findings might provide the basis for a better management and follow-up of KS subjects.

  17. Late-Onset Hypogonadism and Testosterone Replacement in Older Men.

    Science.gov (United States)

    Bhattacharya, Rajib K; Bhattacharya, Shelley B

    2015-11-01

    Late-onset hypogonadism is an underdiagnosed and easily treated condition defined by low serum testosterone levels in men older than 65 years. When treated, a significant improvement in quality of life may be reached in this rapidly rising sector of the population. During the evaluation, laboratory tests and a full medication review should be performed to exclude other illnesses or adverse effects from medications. The major goal of treatment in this population is treating the symptoms related to hypogonadism. There has not been clear evidence supporting universally giving older men with low serum testosterone levels and hypogonadal symptoms testosterone replacement therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The potential for genetically altered microglia to influence glioma treatment.

    Science.gov (United States)

    Li, W; Holsinger, R M D; Kruse, C A; Flügel, A; Graeber, M B

    2013-09-01

    Diffuse and unstoppable infiltration of brain and spinal cord tissue by neoplastic glial cells is the single most important therapeutic problem posed by the common glioma group of tumors: astrocytoma, oligoastrocytoma, oligodendroglioma, their malignant variants and glioblastoma. These neoplasms account for more than two thirds of all malignant central nervous system tumors. However, most glioma research focuses on an examination of the tumor cells rather than on host-specific, tumor micro-environmental cells and factors. This can explain why existing diffuse glioma therapies fail and why these tumors have remained incurable. Thus, there is a great need for innovation. We describe a novel strategy for the development of a more effective treatment of diffuse glioma. Our approach centers on gaining control over the behavior of the microglia, the defense cells of the CNS, which are manipulated by malignant glioma and support its growth. Armoring microglia against the influences from glioma is one of our research goals. We further discuss how microglia precursors may be genetically enhanced to track down infiltrating glioma cells.

  19. Testosterone and the metabolic syndrome

    OpenAIRE

    Muraleedharan, Vakkat; Jones, T. Hugh

    2010-01-01

    Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data ...

  20. Testosterone therapy increased muscle mass and lipid oxidation in aging men

    DEFF Research Database (Denmark)

    Frederiksen, Louise; Højlund, Kurt; Hougaard, David M

    2011-01-01

    The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids...... in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebo-controlled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone 94 cm. Insulin......-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry...

  1. Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?

    NARCIS (Netherlands)

    Michel, M. C.; Klüppel, M.; Philipp, T.; Brodde, O. E.

    1991-01-01

    1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in

  2. Testosterone modulates spatial recognition memory in male rats.

    Science.gov (United States)

    Hawley, Wayne R; Grissom, Elin M; Martin, Ryan C; Halmos, Miklos B; Bart, Corrine L S; Dohanich, Gary P

    2013-04-01

    A growing body of research indicates that testosterone influences spatial cognition in male rats; however, the overwhelming majority of studies have been conducted on tasks motivated by either food deprivation or water escape. The hippocampus-dependent version of the Y-maze task, which characterizes spatial recognition memory, capitalizes on the propensity of rats to gravitate toward novel spatial environments and is not contingent upon either appetite or the stress associated with water escape, two factors also affected by testosterone. Accordingly, the aim of the current study was to examine the effects of orchidectomy and subsequent testosterone treatment on spatial recognition memory. Orchidectomy did not impact spatial recognition memory when the delay between the information and retention trials of the Y-maze task was 24h. Alternatively, on the second Y-maze task, which featured a 48-h delay between trials, orchidectomy reduced, and treatments that produced higher levels of testosterone restored, preference for the arm associated with the novel spatial environment. Importantly, there were no differences in activity levels as a function of orchidectomy or testosterone treatment on either of the two tasks. Consistent with previous findings, orchidectomy attenuated, and testosterone treatment restored, both body weight gain and the relative weight of the androgen-sensitive ischiocavernosus muscle, which confirmed the efficacy of orchidectomy and testosterone treatments on physiological outcomes. Therefore, testosterone influenced spatial cognition on a task that minimized the influence of non-mnemonic factors and took advantage of the innate preference of rodents to seek out novel spatial environments. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Prenatal and pubertal testosterone affect brain lateralization

    NARCIS (Netherlands)

    Beking, T; Geuze, R H; van Faassen, M; Kema, I P; Kreukels, B P C; Groothuis, T G G

    After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in

  4. Testosterone affects language areas of the adult human brain.

    Science.gov (United States)

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  5. Exogenous testosterone decreases men's personal distance in a social threat context.

    Science.gov (United States)

    Wagels, Lisa; Radke, Sina; Goerlich, Katharina Sophia; Habel, Ute; Votinov, Mikhail

    2017-04-01

    Testosterone can motivate human approach and avoidance behavior. Specifically, the conscious recognition of and implicit reaction to angry facial expressions is influenced by testosterone. The study tested whether exogenous testosterone modulates the personal distance (PD) humans prefer in a social threat context. 82 healthy male participants underwent either transdermal testosterone (testosterone group) or placebo application (placebo group). Each participant performed a computerized stop-distance task before (T1) and 3.5h after (T2) treatment, during which they indicated how closely they would approach a human, animal or virtual character with varying emotional expression. Men's PD towards humans and animals varied as a function of their emotional expression. In the testosterone group, a pre-post comparison indicated that the administration of 50mg testosterone was associated with a small but significant reduction of men's PD towards aggressive individuals. Men in the placebo group did not change the initially chosen PD after placebo application independent of the condition. However comparing the testosterone and placebo group after testosterone administration did not reveal significant differences. While the behavioral effect was small and only observed as within-group effect it was repeatedly and selectively shown for men's PD choices towards an angry woman, angry man and angry dog in the testosterone group. In line with the literature, our findings in young men support the influential role of exogenous testosterone on male's approach behavior during social confrontations. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Transdermal testosterone replacement therapy in men

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  7. Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

    Science.gov (United States)

    Mello, Nancy K; Knudson, Inge M; Kelly, Maureen; Fivel, Peter A; Mendelson, Jack H

    2011-01-01

    The neuroactive steroid hormone progesterone attenuates cocaine's abuse-related effects in women and in rodents under some conditions, but the effects of testosterone are unknown. We compared the acute effects of progesterone (0.1, 0.2, and 0.3 mg/kg, intramuscularly (i.m.)), testosterone (0.001, 0.003, and 0.01 mg/kg, i.m.), and placebo on cocaine self-administration and cocaine discrimination dose–effect curves in female rhesus monkeys. Cocaine self-administration (0.03 mg/kg per inj.) was maintained on a fixed ratio 30 schedule of reinforcement, and monkeys had unlimited access to cocaine for 2 h each day. Cocaine doses were administered in an irregular order during each dose–effect curve determination, and the same dose order was used in each subject in all treatment conditions. Blood samples for hormone analysis were collected at the end of each test session. Banana-flavored food pellets (1 g) were also available in three 1-h daily sessions. In drug discrimination studies, the effects of pretreatment with progesterone (0.032–0.32 mg/kg, i.m.) and testosterone (0.001–0.01 mg/kg, i.m.) on the discriminative stimulus effects of cocaine (0.18 mg/kg, i.m.) were examined. Progesterone and testosterone did not alter cocaine discrimination, and did not substitute for cocaine. In contrast, progesterone and testosterone each significantly decreased cocaine self-administration, and produced a downward and rightward shift in the cocaine self-administration dose–effect curve. These findings are concordant with clinical reports that progesterone administration may decrease ratings of positive subjective effects of cocaine in women, and suggest the possible value of neuroactive steroid hormones for the treatment of cocaine abuse and reduction of risk for relapse. PMID:21796112

  8. Has testosterone passed the test in premenopausal women with low libido? A systematic review

    Directory of Open Access Journals (Sweden)

    Reed BG

    2016-10-01

    Full Text Available Beverly G Reed, Laurice Bou Nemer, Bruce R Carr Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, University of Texas Southwestern Medical Center, Dallas, TX, USA Background: There are limited evaluation and treatment options for low libido in premenopausal women. This review sought to evaluate the available evidence supporting the evaluation of testosterone serum levels and testosterone treatment of premenopausal women with low libido. Methods: MEDLINE, PubMed, and ClinicalTrials.gov were searched for articles that referenced the evaluation of testosterone serum level and/or testosterone treatment on premenopausal women with low libido from 1995 to 2015. Additional references were obtained from the reference sections of other papers and from peer review. Studies that included only postmenopausal women were excluded. A total of 13 studies were reviewed in detail. Nine studies examined the relationship between testosterone serum levels and sexuality, an additional three studies examined the effect of testosterone treatment on premenopausal women with low libido, and one study examined both the topics. Results: Six of the ten testosterone serum evaluation studies failed to show a significant association between testosterone serum level and libido. Only one out of four studies examining testosterone treatment in premenopausal women was able to show any clear improvement in libido; however, the effect was limited to only the intermediate dose of testosterone, with the low and high doses of testosterone not producing any effect. Conclusion: The currently available evidence does not support testosterone serum evaluation or treatment in premenopausal women with low libido. Hence, further studies are warranted. Keywords: androgens, hypoactive sexual desire disorder, HSDD, ovary, testis, sexual dysfunction, sexual interest, arousal disorder

  9. Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

    Science.gov (United States)

    Debruyne, Frans M J; Behre, Hermann M; Roehrborn, Claus G; Maggi, Mario; Wu, Frederick C W; Schröder, Fritz H; Jones, Thomas Hugh; Porst, Hartmut; Hackett, Geoffrey; Wheaton, Olivia A; Martin-Morales, Antonio; Meuleman, Eric; Cunningham, Glenn R; Divan, Hozefa A; Rosen, Raymond C

    2017-02-01

    To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. Results support prostate safety of TRT in newly diagnosed men with HG. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  10. Low-dose spironolactone ameliorates insulin resistance and suppresses elevated plasminogen activator inhibitor-1 during gestational testosterone exposure.

    Science.gov (United States)

    Olatunji, Lawrence A; Usman, Taofeek O; Akinade, Aminat I; Adeyanju, Oluwaseun A; Kim, InKyeom; Soladoye, Ayodele O

    2017-12-01

    Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life. We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects. Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19. Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone. These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.

  11. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because...

  12. Testosterone and the Heart.

    Science.gov (United States)

    Goodale, Travis; Sadhu, Archana; Petak, Steven; Robbins, Richard

    2017-01-01

    Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

  13. Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

    DEFF Research Database (Denmark)

    Petersson, Stine J; Christensen, Louise L; Kristensen, Jonas M

    2014-01-01

    therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. METHODS: Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13...... real-time PCR and western blotting. RESULTS: Despite an increase in lipid oxidation (P

  14. Effect of testosterone on antler growth in yearling male reindeer

    Directory of Open Access Journals (Sweden)

    Morten Ryg

    1983-05-01

    Full Text Available 1. The effect of exogenous testosterone on ander growth in yearling male reindeer (Rangifer tarandus tarandus was tested. 2. Testosterone (33 mg/kg inhibited antler growth, and in one animal induced cleaning and subsequent casting of the antlers. This animal grew a new set of antlers, which were cleaned at the normal time. 3. During treatment, there was an inverse relationship between peak testosterone levels and antler growth rate. 4. There was no effect of treatment on body weight or food intake. 5. It is concluded that the effects of testosterone on antler growth are qualitatively the same in reindeer as in other deer. However, because high testosterone doses were necessary to produce effects, it is questionable whether this hormone normally is responsible for the cessation of antler growth in reindeer.Virkningen av testosteron på gevirvekst hos ettårige reinbukker.Abstract in Norwegian / Sammendrag: 1. Virkningen av testosteron på gevirvekst hos ett-årige reinbukker (Rangifer tarandus tarandus ble undersøkt. 2. Testosteron (33 mg/kg hemmet gevirveksten, og hos ett dyr førte behandlingen til at geviret ble feiet og deretter felt. Deretter vokste det ut ett nytt gevir, som ble feiet til vanlig tid. 3. Det var en negativ korrelasjon mellom maksimale testosteronnivåer og gevirvekst under behandlingen. 4. Det var ingen effekt på forinntak eller vektutvikling. 5. Det blir konkludert med at virkningen av testosteron på gevirvekst er kvalitativt den samme hos rein som hos andre hjortedyr. Det er likevel tvilsomt om testosteron normalt er ansvarlig for avslutningen av gevirvekst hos rein, fordi store testosterondoser måtte til for å få noen virkning.Testosteronin vaikutus vuodenikåisten urosporojen sarvien kasvuun.Abstract in Finnish / Tiivistelmä: 1. Tutkimuksessa seurattiin ruiskeena annetun testosteronin vaikutusta vuodenikåisten urosporojen (Rangifer tarandus tarandus sarvien kasvuun. 2. Testosteron! (33 mg/kg hidasti sarvien

  15. Deregulated hepatic metabolism exacerbates impaired testosterone production in Mrp4-deficient mice.

    Science.gov (United States)

    Morgan, Jessica A; Cheepala, Satish B; Wang, Yao; Neale, Geoff; Adachi, Masashi; Nachagari, Deepa; Leggas, Mark; Zhao, Wenchen; Boyd, Kelli; Venkataramanan, Raman; Schuetz, John D

    2012-04-27

    The physiological role of multidrug resistance protein 4 (Mrp4, Abcc4) in the testes is unknown. We found that Mrp4 is expressed primarily in mouse and human Leydig cells; however, there is no current evidence that Mrp4 regulates testosterone production. We investigated its role in Leydig cells, where testosterone production is regulated by cAMP, an intracellular messenger formed when the luteinizing hormone (LH) receptor is activated. Because Mrp4 regulates cAMP, we compared testosterone levels in Mrp4(-/-) and Mrp4(+/+) mice. Young Mrp4(-/-) mice had significantly impaired gametogenesis, reduced testicular testosterone, and disruption of Leydig cell cAMP homeostasis. Both young and adult mice had impaired testosterone production. In Mrp4(-/-) primary Leydig cells treated with LH, intracellular cAMP production was impaired and cAMP-response element-binding protein (CREB) phosphorylation was strongly attenuated. Notably, expression of CREB target genes that regulate testosterone biosynthesis was reduced in Mrp4(-/-) Leydig cells in vivo. Therefore, Mrp4 is required for normal Leydig cell testosterone production. However, adult Mrp4(-/-) mice are fertile, with a normal circulating testosterone concentration. The difference is that in 3-week-old Mrp4(-/-) mice, disruption of gonadal testosterone production up-regulates hepatic Cyp2b10, a known testosterone-metabolizing enzyme. Therefore, defective testicular testosterone production de-regulates hepatic Cyp-mediated testosterone metabolism to disrupt gametogenesis. These findings have important implications for understanding the side effects of therapeutics that disrupt Mrp4 function and are reported to alter androgen production.

  16. Deregulated Hepatic Metabolism Exacerbates Impaired Testosterone Production in Mrp4-deficient Mice*

    Science.gov (United States)

    Morgan, Jessica A.; Cheepala, Satish B.; Wang, Yao; Neale, Geoff; Adachi, Masashi; Nachagari, Deepa; Leggas, Mark; Zhao, Wenchen; Boyd, Kelli; Venkataramanan, Raman; Schuetz, John D.

    2012-01-01

    The physiological role of multidrug resistance protein 4 (Mrp4, Abcc4) in the testes is unknown. We found that Mrp4 is expressed primarily in mouse and human Leydig cells; however, there is no current evidence that Mrp4 regulates testosterone production. We investigated its role in Leydig cells, where testosterone production is regulated by cAMP, an intracellular messenger formed when the luteinizing hormone (LH) receptor is activated. Because Mrp4 regulates cAMP, we compared testosterone levels in Mrp4−/− and Mrp4+/+ mice. Young Mrp4−/− mice had significantly impaired gametogenesis, reduced testicular testosterone, and disruption of Leydig cell cAMP homeostasis. Both young and adult mice had impaired testosterone production. In Mrp4−/− primary Leydig cells treated with LH, intracellular cAMP production was impaired and cAMP-response element-binding protein (CREB) phosphorylation was strongly attenuated. Notably, expression of CREB target genes that regulate testosterone biosynthesis was reduced in Mrp4−/− Leydig cells in vivo. Therefore, Mrp4 is required for normal Leydig cell testosterone production. However, adult Mrp4−/− mice are fertile, with a normal circulating testosterone concentration. The difference is that in 3-week-old Mrp4−/− mice, disruption of gonadal testosterone production up-regulates hepatic Cyp2b10, a known testosterone-metabolizing enzyme. Therefore, defective testicular testosterone production de-regulates hepatic Cyp-mediated testosterone metabolism to disrupt gametogenesis. These findings have important implications for understanding the side effects of therapeutics that disrupt Mrp4 function and are reported to alter androgen production. PMID:22375007

  17. 21 CFR 556.710 - Testosterone propionate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  18. Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: a hypothesis.

    Science.gov (United States)

    Rice, Timothy R

    2017-04-01

    Children born premature are at risk for neurodevelopmental disorders, including autism and schizophrenia. This piece advances the hypothesis that altered androgen exposure observed in premature infants is an important mediator of the neurodevelopmental risk in males associated with prematurity. Specifically, the alterations of normative physiologic postnatal activations of the hypothalamic-pituitary-gonadal axis that occur in preterm males are hypothesized to contribute to the risk of neuropsychiatric pathology of prematurity through altered androgen-mediated organizational effects on the developing brain. The physiology of testosterone and male central nervous system development in full-term births is reviewed and compared to the developmental processes of prematurity. The effects of the altered testosterone physiology observed within prematurity outside of the central nervous system are reviewed as a segue into a discussion of the effects within the nervous system, with a special focus on autism spectrum disorders and attention deficit hyperactivity disorder. The explanatory power of this model is reviewed as a supplement to the preexisting models of prematurity and neurodevelopmental risk, including infection and other perinatal central nervous system insults. The emphasis is placed on altered androgen exposure as serving as just one among many mediators of neurodevelopmental risk that may be of interest for further research and evidence-based investigation. Implications for diagnosis, management and preventative treatments conclude the piece.

  19. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

    Science.gov (United States)

    Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

    2011-07-01

    Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older

  20. Testosterone in obesity, metabolic syndrome and type 2 diabetes.

    Science.gov (United States)

    Stanworth, Roger D; Jones, T Hugh

    2009-01-01

    Testosterone levels are reduced in obesity, the metabolic syndrome and type 2 diabetes. Low testosterone levels are now being recognised as an independent risk factors for these conditions. Findings from men undergoing androgen suppression as treatment for prostate cancer confirm that the hypogonadal state increases body fat mass and serum insulin and there is a high rate of developing new diabetes in this population. Clinical trial data are consistent in showing reductions in body fat mass during testosterone replacement therapy. There are also trials showing improvements in insulin resistance and glycaemic control with testosterone. Most of the trials in this area to date have been of small size and the promising results require confirmation in larger trials, which are underway. In the longer term, large trials should be conducted to assess the potentially beneficial effects of testosterone on cardiovascular risk in this and other patient groups. In the meantime physicians involved in the care of men with diabetes should remain vigilant for the symptoms and signs of hypogonadism. Testosterone replacement therapy should be considered for those men with subsequently confirmed hypogonadism.

  1. Testosterone and weight loss: the evidence

    OpenAIRE

    Traish, Abdulmaged M.

    2014-01-01

    Purpose of review The purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency....

  2. Tank waste remediation system optimized processing strategy with an altered treatment scheme

    International Nuclear Information System (INIS)

    Slaathaug, E.J.

    1996-03-01

    This report provides an alternative strategy evolved from the current Hanford Site Tank Waste Remediation System (TWRS) programmatic baseline for accomplishing the treatment and disposal of the Hanford Site tank wastes. This optimized processing strategy with an altered treatment scheme performs the major elements of the TWRS Program, but modifies the deployment of selected treatment technologies to reduce the program cost. The present program for development of waste retrieval, pretreatment, and vitrification technologies continues, but the optimized processing strategy reuses a single facility to accomplish the separations/low-activity waste (LAW) vitrification and the high-level waste (HLW) vitrification processes sequentially, thereby eliminating the need for a separate HLW vitrification facility

  3. Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME).

    Science.gov (United States)

    Rosen, Raymond C; Wu, Frederick; Behre, Hermann M; Porst, Hartmut; Meuleman, Eric J H; Maggi, Mario; Romero-Otero, Javier; Martinez-Salamanca, Juan I; Jones, Thomas Hugh; Debruyne, Frans M J; Kurth, Karl-Heinz; Hackett, Geoff I; Quinton, Richard; Stroberg, Peter; Reisman, Yacov; Pescatori, Edoardo S; Morales, Antonio; Bassas, Lluis; Cruz, Natalio; Cunningham, Glenn R; Wheaton, Olivia A

    2017-09-01

    The benefits and risks of long-term testosterone administration have been a topic of much scientific and regulatory interest in recent years. To assess long-term quality of life (QOL) and sexual function benefits of testosterone replacement therapy (TRT) prospectively in a diverse, multinational cohort of men with hypogonadism. A multinational patient registry was used to assess long-term changes associated with TRT in middle-age and older men with hypogonadism. Comprehensive evaluations were conducted at 6, 12, 24, and 36 months after enrollment into the registry. QOL and sexual function were evaluated by validated measures, including the Aging Males' Symptom (AMS) Scale and the International Index of Erectile Function (IIEF). A total of 999 previously untreated men with hypogonadism were enrolled at 25 European centers, 750 of whom received TRT at at least one visit during the period of observation. Patients on TRT reported rapid and sustained improvements in QOL, with fewer sexual, psychological, and somatic symptoms. Modest improvements in QOL and sexual function, including erectile function, also were noted in RHYME patients not on TRT, although treated patients showed consistently greater benefit over time in all symptom domains compared with untreated patients. AMS total scores for patients on TRT were 32.8 (95% confidence interval = 31.3-34.4) compared with 36.6 (95% confidence interval = 34.8-38.5) for untreated patients (P Hypogonadism in Men (RHYME). J Sex Med 2017;14:1104-1115. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  4. Osteoprotegerin Levels Decrease During Testosterone Therapy in Aging Men and are Associated with Changed Distribution of Regional Fat

    DEFF Research Database (Denmark)

    Frederiksen, L; Glintborg, D; Højlund, K

    2013-01-01

    The cardiovascular effects of testosterone treatment are debated. Osteoprotegerin (OPG) is an independent marker of cardiovascular risk. We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, pl...... LBM (Δ LBM positive), n=14. Data are presented as median (interquartile range). Testosterone therapy decreased total fat mass and SAT, whereas VAT was unchanged (n=38). OPG levels decreased during testosterone therapy (from 2.0 (1.9-2.5) to 1.9 (1.6-2.2) ng/ml, p...

  5. Effects of testosterone on blood leukocytes in plasmodium berghei-infected mice.

    Science.gov (United States)

    Kamis, A B; Ibrahim, J B

    1989-01-01

    Gonadectomized male mice aged 5 weeks were given 5 mg testosterone propionate daily for 14 days. The treatment significantly decreased the number of blood leukocytes. The number of all individual types of leukocytes except basophils in vehicle-treated gonadectomized mice was increased. Testosterone-treated mice consistently had a lower number of leukocytes after being infected with Plasmodium berghei than did vehicle-treated mice. The results suggest that testosterone suppresses the production of leukocytes and that testosterone-treated mice become more susceptible to parasite infection.

  6. Low Testosterone and Men's Health

    Science.gov (United States)

    ... A genetic condition (Klinefelter syndrome, hemochromatosis, Kallmann syndrome, Prader-Willi syndrome, myatonic dystrophy) Low testosterone is common in older men. In many cases, the cause is not known. How is low ...

  7. Testosterone and metabolic syndrome: The link

    Directory of Open Access Journals (Sweden)

    Ranabir Salam

    2012-01-01

    Full Text Available Metabolic syndrome (MetS or "Syndrome X" which is a constellation of insulin resistance, hyperglycemia, hypertension, low high-density lipoprotein cholesterol (HDL-C, and increased very-low-density lipoprotein (VLDL and triglyceride (TG levels. It is one of the main threats for public health in the 21st century with its associated risk of cardiovascular disease. This condition affects a major chunk of mankind. International Diabetes Federation (IDF estimated that around 20-25% of the adult population of the world has MetS. Several definitions have been put forward by different expert bodies leading to confusion. To overcome this, joint new statement of many expert group have been issued. Serum testosterone (T has been shown to be associated with MetS. Several studies have shown a higher prevalence of MetS in subjects with low testosterone. There are also several studies showing a significant difference in serum T between those with MetS and those without. Serum T has also been shown to be associated with components of MetS and testosterone replacement therapy (TRT improves various metabolic and anthropometric parameters in MetS. Patients with androgen deprivation for treatment of various cancers have also been reported to have higher prevalence of MetS. But the evidence of association is not sufficient evidence for the causation of MetS by low testosterone and long-term studies are needed to confirm whether T deficiency is the cause or is a feature of MetS.

  8. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel.

    Science.gov (United States)

    Kaminetsky, Jed; Werner, Michael; Fontenot, Greg; Wiehle, Ronald D

    2013-06-01

    Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75-334 × 10(6) /mL range. The gel was ineffective in raising sperm counts above 20 × 10(6) /mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts. Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization

  9. Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment - A pilot study.

    LENUS (Irish Health Repository)

    Tsang, J S

    2014-07-28

    In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

  10. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Directory of Open Access Journals (Sweden)

    Tertia D Purves-Tyson

    receptor-driven events as estradiol had minimal effect. We conclude that nigrostriatal responsivity to dopamine may be modulated by testosterone acting via androgen receptors to alter gene expression of molecules involved in dopamine signaling during adolescence.

  11. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    Directory of Open Access Journals (Sweden)

    Newton Robert U

    2012-09-01

    Full Text Available Abstract Background There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. Methods/design We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over. Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and

  12. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    International Nuclear Information System (INIS)

    Newton, Robert U; Taaffe, Dennis R; Spry, Nigel; Cormie, Prue; Chambers, Suzanne K; Gardiner, Robert A; Shum, David HK; Joseph, David; Galvão, Daniel A

    2012-01-01

    There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will take place at baseline, 6

  13. Testosterone and Cardiovascular Disease.

    Science.gov (United States)

    Kloner, Robert A; Carson, Culley; Dobs, Adrian; Kopecky, Stephen; Mohler, Emile R

    2016-02-09

    Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Bennett, Patrick

    1988-01-01

    , it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function...

  15. Testosterone deficiency in the aging male

    Science.gov (United States)

    McBride, J. Abram; Carson, Culley C.; Coward, Robert M.

    2016-01-01

    Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm. PMID:26834840

  16. Testosterone deficiency in the aging male.

    Science.gov (United States)

    McBride, J Abram; Carson, Culley C; Coward, Robert M

    2016-02-01

    Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm.

  17. Effects of testosterone supplementation on prevention of age-related penile remodeling.

    Science.gov (United States)

    Ferreira, Fabio Thadeu; Dambros, Miriam; Bisogni, Sérgio; Dambros, Mara Celia; Scolfaro, Márcia Ribeiro; Palma, Paulo César Rodrigues

    2014-03-01

    Erectile dysfunction develops among 46.2% of men between 40 and 70 years. Studies demonstrated substitution on detrusor muscle by collagen due testosterone deprivation. It is clear the correlation among aging and oxidative stress, accelerating apoptosis process in many tissues. This study aims to demonstrate the collagen substitution over the muscle fibers on muscle structure of rat's penis and the effects of testosterone supplementation. Sixteen senescent Wistar rats were divided into two groups: treatment (receiving standard supplementation testosterone dose) and control (receiving equivalent saline solution). Testosterone was dosed on D0 and D56 of study. All penises were prepared with picrosirius colored histology; stereology was applied to determine the volumetric density of collagen fibers (Vv). Analysis of variance demonstrated testosterone group's replacement therapy to be effective, while the androgenic decline continued by the time of experiment in control group (p Testosterone group had Vv of 20.6%, lower than control group (47.8%); t-test (p testosterone's levels (p testosterone on elderly rat. These finding implicate that the testosterone levels can influence, not only the libido, but also the erectile function.

  18. Testosterone prevents protein loss via the hepatic urea cycle in human.

    Science.gov (United States)

    Lam, Teresa; Poljak, Anne; McLean, Mark; Bahl, Neha; Ho, Ken K Y; Birzniece, Vita

    2017-04-01

    The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied. To determine whether testosterone reduces hepatic urea production. An open-label study. Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day). The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with 15 N 2 -urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated. Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min; P  Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% ( P  testosterone administration ( r 2  = 0.59, P  Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle. © 2017 European Society of Endocrinology.

  19. Aggression frequency and intensity, independent of testosterone levels, relate to neural activation within the dorsolateral subdivision of the ventromedial hypothalamus in the tree lizard Urosaurus ornatus.

    Science.gov (United States)

    Kabelik, David; Crombie, Tim; Moore, Michael C

    2008-06-01

    The mechanisms by which testosterone regulates aggression are unclear and may involve changes that alter the activity levels of one or more brain nuclei. We estimate neural activity by counting immunopositive cells against phosphorylated cyclic AMP response element binding protein (pCREB). We demonstrate increased pCREB immunoreactivity within the dorsolateral subdivision of the ventromedial hypothalamus (VMHdl) following an aggressive encounter in male tree lizards Urosaurus ornatus. This immunoreactivity is induced both by exposure to and performance of aggressive behaviors. This dual activation of the VMHdl suggests its possible role as an integration center for assessment and expression of aggressive behavior. Furthermore, pCREB induction was greater in encounters involving higher frequency and intensity of aggressive display, demonstrating a direct relationship between neural activation and behavior. The VMHdl is also rich in steroid receptors. In a second experiment involving hormone manipulations, testosterone treatment increased aggression levels, though it did not increase the number of pCREB positive cells within the VMHdl. This lack of an effect of testosterone on pCREB induction within the VMHdl may be due to induction arising from the behaviors of conspecifics (especially in low-testosterone, low-aggression individuals), variation in aggression mediated by other variables, or regulation of aggression by circuits outside of the VMHdl. Together, these findings support a notion of the VMHdl as a nucleus involved in integrating afferent and efferent information within the neural aggression-control circuit.

  20. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    International Nuclear Information System (INIS)

    Clow, D.W.; Hammer, R.P. Jr.

    1991-01-01

    2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine

  1. The benefits and risks of testosterone replacement therapy: a review

    Directory of Open Access Journals (Sweden)

    Nazem Bassil

    2009-06-01

    Full Text Available Nazem Bassil1, Saad Alkaade2, John E Morley1,31Division of Geriatric Medicine; 2Internal Medicine, Saint Louis University Health Sciences Center, St. Louis, Missouri, USA; 3GRECC, VA Medical Center, St. Louis, Missouri, USAAbstract: Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.Keywords: hypogonadism, testosterone replacement therapy, erectile dysfunction, osteoporosis, cardiovascular disease

  2. Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study.

    Science.gov (United States)

    Glaser, R L; Dimitrakakis, C; Messenger, A G

    2012-02-01

    Androgens are thought to have an adverse effect on female scalp hair growth. However, our clinical experience of androgen replacement therapy in women with androgen deficiency, in which hair loss was seldom reported, led us to question this concept. To evaluate the effect of subcutaneous testosterone therapy on scalp hair growth in female patients. A total of 285 women, treated for a minimum of 1year with subcutaneous testosterone implants for symptoms of androgen deficiency, were asked to complete a survey that included questions on scalp and facial hair. Age, body mass index (BMI) and serum testosterone levels were examined. Out of the 285 patients, 76 (27%) reported hair thinning prior to treatment; 48 of these patients (63%) reported hair regrowth on testosterone therapy (responders). Nonresponders (i.e. no reported hair regrowth on therapy) had significantly higher BMIs than responders (P=0·05). Baseline serum testosterone levels were significantly lower in women reporting hair loss prior to therapy than in those who did not (P=0·0001). There was no significant difference in serum testosterone levels, measured 4weeks after testosterone implantation, between responders and nonresponders. No patient in this cohort reported scalp hair loss on testosterone therapy. A total of 262 women (92%) reported some increase in facial hair growth. Subcutaneous testosterone therapy was found to have a beneficial effect on scalp hair growth in female patients treated for symptoms of androgen deficiency. We propose this is due to an anabolic effect of testosterone on hair growth. The fact that no subject complained of hair loss as a result of treatment casts doubt on the presumed role of testosterone in driving female scalp hair loss. These results need to be confirmed by formal measurements of hair growth. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  3. Coping with an altered mouth and perceived supportive care needs following head and neck cancer treatment.

    Science.gov (United States)

    Pateman, K A; Ford, P J; Batstone, M D; Farah, C S

    2015-08-01

    Oral health is essential to general health and well-being and is severely impacted by head and neck cancer (HNC) and its treatment. This study aimed to describe how people who have been treated for HNC cope with altered oral health and function and to identify their supportive care needs. A qualitative, descriptive approach was used. Data was collected from individual interviews with six participants 6 months after treatment. Data analysis was performed by qualitative content analysis involving inductive and directed approaches. Directed content analysis was guided by the Stress, Appraisal and Coping Model. Three themes describing changed oral health were identified from the data: dimensions of eating, maintaining oral health after treatment and adapting to the chronic side effects of treatment. A strong use of problem-focussed coping was described, in addition to the importance of peer support in adapting to the psychosocial outcomes of treatment. Support needs identified related to increased access to specialist dental oncology services post treatment, information needs and a need for more psychological support. The study findings describe the experience of a sample of people who have received treatment for HNC. Due to a demographically homogenous sample and the strong use of positive coping strategies, the results presented may not describe the experience of the wider HNC population; however, these results provide insight into factors that may influence positive coping.

  4. Testosterone administration decreases generosity in the ultimatum game.

    Science.gov (United States)

    Zak, Paul J; Kurzban, Robert; Ahmadi, Sheila; Swerdloff, Ronald S; Park, Jang; Efremidze, Levan; Redwine, Karen; Morgan, Karla; Matzner, William

    2009-12-16

    How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72); 95% CI T: (.98, 2.30)). This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT). Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially.

  5. Testosterone administration decreases generosity in the ultimatum game.

    Directory of Open Access Journals (Sweden)

    Paul J Zak

    Full Text Available How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72; 95% CI T: (.98, 2.30. This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT. Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially.

  6. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery.

    Science.gov (United States)

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-04-15

    Clenbuterol is a β2 -adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg(-1) day(-1) ) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po ) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P clenbuterol-treated animals demonstrated decreased amplitude after 14 days (-19%, P clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca(2+) release during contraction could partially explain these deleterious effects. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  7. Testosterone induces cell proliferation and cell cycle gene overexpression in human visceral preadipocytes.

    Science.gov (United States)

    Barbosa-Desongles, Anna; Hernández, Cristina; Simó, Rafael; Selva, David M

    2013-08-01

    Evidence from the literature suggests that testosterone plays an important role in visceral fat accumulation since both men and women with hyperandrogenism accumulate more adipose tissue in the abdominal cavity than healthy women. However, the underlying mechanisms remain to be elucidated. To shed light on this issue, we have used an in vitro approach to examine the effect of testosterone on human visceral preadipocyte proliferation. Our results showed that testosterone treatment significantly increased proliferation of human visceral preadipocytes in proliferation assays using flow cytometric analysis. We next performed a microarray gene expression analysis of human visceral preadipocytes treated with testosterone or vehicle to identify which genes were involved in the testosterone-induced increase in preadipocyte proliferation. The results showed a total of 140 genes differentially expressed between testosterone vs. vehicle. Among the top 10 upregulated genes, 5 were involved in cellular cycle and proliferation, and 3 (APOBEC3b, CCNA2, and PRC1) were significantly overexpressed by testosterone treatment when analyzed by real-time PCR. We conclude that testosterone exerts a proliferative effect on preadipocytes that may participate in the sex differences in fat distribution and that it may explain visceral fat accumulation in women with hyperandrogenism.

  8. Gender-Typed Play and Amniotic Testosterone

    Science.gov (United States)

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  9. An Investigation into the Effect of Testosterone on Plasma ...

    African Journals Online (AJOL)

    Experiments were carried out on 30 intact adult male rats weighing 200-300gm. The rats were divided randomly into six groups that received different treatments of testosterone, adrenaline, and propranolol. Blood samples were obtained from all the rats by cardiac puncture and plasma samples were assayed for triglyceride ...

  10. the effect of intramuscular implantation of testosterone on growth ...

    African Journals Online (AJOL)

    The experimental design was factorial (2 x 2 with four replicates). There were two nutritional treatments ... The crystalline implant of testosterone was placed in the gluteal muscle by means of a trocar and cannula. Animals were weighed (± 0,5 kg at 0700) at inter- vals of two weeks. Feed and water were withdrawn at.

  11. Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep.

    Science.gov (United States)

    Veiga-Lopez, Almudena; Steckler, Teresa L; Abbott, David H; Welch, Kathleen B; MohanKumar, Puliyur S; Phillips, David J; Refsal, Kent; Padmanabhan, Vasantha

    2011-01-01

    Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ~147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64-66, 87-90, and 139-140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep.

  12. Testosterone vs. aromatase inhibitor in older men with low testosterone: effects on cardiometabolic parameters.

    Science.gov (United States)

    Dias, J P; Shardell, M D; Carlson, O D; Melvin, D; Caturegli, G; Ferrucci, L; Chia, C W; Egan, J M; Basaria, S

    2017-01-01

    Testosterone (T) replacement is being increasingly offered to older men with age-related decline in testosterone levels. The effects of long-term testosterone replacement and aromatase inhibition (AI) on glucose homeostasis and cardiometabolic markers were determine in older non-diabetic men with low testosterone levels. Men ≥65 years, mean age 71 ± 3 years with serum total T testosterone gel (TT) (n = 10), 1 mg anastrozole (n = 10) or placebo (n = 9) daily for 12 months. Homeostatic Model Assessment of insulin resistance (HOMA IR ) was the primary outcome. Secondary outcomes included OGIS in response to OGTT, fasting lipids, C-reactive protein (CRP), adipokines, and abdominal and mid-thigh fat by computed tomography. All outcomes were assessed at baseline and 12 months. After 12 months, absolute changes in HOMA IR in both treatment arms (TT group: -0.05 ± 0.21); (AI group: 0.15 ± 0.10) were similar to placebo (-0.11 ± 0.26), as were CRP and fasting lipid levels. Adiponectin levels significantly decreased in the TT group (-1.8 ± 0.9 mg/L, p = 0.02) and abdominal subcutaneous fat (-60.34 ± 3.19 cm 2 , p = 0.003) and leptin levels (-1.5 ± 1.2 ng/mL, p = 0.04) were significantly lower with AI. Mid-thigh subcutaneous fat was reduced in both treatment arms (TT group: -4.88 ± 1.24 cm 2 , p = 0.008); (AI group: -6.05 ± 0.87 cm 2 , p = 0.0002). In summary, in this proof-of-concept trial, changes in HOMA IR AI were similar in all three groups while the effects of intervention on subcutaneous fat distribution and adipokines were variable. Larger efficacy and safety trials are needed before AI pharmacotherapy can be considered as a treatment option for low T levels in older men. © 2016 American Society of Andrology and European Academy of Andrology.

  13. Testosterone replacement, weight lifting help wasting.

    Science.gov (United States)

    1996-06-01

    Many individuals with AIDS will experience HIV wasting syndrome at some time in their disease progression. However, a number of new treatments, including anabolic steroids and a regular regimen of weight lifting, are providing benefits to those who experience this condition. Because wasting is difficult to stop once it has started, preventing or delaying the condition is imperative. Preventive measures include eating well, avoiding infections, and exercising. Treatments and interventions for wasting include nutritional supplements, appetite stimulants, anabolic steroids such as testosterone replacement, human growth hormone therapy, and weight lifting. However, the most effective human growth hormone therapy is probably expensive. Anabolic steroids can be valuable for the 20 percent of HIV-positive males who have below-normal levels of testosterone. Two appetite stimulants approved for use in AIDS patients with weight loss are megestrol acetate (Megace) and dronabinol (Marinol). Weight lifting is a natural way to gain lean body mass and muscle and has been shown to be effective in people who have advanced to a diagnosis of AIDS. Seven tips for fighting weight loss are included.

  14. Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation.

    Science.gov (United States)

    Sharma, Rishi; Oni, Olurinde A; Gupta, Kamal; Sharma, Mukut; Sharma, Ram; Singh, Vikas; Parashara, Deepak; Kamalakar, Surineni; Dawn, Buddhadeb; Chen, Guoqing; Ambrose, John A; Barua, Rajat S

    2017-05-09

    Atrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone. Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score-weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post-TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81-0.99, P =0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70-0.89, P =0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78- 1.0009, P =0.0675) in incidence of AF. These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis.

    Science.gov (United States)

    Eriksson, Joel; Haring, Robin; Grarup, Niels; Vandenput, Liesbeth; Wallaschofski, Henri; Lorentzen, Erik; Hansen, Torben; Mellström, Dan; Pedersen, Oluf; Nauck, Matthias; Lorentzon, Mattias; Nystrup Husemoen, Lise Lotte; Völzke, Henry; Karlsson, Magnus; Baumeister, Sebastian E; Linneberg, Allan; Ohlsson, Claes

    2017-01-01

    Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. Bi-directional Mendelian randomization (MR) analysis on prospective cohorts. Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden). 7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs. BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site. 1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349). Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.

  16. Myocardial Infarction and Stroke Risk in Young Healthy Men Treated with Injectable Testosterone

    Directory of Open Access Journals (Sweden)

    Robert S. Tan

    2015-01-01

    Full Text Available This study was conducted to examine the association between testosterone therapy and new myocardial infarction (MI and stroke events in a series of patients treated at Low T Centers across the United States, consisting of mainly young (mean age = 46, otherwise, healthy men. Electronic medical records were queried between the years 2009 and 2014 to identify patients diagnosed with hypogonadism, MI, and stroke, as indicated by ICD-9 codes. The incidence of MI and stroke events was compared to community-based registries. 39,936 patients recruited from 40 Low T Centers across the United States were treated and 19,968 met eligibility criteria for receiving testosterone treatment. The incidence rate ratio (IRR for MI in testosterone- (T- treated versus nontreated patients was 0.14 (C.I. = 0.08 to 0.18, P<0.0001 whereas the IRR for stroke for T-treated versus nontreated patients was 0.11 (C.I. = 0.02 to 0.13, P<0.0001. There was no evidence of worsening preexisting MI or stroke in patients treated with testosterone. The experience in Low T Centers shows that, in an injectable testosterone patient registry, testosterone is generally safe for younger men who do not have significant risk factors. Of patients that developed MI with testosterone, there was no association with testosterone or hematocrit levels.

  17. The effects of chronic testosterone administration on body weight, food intake, and fat weight were age-dependent.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Yiliyasi, Mayila; Yano, Kiyohito; Irahara, Minoru

    2017-11-01

    Previously, we showed that chronic testosterone administration increased body weight (BW) and food intake (FI), but did not alter fat weight, in young female rats. To examine our hypothesis that the effects of androgens on BW, FI and body composition might be age-dependent, the effects of chronic testosterone administration were evaluated in rats of different ages; i.e., young and middle-aged rats. Although chronic testosterone administration increased BW gain, FI, and feed efficiency in both young and middle-aged rats, it increased visceral fat weight in middle-aged rats, but not in young rats. Therefore, it is possible that testosterone promotes the conversion of energy to adipose tissue and exacerbates fat accumulation in older individuals. In addition, although the administration of testosterone increased the serum leptin level, it did not alter hypothalamic neuropeptide Y mRNA expression in middle-aged rats. On the contrary, the administration of testosterone did not affect the serum leptin levels of young rats. Thus, testosterone might induce hypothalamic leptin resistance, which could lead to fat accumulation in older individuals. Testosterone might disrupt the mechanisms that protect against adiposity and hyperphagia and represent a risk factor for excessive body weight and obesity, especially in older females. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Testosterone Effects on the Brain in Transgender Men.

    Science.gov (United States)

    Burke, Sarah M; Manzouri, Amir H; Dhejne, Cecilia; Bergström, Karin; Arver, Stefan; Feusner, Jamie D; Savic-Berglund, Ivanka

    2017-03-10

    Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  19. Testosterone for low libido in postmenopausal women not taking estrogen.

    Science.gov (United States)

    Davis, Susan R; Moreau, Michele; Kroll, Robin; Bouchard, Céline; Panay, Nick; Gass, Margery; Braunstein, Glenn D; Hirschberg, Angelica Linden; Rodenberg, Cynthia; Pack, Simon; Koch, Helga; Moufarege, Alain; Studd, John

    2008-11-06

    The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 microg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 microg per day, P<0.001; 150 microg per day, P=0.04) and decreases in distress (300 microg per day, P<0.001; 150 microg per day, P=0.04). The rate of androgenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. (ClinicalTrials.gov number, NCT00131495.) Copyright

  20. Molecular alterations in signal pathways of melanoma and new personalized treatment strategies: Targeting of Notch

    Directory of Open Access Journals (Sweden)

    Julija Mozūraitienė

    2015-01-01

    Full Text Available Despite modern achievements in therapy of malignant melanomas new treatment strategies are welcomed in clinics for survival of patients. Now it is supposed that personalized molecular therapies for each patient are needed concerning a specificity of molecular alterations in patient's tumors. In human melanoma, Notch signaling interacts with other pathways, including MAPK, PI3K-AKT, NF-kB, and p53. This article discusses mutated genes and leading aberrant signal pathways in human melanoma which are of interest concerning to their perspective for personalized treatment strategies in melanoma. We speculate that E3 ubiquitin ligases MDM2 and MDM4 can be attractive therapeutic target for p53 and Notch signaling pathways in malignant melanoma by using small molecule inhibitors. It is possible that restoration of p53-MDM2-NUMB complexes in melanoma can restore wild type p53 function and positively modulate Notch pathway. In this review we summarize recent data about novel US Food and Drug Administration approved target drugs for metastatic melanoma treatment, and suppose model for treatment strategy by targeting Notch.

  1. Breaking the vicious circle of obesity: the metabolic syndrome and low testosterone by administration of testosterone to a young man with morbid obesity.

    Science.gov (United States)

    Tishova, Yuliya; Kalinchenko, Svetlana Y

    2009-11-01

    The metabolic syndrome (MS) is associated with low serum testosterone levels. Conversely, low testosterone levels induce MS. These operational mechanisms reinforce one another and induce a vicious cycle. This is a report on a morbid obesity 42 year-old man with the MS and serum testosterone of 5.0 nmol/L (N: 12.0-33.0), who was resistant to treatment with diet and exercise. He was treated with testosterone undecanoate for 16 months. Anthropological and laboratory variables were measured before and during testosterone administration. Also the Aging Male Symptom Scale (AMS), the International Index of Erectile Function (IIEF) and Beck's Depression Inventory were assessed. After 16 months, there was a weight loss of 50 kg and a decrease in waist circumference of 36.5 cm. Blood pressure normalized and laboratory variables returned to the normal range. The patient did not meet the criteria for the MS anymore. There were improvements on the AMS, the IIEF and Beck's Depression Inventory. Normalizing testosterone in men with morbid obesity in combination with diet and exercise, with the MS and low testosterone levels, may rescue them from the MS, improving their mood and their stamina to follow a diet and to exercise.

  2. Testosterone replacement in transgenic sickle cell mice controls priapic activity and upregulates PDE5 expression and eNOS activity in the penis.

    Science.gov (United States)

    Musicki, B; Karakus, S; Akakpo, W; Silva, F H; Liu, J; Chen, H; Zirkin, B R; Burnett, A L

    2018-01-01

    Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5. Adult male transgenic Berkeley sickle cell (Sickle) and wild-type (WT) mice were implanted with testosterone pellets, which release 1.2 μg testosterone/day for 21 days, or vehicle. After 21 days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone-responsive tissue. Serum testosterone levels were measured by radioimmunoassay; protein expressions of PDE5, α-smooth muscle actin, eNOS and nNOS, and phosphorylation of PDE5 at Ser-92, eNOS at Ser-1177, neuronal (n) NOS at Ser-1412, and Akt at Ser-473 were measured by Western blot in penile tissue. Testosterone treatment reversed downregulated serum testosterone levels and increased (p testosterone levels in Sickle mice. Testosterone treatment reduced (p penis. Testosterone treatment did not affect P-nNOS (Ser-1412), eNOS, nNOS, or α-smooth muscle actin protein expressions in the Sickle mouse penis. In conclusion, in the mouse model of human SCD, increasing testosterone to eugonadal levels reduced priapic activity and reversed impaired Akt/eNOS activity and PDE5 protein expression in the penis. © 2017 American Society of Andrology and European Academy of Andrology.

  3. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies.

    Science.gov (United States)

    Saad, F; Yassin, A; Doros, G; Haider, A

    2016-01-01

    Long-term testosterone replacement therapy (TRT) up to 5 years has been shown to produce progressive and sustainable weight loss (WL) in hypogonadal men. This study investigated effects of long-term TRT up to 8 years in hypogonadal men with different obesity classes. From two independent observational registries we identified a total of 411 obese, hypogonadal men receiving TRT in urological clinics. The effects of TRT on anthropometric as well as metabolic parameters were studied for a maximum duration of 8 years, mean follow-up: 6 years. All men received long-acting injections of testosterone undecanoate in 3-monthly intervals. In all three classes of obesity, T therapy produced significant WL, decrease in waist circumference (WC) and body mass index (BMI). In patients with class I obesity, mean weight decreased from 102.6±6.4 to 84.1±4.9 kg, change from baseline: -17.4±0.5 kg and -16.8±0.4%. WC in this group of patients decreased from 106.8±7.4 to 95.1±5.3 cm, change from baseline: -10.6±0.3 cm. BMI decreased from 32.69±1.4 to 27.07±1.57, change from baseline: -5.52±0.15 kg m(-2). In patients with class II obesity, weight decreased from 116.8±6.9 to 91.3±6.3 kg, change from baseline: -25.3±0.5 kg and -21.5±0.4%. WC decreased from 113.5±7.5 to 100.0±5.4 cm, change from baseline: -13.9±0.4 cm. BMI decreased from 37.32±1.45 to 29.49±1.71, change from baseline: -8.15±0.17 kg m(-2). In patients with class III obesity, weight decreased from 129.0±5.6 to 98.9±4.8 kg, change from baseline: -30.5±0.7 kg and -23.6±0.5%. WC decreased from 118.5±5.6 to 103.8±4.9 cm, change from baseline: -14.3±0.4 cm. BMI decreased from 41.93±1.48 to 32.46±1.59, change from baseline -9.96±0.29 kg m(-2). Testosterone therapy appears to be an effective approach to achieve sustained WL in obese hypogonadal men irrespective of severity of obesity. Based on these findings we suggest that T therapy offers safe and effective

  4. Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    C.Q. Conceição

    2017-11-01

    Full Text Available The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days. After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

  5. Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats.

    Science.gov (United States)

    Conceição, C Q; Engi, S A; Cruz, F C; Planeta, C S

    2017-11-17

    The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

  6. Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus

    International Nuclear Information System (INIS)

    Freimann, Florian Baptist; Sprung, Christian; Streitberger, Kaspar-Josche; Klatt, Dieter; Sack, Ingolf; Lin, Kui; McLaughlin, Joyce; Braun, Juergen

    2012-01-01

    Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 ± 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters μ and α, related to the inherent rigidity and topology of the mechanical network of brain tissue. The viscoelastic parameters μ and α were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, α increased after shunt placement (P < 0.001) to almost normal values whereas μ remained symptomatically low. The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded. (orig.)

  7. Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Freimann, Florian Baptist; Sprung, Christian [Charite - University Medicine Berlin, Campus Virchow-Klinikum, Neurosurgical Department, Berlin (Germany); Streitberger, Kaspar-Josche; Klatt, Dieter; Sack, Ingolf [Charite - University Medicine Berlin, Campus Charite Mitte, Department of Radiology, Berlin (Germany); Lin, Kui; McLaughlin, Joyce [Rensselaer Polytechnic Institute, Mathematics Department, Troy, NY (United States); Braun, Juergen [Charite - University Medicine Campus Benjamin Franklin, Institute of Medical Informatics, Berlin (Germany)

    2012-03-15

    Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 {+-} 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters {mu} and {alpha}, related to the inherent rigidity and topology of the mechanical network of brain tissue. The viscoelastic parameters {mu} and {alpha} were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, {alpha} increased after shunt placement (P < 0.001) to almost normal values whereas {mu} remained symptomatically low. The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded. (orig.)

  8. Deficient testosterone levels in men above 45 years with major depressive disorder - an age-matched case control study

    Directory of Open Access Journals (Sweden)

    A M Dikobe

    2007-08-01

    Full Text Available Background. Symptoms of partial androgen deficiency in ageing men (PADAM overlap considerably with those of major depressive disorder. The relationship between these conditions is complicated by the usual age-related decline in serum testosterone concentrations. Objectives. To test the hypothesis that depressed men above 45 years of age have lower serum testosterone concentrations than age-matched controls. Method. Serum testosterone fractions of 20 men above the age of 45 years suffering from a major depressive disorder were compared with those of 20 healthy men. An age-matched controlled design was used to account for the usual age-related decline in serum testosterone concentrations. Results. Testosterone concentrations of men suffering from a major depressive disorder were statistically significantly lower than those of an age-matched control group without depression. Conclusion. The role of testosterone deficiency in depressed men needs to be examined further in order for appropriate treatment options to be developed.

  9. Testosterone and muscle hypertrophy in female rats

    Science.gov (United States)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  10. EMAS position statement: Testosterone replacement therapy in the aging male‏.

    Science.gov (United States)

    Dimopoulou, Christina; Ceausu, Iuliana; Depypere, Herman; Lambrinoudaki, Irene; Mueck, Alfred; Pérez-López, Faustino R; Rees, Margaret; van der Schouw, Yvonne T; Senturk, Levent M; Simonsini, Tommaso; Stevenson, John C; Stute, Petra; Goulis, Dimitrios G

    2016-02-01

    Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. Literature review and consensus of expert opinion. Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. [Height alterations and calcium metabolism after prolongated phenobarbital treatment (author's transl)].

    Science.gov (United States)

    Baldellou Vázquez, A; Gomá Brufau, A; Vargas Torcal, F; Pastor Mourón, I; Ros Mar, L; Ferrández Longás, A

    1977-05-01

    In order to know if small children subjected to a long-term treatment with phenobarbital can suffer some alterations in their lineal growth or in their osseous maturity in the same way as those showed by epileptical mother's sons, 85 patients between six months and three years old, who had suffered fit convulsions during a fever process, 20 of them subjected to antithermic treatment, and the 65 left who received a phenobarbital treatment in doses of 5 mg./kg./day have been controlled. In each child, at the beginning of the control and after 12 months, their height, diaphysial diameter and cortical thickness of the metacarpal bones, and bone age is valued. At the same time a calcium, phosphorous and phosphatase-alcaline control was done. The group who had received anti-convulsivants drugs, showed a significant decrease in their lineal growth and in calcium concentration in blood. The control group didn't present any significant variation in any of the controls performed.

  12. Alteration of heterostyly in Solanum melongena L. through gamma-radiation and hormonal treatment

    International Nuclear Information System (INIS)

    Handique, A.K.; Sarma, A.

    1995-01-01

    Treatment of seeds with 4 kR and 8 kR gamma radiation significantly altered heterostyly in Solanum melongena by way of reducing the frequency of short style (sterile) and enhancing the frequency of long style (fertile) flowers in the synthetic varieties. Both the concentrations of kinetin were highly effective in enhancing the proportion of long style flowers in all the cultivars; 40 ppm being more effective than 20 ppm. α-NAA at lower concentration was effective in only one local land race, whereas higher concentration (25 ppm) of α-NAA suppressed the frequency of long style and enhanced the frequency of short style flowers. (author). 14 refs., 1 fig., 1 tab

  13. Effects of high-fat diet on the patterns of prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine and testosterone.

    Science.gov (United States)

    Pour, P M; Groot, K; Kazakoff, K; Anderson, K; Schally, A V

    1991-09-15

    Controversial views exist on the link between prostatic cancer and consumption of high-fat (HF) diet. This topic was examined in experimental prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine (BOP). Groups of Wistar-derived MRC rats were fed a semipurified diet containing either 5% (low fat = LF) or 24.6% (HF) corn oil for life, beginning after weaning. In the short-term study, treatment with testosterone significantly increased the rate of cellular DNA synthesis (as determined by autoradiographs after tritiated thymidine injection) that was not influenced by the level of dietary fat. HF diet alone depressed the rate significantly in the dorsal lobe only. There was a significant increase in the plasma level of estradiol, a decrease in the level of luteinizing hormone, but no changes in the level of follicle-stimulating hormone (FSH) in rats treated with testosterone, with no differences between the HF and LF groups. However, HF in the absence of testosterone depressed the serum FSH level. In the carcinogenicity experiment, all rats fed HF or LF diet developed prostatic cancers (mostly adenocarcinomas). The incidence, however, was significantly higher in testosterone-treated rats. Dietary fat did not influence the incidence, histological patterns, or anatomical distribution of tumors, and there were no differences in the parameters between the HF- and LF-fed groups. Long-term administration of testosterone significantly lowered serum levels of luteinizing hormone but did not change the FSH level and affected estradiol levels to a variable extent. These values were not influenced by dietary fat. However, in the HF-BOP group, significantly higher levels of FSH were found compared with the values in the LF-BOP group. We concluded that (a) under the described experimental conditions, dietary fat, fed ad libitum, does not influence the patterns of prostatic cancer induced in rats by BOP; (b) testosterone alters the serum levels of estradiol and

  14. Testosterone Therapy: Review of Clinical Applications.

    Science.gov (United States)

    Petering, Ryan C; Brooks, Nathan A

    2017-10-01

    Testosterone therapy is increasingly common in the United States, and many of these prescriptions are written by primary care physicians. There is conflicting evidence on the benefit of male testosterone therapy for age-related declines in testosterone. Physicians should not measure testosterone levels unless a patient has signs and symptoms of hypogonadism, such as loss of body hair, sexual dysfunction, hot flashes, or gynecomastia. Depressed mood, fatigue, decreased strength, and a decreased sense of vitality are less specific to male hypogonadism. Testosterone therapy should be initiated only after two morning total serum testosterone measurements show decreased levels, and all patients should be counseled on the potential risks and benefits before starting therapy. Potential benefits of therapy include increased libido, improved sexual function, improved mood and well-being, and increased muscle mass and bone density; however, there is little or mixed evidence confirming clinically significant benefits. The U.S. Food and Drug Administration warns that testosterone therapy may increase the risk of cardiovascular complications. Other possible risks include rising prostate-specific antigen levels, worsening lower urinary tract symptoms, polycythemia, and increased risk of venous thromboembolism. Patients receiving testosterone therapy should be monitored to ensure testosterone levels rise appropriately, clinical improvement occurs, and no complications develop. Testosterone therapy may also be used to treat hypoactive sexual desire disorder in postmenopausal women and to produce physical male sex characteristics in female-to-male transgender patients.

  15. Effects of testosterone on spatial learning and memory in adult male rats

    Science.gov (United States)

    Spritzer, Mark D.; Daviau, Emily D.; Coneeny, Meagan K.; Engelman, Shannon M.; Prince, W. Tyler; Rodriguez-Wisdom, Karlye N.

    2011-01-01

    A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting seven days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects. PMID:21295035

  16. Is Testosterone a Food for the Brain?

    Science.gov (United States)

    Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Di Sante, Stefania; Gravina, Giovanni L; Mollaioli, Daniele; Gianfrilli, Daniele; Lenzi, Andrea; Jannini, Emmanuele A

    2016-01-01

    Testosterone is fundamental for psychological, sexological, cognitive, and reproductive aspects, and its lack or reduction largely impacts the quality of life in males and females. Therefore, the aim of this review is to describe the role of testosterone in the neurophysiology of the brain and related aspects regarding the quality of general and sexual life. We listed and discussed the principal studies on the role of testosterone in the brain regarding sexual health, psychopathological conditions, and the elderly. The search strategies were composed by the insertion of specific terms in PubMed regarding the main studies from January 2000 to June 2015. Using a psychoneuroendocrinologic perspective, we considered 4 main sections: brain and testosterone, sexuality and testosterone, psychopathology and testosterone, and cognitive impairment and testosterone. Much evidence on the neuroendocrinology of testosterone regarding brain activity, sexual function, psychological health, and senescence was found. In any case, it is known that testosterone deficiency negatively impacts quality of life, first, but not exclusively, through a central effect. Moreover, testosterone and androgen receptors are differently expressed according to age and gender. This aspect contributes to gender differences and to the dimorphic physiological role of this hormone. A universal role for testosterone can be recognized: low levels of testosterone are associated with mental disorders, sexual dysfunction, and cognitive impairment in both sexes. Hence, physicians should carefully assess testosterone levels, not only in the management of sexual dysfunctions but also when seeking to help patients with severe mental or organic diseases. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  17. Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone.

    Science.gov (United States)

    Petersson, Stine J; Christensen, Louise L; Kristensen, Jonas M; Kruse, Rikke; Andersen, Marianne; Højlund, Kurt

    2014-07-01

    Recent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting. Despite an increase in lipid oxidation (Ptestosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy. The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. © 2014 European Society of Endocrinology.

  18. Reduction of calprotectin and phosphate during testosterone therapy in aging men: a randomized controlled trial.

    Science.gov (United States)

    Pedersen, L; Christensen, L L; Pedersen, S M; Andersen, M

    2017-05-01

    To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 (FGF23), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. Randomized, double-blinded, placebo-controlled study. Odense Androgen Study-the effect of Testim and training in hypogonadal men. Men aged 60-78 years old with a low normal concentration of free of bioavailable testosterone 94 cm recruited from 2008 to 2009 (N = 48) by advertisement. Participants were randomized to receive 5-10 g gel/50-100 mg testosterone (Testim ® , Ipsen, France) or 5-10 g gel/placebo. The plasma levels of calprotectin and phosphate were significantly reduced in the group receiving testosterone therapy (gel) compared to the placebo group (p Testosterone treatment did not have any significant effect on plasma levels of FGF23 or soluble Klotho. The reduction in phosphate levels was inversely associated with bioavailable testosterone. Compared to the placebo group, 6 months of testosterone therapy (gel) reduced calprotectin and phosphate levels suggesting decreased inflammation and decreased cardiovascular risk.

  19. The many faces of testosterone

    OpenAIRE

    Bain, Jerald

    2007-01-01

    Jerald BainDepartment of Medicine, Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario, CanadaAbstract: Testosterone is more than a “male sex hormone”. It is an important contributor to the robust metabolic functioning of multiple bodily systems. The abuse of anabolic steroids by athletes over the years has been one of the major detractors from the investigation an...

  20. Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus.

    Science.gov (United States)

    Alboni, Silvia; Benatti, Cristina; Montanari, Claudia; Tascedda, Fabio; Brunello, Nicoletta

    2013-12-05

    To gain insight into the possible immune targets of antidepressant, we evaluated the expression of several inflammatory mediators in the hypothalamus of rats chronically (28 days) treated with the serotonin selective reuptake inhibitor fluoxetine (5mg/kg, i.p.) or the tricyclic compound imipramine (15 mg/kg, i.p.). We focused our attention on the hypothalamus as it plays a key role in determining many of the somatic symptoms experienced by depressed patients. This brain region, critical also for expression of motivated behaviours, participates in the control of the hypothalamic-pituitary-adrenal axis activity and in stress response as well as coordinates physiological functions such as sleep and food intake that have been found altered in a high percentage of depressed patients. Notably, hypothalamus is a key structure for brain cytokine expression and function as it integrates signals from the neuro, immune, endocrine systems. By means of quantitative Real Time PCR experiments we demonstrated that a chronic treatment with either fluoxetine or imipramine resulted in a reduction of IL-6 and IFN-γ mRNAs and increased IL-4 mRNA expression in the rat hypothalamus. Moreover, we demonstrated that hypothalamic expression of members of IL-18 system was differentially affected by chronic antidepressant treatments. Chronically administered fluoxetine decreased IL-8 and CX3CL1 hypothalamic expression, while a chronic treatment with imipramine decreased p11 mRNA. Our data suggest that a shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus may represent a common mechanism of action of both the chronic treatments with fluoxetine and imipramine. © 2013 Published by Elsevier B.V.

  1. Comprehensive analysis of temporal alterations in cellular proteome of Bacillus subtilis under curcumin treatment.

    Directory of Open Access Journals (Sweden)

    Panga Jaipal Reddy

    Full Text Available Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division.

  2. Sustained Treatment with Insulin Detemir in Mice Alters Brain Activity and Locomotion.

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available Recent studies have identified unique brain effects of insulin detemir (Levemir®. Due to its pharmacologic properties, insulin detemir may reach higher concentrations in the brain than regular insulin. This might explain the observed increased brain stimulation after acute insulin detemir application but it remained unclear whether chronic insulin detemir treatment causes alterations in brain activity as a consequence of overstimulation.In mice, we examined insulin detemir's prolonged brain exposure by continuous subcutaneous (s.c. application using either micro-osmotic pumps or daily s.c. injections and performed continuous radiotelemetric electrocorticography and locomotion recordings.Acute intracerebroventricular injection of insulin detemir activated cortical and locomotor activity significantly more than regular insulin in equimolar doses (0.94 and 5.63 mU in total, suggesting an enhanced acute impact on brain networks. However, given continuously s.c., insulin detemir significantly reduced cortical activity (theta: 21.3±6.1% vs. 73.0±8.1%, P<0.001 and failed to maintain locomotion, while regular insulin resulted in an increase of both parameters.The data suggest that permanently-increased insulin detemir levels in the brain convert its hyperstimulatory effects and finally mediate impairments in brain activity and locomotion. This observation might be considered when human studies with insulin detemir are designed to target the brain in order to optimize treatment regimens.

  3. Polycystic Ovary Induction in Mouse by Testosterone Enanthate

    Directory of Open Access Journals (Sweden)

    Zahra Kalhori

    2014-03-01

    Full Text Available Background &Objective: Polycystic ovary is the most common cause of infertility in Women. Animal models are required for understanding the pathogenesis of polycystic ovary. The objective of this study then was to develop an animal model for inducing the polycystic ovaries using testosterone enanthate.Materials & Methods: In this study, for inducing the polycystic ovary phenotype, female rats about12-14 days-old were injected daily with testosterone enanthate for 2 and 4 weeks (experiment groups: 1 and 2, while the control groups (1 and 2 were injected only with vehicle.The ovaries from both groups were fixed and then were used for histological studies.Results: Testosterone enanthate treatment causes the histological changes in mouse ovary and significantly increased the percentage of preantral and cystic follicles and decreased the percentage of antral follicles in the experiment group, comparing with the control group (P<0.05.Conclusion: It concluded that testosterone enanthate can induces polycystic ovary in mouse.

  4. Alterations in cardiomyocyte function after pulmonary treatment with stainless steel welding fume in rats.

    Science.gov (United States)

    Popstojanov, Risto; Antonini, James M; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B; Kan, Hong

    2014-01-01

    Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.

  5. Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression.

    Science.gov (United States)

    Veiga-Lopez, Almudena; Luense, Lacey J; Christenson, Lane K; Padmanabhan, Vasantha

    2013-05-01

    Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (>1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.

  6. Analysis of testosterone fatty acid esters in the digestive gland of mussels by liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Guercia, Cesare; Cianciullo, Piergiorgio; Porte, Cinta

    2017-07-01

    Several studies have indicated that up to 70% of the total steroids detected in molluscs are in the esterified form and that pollutants, by modifying the esterification of steroids with fatty acids, might act as endocrine disrupters. However, despite the strong physiological significance of this process, there is almost no information on which fatty acids form the steroid esters and how this process is modulated. This study (a) investigates the formation of fatty acid esters of testosterone in digestive gland microsomal fractions of the mussel Mytilus galloprovincialis incubated with either palmitoly-CoA or CoA and ATP, and (b) assesses whether the endocrine disruptor tributyltin (TBT) interferes with the esterification of testosterone. Analysis of testosterone esters was performed by liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). When microsomal fractions were incubated with testosterone and palmitoly-CoA, the formation of testosterone palmitate was detected. However, when microsomes were incubated with CoA and ATP, and no exogenous activated fatty acid was added, the synthesis of 16:0, 16:1, 20:5 and 22:6 testosterone esters was observed. The presence of 100µM TBT in the incubation mixture did not significantly alter the esterification of testosterone. These results evidence the conjugation of testosterone with the most abundant fatty acids in the digestive gland microsomal fraction of mussels. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?

    Science.gov (United States)

    van Raalte, Daniël H; Kwa, Kelly A A; van Genugten, Renate E; Tushuizen, Maarten E; Holst, Jens J; Deacon, Carolyn F; Karemaker, John M; Heine, Robert J; Mari, Andrea; Diamant, Michaela

    2013-04-01

    Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system. A randomized, placebo-controlled, double-blind, dose-response intervention study was conducted in 32 healthy males (age: 21±2years; BMI: 21.9±1.7kg/m(2)). Participants were allocated to prednisolone 7.5mg once daily (n=12), prednisolone 30mg once daily (n=12), or placebo (n=8) for two weeks. Beta-cell function was measured by hyperglycemic clamp with arginine stimulation, glucagon levels were measured following a standardized meal test. We found that prednisolone treatment dose-dependently reduced C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUCCP): -2.8 (-5.2;0.2) and -3.1 (-8.8; -1.0) nmolL(-1)min(-1) for prednisolone 7.5mg and prednisolone 30mg, respectively (P=0.035 vs. placebo). Fasting glucagon levels increased dose-dependently (vs. placebo; P=0.001), whereas postprandial glucagon levels were only increased by prednisolone 30mg. Changes in parasympathetic activity related with changes in fasting glucose levels (r=-0.407; P=0.03) and showed a trend towards correlation with fasting glucagon concentrations (r=-0.337; P=0.07). The change in sympathovagal balance was inversely related to ASI-iAUCCP (r=-0.365; P=0.05). We conclude that in addition to inducing insulin resistance, prednisolone treatment dose-dependently impaired islet-cell function. Altered sympathovagal balance may be related to these effects. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Does Scoliosis-Specific Exercise Treatment in Adolescence Alter Adult Quality of Life?

    Directory of Open Access Journals (Sweden)

    Maciej Płaszewski

    2014-01-01

    Full Text Available Objective. Health-related quality of life in adults, who in adolescence participated in a scoliosis-specific exercise program, was not previously studied. Design. Cross-sectional study, with retrospective data collection. Material and Methods. Homogenous groups of 68 persons (43 women aged 30.10 (25–39 years, with mild or moderate scoliosis, and 76 (38 women able-bodied persons, aged 30.11 (24–38 years, who 16.5 (12–26 years earlier had completed scoliosis-specific exercise or observation regimes, participated. Their respiratory characteristics did not differ from predicted values. The WHOQOL-BREF questionnaire, Oswestry Disability Questionnaire, and pain scale (VAS were applied. Results. The transformed WHOQOL-BREF scores ranged from 54.6 ± 11.19 in the physical domain in the mild scoliotic subgroup to 77.1 ± 16.05 in the social domain in the able-bodied subgroup. The ODQ values did not generally exceed 5.3 ± 7.53. Inter- and intragroup differences were nonsignificant. Age, marital status, education, and gender were significantly associated with the ODQ scores. Significant association between the ODQ and WHOQOL-BREF social relationships domain scores with the participation in exercise treatment was found. Conclusions. Participants with the history of exercise treatment generally did not differ significantly from their peers who were only under observation. This study cannot conclude that scoliosis-specific exercise treatment in adolescence alters quality of life in adulthood.

  9. A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

    Science.gov (United States)

    Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

    2016-02-01

    In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Hot or not: the effects of exogenous testosterone on female attractiveness to male conspecifics in the budgerigar.

    Directory of Open Access Journals (Sweden)

    Stefanie E P Lahaye

    Full Text Available An increasing number of studies indicate that not only females but also males can be selective when choosing a mate. In species exhibiting male or mutual mate choice, females may benefit from being attractive. While male attractiveness is often positively influenced by higher plasma levels of the androgenic hormone testosterone, it has been shown that testosterone can masculinise female behavior and morphology in several bird species, potentially rendering them less attractive. In this study, we investigated whether female budgerigars, Melopsittacusundulatus, suffer from increased plasma testosterone levels through a negative effect on their attractiveness to males. We experimentally increased plasma testosterone levels in testosterone-treated females (T-females compared to controls (C-females and allowed males to choose between a T- and a C-female in a two-way choice situation. Although testosterone treatment significantly affected female behavioral and morphological characteristics, males did not show a significant difference in preference between T- and C-females. These results suggest that experimentally increasing testosterone levels in females does not appear to influence male preference during initial mate choice. Our findings indicate that selection for higher levels of testosterone in male budgerigars is probably not constrained by a correlated response to selection causing negative effects on female attractiveness during initial mate choice. Evaluating whether or not a potential constraint may arise from negative testosterone-induced effects on other fitness related traits in females requires further work.

  11. Radioimmunoassay of testosterone and of sexual hormone-binding globulin in plasma of women with hirsutism

    International Nuclear Information System (INIS)

    Warenik-Szymankiewicz, A.; Baron, J.; Chawlisz, K.

    1980-01-01

    Plasma-borne testosterone was determined in 176 women with hirsutism, and in 47 patients sexual hormone-binding globulin was determined as well. The highest average testosterone values were recorded from cases with congenital adrenogenital syndrome (AGS). In cases of postnatal AGS values were much lower, but they were clearly in excess of those recordable from Stein-Leventhal syndrome. Plasma borne testosterone in cases of hirsutism came very close to testosterone levels established in the context of Stein-Leventhal syndrome. Testosterone levels dropped with significance, following AGS treatment, using cortisol derivatives, and following wedge-shaped ovariectomy. Sexual hormone binding-globulin was found to be strongly reduced in almost all women with hirsutism. Such reduction seemed to suggest the presence of increased amounts of free active testosterone in the blood of those patients. Determination of plasma-borne testosterone in cases of hirsutism is considered to be essential to both diagnosis of the endocrinological syndromes and monitoring of therapy. (author)

  12. Role of metabolic factors in the association between osteocalcin and testosterone in Chinese men.

    Science.gov (United States)

    Liao, Ming; Guo, Xuefeng; Yu, Xiaoxiang; Pang, Guijian; Zhang, Shijun; Li, Jianling; Tan, Aihua; Gao, Yong; Yang, Xiaobo; Zhang, Haiying; Qin, Xue; Mo, Linjian; Lu, Zheng; Wu, Chunlei; Mo, Zengnan

    2013-08-01

    Osteocalcin can regulate energy metabolism and increase testosterone production. Although previous studies have shown the positive association between osteocalcin and testosterone, the effect of metabolic factors in the association is unclear. Osteocalcin, testosterone, and metabolic factors were accessed in 2400 men aged 20 to 69 years, who participated in the population-based Fangchenggang Area Male Health and Examination Survey in Guangxi province of China from September 2009 to December 2009. Metabolic syndrome was defined based on the updated report of National Cholesterol Education Program Adult Treatment Panel III criteria. Serum total osteocalcin, total testosterone (TT), and sex hormone binding globulin (SHBG) were measured, whereas free testosterone (FT) and bioavailable testosterone (BT) were calculated based on Vermeulen's formula. The multivariable linear regression analysis was used. Osteocalcin was positively associated with TT, FT, and BT in the unadjusted model (all P obesity (waist circumstance ≥90 cm), the association appeared significantly stronger (β = 0.21, 95% confidence interval = 0.12-0.30). After further adjusting for SHBG, osteocalcin was positively associated with TT, FT, and BT in men with central obesity or men with any two MetS components (all P testosterone, which is probably modified by SHBG and central obesity.

  13. PRESENTED AT THE TRIANGLE CONSORTIUM FOR REPRODUCTIVE BIOLOGY MEETING ON 2/11/06: DI(N-BUTYL) PHTHALATE AND DIETHYLHEXYL PHTHALATE IN COMBINATION ALTER SEXUAL DIFFERENTIATION IN A CUMULATIVE MANNER AS A RESULT OF DEPRESSED FETAL TESTOSTERONE PRODUCTION AND INSL3 GENE EXPRESSION IN MALE RATS

    Science.gov (United States)

    Plasticizers di(n-butyl) phthalate (DBP) and diehtylhexyl phthalate (DEHP) have similar modes of action: in utero exposure reduces testosterone (T) production in fetal male rats, inhibits reproductive tract differentiation, and induces reproductive organ malformations. In utero e...

  14. Alteração da relação testosterona: cortisol induzida pelo treinamento de força em mulheres Alteración de la relación testosterona: cortisol inducida por el entrenamiento de fuerza en mujeres Alteration of testosterone: cortisol ratio induced by resistance training in women

    Directory of Open Access Journals (Sweden)

    Marco Carlos Uchida

    2004-06-01

    con un año de experiencia en entrenamiento de fuerza fueron sometidas al protocolo MS. Las muestras de sangre fueron colectadas antes e imediatamente después del ejercicio, en el primer día y después de ocho semanas de entrenamiento. Los tests de 1-RM y de repeticiones máximas fueron realizados también al inicio y al final después de las ocho semanas del entrenamiento de fuerza. No fueron observadas alteraciones de la masa corporal, IMC, porcentaje de masa grasa, fuerza (1-RM para los ejercicios supino, agachamiento y rosca directa. El número de repeticiones máximas al 50% de 1-RM fue aumentando solamente apenas para el supino (p The ratio between the concentration of testosterone and cortisol (T:C is frequently used as indicative of the stress level imposed by the exercise. Alterations in the concentration of these hormones are responsible for modulating several responses induced by training, such as hypertrophy and strength gain. The objective of the present study was to investigate the influence of the resistance training protocol, also known as multiple-series (MS, on the strength gain, the muscular endurance and the relation between the concentration of catabolic hormones (cortisol and anabolic hormones (testosterone. In order to test this hypothesis, five young women with one-year of strength training practice were submitted to the MS protocol. The blood samples were collected before and immediately after the exercise at the first day and after eight weeks of training. The 1-RM and the maximal repetition tests were also performed at the beginning and after eight weeks of strength training. No alterations on the body mass, on the IMC, on the fat mass percentage and on the maximal strength (1-RM on bench press, squat and arm curl were observed. The number of maximal repetitions at 50% of the 1-RM was increased only for the bench press (p < 0.05. No alterations on the concentration of the total testosterone were observed. The cortisol plasmatic

  15. Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells.

    Science.gov (United States)

    Xie, Weiguo; Ren, Mingming; Li, Ling; Zhu, Yin; Chu, Zhigang; Zhu, Zhigang; Ruan, Qiongfang; Lou, Wenting; Zhang, Haimou; Han, Zhen; Huang, Xiaodong; Xiang, Wei; Wang, Tao; Yao, Paul

    2017-01-01

    Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect. Further investigation showed that ERβ suppression is due to perinatal testosterone exposure-induced epigenetic changes with altered DNA methylation on the ERβ promoter. During aging, EPCs with ERβ suppression mobilize to the vascular wall, differentiate into ERβ-suppressed mouse endothelial cells (MECs) with downregulated expression of SOD2 (mitochondrial superoxide dismutase) and ERRα (estrogen-related receptor α). This results in reactive oxygen species (ROS) generation and DNA damage, and the dysfunction of mitochondria and fatty acid metabolism, subsequently potentiating vascular dysfunction. Bone marrow transplantation of EPCs that overexpressed with either ERβ or a SIRT1 single mutant SIRT1-C152(D) that could modulate SIRT1 phosphorylation significantly ameliorated vascular dysfunction, while ERβ knockdown worsened the problem. We conclude that perinatal testosterone exposure potentiates vascular dysfunction through ERβ suppression in EPCs.

  16. Reduction in 24-Hour Plasma Testosterone Levels in Subjects Who Showered 15 or 30 Minutes After Application of Testosterone Gel

    NARCIS (Netherlands)

    de Ronde, W.; Vogel, S.; Bui, H.N.; Heijboer, A.C.

    2011-01-01

    Study Objective. To investigate whether showering, to prevent the involuntary transfer of testosterone to others through skin contact, either 15 or 30 minutes after application of testosterone gel would significantly affect plasma testosterone levels. Design. Prospective 3-way crossover trial.

  17. Effects of In Vivo Testosterone Manipulation on Ovarian Morphology, Follicular Development, and Follicle Yolk Testosterone in the Homing Pigeon

    NARCIS (Netherlands)

    Goerlich, Vivian C.; Dijkstra, Cor; Groothuis, Ton G. G.

    2010-01-01

    To date, our understanding of the function of testosterone in female reproductive physiology is only marginal although there are indications that testosterone is involved in modulating follicular recruitment, growth, atresia, and ovulation. Studies elevating testosterone in breeding female birds

  18. Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate.

    Directory of Open Access Journals (Sweden)

    Anouk Schrantee

    Full Text Available Dexamphetamine (AMPH is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart, followed by a 1-week washout period. We then used pharmacological MRI (phMRI with a methylphenidate (MPH challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies showed that AMPH pre-treatment significantly reduced DA transporter (DAT density in the caudate-putamen (CPu and nucleus accumbens, whereas HPLC analysis revealed increases in the DA metabolite homovanillic acid in the CPu. Our results suggest that AMPH pre-treatment alters DAergic responsivity, a change that can be detected with phMRI in rats. These phMRI changes likely reflect increased DA release together with reduced DAT binding. The ability to assess subtle synaptic changes using phMRI is promising for both preclinical studies of drug discovery, and for clinical studies where phMRI can be a useful tool to non-invasively investigate DA abnormalities, e.g. in neuropsychiatric disorders.

  19. The costs of dominance: testosterone, cortisol and intestinal parasites in wild male chimpanzees

    Directory of Open Access Journals (Sweden)

    Watts David P

    2010-12-01

    Full Text Available Abstract Background Male members of primate species that form multi-male groups typically invest considerable effort into attaining and maintaining high dominance rank. Aggressive behaviors are frequently employed to acquire and maintain dominance status, and testosterone has been considered the quintessential physiological moderator of such behaviors. Testosterone can alter both neurological and musculoskeletal functions that may potentiate pre-existing patterns of aggression. However, elevated testosterone levels impose several costs, including increased metabolic rates and immunosuppression. Cortisol also limits immune and reproductive functions. Methods To improve understanding of the relationships between dominance rank, hormones and infection status in nonhuman primates, we collected and analyzed 67 fecal samples from 22 wild adult male chimpanzees (Pan troglodytes schweinfurthii at Ngogo, Kibale National Park, Uganda. Samples were analyzed for cortisol and testosterone levels as well as intestinal parasite prevalence and richness. 1,700 hours of observation data were used to determine dominance rank of each animal. We hypothesized that dominance rank would be directly associated with fecal testosterone and cortisol levels and intestinal parasite burden. Results Fecal testosterone (but not cortisol levels were directly associated with dominance rank, and both testosterone and cortisol were directly associated with intestinal parasite richness (number of unique species recovered. Dominance rank was directly associated with helminth (but not protozoan parasite richness, so that high ranking animals had higher testosterone levels and greater helminth burden. Conclusions One preliminary interpretation is that the antagonist pleiotropic effects of androgens and glucocorticoids place a cost on attaining and maintaining high dominance rank in this species. Because of the costs associated with elevated steroid levels, dominance status may be an

  20. Manipulation of postnatal testosterone levels affects phallic and clitoral development in infant rhesus monkeys.

    Science.gov (United States)

    Brown, G R; Nevison, C M; Fraser, H M; Dixson, A F

    1999-04-01

    Male primates exhibit marked elevation of circulating testosterone levels during the early postnatal period. The aim of this project was to test whether experimental manipulation of circulating testosterone levels in male and female infant rhesus monkeys affected development of the external genitalia during the first six months of life. Four groups of infants were studied. Seven control male infants exhibited high circulating testosterone levels during the first three months of life. Seven males were treated with a GnRH agonist (avorelin) from the first week of life onwards, which suppressed the postnatal testosterone surge. Ten control females exhibited low circulating testosterone levels during the early postnatal period. Administration of testosterone to 10 females resulted in high circulating levels in these infants. Fortnightly blood samples and genital measurements were taken from all infants during the first six months of life. Growth of the penis of avorelin-treated males was significantly retarded when compared to control males. Average length of the penis at six months of age was significantly (p = 0.012) smaller for avorelin-treated males (25.2 +/- 2.8 mm) than for control males (37.3 +/- 3.0 mm). Avorelin-treated males attained only around 50% detachment of the prepuce from the glans of the penis, while control males averaged 90% detachment. Treatment of females with testosterone resulted in significant growth of the clitoris in comparison to control females. The growth rates of the penis of control males and clitorides of testosterone-treated females were similar and greatest during the first two months of life. Gain in body weight was not affected by either hormonal manipulation. It is concluded that manipulation of circulating testosterone levels during the early postnatal period affects penile and clitoral development of infant rhesus monkeys. This postnatal period may therefore represent an important stage in penile development in primates.

  1. Testosterone supplementation in men: a practical guide for the gynecologist and obstetrician.

    Science.gov (United States)

    Owen, Ryan C; Elkelany, Osama O; Kim, Edward D

    2015-08-01

    Prescribing habits for the treatment of symptomatic hypogonadism have recently stirred controversy surrounding testosterone replacement therapy. As a result, the gynecologist will need to recognize this iatrogenic form of decreased sperm production in couples seeking fertility advice. We have compiled a review of the current literature on testosterone supplementation pertaining to the gynecologic practice. Over the last decade, testosterone use has seen a recent increase including in men desiring to become fathers. Many physicians and hypogonadal men do not recognize that testosterone replacement therapy can have a detrimental effect on spermatogenesis. Fortunately, the cessation of treatment will yield predictable recovery of sperm production for most men. A growing body of evidence supports the use of selective estrogen receptor modulators, such as clomiphene citrate, or human chorionic gonadotropin for the treatment of hypogonadism in men who wish to maintain fertility potential. Recently, the Food and Drug Administration has recommended a labeling update on testosterone products to warn of possible increased risk of venous thromboembolism, cardiovascular events and stroke. Clinicians should be familiar with current practices involving testosterone replacement therapy and the implications on male factor fertility.

  2. Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome

    Directory of Open Access Journals (Sweden)

    Kimball Scot R

    2011-05-01

    Full Text Available Abstract Background Diabetic retinopathy (DR is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia. Methods The retina transcriptome (22,523 genes and transcript variants was examined after three months of streptozotocin-induced diabetes in male Sprague Dawley rats with and without insulin replacement for the later one and a half months of diabetes. Selected gene expression changes were confirmed by qPCR, and also examined in independent control and diabetic rats at a one month time-point. Results Transcriptomic alterations in response to diabetes (1376 probes were clustered according to insulin responsiveness. More than half (57% of diabetes-induced mRNA changes (789 probes observed at three months were fully normalized to control levels with insulin therapy, while 37% of probes (514 were only partially normalized. A small set of genes (5%, 65 probes was significantly dysregulated in the insulin-treated diabetic rats. qPCR confirmation of findings and examination of a one month time point allowed genes to be further categorized as prevented or rescued with insulin therapy. A subset of genes (Ccr5, Jak3, Litaf was confirmed at the level of protein expression, with protein levels recapitulating changes in mRNA expression. Conclusions These results provide the first genome-wide examination of the effects of insulin therapy on retinal gene expression changes with diabetes. While insulin clearly normalizes the majority of genes dysregulated in response to diabetes, a number of genes related to inflammatory processes, microvascular integrity, and neuronal function are still altered in expression in

  3. Serum testosterone concentration in chloroquine- treated rats ...

    African Journals Online (AJOL)

    ONOS

    2010-07-05

    Jul 5, 2010 ... The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone ... chloroquine are probably mediated via the generation of free radicals. ... Effects of ascorbic acid and alpha-tocopherol on serum testosterone concentration in chloroquine-treated rats. Groups.

  4. Testosterone in women-the clinical significance

    DEFF Research Database (Denmark)

    Davis, Susan R; Jacobsen, Sarah Wåhlin

    2015-01-01

    action and the effects of testosterone deficiency and replacement in women are scarce. The primary indication for the prescription of testosterone for women is loss of sexual desire, which causes affected women substantial concern. That no formulation has been approved for this purpose has not impeded...

  5. Review Article: Practical Aspects of Testosterone Deficiency ...

    African Journals Online (AJOL)

    In this review we describe the clinical manifestations associated with testosterone deficiency in aging men, termed the testosterone deficiency syndrome (TDS). Since aging men suffer from multiple urological and andrological symptoms, TDS is an important medical condition to be suspected, recognized, clinically ...

  6. Large-scale downy brome treatments alter plant-soil relationships and promote perennial grasses in salt desert shrublands

    Science.gov (United States)

    The interrelationship between invasive annual grass abundance and soil resource availability varies spatially and temporally within ecosystems and may be altered by land treatments. We evaluated these relationships in two salt desert landscapes where the local abundance of Bromus tectorum L. (downy...

  7. Testosterone Replacement Therapy and the Cardiovascular System.

    Science.gov (United States)

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  8. [Testosterone deficiency, metabolic syndrome and diabetes mellitus].

    Science.gov (United States)

    Fernández-Miró, Mercè; Chillarón, Juan J; Pedro-Botet, Juan

    2016-01-15

    Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  9. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells.

    Science.gov (United States)

    Rato, Luís; Alves, Marco G; Duarte, Ana I; Santos, Maria S; Moreira, Paula I; Cavaco, José E; Oliveira, Pedro F

    2015-09-01

    The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Altered fractionation of hemithorax irradiation for pleural mesothelioma and failure patterns after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Holsti, L.R. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Pyrhoenen, S. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Kajanti, M. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Maentylae, M. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Mattson, K. [Dept. of Internal Medicine, Div. of Pulmonary Medicine, Helsinki University Central Hospital (Finland); Maasilta, P. [Dept. of Internal Medicine, Div. of Pulmonary Medicine, Helsinki University Central Hospital (Finland); Kivisaari, L. [Dept. of Diagnostic Radiology, Helsinki University Central Hospital (Finland)

    1997-09-01

    Malignant pleural mesothelioma is a rare malignancy with a bleak prognosis. The role of radiotherapy has not yet been clarified. Our aim was to study the effect of altered fractionation on mesothelioma. We have treated 57 patients, 41 males and 16 females, with hemithorax irradiation with six different fractionation schedules. All the patients have been included in a combined modality program consisting of surgery followed by chemotherapy and finally by hemithorax irradiation. The radiotherapy schedules used were: I. Conventional fractionation of 20 Gy in 10 fractions over 12 days. II, Split-course radiotherapy 55 Gy in 25 fractions of 2.2 Gy over 7 weeks (a two weeks rest halfways) followed by a boost dose of 15 Gy over 8 days to the major tumour area. III. Hyperfractionation of 70 Gy over 7 weeks, 1.25 Gy BID with a 6-h interval and a 10-day rest halfways. IV. Combined hyperfractionation and hypofractionation, 35 Gy hyperfractionation in 28 fractions (1.25 Gy BID with a 6-h interval) over three weeks followed by 36 Gy hypofractionation 9 fractions of 4 Gy given every other day over 3 weeks to the major tumour areas only. V. Hypofractionation of 38.5 Gy over 15 days (9x3.5 Gy). VI. Combined conventional radiotherapy and hypofractionation with 20 Gy given conventionally in 10 fractions followed by 10 fractions of 3 Gy over two weeks, overall time 4 weeks. The 2-year survival rate of all patients was 21% and the 5-year survival rate 9%. Two patients are still alive more than 6 and 9 years after radiotherapy. Progression occurred after surgery in four patients, during and after chemotherapy in 22 patients and after completed radiotherapy in 29 patients. The pattern of progression was similar in each treatment group. (orig.).

  11. ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

    Science.gov (United States)

    Han, Aijie; Zou, Lingyue; Gan, Xiaoqin; Li, Yu; Liu, Fangfang; Chang, Xuhong; Zhang, Xiaotian; Tian, Minmin; Li, Sheng; Su, Li; Sun, Yingbiao

    2018-06-15

    Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

    Science.gov (United States)

    Nagels, Helen E; Rishworth, Josephine R; Siristatidis, Charalampos S; Kroon, Ben

    2015-11-26

    Infertility is a condition affecting 10% to 15% of couples of reproductive age. It is generally defined as "the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse". The treatment of infertility may involve manipulation of gametes or of the embryos themselves. These techniques are together known as assisted reproductive technology (ART). Practitioners are constantly seeking alternative or adjunct treatments, or both, in the hope that they may improve the outcome of assisted reproductive techniques. This Cochrane review focusses on the adjunct use of synthetic versions of two naturally-produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction.DHEA and its derivative testosterone are steroid hormones proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation, leading to greater oocyte yields and, in turn, increased chance of pregnancy. To assess the effectiveness and safety of DHEA and testosterone as pre- or co-treatments in subfertile women undergoing assisted reproduction. We searched the following electronic databases, trial registers and websites up to 12 March 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the Web of Science, PubMed and OpenSIGLE. We also carried out handsearches. There were no language restrictions. We included randomised controlled trials (RCTs) comparing DHEA or testosterone as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. Two review authors independently selected studies, extracted relevant data and assessed them for risk of bias. We pooled studies using fixed-effect models. We calculated

  13. Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Prasanth N. Surampudi

    2012-01-01

    Full Text Available Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men.

  14. Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

    Science.gov (United States)

    Surampudi, Prasanth N.; Wang, Christina; Swerdloff, Ronald

    2012-01-01

    Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men. PMID:22505891

  15. Developmental Programming: Impact of Excess Prenatal Testosterone on Intrauterine Fetal Endocrine Milieu and Growth in Sheep1

    Science.gov (United States)

    Veiga-Lopez, Almudena; Steckler, Teresa L.; Abbott, David H.; Welch, Kathleen B.; MohanKumar, Puliyur S.; Phillips, David J.; Refsal, Kent; Padmanabhan, Vasantha

    2010-01-01

    Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ∼147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64–66, 87–90, and 139–140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep. PMID:20739662

  16. Effect of deodorant and antiperspirant use and presence or absence of axillary hair on absorption of testosterone 2% solution applied to men's axillae.

    Science.gov (United States)

    Small, David S; Ni, Xiao; Polzer, Paula; Vart, Richard; Satonin, Darlene K; Mitchell, Malcolm I

    2014-11-01

    Testosterone 2% solution is applied to axillae and is indicated for testosterone replacement therapy in males deficient in endogenous testosterone. This open-label crossover study evaluated the effect of deodorant/antiperspirant use and presence or absence of axillary hair on absorption of testosterone solution. Healthy males (N = 30; ≥50 years of age with baseline testosterone deodorant/antiperspirant. Blood samples were taken over 72 hours after each dose for measuring serum testosterone concentrations. Profiles of mean testosterone concentrations were similar across treatments. For all treatments, area under the concentration-time curve through 24 hours (AUC[0-24] ) and 72 hours (AUC[0-72] ), and maximum total testosterone concentration (Cmax ) were similar except for 15% lower Cmax when treatment was applied after deodorant/antiperspirant to shaved vs. unshaved axillae (least squares mean, 531 ng/dL vs. 626 ng/dL, respectively; P = 0.011). This difference is not considered clinically significant. The 95% confidence intervals for AUC(0-24) , AUC(0-72) , and Cmax fell within the traditional bioequivalence limits of 0.8 to 1.25. Incidence of treatment-emergent adverse events (TEAEs) was low (deodorant/antiperspirant or by the presence or absence of axillary hair. Testosterone solution was generally well tolerated. © 2014 International Society for Sexual Medicine.

  17. Association Between Direct-to-Consumer Advertising and Testosterone Testing and Initiation in the United States, 2009-2013.

    Science.gov (United States)

    Layton, J Bradley; Kim, Yoonsang; Alexander, G Caleb; Emery, Sherry L

    2017-03-21

    Testosterone initiation increased substantially in the United States from 2000 to 2013, especially among men without clear indications. Direct-to-consumer advertising (DTCA) also increased during this time. To investigate associations between televised DTCA and testosterone testing and initiation in the United States. Ecologic study conducted in designated market areas (DMAs) in the United States. Monthly testosterone advertising ratings were linked to DMA-level testosterone use data from 2009-2013 derived from commercial insurance claims. Associations between DTCA and testosterone testing, initiation, and initiation without recent baseline tests were estimated using Poisson generalized estimating equations. Monthly Nielsen ratings for testosterone DTCA in the 75 largest DMAs. (1) Rates of new serum testosterone testing; (2) rates of testosterone initiation (in-office injection, surgical implant, or pharmacy dispensing) for all testosterone products combined and for specific brands; and (3) rates of testosterone initiation without recent serum testosterone testing. Of 17 228 599 commercially insured men in the 75 DMAs, 1 007 990 (mean age, 49.6 [SD, 11.5] years) had new serum testosterone tests and 283 317 (mean age, 51.8 [SD, 11.3] years) initiated testosterone treatment. Advertising intensity varied by geographic region and time, with the highest intensity seen in the southeastern United States and with months ranging from no ad exposures to a mean of 13.6 exposures per household. Nonbranded advertisements were common prior to 2012, with branded advertisements becoming more common during and after 2012. Each household advertisement exposure was associated with a monthly increase in rates of new testosterone testing (rate ratio [RR], 1.006; 95% CI, 1.004-1.008), initiation (RR, 1.007; 95% CI, 1.004-1.010), and initiation without a recent test (RR, 1.008; 95% CI, 1.002-1.013). Mean absolute rate increases were 0.14 tests (95% CI, 0.09-0.19), 0.05 new

  18. White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment.

    Science.gov (United States)

    Su, Tanja; Caan, Matthan W A; Wit, Ferdinand W N M; Schouten, Judith; Geurtsen, Gert J; Cole, James H; Sharp, David J; Vos, Frans M; Prins, Maria; Portegies, Peter; Reiss, Peter; Majoie, Charles B

    2016-01-01

    Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIV+ patients remains unknown, as well as its possible association with cognitive impairment. We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV+ patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. We compared 100 aviraemic HIV+ men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. HIV+ patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increased mean diffusion. These white matter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/μl, but not with HIV-associated cognitive deficits. Cerebral white matter structure alterations are found in middle-aged HIV+ men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits. .

  19. Male osteoporosis and androgenic therapy: from testosterone to SARMs.

    Science.gov (United States)

    Cilotti, Antonio; Falchetti, Alberto

    2009-09-01

    As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance.Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials.

  20. The Response of Prostate Smooth Muscle Cells to Testosterone Is Determined by the Subcellular Distribution of the Androgen Receptor.

    Science.gov (United States)

    Peinetti, Nahuel; Scalerandi, María Victoria; Cuello Rubio, Mariana Micaela; Leimgruber, Carolina; Nicola, Juan Pablo; Torres, Alicia Ines; Quintar, Amado Alfredo; Maldonado, Cristina Alicia

    2018-02-01

    Androgen signaling in prostate smooth muscle cells (pSMCs) is critical for the maintenance of prostate homeostasis, the alterations of which are a central aspect in the development of pathological conditions. Testosterone can act through the classic androgen receptor (AR) in the cytoplasm, eliciting genomic signaling, or through different types of receptors located at the plasma membrane for nongenomic signaling. We aimed to find evidence of nongenomic testosterone-signaling mechanisms in pSMCs and their participation in cell proliferation, differentiation, and the modulation of the response to lipopolysaccharide. We demonstrated that pSMCs can respond to testosterone by a rapid activation of ERK1/2 and Akt. Furthermore, a pool of ARs localized at the cell surface of pSMCs is responsible for a nongenomic testosterone-induced increase in cell proliferation. Through membrane receptor stimulation, testosterone favors a muscle phenotype, indicated by an increase in smooth muscle markers. We also showed that the anti-inflammatory effects of testosterone, capable of attenuating lipopolysaccharide-induced proinflammatory actions, are promoted only by receptors located inside the cell. We postulate that testosterone might perform prohomeostatic effects through intracellular-initiated mechanisms by modulating cell proliferation and inflammation, whereas some pathological, hyperproliferative actions would be induced by membrane-initiated nongenomic signaling in pSMCs. Copyright © 2018 Endocrine Society.

  1. Marital sex frequency and midcycle female testosterone.

    Science.gov (United States)

    Morris, N M; Udry, J R; Khan-Dawood, F; Dawood, M Y

    1987-02-01

    The purpose of the study was to attempt to replicate a finding of Persky et al. (1978) that midcycle peak values of testosterone (T) in women predicted differences in frequency of intercourse among married couples. Luteinizing hormone (LH), total testosterone (TT), and free testosterone (FT) values from 10 to 14 daily midcycle blood samples donated by 43 volunteering wives were analyzed against sexual activity patterns reported by the couples over a longer period of time. All couples were contracepting by means other than exogenous hormones or the rhythm method. Each morning through three menstrual cycles husbands and wives recorded independently and on separate forms answers to a series of questions concerning sexual activity in the previous 24 hr. Wives also recorded basal body temperatures (BBT). We designated midcycle values of TT and FT according to several definitions of midcycle. Total testosterone levels at the day of the BBT nadir and the day before the nadir correlated significantly with average intercourse frequency. Correlations with FT were statistically significant regardless of which midcycle measure was used; the day before the BBT nadir gave the highest correlation, 0.618, p = 0.01. Mean testosterone (TT or FT) values were not significantly related. We conclude that female midcycle total testosterone or free testosterone is indexing some unobserved event that affects the frequency of intercourse of couples. We speculate that this event affects the motivation of females, which influences the set point of the compromise frequency characteristic of couples.

  2. Obesity, low testosterone levels and erectile dysfunction.

    Science.gov (United States)

    Diaz-Arjonilla, M; Schwarcz, M; Swerdloff, R S; Wang, C

    2009-01-01

    Obesity is an important risk factor for many common diseases including cardiovascular disease (CVD), type 2 diabetes, cancer and erectile dysfunction (ED). Adipose tissues produce a number of adipokines and cytokines, which affect endothelial and metabolic function resulting in insulin resistance and the metabolic syndrome (risks factors for CVD). Both ED and metabolic syndrome improve with a reduction in body mass index (BMI). The relationships among obesity, metabolic syndrome, ED, sex hormone-binding globulin (SHBG) and serum total and free testosterone levels are complex and often confusing to the physician. It is known that BMI is inversely proportional to serum total testosterone concentrations; low serum SHBG levels in obesity contribute to the low serum total testosterone. Recent studies show that BMI is also inversely proportional to free testosterone concentration. The characteristic low serum testosterone concentrations observed in obese men are also present in men with the metabolic syndrome and type 2 diabetes mellitus. A small proportion of men with ED have hypogonadism; however, the proportion increases if these men are obese with manifestations of the metabolic syndrome or type 2 diabetes mellitus. ED is a common symptom in patients with type 2 diabetes who also have low testosterone levels. This review describes the relationships between low serum testosterone concentrations and ED in obese patients and those with metabolic syndrome and type 2 diabetes mellitus.

  3. Use of parenteral testosterone in hypospadias cases

    Directory of Open Access Journals (Sweden)

    Vikram Satav

    2015-01-01

    Full Text Available Objectives: The aim was to evaluate the effect of parenteral testosterone on penile length, preputial hood, vascularity of dartos pedicle in patients with hypospadias. Materials and Methods: A total of 42 patients with hypospadias were included in this study. Injection aquaviron (oily solution each ml containing testosterone propionate 25 mg was given deep intramuscularly in three doses with an interval of 3 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Preoperatively penile length, transverse preputial width and diameter at the base of the penis were measured. Basal testosterone levels were obtained before the institution of therapy and on the day of operation. Results: Following parenteral testosterone administration, the mean increase in penile length, transverse preputial width and diameter at the base of penis was 1.01 ± 0.25 cm (P < 0.001, 1.250 ± 0.52 cm and 0.61 ± 0.35 cm, respectively, (P < 0.001. Serum testosterone level after injection was well within normal range for that age. Conclusion: Parenteral testosterone increased phallus size, diameter and prepuce hypertrophy without any adverse effects. However, due to lack of a control group we cannot make any inferences. Controlled studies are required to establish the benefits of parenteral testosterone.

  4. Testosterone and cardiovascular disease in men

    Science.gov (United States)

    Morris, Paul D; Channer, Kevin S

    2012-01-01

    Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ‘Perspectives' article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ‘cause' versus ‘effect' controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease. PMID:22522504

  5. The role of testosterone in social interaction.

    Science.gov (United States)

    Eisenegger, Christoph; Haushofer, Johannes; Fehr, Ernst

    2011-06-01

    Although animal researchers established the role of testosterone as a 'social hormone' decades ago, the investigation of its causal influence on human social behaviors has only recently begun. Here, we review and discuss recent studies showing the causal effects of testosterone on social interactions in animals and humans, and outline the basic neurobiological mechanisms that might underlie these effects. Based on these recent findings, we argue that the role of testosterone in human social behavior might be best understood in terms of the search for, and maintenance of, social status. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Sex Reversal Of Nila Gift (Oreochromis Niloticus) After Feeding By Natural Testosteron Hormone

    International Nuclear Information System (INIS)

    Hasibuan, Adria PM.; Umar, Jenny M.

    2002-01-01

    Natural testosteron hormonal derived from cow testis was given on fish larva for sex reversal. Concentration of natural testosteron hormone was determined by isotopic dilution technique using Radioimmunoassay (RIA). Results of experiments in aquarium showed that the A treatment produced only 24% of male nila gift, B treatment was 87%, and C treatment was 92%. While result of sex reversal was observed in fish pond was 29%, 83%, and 87% for A,B, and C treatments respectively. Fish weight after 40 days was 2.60 gram and 0.65 gram for male and female respectively. Natural testosteron hormone given to nila gift as sex reversal, was successful to produce male nila gift

  7. Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function.

    Science.gov (United States)

    Jayaraman, Anusha; Lent-Schochet, Daniella; Pike, Christian J

    2014-09-16

    Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices in the central and peripheral nervous systems. Male C57B6/J mice were maintained on normal or high-fat diet under varying testosterone conditions for a four-month treatment period, after which metabolic indices were measured and RNA isolated from cerebral cortex and sciatic nerve. Cortices were used to generate mixed glial cultures, upon which embryonic cerebrocortical neurons were co-cultured for assessment of neuron survival and neurite outgrowth. Peripheral nerve damage was determined using paw-withdrawal assay, myelin sheath protein expression levels, and Na+,K+-ATPase activity levels. Our results demonstrate that detrimental effects on both metabolic (blood glucose, insulin sensitivity) and proinflammatory (cytokine expression) responses caused by diet-induced obesity are exacerbated by testosterone depletion. Mixed glial cultures generated from obese mice retain elevated cytokine expression, although low testosterone effects do not persist ex vivo. Primary neurons co-cultured with glial cultures generated from high-fat fed animals exhibit reduced survival and poorer neurite outgrowth. In addition, low testosterone and diet-induced obesity combine to increase inflammation and evidence of nerve damage in the peripheral nervous system. Testosterone and diet-induced obesity independently and cooperatively regulate neuroinflammation in central and peripheral nervous systems, which may contribute to observed impairments in neural health. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that, in combination with adipose-derived inflammatory pathways and other factors

  8. The effect of food composition on serum testosterone levels after oral administration of Andriol Testocaps.

    Science.gov (United States)

    Schnabel, Peter G; Bagchus, Wilma; Lass, Holger; Thomsen, Torben; Geurts, T B Paul

    2007-04-01

    Andriol Testocaps is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. An open-label, single-centre, four-way crossover study. With a washout period of 6-7 days, 80 mg TU was administered in the morning 5 min after consuming each of four different meals in a randomized order (A: 230 kcal, 0.6 g lipid; B: 220 kcal, 5 g lipid; C: 474 kcal, 19 g lipid; D: 837 kcal, 44 g lipid). Twenty-four postmenopausal volunteers. Serial blood samples were collected until 24 h after dosing to determine testosterone and dihydrotestosterone (DHT) by gas chromatography-mass spectroscopy (GC-MS). The bioavailability of testosterone after a low-calorie meal containing 0.6 g lipid or 5 g lipid was relatively low, the area under the concentration-time curve (AUC(0-tlast)) for testosterone being 30.7 and 43.5 nmol h/l, respectively. The bioavailability of testosterone after a meal containing 19 g lipid was considerably higher (AUC(0-tlast) = 146 nmol h/l), whereas increasing the lipid content to 44 g lipid did not further increase the bioavailability of testosterone (AUC(0-tlast) = 154 nmol h/l). Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.

  9. Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men

    Science.gov (United States)

    Basaria, Shehzad; Traustadottir, Tinna; Harman, S. Mitchell; Pencina, Karol; Li, Zhuoying; Travison, Thomas G.; Miciek, Renee; Tsitouras, Panayiotis; Hally, Kathleen; Huang, Grace; Bhasin, Shalender

    2017-01-01

    Context: Findings of studies of testosterone’s effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied. Objective: To determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability, and physical function. Design, Setting, and Participants: This was a double-blind, placebo-controlled, randomized trial of healthy men ≥60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels testosterone or placebo gel daily for 3 years. Outcome Measures: Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months. Results: The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean estimated between-group difference, 10.7 W [95% confidence interval (CI), −4.0 to 25.5], P = 0.026; and 22.4 W [95% CI, 4.6 to 40.3], P = 0.027), respectively. Changes in chest-press strength (estimated mean difference, 16.3 N; 95% CI, 5.5 to 27.1; P testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group. Conclusion: Compared with placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass, and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied. PMID:27754805

  10. Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep.

    Science.gov (United States)

    Veiga-Lopez, A; Ye, W; Phillips, D J; Herkimer, C; Knight, P G; Padmanabhan, V

    2008-04-01

    Prenatal testosterone excess leads to neuroendocrine, ovarian, and metabolic disruptions, culminating in reproductive phenotypes mimicking that of women with polycystic ovary syndrome (PCOS). The objective of this study was to determine the consequences of prenatal testosterone treatment on periovulatory hormonal dynamics and ovulatory outcomes. To generate prenatal testosterone-treated females, pregnant sheep were injected intramuscularly (days 30-90 of gestation, term=147 days) with 100 mg of testosterone-propionate in cottonseed oil semi-weekly. Female offspring born to untreated control females and prenatal testosterone-treated females were then studied during their first two breeding seasons. Sheep were given two injections of prostaglandin F2alpha 11 days apart, and blood samples were collected at 2-h intervals for 120 h, 10-min intervals for 8 h during the luteal phase (first breeding season only), and daily for an additional 15 days to characterize changes in reproductive hormonal dynamics. During the first breeding season, prenatal testosterone-treated females manifested disruptions in the timing and magnitude of primary gonadotropin surges, luteal defects, and reduced responsiveness to progesterone negative feedback. Disruptions in the periovulatory sequence of events during the second breeding season included: 1) delayed but increased preovulatory estradiol rise, 2) delayed and severely reduced primary gonadotropin surge in prenatal testosterone-treated females having an LH surge, 3) tendency for an amplified secondary FSH surge and a shift in the relative balance of FSH regulatory proteins, and 4) luteal responses that ranged from normal to anovulatory. These outcomes are likely to be of relevance to developmental origin of infertility disorders and suggest that differences in fetal exposure or fetal susceptibility to testosterone may account for the variability in reproductive phenotypes.

  11. Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring.

    Science.gov (United States)

    Intapad, Suttira; Dasinger, John Henry; Fahling, Joel M; Backstrom, Miles A; Alexander, Barbara T

    2017-01-01

    Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis.

  12. Pulmonary Embolism Secondary to Testosterone-Enhancing Herbal Supplement Use

    OpenAIRE

    Nguyen, Steven M; Ko Ko, Nway; Sattar, Asad S; Gucuk Ipek, Esra; Ali, Sayed

    2017-01-01

    Decreased testosterone levels in men are often a normal sign of aging. Testosterone replacement therapy (TRT) is a well-established option for those with symptomatic hypogonadism related to low testosterone levels. Conversely, designer herbal supplements in the context of testosterone supplementation are poorly studied, yet remain popular among aging men who seek the well-known, often enhancing, effects of testosterone that involve muscle mass and sexual function/drive. In 2014, the Food and ...

  13. Re: Could Testosterone Replacement Therapy in Hypogonadal Men Ameliorate Anemia, a Cardiovascular Risk Factor? An Observational, 54-week Cumulative Registry Study

    Directory of Open Access Journals (Sweden)

    Emre Bakırcıoğlu

    2016-09-01

    Full Text Available Testosterone deficiency syndrome may associate with erectile dysfunction, increased abdominal fat and reduced muscle mass. Low serum testosterone is also related with anemia, metabolic syndrome and cardiovascular disease. In this study, the authors investigated if testosterone undecanoate (TU reduces anemia and the risk of cardiovascular disease in patients with hypogonadism A total of 58 participants with a total testosterone level of less than 2.35 ng/ml received an injection of 1.000 mg TU 6 times; at initial visit, 6, 18, 30, 42 and 54 weeks. They observed that total testosterone and free testosterone levels were restored by TU. Hemoglobin and hematocrit levels significantly increased while anemia and total cholesterol levels significantly reduced. Although there are some limitations of this study e.g. it is not a randomized controlled and a long-term study, TU treatment in hypogonadal men decreased the prevalence of anemia, improved lipid profiles and lowered the risk of cardiovascular disease.

  14. Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

    Science.gov (United States)

    Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

    2008-04-01

    The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

  15. White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment

    NARCIS (Netherlands)

    Su, Tanja; Caan, Matthan W. A.; Wit, Ferdinand W. N. M.; Schouten, Judith; Geurtsen, Gert J.; Cole, James H.; Sharp, David J.; Vos, Frans M.; Prins, Maria; Portegies, Peter; Reiss, Peter; Majoie, Charles B.

    2016-01-01

    Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in

  16. Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats

    Directory of Open Access Journals (Sweden)

    Chin KY

    2014-08-01

    Full Text Available Kok-Yong Chin, Soelaiman Ima-Nirwana Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT using a testosterone-deficient osteoporotic rat model. Methods: Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined. Results: There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05, but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05 when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05 and significantly increased expression of bone formation genes (P<0.05. Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05. Conclusion: AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration. Keywords: bone remodeling

  17. Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone.

    Science.gov (United States)

    Ghanim, Husam; Dhindsa, Sandeep; Abuaysheh, Sanaa; Batra, Manav; Kuhadiya, Nitesh D; Makdissi, Antoine; Chaudhuri, Ajay; Dandona, Paresh

    2018-03-01

    One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression. This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism. The mRNA expression of AR, ERα (ESR1) and aromatase in adipose tissue from hypogonadal men was significantly lower as compared to eugonadal men, and it increased significantly to levels comparable to those in eugonadal patients with T2DM following testosterone treatment. AR mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored AR mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are lower in men with hypogonadism. Testosterone treatment restored AR expression levels to that comparable to levels in eugonadal men. We conclude that, contrary to our hypothesis, the expression of AR, ERα and aromatase is significantly diminished in hypogonadal men as compared to eugonadal men with type 2 diabetes. Following testosterone replacement, there is a reversal of these deficits. © 2018 European Society of Endocrinology.

  18. Effect of caponization and testosterone implantation on hepatic lipids and lipogenic enzymes in male chickens.

    Science.gov (United States)

    Chen, K L; Chi, W T; Chu, C; Chen, R S; Chiou, P W S

    2007-08-01

    This study was conducted to determine the role and effects of testosterone in lipogenesis by measuring and analyzing the lipid composition and lipogenic enzyme activity of livers from capons treated with various doses of exogenous testosterone implant. Healthy and uniform male Single Comb White Leghorn chickens were caponized at 12 wk of age. Sixteen-week-old capons were randomly selected for a 10-wk experiment. Fifteen intact males and 15 capons were used for trial 1. In trial 2, 10 sham-operated males and 40 capons were used. The capons were randomly divided into 4 independent treatments with sialistic implants of cholesterol (1.62 mm i.d., 3.6 mm o.d., 9.24 +/- 0.36 mg; CHOL), low testosterone (1 mm i.d., 3 mm o.d., 5.88 +/- 0.23 mg), medium testosterone (1.62 mm i.d., 3.16 mm o.d., 9.81 +/- 0.17 mg), or high testosterone (2 mm i.d., 4 mm o.d., 16.7 +/- 0.24 mg). In trial 1, the results showed that caponization increased total hepatic lipid and triacylglycerol contents and decreased the nonesterified fatty acid content (P malic dehydrogenase (MDH) activity and MDH mRNA content (P = 0.09) simultaneously. In trial 2, comparing treatments with the various implantation doses of testosterone, the liver triacylglycerol content of capons the medium-dose implantation was decreased as compared with those receiving CHOL (P 0.05). With an increased implantation dose, MDH activity of capons receiving the medium dose or higher was not different from those receiving the CHOL and sham treatments (P > 0.05). The increase in MDH activity at the transcriptional and translational levels suggests that caponization may positively regulate hepatic lipogenesis. In contract, implantation of testosterone up to the threshold concentration depressed hepatic lipogensis and lipid accumulation.

  19. Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial.

    Science.gov (United States)

    Wu, Brian; Lorezanza, Dan; Badash, Ido; Berger, Max; Lane, Christianne; Sum, Jonathan C; Hatch, George F; Schroeder, E Todd

    2017-08-01

    reconstruction, suggesting that this treatment may help minimize the effects of muscle atrophy associated with ACL injuries and repair. This study was not powered to detect differences in strength or clinical outcome scores to assess the incidence of testosterone-related adverse events. Supraphysiological testosterone supplementation may be a useful adjunct therapy for counteracting muscle atrophy after ACL reconstruction. Further investigation is necessary to determine the safety profile and effects of perioperative testosterone administration on leg strength and clinical outcomes after surgery. NCT01595581 (ClinicalTrials.gov).

  20. Testosterone Replacement, Muscle Strength, and Physical Function

    Directory of Open Access Journals (Sweden)

    You-Seon Nam

    2018-05-01

    Full Text Available Muscle strength and physical function decrease in older men, as do testosterone levels. Nonetheless, the effects of testosterone replacement therapy on muscle strength and physical function remain inconclusive and equivocal. We conducted a rapid systematic review, the results of which showed that testosterone replacement does not affect muscle strength (measured by hand grip strength and leg muscle strength, although it may increase physical function (measured by the 6-minute walk test, Physical Activity Scale for the Elderly score, and other physical performance tests. However, most of the studies were conducted in the United States or Europe and did not include participants from Asian or other ethnic backgrounds; therefore, further studies are needed to evaluate the effects of testosterone replacement in a broader population.

  1. Relationship between Testosterone, Oxidative Stress Biomarkers ...

    African Journals Online (AJOL)

    Hypogonadism attributable to males with metabolic syndrome was also observed in automechanics occupationally exposed to mixed chemicals accompanied by oxidative stress (OS). We evaluated associations among testosterone, OS biomarkers, enzymatic and non-enzymatic antioxidants in normal weight ...

  2. Aggression: the testosterone-serotonin link.

    Science.gov (United States)

    Birger, Moshe; Swartz, Marnina; Cohen, David; Alesh, Ya'akov; Grishpan, Chaim; Kotelr, Moshe

    2003-09-01

    The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and animals. Among other findings, there are abundant data relating low serotonergic activity--as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine--to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonergic receptor activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.

  3. Testosterone and aging: clinical research directions

    National Research Council Canada - National Science Library

    Liverman, Catharyn T; National Research Council (U.S.). Committee on Assessing the Need for Clinical Trials of Testosterone Replacement Therapy; Blazer, Dan G. (Dan German)

    2004-01-01

    .... In particular there has been growing concern about an increase in the number of middle-aged and older men using testosterone and the lack of scientific data on the effect it may have on aging males...

  4. Use of parenteral testosterone in hypospadias cases

    OpenAIRE

    Vikram Satav; Vilas P Sabale; Sharad P Kankalia; Bhupender Kadyan; Abhirudra Mulay; Deepak Mane; Rohit Singh; Thakur Naveen

    2015-01-01

    Objectives: The aim was to evaluate the effect of parenteral testosterone on penile length, preputial hood, vascularity of dartos pedicle in patients with hypospadias. Materials and Methods: A total of 42 patients with hypospadias were included in this study. Injection aquaviron (oily solution each ml containing testosterone propionate 25 mg) was given deep intramuscularly in three doses with an interval of 3 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Preoperative...

  5. Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat.

    Science.gov (United States)

    Frederiksen, L; Glintborg, D; Højlund, K; Hougaard, D M; Brixen, K; Rasmussen, L M; Andersen, M

    2013-04-01

    The cardiovascular effects of testosterone treatment are debated. Osteoprotegerin (OPG) is an independent marker of cardiovascular risk. We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, placebo-controlled study of 6 months testosterone therapy (gel) in 38 men aged 60-78 years with bioavailable testosterone 94 cm was performed. Clinical evaluation, OPG, and C-reactive protein (CRP) measurements were carried out. Lean body mass (LBM), total fat mass, and bone mineral density (BMD) were established by dual X-ray absorptiometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by magnetic resonance imaging. Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM (Δ LBM positive), n=14. Data are presented as median (interquartile range). Testosterone therapy decreased total fat mass and SAT, whereas VAT was unchanged (n=38). OPG levels decreased during testosterone therapy (from 2.0 (1.9-2.5) to 1.9 (1.6-2.2) ng/ml, ptestosterone therapy (n=14), ΔOPG levels were inversely associated with ΔSAT (r= - 0.60, p=0.03) and positively associated with ΔVAT (r=0.56, p=0.04). OPG levels decreased during testosterone therapy suggesting decreased cardiovascular risk. Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution. © Georg Thieme Verlag KG Stuttgart · New York.

  6. A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.

    Science.gov (United States)

    Wheeler, Karen M; Smith, Ryan P; Kumar, Raj A; Setia, Shaan; Costabile, Raymond A; Kavoussi, Parviz K

    2017-04-01

    We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Methylphenidate treatment causes oxidative stress and alters energetic metabolism in an animal model of attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Comim, Clarissa M; Gomes, Karin M; Réus, Gislaine Z; Petronilho, Fabrícia; Ferreira, Gabriela K; Streck, Emílio L; Dal-Pizzol, Felipe; Quevedo, João

    2014-04-01

    To evaluate oxidative damage through the thiobarbituric acid-reactive species (TBARS) and protein carbonyl groups; antioxidant enzymatic system - superoxide dismutase (SOD) and catalase (CAT); and energetic metabolism in the brain of spontaneously hypertensive adult rats (SHR) after both acute and chronic treatment with methylphenidate hydrochloride (MPH). Adult (60 days old) SHRs were treated during 28 days (chronic treatment), or 1 day (acute treatment). The rats received one i.p. injection per day of either saline or MPH (2 mg/kg). Two hours after the last injection, oxidative damage parameters and energetic metabolism in the cerebellum, prefrontal cortex, hippocampus, striatum and cortex were evaluated. We observed that both acute and/or chronic treatment increased TBARS and carbonyl groups, and decreased SOD and CAT activities in many of the brain structures evaluated. Regarding the energetic metabolism evaluation, the acute and chronic treatment altered the energetic metabolism in many of the brain structures evaluated. We observed that both acute and chronic use of methylphenidate hydrochloride (MPH) in adult spontaneously hypertensive rats (SHRs) was associated with increased oxidative stress and energetic metabolism alterations. These data also reinforce the importance of the SHR animal model in further studies regarding MPH.

  8. Circatrigintan cycle of testosterone in human male

    International Nuclear Information System (INIS)

    Celec, P.; Kudela, M.; Bursky, P.; Ostatnikova, D.; Zdenek PUTZ, Z.

    2002-01-01

    In recent years the influence of testosterone on physical and mental well-being has become a focus of research attention. Testosterone is no more considered the m ale hormone . It was proved to influence woman's behaviour and mental functioning as well as that of a man. Cyclic changes throughout the menstrual cycle in women are known. To search for the infradian variations of human male testosterone levels in a follow up study, which was held in autumn 1999 (one month of continuous sampling) and in autumn 2000 (two and a half months of continuous sampling). Testosterone was determined in saliva, which contains biologically active fraction, unbound to proteins. In autumn 2000 sampling of 31 males (mean age 21.3 ± 1.3) collected saliva in the morning 30 minutes after waking-up every second day during one month and every third day during the following 6 weeks. Saliva was deeply frozen and analyzed by radioimmunoassay. Data of our preliminary study (based on samples collected in 1999) indicated circatrigintan variations of male salivary testosterone. By the use of two different methods (zones of minimum-moving averages and analysis of variance) circatrigintan and circavigintan cycles of salivary testosterone were found in the collected data of our subjects. The article considerates clinical applications of variation of hormonal levels. (authors)

  9. Effects of transdermal testosterone or oral dydrogesterone on hypoactive sexual desire disorder in transsexual women: results of a pilot study.

    Science.gov (United States)

    Kronawitter, Desiree; Gooren, Louis J; Zollver, Hendryk; Oppelt, Patricia G; Beckmann, Matthias W; Dittrich, Ralf; Mueller, Andreas

    2009-08-01

    It has been reported that hypoactive sexual desire disorder (HSDD) affects one-third of transsexual women (defined as postoperative male-to-female transsexuals) receiving estrogen replacement whose bioavailable androgen levels are lower than in ovulating women and comparable with those in surgically postmenopausal women. The aim of this study was to evaluate the efficacy of transdermal testosterone treatment and of oral dydrogesterone in transsexual women with HSDD receiving estrogens. Seven transsexual women with HSDD were treated with a testosterone patch and nine transsexual women with HSDD were treated with oral dydrogesterone over 24 weeks. The primary end point was the change in the brief profile of female sexual function (B-PFSF) score. Secondary end points were changes in hormonal parameters and side effect assessments. A significant increase in total testosterone and free testosterone levels was observed in the group receiving transdermal testosterone. At 24 weeks, there was a significant improvement in the B-PFSF score showing an improvement in sexual desire among transsexual women treated with the testosterone patch, whereas no change in the B-PFSF score was observed in transsexual women treated with oral dydrogesterone. No side effects were reported. In this pilot study, sexual desire in transsexual women improved significantly after treatment with the testosterone patch, without noticeable side effects.

  10. UGT2B17 genotype and the pharmacokinetic serum profile of testosterone during substitution therapy with testosterone undecanoate. A retrospective experience from 207 men with hypogonadism

    DEFF Research Database (Denmark)

    Bang, Anne Kirstine; Jørgensen, Niels; Rajpert-De Meyts, Ewa

    2013-01-01

    analyzed for the levels of T, luteinizing hormone (LH), sex-hormone-binding globulin, estradiol, prostate specific antigen, hematocrit, hemoglobin, and total cholesterol. Results: The UGT2B17 genotype frequency was: ins/ins: 42%, ins/del: 44%, and del/del: 14%. During the initial 18 weeks of TU treatment......Background: Testosterone (T) is mainly excreted in the urine as testosterone glucuronide (TG). This glucuronidation is partly dependent on the UGT2B17 genotype, and TG excretion is therefore lower in men having the UGT2B17 deletion. However, the possible influence of UGT2B17 genotype on serum T...... during androgen therapy is unknown. We retrospectively investigated the possible association between the UGT2B17 gene polymorphism and serum T levels in hypogonadal men during Testosterone undecanoate (TU) substitution therapy. Subjects and Methods: Two hundred and seven patients treated with TU (Nebido...

  11. [Patient with testosterone deficit syndrome and dyslipemia].

    Science.gov (United States)

    Sola Galarza, Ignacio; López López, Borja; Llorente Abarca, Carlos

    2013-09-01

    erectile dysfunction due to endothelial dysfunction, but also it generally appears years before the cardiovascular event. On the other hand, and in relation to the hypogonadotropic hypogonadism of patients with MS, we urologists may contributein greatly to the detection of patients with MS whose only symptom is erectile dysfunction or diminished libido, but specially we may play a key role in the improvement of these patients, since it is known that testosterone replacement therapy has a major potential to diminish or stop the progression of MS or its cardiovascular effects. Testosterone treatment not only improves the lipid profile, hypertension, insulin resistance, or reduces the abdominal circumference, but also it may help to get a better adherence to diet and exercise, so contributing to change unhealthy lifestyle habits whch are the origin of the problem.

  12. Low serum testosterone predicts upgrading and upstaging of prostate cancer after radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2016-01-01

    Full Text Available Often, pathological Gleason Score (GS and stage of prostate cancer (PCa were inconsistent with biopsy GS and clinical stage. However, there were no widely accepted methods predicting upgrading and upstaging PCa. In our study, we investigated the association between serum testosterone and upgrading or upstaging of PCa after radical prostatectomy (RP. We enrolled 167 patients with PCa with biopsy GS ≤6, clinical stage ≤T2c, and prostate-specific antigen (PSA <10 ng ml−1 from April 2009 to April 2015. Data including age, body mass index, preoperative PSA level, comorbidity, clinical presentation, and preoperative serum total testosterone level were collected. Upgrading occurred in 62 (37.1% patients, and upstaging occurred in 73 (43.7% patients. Preoperative testosterone was lower in the upgrading than nonupgrading group (3.72 vs 4.56, P< 0.01. Patients in the upstaging group had lower preoperative testosterone than those in the nonupstaging group (3.84 vs 4.57, P= 0.01. In multivariate logistic regression analysis, as both continuous and categorical variables, low serum testosterone was confirmed to be an independent predictor of pathological upgrading (P = 0.01 and P= 0.01 and upstaging (P = 0.01 and P = 0.02 after RP. We suggest that low serum testosterone (<3 ng ml−1 is associated with a high rate of upgrading and upstaging after RP. It is better for surgeons to ensure close monitoring of PSA levels and imaging examination when selecting non-RP treatment, to be cautious in proceeding with nerve-sparing surgery, and to be enthusiastic in performing extended lymph node dissection when selecting RP treatment for patients with low serum testosterone.

  13. Endogenous testosterone and mortality risk

    Directory of Open Access Journals (Sweden)

    Emily J Meyer

    2018-01-01

    Full Text Available In men, obesity and metabolic complications are associated with lower serum testosterone (T and dihydrotestosterone (DHT and an increased risk of, and mortality from, multiple chronic diseases in addition to cardiovascular disease (CVD. The causal interrelationships between these factors remain a matter of debate. In men with untreated congenital and lifelong forms of hypogonadotropic hypogonadism, there appears to be no increased risk. Men with Klinefelter's syndrome have an increased risk of various types of cancers, as well as CVD, which persist despite T therapy. In the absence of pathology of the hypothalamic–pituitary–gonadal axis, the effect of modest reductions in serum T in aging men is unclear. The prevalence of low serum T concentrations is high in men with cancer, renal disease, and respiratory disease and is likely to be an indicator of severity of systemic disease, not hypogonadism. Some population-based studies have found low serum T to be associated with a higher risk of deaths attributed to cancer, renal disease, and respiratory disease, while others have not. Although a meta-analysis of longitudinal studies has shown an association between low serum T and all-cause mortality, marked heterogeneity between studies limited a firm conclusion. Therefore, while a decrease in T particularly occurring later in life may be associated with an increase in all-cause and specific types of mortality in men, the differential effects, if any, of T and other sex steroids as compared to health and lifestyle factors are unknown at the current time.

  14. Transcriptomic analysis of hepatic responses to testosterone deficiency in miniature pigs fed a high-cholesterol diet.

    Science.gov (United States)

    Cai, Zhaowei; Jiang, Xiaoling; Pan, Yongming; Chen, Liang; Zhang, Lifan; Zhu, Keyan; Cai, Yueqin; Ling, Yun; Chen, Fangming; Xu, Xiaoping; Chen, Minli

    2015-02-06

    Recent studies have indicated that low serum testosterone levels are associated with increased risk of developing hepatic steatosis; however, the mechanisms mediating this phenomenon have not been fully elucidated. To gain insight into the role of testosterone in modulating hepatic steatosis, we investigated the effects of testosterone on the development of hepatic steatosis in pigs fed a high-fat and high-cholesterol (HFC) diet and profiled hepatic gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT). Serum testosterone levels were significantly decreased in CM pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. CM pigs showed increased liver injury accompanied by increased hepatocellular steatosis, inflammation, and elevated serum alanine aminotransferase levels compared with IM pigs. Moreover, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were markedly increased in CM pigs. Testosterone replacement decreased serum and hepatic lipid levels and improved liver injury in CM pigs. Compared to IM and CMT pigs, CM pigs had lower serum levels of superoxide dismutase but higher levels of malondialdehyde. Gene expression analysis revealed that upregulated genes in the livers of CM pigs were mainly enriched for genes mediating immune and inflammatory responses, oxidative stress, and apoptosis. Surprisingly, the downregulated genes mainly included those that regulate metabolism-related processes, including fatty acid oxidation, steroid biosynthesis, cholesterol and bile acid metabolism, and glucose metabolism. KEGG analysis showed that metabolic pathways, fatty acid degradation, pyruvate metabolism, the tricarboxylic acid cycle, and the nuclear factor-kappaB signaling pathway were the major pathways altered in CM pigs. This study demonstrated that testosterone deficiency aggravated

  15. Changes in blood testosterone concentrations after surgical and chemical sterilization of male free-roaming dogs in southern Chile.

    Science.gov (United States)

    Vanderstichel, R; Forzán, M J; Pérez, G E; Serpell, J A; Garde, E

    2015-04-01

    There is a growing interest in chemical sterilization as an alternative to surgical castration in large-scale sterilization campaigns to control canine populations. An important step toward understanding the short-term and long-term effects of chemical sterilants is to determine their impact on blood testosterone concentrations, particularly as these could influence dog behavior after treatment. A field trial was conducted with 118 free-roaming male dogs in the Chilean Patagonia, where 36 dogs were chemically sterilized using EsterilSol, 39 dogs were surgically castrated, and 43 dogs remained intact as controls. Blood testosterone levels were determined at four time periods: on enrollment 6 months before treatment (t-6m), at the time of treatment (t0, within one hour after surgical castration or chemical sterilization and during a concurrent 2-week period for the control group), four (t+4m), and six (t+6m) months after treatment. Intrinsic and temporal factors were evaluated; age was significantly associated with testosterone, where dogs 2- to 4-year-old had the highest testosterone concentrations (P = 0.036), whereas body weight and body condition scores were not associated with testosterone; testosterone concentration was not influenced by time of day, month, or season. After treatment (t+4m and t+6m), all of the surgically castrated dogs had testosterone concentrations below 1.0 ng/mL. On the basis of this cut point (sterilized dogs at both t+4m and t+6m; it remained low for 22% of dogs at both t+4m and t+6m; it was unchanged at t+4m but low at t+6m in 9% of dogs; and, it was low at t+4m but reverted back to unchanged at t+6m in one dog (3%). Incidentally, testosterone in chemically sterilized dogs increased dramatically within 1 hour of treatment (t0), more than doubling (131%) the concentration of control dogs at the time of treatment (t0), likely because of severe necrosis of interstitial cells. The use of EsterilSol as a method of sterilizing dogs had a

  16. The role of testosterone in sexuality and paraphilia--a neurobiological approach. Part II: testosterone and paraphilia.

    Science.gov (United States)

    Jordan, Kirsten; Fromberger, Peter; Stolpmann, Georg; Müller, Jürgen Leo

    2011-11-01

    Antiandrogen therapy has been used for 30 years to treat paraphilic patients and sexual offenders. Yet the therapeutic success of antiandrogens is uncertain. Furthermore, there is still a lack of comprehensive knowledge about the effects of androgen-lowering therapy in paraphilic patients. We discuss endocrinological, neurobiological, and therapeutic aspects of paraphilia with the aim of integrating these on the basis of the current neurobiological and clinical knowledge on testosterone that was set out in Part I of this review. Our review of the human literature comprises the current knowledge about the neurobiology of paraphilia and the known endocrinological, pathophysiological, and genetic aspects of this disorder. The role of testosterone is discussed. A survey of antiandrogen therapy and its outcome in paraphilic patients and sex offenders is provided. Although not all data are consistent, current imaging research suggests that structural and functional changes in pedophilia appear for the most part in brain regions also involved in sexual functions. Not exclusively testosterone but also some other endocrinological and neurochemical parameters could be disturbed in pedophilic patients and child molesters; these include changes in hypothalamic-pituitary function, prolactin levels, and dopaminergic or serotonergic functions. There appears to be a sex-steroid-related genetic influence on antisocial traits, externalizing behavior, and sexual behavior. Most of the studies in which antiandrogen therapy in paraphilic patients and sex offenders have been examined were case reports, or observational or open-label studies, and many did not include adequate control groups. Only a few placebo-controlled double-blind studies have been published with inconsistent results concerning treatment effects. Outcome measures differ between the studies and do not seem ideally suited to their purpose. On the basis of the current knowledge about testosterone and its effects on brain

  17. Testosterone and growth hormone normalization: a retrospective study of health outcomes

    Directory of Open Access Journals (Sweden)

    Enrique Ginzburg

    2008-09-01

    Full Text Available Enrique Ginzburg1, Alvin Lin2, Michael Sigler1, Denise Olsen2, Nancy Klimas1, Alan Mintz21University of Miami Miller School of Medicine, Miami, Florida, USA; 2Cenegenics® Medical Institute, Las Vegas, Nevada, USABackground: Age-related declines in testosterone and growth hormone (GH are associated with increased adiposity and decreases in lean mass and bone mineral density (BMD. A long-term retrospective study examined the effects of testosterone and/or GH supplementation on body composition and quality of life (QoL.Methods: A database survey assessed the records of 91 men and 97 women (ages 25–82 in treatment groups based on their hormonal status: dehydroepiandrosterone but no hormonal supplementation (control; testosterone only (Tes; GH only (GH; and testosterone plus GH (Tes+GH. Pre- and post-treatment assessments recorded changes in fat and lean mass, BMD, and QoL.Results: After an average of 3 years of treatment, weight decreased in women in the control and Tes+GH groups but remained stable in men in all groups. Tes and Tes+GH produced statistically significant increases in lean mass, reductions in fat mass, and improvements in BMD in both sexes; GH produced similar changes in women. QoL and mood improved in all groups. Treatments were generally safe and well tolerated.Conclusions: In this retrospective survey, treatment with testosterone and/or GH was associated with favorable effects in men and women across a wide age range.Keywords: testosterone, growth hormone, body composition, quality of life

  18. Prenatal testosterone exposure induces hypertension in adult females via androgen receptor-dependent protein kinase Cδ-mediated mechanism.

    Science.gov (United States)

    Blesson, Chellakkan S; Chinnathambi, Vijayakumar; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

    2015-03-01

    Prenatal exposure to excess testosterone induces hyperandrogenism in adult females and predisposes them to hypertension. We tested whether androgens induce hypertension through transcriptional regulation and signaling of protein kinase C (PKC) in the mesenteric arteries. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate (0.5 mg/kg per day from gestation days 15 to 19, SC) and their 6-month-old adult female offspring were examined. Plasma testosterone levels (0.84±0.04 versus 0.42±0.09 ng/mL) and blood pressures (111.6±1.3 versus 104.5±2.4 mm Hg) were significantly higher in prenatal testosterone-exposed rats compared with controls. This was accompanied with enhanced expression of PKCδ mRNA (1.5-fold) and protein (1.7-fold) in the mesenteric arteries of prenatal testosterone-exposed rats. In addition, mesenteric artery contractile responses to PKC activator, phorbol-12,13-dibutyrate, was significantly greater in prenatal testosterone-exposed rats. Treatment with androgen receptor antagonist flutamide (10 mg/kg, SC, BID for 10 days) significantly attenuated hypertension, PKCδ expression, and the exaggerated vasoconstriction in prenatal testosterone-exposed rats. In vitro exposure of testosterone to cultured mesenteric artery smooth muscle cells dose dependently upregulated PKCδ expression. Analysis of PKCδ gene revealed a putative androgen responsive element in the promoter upstream to the transcription start site and an enhancer element in intron-1. Chromatin immunoprecipitation assays showed that androgen receptors bind to these elements in response to testosterone stimulation. Furthermore, luciferase reporter assays showed that the enhancer element is highly responsive to androgens and treatment with flutamide reverses reporter activity. Our studies identified a novel androgen-mediated mechanism for the control of PKCδ expression via transcriptional regulation that controls vasoconstriction and blood pressure. © 2014

  19. Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry.

    Science.gov (United States)

    Morales, Alvaro

    2011-05-01

    To assess the evidence for the concept that the androgen receptor of prostate cancer (PCa) cells becomes saturated when testosterone values exceed castrate levels, so that testosterone administration in hypogonadal men with untreated PCa does not stimulate tumour growth. To propose basic criteria for administration of testosterone to untreated patients with PCa and, as this is a rare clinical situation, to encourage the establishment of an international registry for these patients. Men with a diagnosis of PCa and symptomatic testosterone deficiency received testosterone therapy (TTh). Patients were assessed quarterly. Prostate-specific antigen (PSA) velocity was used as the criterion to discontinue therapy and a return to nadir PSA levels allowed re-initiation of testosterone supplementation. The responses to testosterone supplementation were varied according to each individual and were unpredictable. While some men showed little change after years of treatment, others exhibited a rapid and significant increase in PSA levels. In others, the use of intermittent therapy resulted in synchronous changes in PSA levels. Interruption of TTh invariably translated into a decrease in PSA to pre-therapy levels. Available evidence regarding the effect of testosterone administration to hypogonadal men with untreated PCa is too limited to be considered reliable. In addition, the response to this treatment appears to be varied and unpredictable. Hypogonadism associated with untreated PCa is not common, therefore, we propose the establishment of an international registry as the quickest way to establish the basic parameters for consideration of TTh in this situation and recommendations for follow-up. Until credible evidence becomes available, the current restrictions regarding the administration of testosterone to men with PCa should remain in place. © 2011 THE AUTHOR. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  20. Radioimmunoassay of total testosterone in urine of men

    International Nuclear Information System (INIS)

    Bilek, R.; Chundela, B.; Hampl, R.; Starka, L.

    1985-01-01

    The results are described and evaluated of the radioimmunoas radioimmunoassay of total testosterone in the urine in a sample of five men of the ages between 18 and 21 years. The levels of testosterone were related to creatinine in the urine in order to eliminate the effect of urine dilution. The analysis of the results showed that there exists a statistical difference between the levels of total testosterone related to creatinine in dependence on the time of sampling. The average value with standard deviation of total testosterone was 109 +- 41 ng testosterone/1 ml urine, 24.07 +- 8.33 pmol testosterone/1 μmol creatinine. (author)

  1. Treatment of Paroxysmal Perceptual Alteration in Catatonic Schizophrenia by Switching to Aripiprazole from Risperidone: A Case Report.

    Science.gov (United States)

    Yamashita, Satoko; Miyaoka, Tsuyoshi; Nagahama, Michiharu; Ieda, Masa; Tsuchie, Keiko; Wake, Rei; Horiguchi, Jun

    2016-01-01

    Paroxysmal perceptual alteration (PPA) is the occurrence of brief and recurrent episodes of perceptual changes. It is mainly caused by the treatment of schizophrenia patients with antipsychotics. However, diagnosis of PPA is not very prevalent among psychiatrists, partly due to underrecognition or misunderstanding that it is a worsening of psychiatric symptoms. If psychiatrists do not understand PPA, they cannot treat it appropriately, and the patient's quality of life is impaired. We present a case of PPA in catatonic schizophrenia that was successfully treated by switching to aripiprazole from risperidone. We suggest that the disappearance of PPA in our case was due to both discontinuing risperidone, which completely blocks D2 receptors, and replacing it with aripiprazole, which is characterized as a partial agonist of D2 receptors. Treatment of PPA will improve medication adherence and quality of life. It is important to recognize PPA as a possible side effect of treatment with antipsychotics.

  2. Very Late Treatment-Related Alterations in Brain Function of Breast Cancer Survivors

    NARCIS (Netherlands)

    Stouten-Kemperman, Myrle M.; de Ruiter, Michiel B.; Boogerd, Willem; Veltman, Dick J.; Reneman, Liesbeth; Schagen, Sanne B.

    2015-01-01

    Although adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on cognition and brain function, studies on adverse effects of specific treatment regimens are scarce. Here, neurotoxicity profiles after different treatment strategies were compared in BC survivors

  3. Cardiac alterations in human African trypanosomiasis (T.b. gambiense with respect to the disease stage and antiparasitic treatment.

    Directory of Open Access Journals (Sweden)

    Johannes A Blum

    Full Text Available In Human African Trypanosomiasis, neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The aims of the study were to assess the frequency and characteristics of electrocardiographic findings in the first stage of HAT, to compare these findings to those of second stage patients and healthy controls and to assess any potential effects of different therapeutic antiparasitic compounds with respect to ECG changes after treatment.Four hundred and six patients with first stage HAT were recruited in the Democratic Republic of Congo, Angola and Sudan between 2002 and 2007 in a series of clinical trials comparing the efficacy and safety of the experimental treatment DB289 to the standard first stage treatment, pentamidine. These ECGs were compared to the ECGs of healthy volunteers (n = 61 and to those of second stage HAT patients (n = 56.In first and second stage HAT, a prolonged QTc interval, repolarization changes and low voltage were significantly more frequent than in healthy controls. Treatment in first stage was associated with repolarization changes in both the DB289 and the pentamidine group to a similar extent. The QTc interval did not change during treatment.Cardiac involvement in HAT, as demonstrated by ECG alterations, appears early in the evolution of the disease. The prolongation of the QTC interval comprises a risk of fatal arrhythmias if new drugs with an additional potential of QTC prolongation will be used. During treatment ECG abnormalities such as repolarization changes consistent with peri-myocarditis occur frequently and appear to be associated with the disease stage, but not with a specific drug.

  4. Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

    Science.gov (United States)

    Akar, Melek; Yildirim, Tulin G; Sandal, Gonca; Bozdag, Senol; Erdeve, Omer; Altug, Nahide; Uras, Nurdan; Oguz, Serife S; Dilmen, Ugur

    2017-04-01

    Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

  5. Testosterone levels and clinical features of schizophrenia with emphasis on negative symptoms and aggression.

    Science.gov (United States)

    Sisek-Šprem, Mirna; Križaj, Aida; Jukić, Vlado; Milošević, Milan; Petrović, Zrinka; Herceg, Miroslav

    2015-02-01

    Aggressive behavior and negative symptoms are two features of schizophrenia that may have a hormonal basis. The aim of this study was to compare testosterone level with clinical features of schizophrenia, focusing on negative symptoms and aggressive behavior. The study population consisted of 120 male schizophrenic patients (ages 18-40) classified into non-aggressive (n = 60) and aggressive (n = 60) groups. Depending on the type of aggression that was manifested prior to admission, the aggressive group was divided into violent (n = 32) and suicidal (n = 28) subgroups. Psychopathological severity, violence and suicidality were assessed using the Positive and Negative Syndrome Scale (PANSS), Overt Aggression Scale and Columbia Suicide Severity Rating Scale, respectively. Total serum testosterone level was determined on the same morning that symptoms were assessed. In the non-aggressive group, testosterone level was negatively correlated with the score on the negative subscale of PANSS (P = 0.04) and depression (P = 0.013), and positively correlated with excitement (P = 0.027), hostility (P = 0.02) and impulsive behavior (P = 0.008). In the aggressive group, testosterone level had non-significant correlation with these parameters, and with violent or suicidal behavior. The results confirmed that non-aggressive male schizophrenic patients with lower levels of testosterone had a greater severity of negative symptoms. In aggressive patients, there was no correlation between testosterone and clinical features of the disorder or the degree or type of aggression. These findings indicate that therapeutic strategies targeting testosterone could be useful in the treatment of negative symptoms of schizophrenia.

  6. Testosterone delivered with a scaffold is as effective as bone morphologic protein-2 in promoting the repair of critical-size segmental defect of femoral bone in mice.

    Directory of Open Access Journals (Sweden)

    Bi-Hua Cheng

    Full Text Available Loss of large bone segments due to fracture resulting from trauma or tumor removal is a common clinical problem. The goal of this study was to evaluate the use of scaffolds containing testosterone, bone morphogenetic protein-2 (BMP-2, or a combination of both for treatment of critical-size segmental bone defects in mice. A 2.5-mm wide osteotomy was created on the left femur of wildtype and androgen receptor knockout (ARKO mice. Testosterone, BMP-2, or both were delivered locally using a scaffold that bridged the fracture. Results of X-ray imaging showed that in both wildtype and ARKO mice, BMP-2 treatment induced callus formation within 14 days after initiation of the treatment. Testosterone treatment also induced callus formation within 14 days in wildtype but not in ARKO mice. Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing. These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy. Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.

  7. Genetic Determinants of Serum Testosterone Concentrations in Men

    Science.gov (United States)

    Maggio, Marcello; Coviello, Andrea D.; Ferrucci, Luigi; Heier, Margit; Hofman, Albert; Holliday, Kate L.; Jansson, John-Olov; Kähönen, Mika; Karasik, David; Karlsson, Magnus K.; Kiel, Douglas P.; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Mattias; Lyytikäinen, Leo-Pekka; Meitinger, Thomas; Mellström, Dan; Melzer, David; Miljkovic, Iva; Nauck, Matthias; Nilsson, Maria; Penninx, Brenda; Pye, Stephen R.; Vasan, Ramachandran S.; Reincke, Martin; Rivadeneira, Fernando; Tajar, Abdelouahid; Teumer, Alexander; Uitterlinden, André G.; Ulloor, Jagadish; Viikari, Jorma; Völker, Uwe; Völzke, Henry; Wichmann, H. Erich; Wu, Tsung-Sheng; Zhuang, Wei Vivian; Ziv, Elad; Wu, Frederick C. W.; Raitakari, Olli; Eriksson, Anna; Bidlingmaier, Martin; Harris, Tamara B.; Murray, Anna; de Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender; Vandenput, Liesbeth; Haring, Robin

    2011-01-01

    Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (ptestosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. PMID:21998597

  8. Racial differences in hypogonadal improvement and prostate-specific antigen levels in hypogonadal men treated with testosterone replacement therapy

    OpenAIRE

    Coward, Robert M.; Simhan, Jay; Carson III, Culley C.

    2010-01-01

    PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy (TRT) and assess racial differences in hypogonadal improvement and prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: In a retrospective analysis, 75 hypogonadal men were followed for an average 34 months after initiating TRT. Total testosterone and PSA levels were assessed every 6 months, and patients diagnosed with prostatitis or prostate cancer during treatment were excluded. RESULTS: For 16 African...

  9. Mesolimbic dopamine function is not altered during continuous chronic treatment of rats with typical or atypical neuroleptic drugs

    International Nuclear Information System (INIS)

    Rupniak, N.M.J.; Hall, M.D.; Kelly, E.; Fleminger, S.; Kilpatrick, G.; Jenner, P.; Marsden, C.D.

    1985-01-01

    Rats were treated continuously for up to 20 months with either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day) or clozapine (24-27 mg/kg/day). Bsub(max) for specific mesolimbic binding of 3 H-spiperone, 3 H-N, n-propylnorapomorphine or 3 H-piflutixol did not differ in tissue taken from animals treated for up to 12 months with haloperidol, sulpiride or clozapine by comparison to age-matched control rats. Mesolimbic dopamine (50 μM)-stimulated adenylate cyclase activity was not altered in any drug treatment group. Spontaneous locomotor activity was transiently decreased during treatment with haloperidol for 1 or 3 months, but not by chronic sulpiride or clozapine treatment. Locomotor activity was not consistently increased in any drug treatment group. After 20 months of continuous drug treatment, focal bilateral application of dopamine (12.5 or 25 μg) into the nucleus accumbens caused equivalent increases in locomotor activity in control rats and in animals receiving haloperidol, sulpiride of clozapine. These findings suggest that dopamine receptor blockade is not maintained in the mesolimbic area following chronic treatment with haloperidol, sulpiride or clozapine, and indicate that, under these conditions, clozapine and sulpiride may not act selectively on mesolimbic dopamine receptors. (Author)

  10. Exercise training improves free testosterone in lifelong sedentary aging men

    Directory of Open Access Journals (Sweden)

    Lawrence D Hayes

    2017-07-01

    Full Text Available As the impact of high-intensity interval training (HIIT on systemic hormones in aging men is unstudied to date, we investigated whether total testosterone (TT, sex hormone-binding globulin (SHBG, free testosterone (free-T and cortisol (all in serum were altered following HIIT in a cohort of 22 lifelong sedentary (62 ± 2 years older men. As HIIT requires preconditioning exercise in sedentary cohorts, participants were tested at three phases, each separated by six-week training; baseline (phase A, following conditioning exercise (phase B and post-HIIT (phase C. Each measurement phase used identical methods. TT was significantly increased following HIIT (~17%; P < 0.001 with most increase occurring during preconditioning (~10%; P = 0.007. Free-T was unaffected by conditioning exercise (P = 0.102 but was significantly higher following HIIT compared to baseline (~4.5%; P = 0.023. Cortisol remained unchanged from A to C (P = 0.138. The present data indicate a combination of preconditioning, and HIIT increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting for a small but statistically significant increase in free-T. Further study is required to determine the biological importance of small improvements in free-T in aging men.

  11. Exercise training improves free testosterone in lifelong sedentary aging men.

    Science.gov (United States)

    Hayes, Lawrence D; Herbert, Peter; Sculthorpe, Nicholas F; Grace, Fergal M

    2017-07-01

    As the impact of high-intensity interval training (HIIT) on systemic hormones in aging men is unstudied to date, we investigated whether total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (free-T) and cortisol (all in serum) were altered following HIIT in a cohort of 22 lifelong sedentary (62 ± 2 years) older men. As HIIT requires preconditioning exercise in sedentary cohorts, participants were tested at three phases, each separated by six-week training; baseline (phase A), following conditioning exercise (phase B) and post-HIIT (phase C). Each measurement phase used identical methods. TT was significantly increased following HIIT (~17%; P  HIIT compared to baseline (~4.5%; P  = 0.023). Cortisol remained unchanged from A to C ( P  = 0.138). The present data indicate a combination of preconditioning, and HIIT increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting for a small but statistically significant increase in free-T. Further study is required to determine the biological importance of small improvements in free-T in aging men. © 2017 The authors.

  12. Phosphorus availability from the solid fraction of pig slurry is altered by composting or thermal treatment

    DEFF Research Database (Denmark)

    Christel, Wibke; Bruun, Sander; Magid, Jakob

    2014-01-01

    The alteration of easily available phosphorus (P) from the separated solid fraction of pig slurry by composting and thermal processing (pyrolysis or combustion at 300-1000. °C) was investigated by water and acidic extractions and the diffusive gradients in thin films (DGT) technique. Temporal...... changes in P availability were monitored by repeated DGT application in three amended temperate soils over 16. weeks. P availability was found to decrease in the order: drying. >. composting. >. pyrolysis. >. combustion with increasing degree of processing. Water extractions suggested that no P would...... be available after pyrolysis above 700. °C or combustion above 400. °C, respectively, but during soil incubation, even char and ash, processed at 800. °C, increased P availability. Low-temperature pyrolysis vs. combustion was found to favor P availability as did application to acidic vs. neutral soil...

  13. Alteration of myocardial metaiodobenzylguanidine uptake after treatment of phaeochromocytoma and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Suga, Kazuyoshi; Ogasawara, Nobuhiko; Ariga, Misako; Motoyama, Kazumi; Hara, Akiko; Kume, Norihiko; Matsunaga, Naofumi [Department of Radiology, Yamaguchi University School of Medicine, Ube, Yamaguchi (Japan)

    2000-05-01

    The relationships between changes in myocardial uptake of metaiodobenzylguanidine (MIBG) and those in circulating catecholamines and cardiac function after treatment of phaeochromocytoma and neuroblastoma were evaluated. Iodine-123 or iodine-131 MIBG scintigraphy was performed before and after surgical resection and/or chemotherapy for primary tumours in nine patients with phaeochromocytoma and 13 patients with neuroblastoma. Changes in myocardial MIBG uptake after treatment were estimated by the heart-to-upper mediastinum (H/M) uptake ratios on the images obtained 24 h after MIBG injection, which were compared with serum levels of noradrenaline (NA) and adrenaline (A). Cardiac function was assessed by echocardiography, with measurements of the left ventricular ejection fraction (LVEF). Before treatment, eight patients with phaeochromocytoma and three with neuroblastoma showed poor myocardial MIBG uptake, with highly elevated circulating NA and A. Echocardiography, however, did not show cardiac dysfunction in these patients with the exception of two patients with phaeochromocytoma. With normalization of NA and A levels after treatment, all of these patients except for the two with persistent cardiac dysfunction showed restoration of myocardial MIBG uptake. The H/M ratios increased significantly after treatment in both patient groups, i.e. with phaeochromocytoma and with neuroblastoma (P<0.0001 and P<0.05, respectively), and these ratios correlated inversely with circulating NA and A before and after treatment. By contrast, there was no significant correlation between H/M ratios and LVEF in these two groups. These results indicate that suppression of myocardial MIBG uptake usually may not be related to cardiac dysfunction and may be reversible following normalization of excess catecholamine levels after treatment in patients with neuroadrenergic tumours. However, the suppression may persist in the presence of catecholamine-induced cardiac dysfunction. The assessment

  14. Testosterone replacement therapy among elderly males: the Testim Registry in the US (TRiUS

    Directory of Open Access Journals (Sweden)

    Bhattacharya RK

    2012-08-01

    Full Text Available Rajib K Bhattacharya,1 Mohit Khera,2 Gary Blick,3 Harvey Kushner,4 Martin M Miner51Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA; 3Circle Medical LLC, Norwalk, CT, USA; 4Biometrics, Auxilium Pharmaceuticals, Malvern, PA, USA; 5Men's Health Center, Miriam Hospital, Providence, RI, USABackground: Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism. However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years men.Objective: To compare data at baseline and after 12 months of testosterone replacement therapy (TRT in hypogonadal men ≥65 vs <65 years old. Data for participants 65–74 vs ≥75 years old were also compared.Methods: Data were from TRiUS (Testim Registry in the United States, which enrolled 849 hypogonadal men treated with Testim® 1% (50–100 mg testosterone gel/day for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT, free testosterone (FT, and prostate-specific antigen (PSA levels. Comparisons of parameters were made using Fisher's exact test or analysis of variance. Nonparametric Spearman's ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters.Results: Of the registry participants at baseline with available age information, 16% (133/845 were ≥65 years old. They were similar to men <65 years old in the duration of hypogonadism prior to enrollment (~1 year, TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng

  15. Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

    Science.gov (United States)

    Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

    2016-11-01

    Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled

  16. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

    Directory of Open Access Journals (Sweden)

    Lara Bull-Otterson

    Full Text Available Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD. Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

  17. Fathers' decline in testosterone and synchrony with partner testosterone during pregnancy predicts greater postpartum relationship investment.

    Science.gov (United States)

    Saxbe, Darby E; Edelstein, Robin S; Lyden, Hannah M; Wardecker, Britney M; Chopik, William J; Moors, Amy C

    2017-04-01

    The transition to parenthood has been associated with declines in testosterone among partnered fathers, which may reflect males' motivation to invest in the family. Moreover, preliminary evidence has found that couples show correlations in hormone levels across pregnancy that may also be linked to fathers' preparation for parenthood. The current study used repeated-measures sampling of testosterone across pregnancy to explore whether fathers' change in T, and correlations with mothers' T, were associated with fathers' and mothers' postpartum investment. In a sample of 27 couples (54 individuals) expecting their first child, both parents' salivary testosterone was measured multiple times across pregnancy. At approximately 3.5months postpartum, participants rated their investment, commitment, and satisfaction with their partner. A multilevel model was used to measure change in testosterone over time and associations between mother and father testosterone. Fathers who showed stronger declines in T across pregnancy, and stronger correlations with mothers' testosterone, reported higher postpartum investment, commitment, and satisfaction. Mothers reported more postpartum investment and satisfaction if fathers showed greater prenatal declines in T. These results held even after controlling for paternal investment, commitment, and satisfaction measured prenatally at study entry. Our results suggest that changes in paternal testosterone across pregnancy, and hormonal linkage with the pregnant partner, may underlie fathers' dedication to the partner relationship across the transition to parenthood. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Evaluation of testosterone metabolites/dehydroepiandrosterone as the indicators of testosterone administration in horse doping

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.Y.; Kim, S.J. [Korea Racing Association, Kyonggi (Korea); Kyong, J.B. [Hanyang University, Seoul (Korea); Choi, M.H.; Chung, B.C. [Korea Institute of Science and Technology, Seoul (Korea)

    1999-06-01

    The metabolism of testosterone (17{beta}-hydroxy-androst-4-en-3-one) was confirmed in horse after a single intramuscular administration of testosterone cypionate (750 mg). Solvent extracts of urine obtained with enzymatic hydrolysis and methanolysis were analyzed by GC/MS after oxime t-butyldimethylsilyl (oxime-TBDMS) derivatization. the structures of four urinary metabolite after testosterone administration in horse were determined based on EI mass spectra and 5{alpha}-androstane-3{beta}, 17{alpha}-diol and 5a-androstane-3{beta}-ol--17one as major was confirmed with authentic standard. Also the concentrations of 5{alpha}--androstane-3{beta}, 17{alpha}-diol, 5{alpha}-androstane-3{beta}, 17{beta}-diol, dehydroepiandrosterone (DHEA), 5{alpha}-androstane-3{beta}-ol-17-one and testosterone were determined in the urine of normal subjects and the urine after administration. The recovery and detection limit in the most drugs were 86.3{approx}94.7% and 1{approx}3 ppb, respectively. Correlation coefficients for calibration were in the range of 0.984{approx}0.999. Excretion profile of testosterone presents the rapid and large increasement up to maximum values as days 5 after administration and the slow regression. The relative ratios of testosterone, its metabolites over DHEA were determined for indication of testosterone administration in horse doping. 13 refs., 5 figs., 1 tab.

  19. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma.

    Directory of Open Access Journals (Sweden)

    Harry A Quigley

    Full Text Available To determine if oral losartan treatment decreases the retinal ganglion cell (RGC death caused by experimental intraocular pressure (IOP elevation in mice.We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry.Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13, while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001. The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01. Both losartan and enalapril significantly lowered blood pressure (p< 0.001, but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9. Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007. Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP.The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at

  20. Prednisone treatment alters the serum amylase and lipase activities in normal dogs without causing pancreatitis.

    OpenAIRE

    Fittschen, C; Bellamy, J E

    1984-01-01

    In order to test the hypothesis that treatment with glucocorticoids causes pancreatitis in dogs, 18 mongrel dogs were divided into three groups of six individuals, each group receiving prednisone at different doses orally or intramuscularly for two weeks. Two groups consisting of six dogs each served as controls. Treatment for two weeks with oral prednisone at 1.2 mg/kg body weight or at 4 mg/kg body weight daily decreased the serum amylase activities, but increased the serum lipase activitie...

  1. Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats.

    Science.gov (United States)

    Chin, Kok-Yong; Ima-Nirwana, Soelaiman

    2014-01-01

    Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model. Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined. There were significant degenerative changes in structural indices in the orchidectomized group (P0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05). AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration.

  2. Improved solar light stimulated charge separation of g-C3N4 through self-altering acidic treatment

    Science.gov (United States)

    Leong, Kah Hon; Lim, Ping Feng; Sim, Lan Ching; Punia, Varun; Pichiah, Saravanan

    2018-02-01

    Herein, we report the use of acid treatment to treat g-C3N4 nanostructured by a direct and facile synthesis route. The adopted treatment enhanced photoactivity of g-C3N4 and reflected in the removal of recalcitrant organic pollutant, Bisphenol A under direct sunlight. A complete removal of Bisphenol A was attained in a short duration (225 min) as compared to pure g-C3N4. The analysis clearly substantiated the robustness of acid exfoliation that promoted a blue shift, extended the conjugated length of its respective conduction and valance band. It also drastically prolonged the recombination rate of charge carriers, by producing excess of unpaired electrons in the conduction band for active radicals' generation. Thus, this new findings could offer a new sight of self-alteration in improving the photoactivity of complex organic pollutants for sustainable environmental remediation.

  3. Phytoandrogenic properties of Eurycoma longifolia as natural alternative to testosterone replacement therapy.

    Science.gov (United States)

    George, A; Henkel, R

    2014-09-01

    The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age-depending decline in serum testosterone levels with concentrations being about 40-50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT. © 2014 Blackwell Verlag GmbH.

  4. Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for leydig cell carcinogenesis

    International Nuclear Information System (INIS)

    Coulson, Michelle; Gibson, G. Gordon; Plant, Nick; Hammond, Tim; Graham, Mark

    2003-01-01

    Leydig cell tumours (LCTs) are frequently observed during rodent carcinogenicity studies, however, the significance of this effect to humans remains a matter of debate. Many chemicals that produce LCTs also induce hepatic cytochromes P450 (CYPs), but it is unknown whether these two phenomena are causally related. Our aim was to investigate the existence of a liver-testis axis wherein microsomal enzyme inducers enhance testosterone metabolic clearance, resulting in a drop in circulating hormone levels and a consequent hypertrophic response from the hypothalamic-pituitary-testis axis. Lansoprazole was selected as the model compound as it induces hepatic CYPs and produces LCTs in rats. Male Sprague-Dawley rats were dosed with lansoprazole (150 mg/kg/day) or vehicle for 14 days. Lansoprazole treatment produced effects on the liver consistent with an enhanced metabolic capacity, including significant increases in relative liver weights, total microsomal CYP content, individual CYP protein levels, and enhanced CYP-dependent testosterone metabolism in vitro. Following intravenous administration of [ 14 C]testosterone, lansoprazole-treated rats exhibited a significantly smaller area under the curve and significantly higher plasma clearance. Significant reductions in plasma and testicular testosterone levels were observed, confirming the ability of this compound to perturb androgen homeostasis. No significant changes in plasma LH, FSH, or prolactin levels were detected under our experimental conditions. Lansoprazole treatment exerted no marked effects on testicular testosterone metabolism. In summary, lansoprazole treatment induced hepatic CYP-dependent testosterone metabolism in vitro and enhanced plasma clearance of radiolabelled testosterone in vivo. These effects may contribute to depletion of circulating testosterone levels and hence play a role in the mode of LCT induction in lansoprazole-treated rats

  5. Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function

    NARCIS (Netherlands)

    Vinish, M.; Elnabawi, A.; Milstein, J.A.; Burke, J.S.; Kallevang, J.K.; Turek, K.C.; Lansink, C.S.; Merchenthaler, I.; Bailey, A.M.; Kolb, B.; Cheer, J.F.; Frost, D.O.

    2013-01-01

    Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D₂

  6. Antibiotic treatment preventing necrotising enterocolitis alters urinary and plasma metabolomes in preterm pigs

    DEFF Research Database (Denmark)

    Jiang, Pingping; Trimigno, Alessia; Stanstrup, Jan

    2017-01-01

    microbiome density and NEC lesions as previously reported, the antibiotic treatment employed in the current study affected the abundance of 44 metabolites in different metabolic pathways. In antibiotics-treated pigs, tryptophan metabolism favoured the kynurenine pathway, relative to the serotonin pathway...

  7. Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

    Science.gov (United States)

    Al Kindi, Manal K.; Al Essry, Faiza S.; Al Essry, Fatma S.; Mula-Abed, Waad-Allah S.

    2012-01-01

    Objectives There are technical limitations for the currently available methods of measuring serum total and free testosterone in females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), and calculated free testosterone (CFT) in the assessment of androgen status in women investigated for suspected hyperandrogenism. Methods This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years) whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18). The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19), hirsutism (group 3; n=18), menstrual disturbances (irregularities) or infertility (group 4; n=49), as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5; n=18). Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation. Results There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG 5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73

  8. Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

    Science.gov (United States)

    Anwar, Javed; Spanevello, Roselia Maria; Pimentel, Victor Camera; Gutierres, Jessié; Thomé, Gustavo; Cardoso, Andreia; Zanini, Daniela; Martins, Caroline; Palma, Heloisa Einloft; Bagatini, Margarete Dulce; Baldissarelli, Jucimara; Schmatz, Roberta; Leal, Cláudio Alberto Martins; da Costa, Pauline; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2013-06-01

    This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Acute treatment with pentobarbital alters the kinetics of in vivo receptor binding in the mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Sakiyama, Yojiro [Division of Clinical Research, National Institute of Radiological Sciences, Inage-ku, Chibashi 263-8555 (Japan)]. E-mail: yojiro.sakiyama@pfizer.com; Saito, Masao [Department of Medical Science, Institute of Medical Electronics, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Inoue, Osamu [Department of Medical Physics, School of Allied Health Science, Faculty of Medicine, Osaka University, Suita, Osaka 565-0871 (Japan)

    2006-05-15

    The effect of pentobarbital, a sedative-hypnotic barbiturate, on the in vivo binding of benzodiazepine receptors in the mouse brain was investigated. Dose-related changes in the apparent binding of [{sup 3}H]Ro15-1788 ([{sup 3}H]flumazenil) in the cerebral cortex, cerebellum and pons-medulla were observed by pretreatment with pentobarbital. For quantification of the kinetic properties of the in vivo binding of [{sup 3}H]Ro15-1788, time courses of radioactivity following its injection were examined, and kinetic analysis was performed using the compartment model. The time courses of radioactivity following injection of [{sup 3}H]Ro15-1788 with 3 mg/kg Ro15-1788 were used as input function. In all regions studied, rate constants between input compartment and specific binding compartment were significantly decreased by pentobarbital. However, no significant alterations in the binding potential (BP=K {sub 3}/K {sub 4}) of benzodiazepine receptors by pentobarbital were observed in any of the regions. A saturation experiment indicated that the decrease in the input rate constant (K {sub 3}), which includes both the association rate constant (k {sub on}) and the number of binding sites available (B {sub max}), was mainly due to decrease in k {sub on}. These results suggest that apparent increases in binding at 20 min after tracer injection were due to the decrease in the association and dissociation rates of binding in vivo.

  10. Worm burden and leukocyte response in Angiostrongylus malaysiensis-infected rats: the influence of testosterone.

    Science.gov (United States)

    Kamis, A B; Ahmad, R A; Badrul-Munir, M Z

    1992-01-01

    Gonadectomized male albino rats aged 7 weeks were given 1.5 mg/kg testosterone propionate daily and inoculated with 50 third-stage larvae of Angiostrongylus malaysiensis. The treatment significantly increased the number of larvae and adult worms recovered from the brain and pulmonary arteries, respectively, and the rats exhibited smaller thymus glands. The total numbers of leukocytes, monocytes, neutrophils, and especially eosinophils increased significantly post-infection, but the counts were higher in the untreated infected controls. Presumably, immunosuppressive effects of testosterone may at least partly be responsible for the higher loads of A. malaysiensis worms found in male rats as compared with females in the field.

  11. Reduction of calprotectin and phosphate during testosterone therapy in aging men

    DEFF Research Database (Denmark)

    Pedersen, L; Christensen, L. L.; Pedersen, Susanne Møller

    2017-01-01

    . Setting: Odense Androgen Study—the effect of Testim and training in hypogonadal men. Participants: Men aged 60–78 years old with a low normal concentration of free of bioavailable testosterone 3 nmol/L and waist circumference >94 cm recruited from 2008 to 2009 (N = 48) by advertisement. Intervention......Objectives: To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 (FGF23), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. Design: Randomized, double-blinded, placebo-controlled study...

  12. The prevalence and association of low testosterone levels in a ...

    African Journals Online (AJOL)

    Conclusion: This study confirms the high prevalence of low testosterone levels in diabetic male patients in a tertiary setting. Universal screening remains controversial owing to uncertainty regarding the risks and benefits of testosterone therapy in this population group. Predictors of low testosterone levels were identified.

  13. Testosterone and BMD in elite male lightweight rowers

    DEFF Research Database (Denmark)

    Vinther, A; Kanstrup, I-L; Christiansen, E

    2008-01-01

    The purpose of the present study was to investigate if a relationship between BMD and testosterone levels could be identified in elite male lightweight rowers. Thirteen male lightweight national team rowers had their BMD measured in a DEXA scanner. Plasma concentrations of total testosterone (TT)...... important to BMD than testosterone levels. Prospective investigations are needed to elucidate potential causal relationships....

  14. Pharmacokinetics of testosterone cream applied to scrotal skin.

    Science.gov (United States)

    Iyer, R; Mok, S F; Savkovic, S; Turner, L; Fraser, G; Desai, R; Jayadev, V; Conway, A J; Handelsman, D J

    2017-07-01

    Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route. © 2017 American Society of Andrology and European Academy of Andrology.

  15. Association between low serum free testosterone and adverse ...

    African Journals Online (AJOL)

    Background. The association of serum free testosterone (FT) with prostate cancer is not fully understood. Studies on the results of the relationship between serum testosterone level and prostate cancer are conflicting. However, there is a reported association between lower serum testosterone levels and high-grade prostate ...

  16. Agents that increase phosphatidic acid inhibit the LH-induced testosterone production

    DEFF Research Database (Denmark)

    Lauritzen, L.; Nielsen, L.-L.A.; Vinggaard, Anne Marie

    1994-01-01

    The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 µM) induced an increased level of [H]PtdOH in isolated rat Leydig cells......, prelabeled with [H]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypassed by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydroxycholesterol was added as a direct substrate...... for cytochrome P-450 side chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4ß-phorbol 12-myristate 13-acetate (PMA), A23187, and sphingosine) giving rise...

  17. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma

    Science.gov (United States)

    Pitha, Ian F.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary Ellen; Oglesby, Ericka N.; Berlinicke, Cynthia A.; Mitchell, Katherine L.; Kim, Jessica; Jefferys, Joan J.

    2015-01-01

    Purpose To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice. Methods We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Results Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP. Conclusions The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at the optic nerve head. PMID:26505191

  18. [Tadalafil improves total testosterone, IIEF score and SEP in old and middle-aged males with late-onset hypogonadism].

    Science.gov (United States)

    Wang, Xi-Kun; Luo, Li; Wang, Sen; Li, Jun; Li, Wen-Xiong

    2012-05-01

    To observe the clinical effect of tadalafil combined with testosterone undecanoate on late-onset hypogonadism (LOH) in old and middle-aged males. A total of 125 old and middle-aged (40 to 60 years) males with LOH were randomly assigned to a treatment group (n = 65) and a control group (n = 60) to be treated with tadalafil + testosterone undecanoate and testosterone undecanoate alone, respectively. We compared the levels of total testosterone (T), IIEF scores and the patients' sexual encounter profile (SEP) diaries before and 4 weeks after medication. The T level, IIEF score and SEP score were significantly improved in both groups after medication as compared with the baseline (P SEP score in old and middle-aged males with LOH and increase their sexual satisfaction and self-confidence.

  19. Regulation of androgen receptor mRNA and protein in the rat testis by testosterone

    NARCIS (Netherlands)

    L.J. Blok (Leen); J.M.S. Bartlett (John); J. Bolt-de Vries (Joan); A.P.N. Themmen (Axel); A.O. Brinkmann (Albert); G.F. Weinbauer (G.); E. Nieschlag (Eberhard); J.A. Grootegoed (Anton)

    1991-01-01

    markdownabstract__Abstract__ Adult rats were treated with ethane dimethane sulphonate (EDS), an agent that destroys Leydig cells. Within 5 days after EDS treatment, the levels of testosterone (T) in the circulation and in the testis were decreased to very low values, which makes it possible to

  20. Testosterone regulates keratin 33B expression in rat penis growth through androgen receptor signaling.

    Science.gov (United States)

    Ma, Yan-Min; Wu, Kai-Jie; Dang, Qiang; Shi, Qi; Gao, Yang; Guo, Peng; Xu, Shan; Wang, Xin-Yang; He, Da-Lin; Gong, Yong-Guang

    2014-01-01

    Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR) protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b). Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.

  1. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men

    Directory of Open Access Journals (Sweden)

    Pranav Dadhich

    2017-01-01

    Conclusions: Both TST and CC are effective medications in treating hypogonadism; however, our study indicates that TST is more effective in raising serum testosterone levels and improving hypogonadal symptoms. CC remains a viable treatment modality for hypogonadal men but its adverse effect on libido warrant further study.

  2. Testosterone regulates keratin 33B expression in rat penis growth through androgen receptor signaling

    Directory of Open Access Journals (Sweden)

    Yan-Min Ma

    2014-12-01

    Full Text Available Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b. Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.

  3. Serum testosterone level as a predictor of biochemical failure after radical prostatectomy for localized prostate cancer

    DEFF Research Database (Denmark)

    Røder, Martin Andreas; Christensen, Ib Jarle; Berg, Kasper Drimer

    2012-01-01

    Study Type - Aetiology (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The precise relationship between serum testosterone (T) and prostate cancer (PCa) incidence and progression is controversial. Low pre-treatment serum T correlates with higher...

  4. Food conditions affect yolk testosterone deposition but not incubation attendance.

    Science.gov (United States)

    Vergauwen, Jonas; Goerlich, Vivian C; Groothuis, Ton G G; Eens, Marcel; Müller, Wendt

    2012-03-01

    In many bird species with hatching asynchrony, yolk androgens increase across the laying sequence. This has been hypothesized to represent a compensatory mechanism for disadvantages of later-hatching chicks - via positive effects of yolk androgens on early competitiveness and growth. However, the costs and benefits of this compensatory strategy probably depend on environmental factors determining the survival chances of the chicks such as the food conditions, which should, therefore, influence maternal yolk androgen deposition. We studied the consequences of manipulated food conditions on the expected level of hatching asynchrony in canaries (Serinus canaria) assigning females to either a low (=LQ) or high quality (=HQ) diet. We measured the incubation behaviour (as incubation attendance) and the yolk androgen deposition in order to investigate whether and how females modulate hatching asynchrony in relation to the food conditions. Females on a HQ diet laid larger and heavier clutches, showed a stronger increase in yolk testosterone content towards the last-laid eggs, but did not alter their incubation attendance. Thus, females on a HQ diet seem to favour the survival of later hatching chicks, as indicated by their yolk testosterone deposition pattern. However, females on a HQ diet laid larger clutches and might need to compensate more in order to achieve a similar degree of hatching asynchrony than females on a LQ diet, given the lack of plasticity in incubation attendance. This suggests that canary females respond to food manipulations mainly via changes in clutch size rather than by altering the degree of hatching asynchrony. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Effect of Testosterone on Hepcidin, Ferroportin, Ferritin and Iron Binding Capacity in Patients with Hypogonadotropic Hypogonadism and Type 2 Diabetes

    Science.gov (United States)

    DHINDSA, SANDEEP; GHANIM, HUSAM; BATRA, MANAV; KUHADIYA, NITESH D.; ABUAYSHEH, SANAA; GREEN, KELLY; MAKDISSI, ANTOINE; CHAUDHURI, AJAY; DANDONA, PARESH

    2016-01-01

    Context Since the syndrome of hypogonadotropic hypogonadism (HH) is associated with anemia and the administration of testosterone restores hematocrit to normal, we investigated the potential underlying mechanisms. Design Randomized, double blind, placebo controlled trial Methods We measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. 44 men had HH (defined as subnormal free testosterone along with low or normal LH concentrations) while 50 were eugonadal. Men with HH were randomized to testosterone or placebo treatment every 2 weeks for 15 weeks. Blood samples were collected at baseline, 3 and 15 weeks after starting treatment. 20 men in testosterone group and 14 men in placebo group completed the study. Results Hematocrit levels were lower in men with HH (41.1±3.9% vs. 43.8±3.4%, p=0.001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin or iron, or in the expression of ferroportin or TR in MNC among HH and eugonadal men. Hematocrit increased to 45.3±4.5%, hepcidin decreased by 28±7% and erythropoietin increased by 21±7% after testosterone therapy (ptestosterone therapy. Conclusions The increase in hematocrit following testosterone therapy is associated with an increase in erythropoietin, the suppression of hepcidin, and an increase in the expression of ferroportin and transferrin receptor. PMID:27292585

  6. Testosterone Replacement Therapy and Mortality in Older Men.

    Science.gov (United States)

    Hackett, G I

    2016-02-01

    While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Several authors blame advertising and the availability of more convenient formulations, whilst others have pointed out that the routine testing of men with erectile dysfunction (ED) (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous under-diagnosis and under-treatment in line with evidence based guidelines. It is unlikely that persuasive advertising or convenient formulations could grow a market over such a sustained period if the treatment was not effective. Urologists and primary care physicians are the most frequent initiators of TRT usually for ED. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with a possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing that therapy associated with clear increases in serum testosterone levels to the normal range is associated with reduced all-cause mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively, they have compared non-treated patients with under-treated or non-compliant subjects involving a range of different therapy regimes. Recent evidence suggests long-acting injections may be associated with decreased cardiovascular risk, but the

  7. Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract.

    Science.gov (United States)

    Maulidiani; Abas, F; Khatib, A; Perumal, V; Suppaiah, V; Ismail, A; Hamid, M; Shaari, K; Lajis, N H

    2016-03-02

    'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the 'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach. In this study, an obese diabetic (mimic of T2DM condition) animal model was developed using Sprague-Dawley rats fed with a high-fat diet and induced into diabetic condition by the treatment of a low dose of streptozotocin (STZ). The effect of C. asiatica extract on the experimental animals was followed based on the changes observed in the urinary and serum metabolites, measured by (1)H NMR of urine and blood samples collected over the test period. A long-term treatment of obese diabetic rats with CA extract could reverse the glucose and lipid levels, as well as the tricarboxylic acid cycle and amino acid metabolic disorders, back towards normal states. Biochemical analysis also showed an increase of insulin production in diabetic rats upon treatment of CA extract. This study has provided evidence that clearly supported the traditional use of CA as a remedy for diabetes. NMR-based metabolomics was successfully applied to show that CA produced both anti-hyperglycemic and anti-hyperlipidemic effects on a rat model. In addition to increasing the insulin secretion, the CA extract also ameliorates the metabolic pathways affected in the induced diabetic rats. This study further revealed the potential usage of CA extract in managing diabetes mellitus and the results of this work may contribute towards the further understanding of the underlying molecular mechanism of this herbal remedy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Diurnal alterations in circadian genes and peptides in major depressive disorder before and after escitalopram treatment.

    Science.gov (United States)

    Li, Su-Xia; Liu, Li-Jing; Xu, Ling-Zhi; Gao, Lei; Wang, Xin-Fu; Zhang, Jing-Tao; Lu, Lin

    2013-11-01

    Strong links exist between circadian disturbances and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However, changes in the expression of clock genes or neuropeptides related to the regulation of circadian rhythm that may influence the susceptibility to recurrence after antidepressant treatment in MDD have not been investigated. Blood samples were collected at 4h intervals for 24h from 12 male healthy controls and 12 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included the relative expression of clock gene mRNA (PERIOD1, PERIOD2, PERIOD3, CRY1, BMAL1, NPAS2, and GSK-3β), and the levels of serum melatonin, vasoactive intestinal polypeptide (VIP), cortisol, adrenocorticotropic hormone (ACTH), insulin-like growth factor-1 (IGF-1), and growth hormone (GH). Compared with healthy controls, MDD patients showed disruptions in the diurnal rhythms of the expression of PERIOD1, PERIOD2, CRY1, BMAL1, NPAS2, and GSK-3β and disruptions in the diurnal rhythms of the release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (i.e., PER1, CRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted 8 weeks after escitalopram treatment, similar to the increase in the 24h levels of VIP and decreases in the 24h levels of cortisol and ACTH. These persistent neurobiological changes may play a role in MDD symptoms that are thought to contribute to the vulnerability to recurrence and long-term maintenance therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Intracranial structural alteration predicts treatment outcome in patients with spontaneous intracranial hypotension.

    Science.gov (United States)

    Choi, Hanna; Lee, Mi Ji; Choi, Hyun Ah; Cha, Jihoon; Chung, Chin-Sang

    2018-02-01

    Background Intracranial structural dislocation in spontaneous intracranial hypotension (SIH) can be measured by various intracranial angles and distances. We aimed to identify the clinical significance of structural dislocation in relation to treatment outcome in patients with SIH. Methods In this retrospective analysis, we identified patients with SIH who received an epidural blood patch (EBP) at Samsung Medical Center from January 2005 to March 2015. Structural dislocation in pretreatment MRIs of SIH patients was assessed by measuring tonsillar herniation, mamillopontine distance, the angle between the vein of Galen and straight sinus (vG/SS angle), the pontomesencephalic angle, and the lateral ventricular angle. After the first EBP, poor response was defined as the persistence of symptoms that prompted a repeat EBP. Results Out of the 95 patients included, 31 (32.6%) showed poor response. Among the radiological markers of structural dislocation, the vG/SS angle was associated with poor response (49.82 ± 16.40° vs 66.58 ± 26.08°, p = 0.002). Among clinical variables, premorbid migraine ( p = 0.036) was related to poor response. In multivariate analysis, reduced vG/SS angle was independently associated with poor response (OR 1.04 [95% CI 1.01 - 1.07] per 1° decrease, p = 0.006). In 23 patients who underwent MRI after successful treatment, the vG/SS angle significantly increased after the EBP ( p < 0.001, by paired t-test), while two patients with aggravation or recurrence showed a further reduction of their vG/SS angles. Conclusions Intracranial structural dislocation, measured by the vG/SS angle, is associated with poor response to the first EBP in patients with SIH. Successful treatment can reverse the structural dislocation.

  10. Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Anna-Maria Pehserl

    2016-12-01

    Full Text Available MicroRNAs (miRNAs are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC. Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18, and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720 and two small RNAs (SNORD 13 and hsa-miR-3182 were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720 were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle–arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.

  11. Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial.

    Science.gov (United States)

    Huang, Grace; Wharton, Whitney; Bhasin, Shalender; Harman, S Mitchell; Pencina, Karol M; Tsitouras, Panayiotis; Li, Zhuoying; Hally, Kathleen A; Asthana, Sanjay; Storer, Thomas W; Basaria, Shehzad

    2016-08-01

    The effects of testosterone on cognitive function in older men are incompletely understood. We aimed to establish the effects of long-term testosterone administration on multiple domains of cognitive function in older men with low or low-to-normal testosterone concentrations. We did the randomised, double-blind, placebo-controlled, parallel-group TEAAM trial at three medical centres in Boston, Phoenix, and Los Angeles, USA. Men aged 60 years and older with low or low-to-normal testosterone concentrations (3·47-13·9 nmol/L, or free testosterone 75 years) and study site. The testosterone dose was adjusted to achieve concentrations of 17·3-31·2 nmol/L. Participants and all study personnel were masked to treatment allocation. Multiple domains of cognitive function were assessed as prespecified secondary outcomes by use of standardised tests at baseline and months 6, 18, and 36. We did analyses by intention to treat (in men who had baseline assessments of cognitive function) and per protocol (restricted to participants who completed the study drug and had both baseline and 36 month assessments of cognitive function). The TEAAM trial is registered with ClinicalTrials.gov, number NCT00287586. Between Sept 1, 2004, and Feb 12, 2009, we randomly assigned 308 participants to receive either testosterone (n=156) or placebo (n=152). 280 men had baseline cognitive assessments (n=140 per group). Mean follow-up time was 29·0 months (SD 11·5) in the testosterone group and 31·1 months (9·5) in the placebo group. The last participant completed the study on May 11, 2012. In the testosterone group, mean concentrations of serum total testosterone increased from 10·6 nmol/L (SD 2·2) to 19·7 nmol/L (9·2) and free testosterone concentrations increased from 222 pmol/L (62) to 364 pmol/L (222). In the placebo group, mean concentrations of serum total testosterone were 10·7 nmol/L (SD 2·3) at baseline and 11·1 nmol/L (3·2) post-intervention and free testosterone concentrations

  12. Prenatal Programming by Testosterone of Hypothalamic Metabolic Control Neurones in the Ewe

    Science.gov (United States)

    Sheppard, Kayla M.; Padmanabhan, Vasantha; Coolen, Lique M.; Lehman, Michael N.

    2013-01-01

    Ewes treated prenatally with testosterone (T) develop metabolic deficits, including insulin resistance, in addition to reproductive dysfunctions that collectively mimic polycystic ovarian syndrome (PCOS), a common endocrine disease in women. We hypothesised that metabolic deficits associated with prenatal T excess involve alterations in arcuate nucleus (ARC) neurones that contain either agouti-related peptide (AgRP) or proopiomelanocortin (POMC). Characterization of these neurones in the ewe showed that immunoreactive AgRP and POMC neurones were present in separate populations in the ARC, that AgRP and POMC neurones co-expressed either neuropeptide Y or cocaine- and amphetamine-regulated transcript, respectively, and that each population had a high degree of colocalization with androgen receptors. Examination of the effect of prenatal T exposure on the number of AgRP and POMC neurones in adult ewes showed that prenatal T excess significantly increased the number of AgRP but, not POMC neurones compared to controls; this increase was restricted to the middle division of the ARC, was mimicked by prenatal treatment with dihydrotestosterone, a non-aromatizable androgen, and was blocked by co-treatment of prenatal T with the anti-androgen, flutamide. The density of AgRP fibre immunoreactivity in the preoptic area, paraventricular nucleus, lateral hypothalamus and dorsomedial hypothalamic nucleus was also increased by prenatal T exposure. Thus, ewes that were exposed to androgens during foetal life showed alterations in the number of AgRP-immunoreactive neurones and the density of fibre immunoreactivity in their projection areas, suggestive of permanent prenatal programming of metabolic circuitry that may, in turn, contribute to insulin resistance and increased risk of obesity in this model of PCOS. PMID:21418339

  13. Prolactin is associated with the development of photorefractoriness in intact, castrated, and testosterone-implanted starlings

    International Nuclear Information System (INIS)

    Goldsmith, A.R.; Nicholls, T.J.

    1984-01-01

    Using radioimmunoassays, prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in the plasma of intact, castrated, and testosterone-implanted male starlings. Two groups of birds (intact and castrated males) were transferred when photosensitive from short (8-hr) to long (16-hr) day lengths; in both cases plasma prolactin levels increased steadily reaching a peak after 5 weeks of photostimulation, at the time of the onset of photorefractoriness. Three groups (intacts, castrates, and castrates implanted with Silastic capsules containing testosterone) were exposed to day lengths increasing by 30 min per week from 8 to 16 hr. Again, prolactin levels increased in a similar fashion in all three groups at the time of refractoriness, which occurred when the day length reached 15-16 hr. Thus the timing of photorefractoriness and the associated rise in prolactin secretion which occur in response to photostimulation do not depend upon the presence of the gonads and are not affected when testosterone is maintained at a constant high level. Nor is the increase in prolactin altered when the cycle of gonadotrophin secretion which normally precedes it is completely suppressed by the implantation of a testosterone capsule. It would seem that prolactin secretion in the starling is stimulated by transfer from short to long day lengths, but not as a consequence of high gonadotrophin or androgen secretion rates

  14. Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized women.

    Science.gov (United States)

    Flöter, A; Nathorst-Böös, J; Carlström, K; Ohlsson, C; Ringertz, H; Schoultz, B von

    2005-03-01

    To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen therapy on bone markers, bone mineral density and body composition in oophorectomized women. Fifty women, 45-60 years old, who had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders, were randomly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily. Twenty-four weeks later, cross-over was performed to the other treatment regimen. Forty-four women completed the study. Their serum concentrations of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, osteocalcin, carboxyterminal telopeptide aminoterminal (ICTP), of type I collagen propeptide of type I procollagen (PICP) and interleukin (IL)-1 receptor antagonist were measured at baseline and after 24 weeks of both treatments, as were also their body mass index (BMI) and blood pressure. Bone mineral density of the total body, spine and hip and total body fat, total lean body mass, trunk fat and trunk lean mass were determined by dual-energy X-ray absorptiometry measurements at baseline and after 24 weeks of both regimens. During treatment, the addition of testosterone counteracted the decrease in IGF-I and PICP seen with estrogen therapy alone. Osteocalcin and ICTP were significantly reduced to the same extent by both therapies. No change ocurred in the IL-1 receptor antagonist. A significant increase was seen in total lean body mass with the estrogen/testosterone regimen, but the total fat mass, trunk lean or fat mass remained unchanged after 24 weeks of both treatments. No effect was detected on total, hip or spinal bone mineral density after treatment with estrogen alone or estrogen/testosterone. Likewise, BMI and blood pressure were unaffected. The addition of testosterone to oral estrogen might have positive effects on bone as suggested by the fact that it counteracted the decline in IGF-I and PICP

  15. Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

    Science.gov (United States)

    Duric, Vanja

    2014-01-01

    Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response. PMID:22585060

  16. Treatment implications of the altered cytokine-insulin axis in neurodegenerative disease.

    Science.gov (United States)

    Clark, Ian A; Vissel, Bryce

    2013-10-01

    The disappointments of a series of large anti-amyloid trials have brought home the point that until the driving force behind Alzheimer's disease, and the way it causes harm, are firmly established and accepted, researchers will remain ill-equipped to find a way to treat patients successfully. The origin of inflammation in neurodegenerative diseases is still an open question. We champion and expand the argument that a shift in intracellular location of α-synuclein, thereby moving a key methylation enzyme from the nucleus, provides global hypomethylation of patients' cerebral DNA that, through being sensed by TLR9, initiates production of the cytokines that drive these cerebral inflammatory states. After providing a background on the relevant inflammatory cytokines, this commentary then discusses many of the known alternatives to the primary amyloid argument of the pathogenesis of Alzheimer's disease, and the treatment approaches they provide. A key point to appreciate is the weight of evidence that inflammatory cytokines, largely through increasing insulin resistance and thereby reducing the strength of the ubiquitously important signaling mediated by insulin, bring together most of these treatments under development for neurodegenerative disease under the one roof. Moreover, the principles involved apply to a wide range of inflammatory diseases on both sides of the blood brain barrier. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Deep Brain Stimulation—Possible Treatment Strategy for Pathologically Altered Body Weight?

    Directory of Open Access Journals (Sweden)

    Philip Prinz

    2018-01-01

    Full Text Available The treatment of obesity and eating disorders such as binge-eating disorder or anorexia nervosa is challenging. Besides lifestyle changes and pharmacological options, bariatric surgery represents a well-established and effective-albeit invasive-treatment of obesity, whereas for binge-eating disorder and anorexia nervosa mostly psychotherapy options exist. Deep brain stimulation (DBS, a method that influences the neuronal network, is by now known for its safe and effective applicability in patients with Parkinson’s disease. However, the use does not seem to be restricted to these patients. Recent preclinical and first clinical evidence points towards the use of DBS in patients with obesity and eating disorders as well. Depending on the targeted area in the brain, DBS can either inhibit food intake and body weight or stimulate energy intake and subsequently body weight. The current review focuses on preclinical and clinical evidence of DBS to modulate food intake and body weight and highlight the different brain areas targeted, stimulation protocols applied and downstream signaling modulated. Lastly, this review will also critically discuss potential safety issues and gaps in knowledge to promote further studies.

  18. Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

    Directory of Open Access Journals (Sweden)

    Manal K. Al Kindi

    2012-11-01

    Full Text Available Objectives: There are technical limitations for the currently available methods of measuring serum total and free testosteronein females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG, free androgen index (FAI, and calculated free testosterone (CFT in the assessment of androgen status in women investigated for suspected hyperandrogenism.Methods: This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18. The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19, hirsutism (group 3; n=18, menstrual disturbances (irregularities or infertility (group 4; n=49, as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5;n=18. Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation.Results: There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG 5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73

  19. Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Hyun Jin Jung

    2016-12-01

    Full Text Available Purpose: We aimed to evaluate the effect of testosterone replacement therapy (TRT on cognitive function and depression in men with testosterone deficiency syndrome. Materials and Methods: We carried out a prospective, placebo-controlled trial involving 106 men with total testosterone levels <3.3 ng/mL and symptoms of hypogonadism. Based on whether the patients received TRT (injection with 1,000 mg testosterone undecanoate or a placebo (advice to modify lifestyle, the study population was divided into a TRT group (n=54 and a control group (n=52. Results: The age among patients in the TRT and control groups was 56.7±12.6 years and 57.8±11.4 years, respectively (p> 0.05. At baseline, no significant differences between the TRT and control groups were noted regarding serum testosterone or prostate-specific antigen levels, or regarding the scores for aging symptoms (Aging Males’ Symptoms scale, erectile function (5-item International Index of Erectile Function questionnaire, cognitive function (Korean Mini-Mental State Examination, and depression (Beck Depression Inventory. At 8 months after intervention total serum testosterone levels and erectile function scores had significantly increased (p<0.05, whereas the scores for aging symptoms and depression had significantly decreased (p<0.05 in the TRT group; no significant improvement in any parameters was noted for the control group. Notably, significant improvement in cognitive function was noted among patients with cognitive impairment at baseline (cognitive function score <25 who received TRT. Conclusions: TRT may be considered in men with testosterone deficiency syndrome if low testosterone levels are associated with depression or cognitive impairment.

  20. Serum testosterone concentration in chloroquinetreated rats: effects ...

    African Journals Online (AJOL)

    The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2 ml/kg of normal ...

  1. Testosterone and aggression: Berthold, birds and beyond.

    Science.gov (United States)

    Soma, K K

    2006-07-01

    Berthold's classic study of domesticated roosters in 1849 demonstrated that testicular secretions are necessary for the normal expression of aggressive behaviour. Although this conclusion is undoubtedly correct, field studies of wild songbirds have yielded important modifications and limitations of Berthold's original hypothesis. For example, studies of the North American song sparrow (Melospiza melodia) during the breeding season reveal that not only does testosterone increase aggression, but aggressive interactions also increase plasma testosterone levels. Furthermore, in winter, nonbreeding song sparrows have low plasma testosterone levels but are very aggressive, and castration of nonbreeding song sparrows does not decrease aggression. Interestingly, an aromatase inhibitor (fadrozole) does decrease male aggression in the nonbreeding season, and the effects of fadrozole can be rescued with oestradiol. In winter, dehydroepiandrosterone (DHEA) from the periphery can be metabolised within the brain to supply oestradiol to specific neural circuits. Additionally, oestradiol might be synthesised de novo from cholesterol entirely within the brain. These mechanisms may have evolved to avoid the 'costs' of circulating testosterone in the nonbreeding season. Recent studies in tropical birds, hamsters, and humans suggest that these neuroendocrine mechanisms are important for the control of aggression in many vertebrate species.

  2. Body weight, scrotal circumference and testosterone concentration ...

    African Journals Online (AJOL)

    The aim of this study was to compare testosterone concentration, body weight, scrotal circumference and age to penis detachment from days 30 to 240 in young Boer goat males (n = 22) born during the dry (n = 11) and the rainy (n = 11) seasons. In the dry season the parameters varied as follows: body weight from 3.7 ± 1.1 ...

  3. Testosterone and aging: clinical research directions

    National Research Council Canada - National Science Library

    Liverman, Catharyn T; Blazer, Dan G., II

    2004-01-01

    .... Viewed by some as an “antiaging tonic,†testosterone’s reputation and increased use by men of all ages in the United States have outpaced the scientific evidence about its potential benefits and risks...

  4. Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature.

    Science.gov (United States)

    Rooman, Raoul P A; De Beeck, Lieve Op; Martin, Manou; van Doorn, Jaap; Mohan, Subburaman; Du Caju, Marc V L

    2005-04-01

    Pharmacological doses of estrogens or testosterone are used to limit the final height of girls or boys with constitutional tall stature but the mechanism behind this growth inhibition is still debated. We therefore studied the changes in the circulating components of the insulin-like growth factor (IGF) system during high dose sex steroid therapy. Twenty three girls and twenty boys with constitutional tall stature were treated with 100 microg ethinylestradiol per day or 250 mg testosterone ester every 14 days respectively. In 19 girls and 18 boys, the levels of IGF-I, free IGF-I, IGF-II, acid-labile subunit (ALS) and IGF binding proteins (IGFBP)-2 to -6 were measured before and 3-6 months after the start of therapy (group 1). In 18 girls and 11 boys, samples were collected at the end of therapy and 3 to 6 months afterwards (group 2). Fourteen girls and nine boys belonged to both groups. All parameters were measured by radioimmunoassay or ELISA. Levels of IGF-I were decreased significantly by estrogen treatment but remained unchanged during testosterone treatment. Free IGF-I decreased during estrogen treatment but increased during testosterone therapy. Estrogens increased IGF-II and testosterone reduced it. The important reduction of IGFBP-2 during estrogen therapy is not reproduced by androgen therapy, neither is the stimulation by estrogens of IGFBP-4. IGFBP-3 is not modulated by either sex steroid. We found that IGFBP-6 is up-regulated by testosterone but not by estrogens; the reverse is true for ALS, which increased during estrogen treatment but remained unchanged during testosterone treatment. Our findings demonstrate that androgens and estrogens exert differential effects on the circulating levels of several IGF components.

  5. Genome-wide transcriptomic alterations induced by ethanol treatment in human dental pulp stem cells (DPSCs

    Directory of Open Access Journals (Sweden)

    Omar Khalid

    2014-12-01

    Full Text Available Human dental pulp stem cells (DPSCs isolated from adult dental pulp are multipotent mesenchymal stem cells that can be directed to differentiate into osteogenic/odontogenic cells and also trans-differentiate into neuronal cells. The utility of DPSC has been explored in odontogenic differentiation for tooth regeneration. Alcohol abuse appears to lead to periodontal disease, tooth decay and mouth sores that are potentially precancerous. Persons who abuse alcohol are at high risk of having seriously deteriorated teeth, gums and compromised oral health in general. It is currently unknown if alcohol exposure has any impact on adult stem cell maintenance, stem cell fate determination and plasticity, and stem cell niche environment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO under GSE57255. Our data provide transcriptomic changes that are occurring by EtOH treatment of DPSCs at 24-hour and 48-hour time point.

  6. Genome-wide transcriptomic alterations induced by ethanol treatment in human dental pulp stem cells (DPSCs).

    Science.gov (United States)

    Khalid, Omar; Kim, Jeffrey J; Duan, Lewei; Hoang, Michael; Elashoff, David; Kim, Yong

    2014-12-01

    Human dental pulp stem cells (DPSCs) isolated from adult dental pulp are multipotent mesenchymal stem cells that can be directed to differentiate into osteogenic/odontogenic cells and also trans-differentiate into neuronal cells. The utility of DPSC has been explored in odontogenic differentiation for tooth regeneration. Alcohol abuse appears to lead to periodontal disease, tooth decay and mouth sores that are potentially precancerous. Persons who abuse alcohol are at high risk of having seriously deteriorated teeth, gums and compromised oral health in general. It is currently unknown if alcohol exposure has any impact on adult stem cell maintenance, stem cell fate determination and plasticity, and stem cell niche environment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE57255. Our data provide transcriptomic changes that are occurring by EtOH treatment of DPSCs at 24-hour and 48-hour time point.

  7. Effect of leukocyte alteration on treatment outcomes following preoperative chemoradiotherapy in patients with rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Gyu; Park, Won; Choi, Doo Ho [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); and others

    2017-09-15

    Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.

  8. Default Mode Network Alterations during Implicit Emotional Faces Processing in First-episode, Treatment-naive Major Depression Patients

    Directory of Open Access Journals (Sweden)

    Huqing eShi

    2015-08-01

    Full Text Available Previous studies have focused on resting-state default mode network (DMN alterations in the development and maintenance of depression; however, only a few studies have addressed DMN changes during task-related processing and their results are inconsistent. Therefore, we explored DMN patterns in young adult patients with first-episode, treatment-naïve major depressive disorder (MDD performing an implicit emotional processing task. Patients with MDD (N = 29 and healthy controls (N = 33 were subjected to functional magnetic resonance imaging (fMRI at rest and while performing a gender judgment task. Group independent component analysis (ICA was used to identify DMN component under task state for both groups. The DMN of participants with MDD had decreased functional connectivity in bilateral prefrontal areas compared to controls. Right prefrontal gyrus connectivity for MDD patients correlated negatively with scores on maladaptive scales of the Cognitive Emotion Regulation Questionnaire (CERQ. Our findings suggest that depressed people have altered DMN patterns during implicit emotional processing, which might be related to impaired internal monitoring and emotional regulation ability.

  9. Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment.

    Science.gov (United States)

    Wang, LianLian; Qi, HongBo; Baker, Philip N; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian

    2017-03-01

    BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), pPCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.

  10. Serial follow-up study of serum testosterone and antisperm antibodies in patients with non-obstructive azoospermia after conventional or microdissection testicular sperm extraction.

    Science.gov (United States)

    Komori, K; Tsujimura, A; Miura, H; Shin, M; Takada, T; Honda, M; Matsumiya, K; Fujioka, H

    2004-02-01

    Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection is becoming a first-line treatment even for non-obstructive azoospermia. The current focus of TESE is the identification of seminiferous tubules that contain spermatozoa and minimization of testicular damage. Although microdissection TESE has been introduced as a preferred procedure for sperm retrieval, no serial follow-up studies of testicular damage have been reported. In the present study, we assayed serum testosterone concentrations and for the presence of antisperm antibodies (ASA) for 1 year after conventional multiple TESE or microdissection TESE and compared postoperative testicular damage between procedures. Thirteen patients who underwent conventional multiple TESE and 12 patients who underwent microdissection TESE were included in this study. Serum total and free testosterone concentrations were evaluated before operation and 1, 6 and 12 months after TESE. Serum ASA was also evaluated before and 12 months after TESE. Serum total and free testosterone concentrations in all patients in both groups showed no significant postoperative decrease. A comparison between the two groups of serum total and free testosterone concentrations showed no significant difference (total testosterone, p = 0.2477; free testosterone, p = 0.3098). No incidence of new ASA formation was identified in the present study. In conclusion, TESE procedures cause neither a decrease of serum testosterone nor formation of ASA. Serum testosterone concentration are similar between patients in the conventional multiple TESE and microdissection groups. Therefore, microdissection TESE is safe with respect to testicular damage, particularly for patients with hypogonadism.

  11. Lauric acid and myristic acid prevent testosterone induced prostatic hyperplasia in rats.

    Science.gov (United States)

    Veeresh Babu, S V; Veeresh, B; Patil, Anup A; Warke, Y B

    2010-01-25

    Numerous plants have proven to improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with benign prostatic hyperplasia. Major components of those plants were lauric acid and myristic acid. Our study investigated whether lauric acid or myristic acid prevent testosterone induced prostatic hyperplasia in rats. Rats were divided into negative control and testosterone induced prostatic hyperplasia rats (positive control, low dose lauric acid treated, high dose lauric acid treated, low dose of myristic acid treated, high dose of myristic acid treated, finasteride treated). Testosterone and drug treatment were carried out for 14 days. Body weights were recorded before and after treatment. On 15th day, rats were sacrificed, prostates were weighed and histopathological studies were carried out. Lauric acid/myristic acid treatment showed significant inhibition of prostate enlargement and protection of histoarchitecture of prostate when compared with positive control group. In conclusion, the study showed that lauric acid/myristic acid reduced the increase of both prostate weight and prostate weight:body weight ratio, markers of testosterone induced prostatic hyperplasia in rats.

  12. Sexual desire in female-to-male transsexual persons: exploration of the role of testosterone administration.

    Science.gov (United States)

    Wierckx, Katrien; Elaut, Els; Van Caenegem, Eva; Van De Peer, Fleur; Dedecker, David; Van Houdenhove, Ellen; T'Sjoen, Guy

    2011-08-01

    To describe sexual desire in female-to-male transsexual persons post sex reassignment surgery (SRS). The associations between serum androgen levels and sexual desire are examined. Single center cross-sectional study. Forty-five female-to-male transsexual persons post SRS completed a standardized questionnaire assessing sexual desire (Sexual Desire Inventory). In addition, participants were asked questions on sexual desire before starting hormone treatment and having SRS. Serum levels of testosterone, LH and sex hormone-binding globulin were measured on fasting morning serum samples. In retrospect, 73.9% of the participants reported an increase in sexual desire after hormone treatment and SRS. Solitary sexual desire scores were significantly correlated with frequency of masturbation (r=0.835; Pfemale-to-male transsexual persons with elevated levels of LH, indicating suboptimal testosterone therapy, reported significantly lower solitary sexual desire levels (than those with low LH levels; P=0.007). Suppressed LH levels were also associated with having a higher need for sexual activities (P=0.009) and a higher frequency of excessive sexual desire (P=0.007). Most female-to-male transsexual persons report on a marked increase in sexual desire after testosterone treatment and SRS. No direct associations between levels of testosterone and solitary or dyadic sexual desire were found. However, measures of sexual desire were inversely associated with LH levels.

  13. Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion.

    Science.gov (United States)

    Mechlin, Clay W; Frankel, Jason; McCullough, Andrew

    2014-01-01

    Current U.S. Food and Drug Administration-approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels. We hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions. Men treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test. TT level at 6, 15, or >15 weeks from TP insertion. Thirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group. Men on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression. © 2013 International Society for Sexual Medicine.

  14. A preliminary analysis of microRNA-21 expression alteration after antipsychotic treatment in patients with schizophrenia.

    Science.gov (United States)

    Chen, Sheng-Dong; Sun, Xin-Yang; Niu, Wei; Kong, Ling-Ming; He, Ming-Jun; Fan, Hui-Min; Li, Wan-Shuai; Zhong, Ai-Fang; Zhang, Li-Yi; Lu, Jim

    2016-10-30

    Schizophrenia is a severe and debilitating psychiatric disorder of unknown etiology, and its diagnosis is essentially based on clinical symptoms. Despite growing evidence on the relation of altered expression of miRNAs and schizophrenia, most patients with schizophrenia usually had an extensive antipsychotic treatment history before miRNA expression profile analysis, and the pharmacological effects on miRNA expression are largely unknown. To overcome these impediments, miRNA microarray analysis was performed in peripheral blood mononuclear cells (PBMCs) obtained from patients with schizophrenia who were not on antipsychotic medication and healthy controls. Then, using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we verified the top 10 miRNAs with the highest fold-change values from microarray analysis in 82 patients with schizophrenia and 43 healthy controls, and nine miRNAs demonstrated significant differences in expression levels. Finally, we compared these nine miRNA profiles before and after antipsychotic treatment. Our results revealed that serum miR-21 expression decreased strikingly in patients after antipsychotic treatment. The change of miR-21 expression was negatively correlated with improvement of positive, general psychopathology, and aggressiveness symptoms. This study preliminarily analyzed the possible changes in circulating miRNAs expression in response to antipsychotic medication for schizophrenia, and the molecular mechanisms of this needs to be further explored. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    Science.gov (United States)

    Guasti, Leonardo; Richardson, Denise; Jhaveri, Maulik; Eldeeb, Khalil; Barrett, David; Elphick, Maurice R; Alexander, Stephen PH; Kendall, David; Michael, Gregory J; Chapman, Victoria

    2009-01-01

    Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P endocannabinoids and related compounds in neuropathic pain states. PMID:19570201

  16. Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healing-associated genes

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    Matt C Danzi

    2016-01-01

    Full Text Available Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion (DRG sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

  17. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Elphick Maurice R

    2009-07-01

    Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

  18. Melatonin and its correlation with testosterone in polycystic ovarian syndrome

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    Priyanka Jain

    2013-01-01

    increased in patients (63.27 ΁ 10.97 pg/mL than in controls (32.51 ΁ 7.55 pg/mL. Melatonin was found to be raised in all the cases of PCOS (above cut-off value of ≥45 pg/mL, P < 0.001. Total testosterone level was also raised in 72% of patients. Melatonin levels were found to be positively associated with increased testosterone (P < 0.001. In regression analysis using melatonin as dependent variable and testosterone as an independent variable, the value of R2 Χ 100 (percent variation was found to be 72.1%. Conclusions: Women with PCOS have significantly raised serum melatonin levels and hyperandrogenemia along with increased number of atretic follicles. Further studies are required to establish a definite role of melatonin in PCOS cases with disturbed hormonal milieu. This could open up the way for therapeutic role of melatonin in treatment of patients suffering from PCOS.

  19. Men in committed, romantic relationships have lower testosterone.

    Science.gov (United States)

    Burnham, T C; Chapman, J Flynn; Gray, P B; McIntyre, M H; Lipson, S F; Ellison, P T

    2003-08-01

    Variation in human male testosterone levels may reflect, and effect, differential behavioral allocation to mating and parenting effort. This proposition leads to the hypothesis that, among North American men, those involved in committed, romantic relationships will have lower testosterone levels than men not involved in such relationships. Our study is the first to examine whether being in such a relationship (rather than being married) is the meaningful predictor of male testosterone levels. To test this hypothesis, 122 male Harvard Business School students filled out a questionnaire and collected one saliva sample (from which testosterone level was measured). Results revealed that men in committed, romantic relationships had 21% lower testosterone levels than men not involved in such relationships. Furthermore, the testosterone levels of married men and unmarried men who were involved in committed, romantic relationships did not differ, suggesting that, at least for this sample, male pair bonding status is the more significant predictor of testosterone levels than is marital status.

  20. Insulin Treatment May Alter Fatty Acid Carriers in Placentas from Gestational Diabetes Subjects.

    Science.gov (United States)

    Ruiz-Palacios, Maria; Prieto-Sánchez, Maria Teresa; Ruiz-Alcaraz, Antonio José; Blanco-Carnero, José Eliseo; Sanchez-Campillo, Maria; Parrilla, Juan José; Larqué, Elvira

    2017-06-06

    There is little information available on the effect of Gestational diabetes mellitus (GDM) treatment (diet or insulin) on placental lipid carriers, which may influence fetal fat accretion. Insulin may activate placental insulin receptors protein kinase (AKT) and extracellular signal regulated kinase ERK mediators, which might affect lipid metabolism. Placenta was collected from 25 control women, 23 GDM-Diet and 20 GDM-Insulin. Western blotting of insulin signaling mediators and lipid carriers was performed. The human choricarcinoma-derived cell line BeWo was preincubated with insulin inhibitors protein kinase (AKT) and extracellular signal regulated kinase (ERK) and ERK inhibitors to evaluate insulin regulation of lipid carriers. Maternal serum insulin at recruitment correlated to ultrasound fetal abdominal circumference in offspring of GDM and placental endothelial lipase (EL). Lipoprotein lipase in placenta was significantly reduced in both GDM, while most of the other lipid carriers tended to higher values, although not significantly. There was a significant increase in both phosphorylated-Akt and ERK in placentas from GDM-Insulin patients; both were associated to placental fatty acid translocase (FAT), fatty acid binding protein (A-FABP), and EL. BeWo cells treated with insulin pathway inhibitors significantly reduced A-FABP, fatty acid transport protein (FATP-1), and EL levels, confirming the role of insulin on these carriers. We conclude that insulin promotes the phosphorylation of placental insulin mediators contributing to higher levels of some specific fatty acid carriers in the placenta and fetal adiposity in GDM.

  1. Annual glyphosate treatments alter growth of unaffected bentgrass (Agrostis weeds and plant community composition.

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    Collin W Ahrens

    Full Text Available Herbicide resistance is becoming more common in weed ecotypes and crop species including turfgrasses, but current gaps in knowledge limit predictive ecological risk assessments and risk management plans. This project examined the effect of annual glyphosate applications on the vegetative growth and reproductive potential of two weedy bentgrasses, creeping bentgrass (CB and redtop (RT, where the glyphosate resistance (GR trait was mimicked by covering the bentgrass plants during glyphosate application. Five field plots were studied in habitats commonly inhabited by weedy bentgrasses including an agricultural hayfield, natural meadow, and wasteland. Results showed that annual glyphosate treatment improved bentgrass survivorship, vegetative growth, and reproductive potential compared with bentgrass in unsprayed subplots. In the second year of growth, RT plants had an 86-fold increase in flower number in glyphosate-treated subplots versus controls, while CB plants had a 20-fold increase. At the end of the three year study, plant community composition had changed in glyphosate-treated subplots in hayfield and meadow plots compared to controls. Soils in subplots receiving glyphosate had higher nitrate concentrations than controls. This is the first study to mimic the GR trait in bentgrass plants with the goal of quantifying bentgrass response to glyphosate selection pressure and understanding the impacts on surrounding plant communities.

  2. Annual Glyphosate Treatments Alter Growth of Unaffected Bentgrass (Agrostis) Weeds and Plant Community Composition

    Science.gov (United States)

    Ahrens, Collin W.; Auer, Carol A.

    2012-01-01

    Herbicide resistance is becoming more common in weed ecotypes and crop species including turfgrasses, but current gaps in knowledge limit predictive ecological risk assessments and risk management plans. This project examined the effect of annual glyphosate applications on the vegetative growth and reproductive potential of two weedy bentgrasses, creeping bentgrass (CB) and redtop (RT), where the glyphosate resistance (GR) trait was mimicked by covering the bentgrass plants during glyphosate application. Five field plots were studied in habitats commonly inhabited by weedy bentgrasses including an agricultural hayfield, natural meadow, and wasteland. Results showed that annual glyphosate treatment improved bentgrass survivorship, vegetative growth, and reproductive potential compared with bentgrass in unsprayed subplots. In the second year of growth, RT plants had an 86-fold increase in flower number in glyphosate-treated subplots versus controls, while CB plants had a 20-fold increase. At the end of the three year study, plant community composition had changed in glyphosate-treated subplots in hayfield and meadow plots compared to controls. Soils in subplots receiving glyphosate had higher nitrate concentrations than controls. This is the first study to mimic the GR trait in bentgrass plants with the goal of quantifying bentgrass response to glyphosate selection pressure and understanding the impacts on surrounding plant communities. PMID:23226530

  3. Sensitivity to Ethephon Degreening Treatment Is Altered by Blue LED Light Irradiation in Mandarin Fruit.

    Science.gov (United States)

    Deng, Lili; Yuan, Ziyi; Xie, Jiao; Yao, Shixiang; Zeng, Kaifang

    2017-08-02

    Although citrus fruits are not climacteric, exogenous ethylene is widely used in the degreening treatment of citrus fruits. Irradiation with blue light-emitting diode (LED) light (450 nm) for 10 h can promote the formation of good coloration of ethephon-degreened fruit. This study evaluated the effect of blue LED light irradiation on the pigments contents of ethephon-degreened fruit and evaluated whether the blue LED light irradiation could influence the sensitivity of mandarin fruit to ethylene. The results indicated that blue light can accelerate the color change of ethephon-degreened fruit, accompanied by changes in plastid ultrastructure and chlorophyll and carotenoid contents. Ethephon-induced expressions of CitACS1, CitACO, CitETR1, CitEIN2, CitEIL1, and CitERF2 were enhanced by blue LED light irradiation, which increased the sensitivity to ethylene in ethephon-degreened fruits. These results indicate that blue LED light-induced changes in sensitivity to ethylene in mandarin fruit may be responsible for the improved coloration of ethephon-degreened mandarin fruits.

  4. Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus

    Science.gov (United States)

    Jellyman, Juanita K.; De Blasio, Miles J.; Johnson, Emma; Giussani, Dino A.; Broughton Pipkin, Fiona; Fowden, Abigail L.

    2015-01-01

    Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155

  5. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women.

    Science.gov (United States)

    Wang, Xuewen; Smith, Gordon I; Patterson, Bruce W; Reeds, Dominic N; Kampelman, Janine; Magkos, Faidon; Mittendorfer, Bettina

    2012-03-15

    Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (∼10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P > 0.05); the muscle protein fractional synthesis rate, however, increased by ∼45% (P testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women.

  6. Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species.

    Science.gov (United States)

    Jena, Ashish Kumar; Vasisht, Karan; Sharma, Neetika; Kaur, Ramdeep; Dhingra, Mamta Sachdeva; Karan, Maninder

    2016-08-22

    Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species. In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents. The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC. The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH. These findings are

  7. Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral glucose utilization

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    Engber, T.M.; Susel, Z.; Kuo, S.; Chase, T.N. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1990-12-01

    The effect of chronic levodopa administration on the functional activity of the basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The rates of local cerebral glucose utilization were studied under basal conditions as well as in response to challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100 mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an osmotic pump or intermittently by twice-daily injections. Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula. In control (lesioned and treated chronically with saline) rats, the D1 agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and 56%, respectively. Both continuous and intermittent levodopa blunted the SKF 38393-induced elevation in glucose metabolism in the substantia nigra pars reticulata, while intermittent levodopa also attenuated the increase in the entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not increase glucose utilization in any brain region in control animals; following intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64% in the subthalamic nucleus and by 39% in the deep layers of the superior colliculus on the ipsilateral side.

  8. Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes.

    Science.gov (United States)

    Salehzadeh, Firoozeh; Rune, Anna; Osler, Megan; Al-Khalili, Lubna

    2011-08-01

    Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E(2)) in metabolism and investigated whether either hormone may mediate a sex-specific effect. Myotubes from postmenopausal women and age-matched male donors were treated with 10 nM testosterone or E(2) for 4 days, and assays were performed to measure metabolic readouts, signal transduction, and mRNA expression. Testosterone and E(2) treatment enhanced insulin-stimulated glucose incorporation into glycogen and AKT phosphorylation in myotubes from female donors, highlighting a sex-specific role of sex hormone in glucose metabolism. Testosterone treatment increased palmitate oxidation in myotubes from both female and male donors, while E(2) enhanced palmitate oxidation in myotubes from male donors only. Testosterone-mediated increase in palmitate oxidation was attenuated at the presence of androgen receptor antagonist, which may indicate a role of nuclear steroid receptor in muscle lipid oxidation. Testosterone treatment increased mRNA expression of the insulin receptor substrate 2 in myotubes from male and female donors, whereas it increased mRNA expression of glycogen synthase 1 only in myotubes from male donors. E(2) treatment increased pyruvate dehydrogenase kinase 4 mRNA expression in myotubes from female donors. Thus, our data suggest that testosterone or E(2) modulates muscle glucose and lipid metabolism and may play a role in metabolism in a sex-dependent manner.

  9. Genetic determinants of serum testosterone concentrations in men.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    2011-10-01

    Full Text Available Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871 and two de novo replication cohorts (n = 4,620 to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG locus (17p13-p12 were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41 and rs6258, p = 2.3×10(-22. Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16. The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01. Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

  10. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Desdoits-Lethimonier, Christèle; Mackey, Abigail L

    2018-01-01

    and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby...

  11. Hypoactive sexual desire in transsexual women: prevalence and association with testosterone levels.

    Science.gov (United States)

    Elaut, Els; De Cuypere, Griet; De Sutter, Petra; Gijs, Luk; Van Trotsenburg, Michael; Heylens, Gunter; Kaufman, Jean-Marc; Rubens, Robert; T'Sjoen, Guy

    2008-03-01

    An unknown proportion of transsexual women (defined as post-operative male-to-female transsexuals on oestrogen replacement) experience hypoactive sexual desire disorder (HSDD). It has been suggested that the absence of ovarian androgen production together with oestrogen treatment-related increase in sex hormone-binding globulin (SHBG) levels could be leading to HSDD, due to low levels of biologically available testosterone. This study wishes to document the HSDD prevalence among transsexual women and the possible association to androgen levels. Cross-sectional study. Transsexual women (n=62) and a control group of ovulating women (n=30) participated in this study. Questionnaires measuring sexual desire (sexual desire inventory) and relationship and sexual satisfaction (Maudsley Marital Questionnaire) were completed. Serum levels of total testosterone, LH and SHBG were measured in blood samples o