Sexuality in older adults

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Adrián Sapetti

2015-07-01

Full Text Available Just as the body and its functions undergo changes with age, in the same way sexuality shares this aging process. However, remember a golden rule that we are sexual since we are born until we die; only possibilities are modified with the passage of the years. This article intends to show the changes that occur in the sexual response of the elderly. If sexual life during youth was pleasant and satisfactory this will condition sexuality in the socalled third age and the elderly seek to maintain it, this is not the case for those who had a dysfunctional past. This article briefly describes the andropause and the SIM, vicissitudes, changes and differences in sexual response and chances to maintain eroticism in the older adult. 

"O homem é mesmo a sua testosterona": promoção da andropausa e representações sobre sexualidade e envelhecimento no cenário brasileiro

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Fabíola Rohden

2011-06-01

Full Text Available O artigo trata da construção recente de novos diagnósticos médicos e de um correspondente mercado consumidor em potencial considerando o caso do distúrbio androgênico do envelhecimento masculino ou andropausa, "doença" que afetaria os homens a partir dos 35-40 anos de idade. A perspectiva utilizada centra-se nos estudos sociais da ciência e gênero e particularmente na necessidade de investigar as redes criadas no processo de construção dessa nova categoria. Por meio da análise da produção científica e da trajetória da construção da andropausa como fenômeno de interesse público, elabora-se um processo inédito de medicalização do homem e da sexualidade masculina, via o reforço na centralidade dos hormônios como modelo preponderante de entendimento corporal. Além disso, destaca-se a promoção de uma intrincada conexão simbólica que associa juventude, saúde, beleza e atividade sexual nos processos de patologização das fases ou de condições de vida e na recusa do envelhecimento.The article deals with the recent construction of new medical diagnoses and a corresponding potential consumer market by considering the case of Androgen Disorders of the Male Aging, or Andropause, "disease" that supposedly affected men from 35-40 years old. The approach used focuses on the social studies of science and gender and in particular the need to investigate the networks created in the process of the construction of this new category. Through the analysis of scientifi c production and the trajectory of construction of Andropause as a phenomenon of public interest, an unprecedented process of medicalization of men and male sexuality is enacted, by strengthening the centrality of hormones as predominant model for understanding the body. Moreover, there is the promotion of an intricate symbolic connection that links youth, health, beauty and sexual activity in the pathologization of the phases or conditions of life and the refusal of

Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

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Fernández-Atucha, A; Izagirre, A; Fraile-Bermúdez, A B; Kortajarena, M; Larrinaga, G; Martinez-Lage, P; Echevarría, E; Gil, J

2017-01-01

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

TRPV1 may increase the effectiveness of estrogen therapy on neuroprotection and neuroregeneration

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Ricardo Ramírez-Barrantes

2016-01-01

Full Text Available Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system. Their diminution is associated with impaired cognitive and mental health and increased risk of neurodegenerative diseases. Then, restoring neuroendocrine axes during aging can be key to enhance brain health through neuroprotection and neuroregeneration, depending on the modulation of plasticity mechanisms. Estrogen-dependent transient receptor potential cation channel, subfamily V, member 1 (TRPV1 expression induces neuroprotection, neurogenesis and regeneration on damaged tissues. Agonists of TRPV1 can modulate neuroprotection and repair of sensitive neurons, while modulators as other cognitive enhancers may improve the survival rate, differentiation and integration of neural stem cell progenitors in functional neural network. Menopause constitutes a relevant clinical model of steroidal production decline associated with progressive cognitive and mental impairment, which allows exploring the effects of hormone therapy in health outcomes such as dysfunction of CNS. Simulating the administration of hormone therapy to virtual menopausal individuals allows assessing its hypothetical impact and sensitivity to conditions that modify the effectiveness and efficiency.

The 2017 hormone therapy position statement of The North American Menopause Society.

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2017-07-01

relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended.This NAMS position statement has been endorsed by Academy of Women's Health, American Association of Clinical Endocrinologists, American Association of Nurse Practitioners, American Medical Women's Association, American Society for Reproductive Medicine, Asociación Mexicana para el Estudio del Climaterio, Association of Reproductive Health Professionals, Australasian Menopause Society, Chinese Menopause Society, Colegio Mexicano de Especialistas en Ginecologia y Obstetricia, Czech Menopause and Andropause Society, Dominican Menopause Society, European Menopause and Andropause Society, German Menopause Society, Groupe d'études de la ménopause et du vieillissement Hormonal, HealthyWomen, Indian Menopause Society, International Menopause Society, International Osteoporosis Foundation, International Society for the Study of Women's Sexual Health, Israeli Menopause Society, Japan Society of Menopause and Women's Health, Korean Society of Menopause, Menopause Research Society of Singapore, National Association of Nurse Practitioners in Women's Health, SOBRAC and FEBRASGO, SIGMA Canadian Menopause Society, Società Italiana della Menopausa, Society of Obstetricians and Gynaecologists of Canada, South African Menopause Society, Taiwanese Menopause Society, and the Thai Menopause Society. The American College of Obstetricians and Gynecologists supports the value of this clinical document as an educational tool, June 2017. The British Menopause Society supports this Position Statement.

Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway

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Woong Jin Bae

2017-01-01

Full Text Available The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH symptoms such as erectile dysfunction (ED. A previous research suggested that a modified Ojayeonjonghwan (KH-204 could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1 preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase-1 (HO-1; (2 lowered the expression of transforming growth factor-beta (TGF-β 1/SMAD; (3 increased the average of serum testosterone in androgen-deprived male rats; (4 kept the activation of spermatogenesis; (5 upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG and degraded the contents of superoxide dismutase (SOD; and (6 reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

Towards ICF implementation in menopause healthcare: a systematic review of ICF application in Switzerland.

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Zangger, Martina; Poethig, Dagmar; Meissner, Florian; von Wolff, Michael; Stute, Petra

2017-12-28

To present a systematic literature review on the application and degree of implementation of the International Classification of Functioning, Disability and Health (ICF) across different health conditions and regions in Switzerland in order to develop an ICF classification of the climacteric syndrome in the medium term. A systematic literature search was conducted through Embase and Medline covering the period between 2011 and August 2016. Inclusion criteria were the term ICF in title or abstract and Switzerland as the workplace of the first author. Identified publications were analysed as descriptive statistics. A total of 83 articles were included in the analysis. Forty-seven different first authors from 24 different institutions were identified. The majority of publications were from Swiss Paraplegic Research (68.7%) and focused on neurology (31.3%). Forty-six cohort studies were identified. In most of them, the ICF was used to set up a general language for comparing patients' information (82.9%). Only one paper from the medical specialty gynaecology was identified; this was on breast cancer. No paper on the menopause was found. In Switzerland, the ICF is actively used in various areas of healthcare, especially in the field of neurology and rehabilitation. There is a need for ICF core sets in other medical fields, such as menopause healthcare, in order to accomplish the goal of the European Menopause and Andropause Society, which is a healthcare model for healthy menopause and aging.

Partielle endokrine Veränderungen des alternden Mannes (PEVAM: Facts and Fiction

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Ponholzer A

2000-01-01

Full Text Available Die kontinuierliche Abnahme der Sexualhormone Testosteron und Dehydroepiandrosteronsulfat (DHEA-S in Verbindung mit dem Altern des Mannes steht heutzutage außer Zweifel [1, 2]. Die beim Mann zu beobachtenden Änderungen im Hormonhaushalt unterscheiden sich von denen der Frau durch den langsamen, stetigen Verlauf und die oftmalige Erhaltung der Fertilität bis ins höchste Alter. Es ist daher falsch, von einem "Klimakterium virile" oder von "Andropause" zu sprechen. Das Ausmaß der Abnahme der Androgenspiegel unterliegt, ebenso wie das Bestehen einer assoziierten Symptomatik, einer hohen interindividuellen Streuung. Unter dem Begriff PADAM (partielles Androgendefizit des alternden Mannes werden als Auswirkung verminderter Androgenspiegel vielfältige Symptome beschrieben, wie zum Beispiel Hitzewallungen, Schlafstörungen, Einschränkungen des Wohlbefindens und der Sexualität sowie Abnahme von Knochendichte und Muskelmasse oder Veränderung von Fettverteilungsmuster und Gesamtkörperfettanteil. Bei Vorliegen von einem oder mehreren der oben genannten Symptome in Verbindung mit entsprechend verminderten Testosteronspiegeln existiert die Möglichkeit einer Substitutionstherapie, sowohl zur Prävention, als auch zur Therapie negativer Auswirkungen des Mangels. Potentielle Risiken einer Androgentherapie scheinen kontrollierbar, werden aber erst in Zukunft durch umfassende Langzeitstudien in ihrem ganzen Ausmaß beurteilbar sein. Andere Hormonsysteme, wie etwa Wachstumshormone (GH oder Melatonin unterliegen ebenfalls einer altersassozierten Abnahme. Auch hier darf eine Auswirkung auf die Lebensqualität angenommen werden, die Sinnhaftigkeit einer Ersatztherapie ist bei GH und Melatonin, wie auch bei DHEA-S, jedoch umstritten.

Effects of young-coconut juice on increasing mandibular cancellous bone in orchidectomized rats: Preliminary novel findings

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Pranee Suwanpal

2011-12-01

Full Text Available Androgens play a very important role in building the skeleton in young adults and help to prevent bone loss andosteoporosis in aging men. In addition, in hypogonadism or elderly men, bone mass has been related to estrogen levels ratherthan to testosterone. Estrogen replacement therapy has therefore been proposed to prevent bone loss in males as well as infemales. Estrogen, however, has been considered to be one of the hormonal risk factors for benign prostatic hyperplasia andprostate cancer and also has other side effects. Young coconut juice (YCJ presumably containing phytoestrogen was investigatedin the present study for its possible beneficial effects on delaying osteoporosis using a male rat model, and by this totest the possibility that it might be able to replace estrogen replacement therapy without side effects. In this study, mandibularcancellous bone was used as the osteoporotic model. Using the same model, we have previously found that total cartilagethickness particularly the hypertrophic zone of mandibular condylar cartilage was thicker in the sham-operated rats receivingYCJ orally fed for a 14 day period, compared with sham, orchidectomized animal, orchidectomized rats receiving estradiolbenzoate, and orchidectomized rats receiving YCJ. The present study confirmed our former study that mandibular cancellousbone in the sham-operated rats and in the orchidectomized rats receiving YCJ orally fed for a 14–day period were thicker thanthose of the sham and orchidectomized rat groups. This study results are novel and they indicate that YCJ may have beneficialeffects in the treatment of osteoporosis in andropause men.

Nuevas tendencias de la medicalización New tendencies in medicalization

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José Augusto Cabral Barros

2008-04-01

Full Text Available Comenzando con un análisis crítico del rol de los medicamentos en la práctica de profesionales de salud y consumidores, el texto intenta recalcar la influencia ejercida por las estrategias promocionales, tanto las mas antiguas como las mas recientes, por iniciativa de los productores, con el fin de reforzar valores y creencias que sobrepasan lo que se puede obtener con la utilización de un fármaco. Son seleccionados algunos ejemplos para ilustrar el problema de la intensificación del proceso de "medicalización", particularmente a partir de los equívocos advenidos del uso irracional de anfetaminas volcadas hacia el control del apetito, o hacia los niños clasificados como "hiper-activos" y "con deficit de atención", además de los fármacos para andropausia o depresión.Beginning with a critical analysis of the role drugs play in the behavior of consumers and health professionals, this text aims at evaluating the influence of both traditional and new promotional strategies of the pharmaceutical industry designed to create values and believes that exceed what in fact can be expected from drug consumption. Some examples were chosen to illustrate the intensification of the medicalization process. Special emphasis was given to the irrational use of amphetamines to diminish the appetite and to control weight or to treat children supposedly suffering from Attention-Deficit Hyperactivity Disorder (ADHD as well as to drugs used in cases of depression and supposed andropause.

Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment.

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Huhtaniemi, Ilpo

2014-01-01

Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM). Late-onset hypogonadism (LOH) describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH)) or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH). The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty). A problem with the diagnosis of LOH is that often the symptoms (in 20%-40% of unselected men) and low circulating T (in 20% of men >70 years of age) do not coincide in the same individual. The European Male Ageing Study (EMAS) has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefi ts and short- and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH.

Association between vitamin D deficiency and heart failure risk in the elderly.

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Porto, Catarina Magalhães; Silva, Vanessa De Lima; da Luz, João Soares Brito; Filho, Brivaldo Markman; da Silveira, Vera Magalhães

2018-02-01

The aim of this study was to evaluate the association between vitamin D deficiency and risk of heart failure in elderly patients of cardiology outpatient clinics. A cross-sectional study with an analytical approach was employed. Clinical data were collected from the elderly from August 2015 to February 2016. The dependent variable was the risk of heart failure; the independent variable was vitamin D deficiency; and intervening factors were age, gender, education, ethnicity, hypertension, diabetes mellitus, hypothyroidism, renal failure, dementia, stroke, dyslipidaemia, depression, smoking, alcoholism, obesity, andropause, and cardiac arrhythmia. To analyse the association between vitamin D deficiency and risk of heart failure, we used the bivariate logistic analysis, followed by analysis through the multivariate logistic regression model. Of the 137 elderly, the study found the following: women (75.9%); overweight (48.2%); obese (30.6%); increase in the index waist/hip (88.3%); dyslipidaemia (94.2%) and hypertension (91.2%); coronary artery disease (35.0%); and 27.7% with cardiac arrhythmia or left ventricular hypertrophy. Sixty-five per cent of the elderly were deficient in vitamin D. The risk of heart failure was significantly associated with vitamin D deficiency [odds ratio (OR): 12.19; 95% confidence interval (CI) = 4.23-35.16; P = 0.000], male gender (OR: 15.32; 95% CI = 3.39-69.20, P = 0.000), obesity (OR: 4.17; 95% CI = 1.36-12.81; P = 0.012), and cardiac arrhythmia (OR: 3.69; 95% CI = 1.23-11.11; P = 0.020). There was a high prevalence of vitamin D deficiency in the elderly, and the evidence shows a strong association between vitamin D deficiency and increased risk of heart failure in this population. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Effects of growth hormone and testosterone therapy on aerobic and anaerobic fitness , body composition and lipoprotein profile in middle-aged men

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Adam ZajÄ…c

2014-03-01

Full Text Available Introduction. Andropause and aging are associated with neuroendocrine dysfunctions. Growth hormone and testosterone play a significant role in several processes affecting adaptation and thereby also everyday functioning. The aim of this research project was to evaluate the effects of recombinant human growth hormone and testosterone enanthate injections on body mass and body composition, aerobic and anaerobic fitness and lipid profile in middle-aged men. Materials and method. The research group was comprised of 14 men aged 45 – 60 years. Two series of laboratory analyses were performed. Independent tests were carried out at baseline and after 12 weeks of the experiment. The data were analyzed using Statistica 9.1 software. Results. A two-way repeated measures ANOVA revealed a statistically significant effect of the intervention programme on fat-free mass (η2=0.34, total body fat (η2=0.79, total cholesterol (η2=0.30, high-density lipoprotein cholesterol (η2=0.31, low-density lipoprotein cholesterol (η2=0.42, triglyceride (η2=0.28, testosterone (η2=0.52, insulin-like growth factor 1 (η2=0.47 and growth hormone (η2=0.63. Furthermore, ANOVA revealed a statistically significant effect of the rhGH and T treatment on maximal oxygen uptake (η2=0.63, anaerobic threshold (η2=0.61 and maximal work rate (η2=0.53. Conclusion. It should be emphasized that the lipid profile was affected not only by rhGH+T replacement therapy, but also by the prescribed physical activity programme. The strength and endurance fitness programme alone did not cause significant changes in body mass and composition, nor the anaerobic and aerobic capacity. On the other hand, the rhGH=T treatment stimulated these changes significantly.

Male hypogonadism at a tertiary care hospital in Karachi, Pakistan.

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Ram, Nanik; Asghar, Ali; Hashmi, Fauzan; Islam, Najmul

2012-01-01

Male hypogonadism is defined as 'inadequate gonadal function, manifested by deficiency in gametogenesis and/or secretion of gonadal hormones'. Signs and symptoms of hypogonadism depend primarily on the age of onset. It can be classified according to the site primarily involved: the gonads, the hypothalamus, or the pituitary gland. The objective this study was to determine the presentation and aetiology of male hypogonadism seen in a tertiary care hospital. This cross-sectional study was conducted at Endocrine Clinics, Aga Khan University Hospital Karachi. Data of male patients with hypogonadism who attended clinics during January 2009 to August 2011 were reviewed. All male patients with clinical and biochemical evidence of hypogonadism were included in the study. Patients with Diabetes Mellitus, Metabolic Syndrome, Andropause, AIDS, Chronic Renal Failure, and Cirrhosis were excluded. Mean +/- SD were computed for quantitative variables. Frequency and percentages were computed for qualitative variables. Aetiology of male hypogonadism was categorised as primary and secondary hypogonadism. A total of 85 patients with male hypogonadism attended the endocrine clinic. Mean age of patients was 25 +/- 10 years. Clinical presentations were small genitalia (65%), absent secondary sexual characteristics (53%), not attained puberty (47%), infertility (53%), erectile dysfunction (41%) and loss of libido (29%). Seventy-three (86%) patients had hypogonadotrophic hypogonadism (secondary hypogonadism) and 12 (14%) patients had hypergonadotrophic hypogonadism (primary hypogonadism). Among the patients with hypogonadotrophic hypogonadism 38 had idiopathic hypogonadotrophic hypogonadsim, 7 had pituitary adenoma, 6 had empty sella syndrome, 3 had Kallman's syndrome, and 1 patient had haemosiderosis due to thalassaemia major; 18 patients did not undergo brain imaging. Small genitalia, absent secondary sexual characteristics and infertility were the main presenting features of hypogonad

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

International Nuclear Information System (INIS)

Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

2015-01-01

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

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Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

2015-11-27

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice.

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Syed Nuruddin

Full Text Available Research on Alzheimer's disease (AD has indicated an association between hormones of the hypothalamic-pituitary-gonadal (HPG axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mice with AD pathologies have led to improved understanding of the pathophysiological processes underlying AD. The aims of this study were to explore whether mRNA-levels of gonadotropin-releasing hormone (Gnrh and its receptor (Gnrhr were changed in plaque-bearing Alzheimer's disease transgenic mice and to investigate whether these levels and amyloid plaque deposition were downregulated by treatment with a gonadotropin-releasing hormone analog (Gnrh-a; Leuprorelin acetate. The study was performed on mice carrying the Arctic and Swedish amyloid-β precursor protein (AβPP mutations (tgArcSwe. At 12 months of age, female tgArcSwe mice showed a twofold higher level of Gnrh mRNA and more than 1.5 higher level of Gnrhr mRNA than age matched controls. Male tgArcSwe mice showed the same pattern of changes, albeit more pronounced. In both sexes, Gnrh-a treatment caused significant down-regulation of Gnrh and Gnrhr mRNA expression. Immunohistochemistry combined with quantitative image analysis revealed no significant changes in the plaque load after Gnrh-a treatment in hippocampus and thalamus. However, plaque load in the cerebral cortex of treated females tended to be lower than in female vehicle-treated mice. The present study points to the involvement of hormonal changes in AD mice models and demonstrates that these changes can be effectively counteracted by pharmacological treatment. Although known to increase in normal aging, our study shows that Gnrh/Gnrhr mRNA expression increases much more dramatically in tgArcSwe mice. Treatment with Leuprorelin acetate successfully abolished the transgene specific effects on Gnrh/Gnrhr mRNA expression. The present experimental

Off-label use of hormones as an antiaging strategy: a review

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Samaras N

2014-07-01

Full Text Available Nikolaos Samaras,1 Maria-Aikaterini Papadopoulou,2 Dimitrios Samaras,3 Filippo Ongaro1 1Clinique Générale Beaulieu, Geneva, Switzerland; 2Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland; 3Department of Medical Specialties, Clinical Nutrition, Geneva University Hospitals, Geneva, Switzerland Abstract: Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders

Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

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Ilpo Huhtaniemi

2014-04-01

Full Text Available Although suppressed serum testosterone (T is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction, physical (e.g. loss of vigor and frailty and psychological (e.g., depression symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM. Late-onset hypogonadism (LOH describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty. A problem with the diagnosis of LOH is that often the symptoms (in 20%-40% of unselected men and low circulating T (in 20% of men >70 years of age do not coincide in the same individual. The European Male Ageing Study (EMAS has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T <11 nmol l−1 and free T <220 pmol l−1 and three sexual symptoms (erectile dysfunction, and reduced frequency of sexual thoughts and morning erections. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefi ts and

Hormone replacement therapy in postmenopause - where we stand?

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Damir Franić

2007-02-01

Full Text Available Background: The findings of most relevant randomized clinical studies such as HERS, WHI and MWS, performed in the last decade have shown that hormonal replacement therapy (HRT users are at increased risk for the development of breast cancer, stroke and pulmonary edema. On the other hand they are at a lower risk for the development of large bowel cancer and for hip and vertebral fractures; the incidences of endometrial cancer and coronary heart disease have not been proved to be significantly affected by HRT. As for the prevention of cardiovascular diseases, the findings of these studies differed from those provided by observational studies, it became an imperative to find the causes of these discrepancies. The major criticism of randomized clinical studies was aimed at the inclusion criteria, as the mean women’s age in HERS and in WHI study was 63 years. The women of that age may no longer be healthy, and are particularly exposed to cardiovascular diseases. In all studies the same type of HRT was used, i.e. conjugated equine estrogen alone or in combination with medroxyprogesterone acetate. In Europe, this combination is rarely prescribed; we do not prescribe it in Slovenia either. The same type of HRT used in randomized clinical studies was further criticized, the basic idea of HRT being an individual approach to each woman requiring HRT. For rather sensational and often misinterpreted findings of randomized studies, the largest menopause societies worldwide, the International Menopause Society (IMS, the European Menopause and Andropause Society (EMAS and the North American Menopause Society (NAMS, have revised the guidelines for HRT use in postmenopause. These guidelines have been adopted by the Slovene Menopause Society as well.Conclusions: The indications for HRT remain to be markedly expressed and severe climacteric symptoms, prevention and treatment of osteoporosis, urogenital syndrome and premature menopause. However, the â

Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

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Huhtaniemi, Ilpo

2014-01-01

Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM). Late-onset hypogonadism (LOH) describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH)) or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH). The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty). A problem with the diagnosis of LOH is that often the symptoms (in 20%–40% of unselected men) and low circulating T (in 20% of men >70 years of age) do not coincide in the same individual. The European Male Ageing Study (EMAS) has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T <11 nmol l−1 and free T <220 pmol l−1) and three sexual symptoms (erectile dysfunction, and reduced frequency of sexual thoughts and morning erections). By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short

An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males

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Anderson Mark L

2008-08-01

Full Text Available Abstract Background Maintaining endogenous testosterone (T levels as men age may slow the symptoms of sarcopenia, andropause and decline in physical performance. Drugs inhibiting the enzyme 5α-reductase (5AR produce increased blood levels of T and decreased levels of dihydrotestosterone (DHT. However, symptoms of gynecomastia have been reported due to the aromatase (AER enzyme converting excess T to estradiol (ES. The carotenoid astaxanthin (AX from Haematococcus pluvialis, Saw Palmetto berry lipid extract (SPLE from Serenoa repens and the precise combination of these dietary supplements, Alphastat® (Mytosterone(™, have been reported to have inhibitory effects on both 5AR and AER in-vitro. Concomitant regulation of both enzymes in-vivo would cause DHT and ES blood levels to decrease and T levels to increase. The purpose of this clinical study was to determine if patented Alphastat® (Mytosterone(™ could produce these effects in a dose dependent manner. Methods To investigate this clinically, 42 healthy males ages 37 to 70 years were divided into two groups of twenty-one and dosed with either 800 mg/day or 2000 mg/day of Alphastat® (Mytosterone(™ for fourteen days. Blood samples were collected on days 0, 3, 7 and 14 and assayed for T, DHT and ES. Body weight and blood pressure data were collected prior to blood collection. One-way, repeated measures analysis of variance (ANOVA-RM was performed at a significance level of alpha = 0.05 to determine differences from baseline within each group. Two-way analysis of variance (ANOVA-2 was performed after baseline subtraction, at a significance level of alpha = 0.05 to determine differences between dose groups. Results are expressed as means ± SEM. Results ANOVA-RM showed significant within group increases in serum total T and significant decreases in serum DHT from baseline in both dose groups at a significance level of alpha = 0.05. Significant decreases in serum ES are reported for the 2000

Effects of young coconut juice on the numbers of argyrophil endocrine cells in the gastrointestinal tract of male rats: Novel preliminary findings

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Nisaudah Radenahmad

2014-12-01

shaped and occasionally spherical. There was a regional distribution of the argyrophil endocrine cells in all regions of the GI tract: stomach, duodenum, jejunum, ileum and colon, and that of the orx group had the lowest numbers. Estradiol benzoate (EB injection and YCJ feeding in the orx group reversed this phenomenon in all regions of GI tract except for the colon. The sham+YCJ group had the highest number of argyrophil cells. Regression correlation analysis between the argyrophil cell numbers and serum estrogen and testosterone levels were R2 0.0054 and 0.0355, respectively. The changes in the density of the GI argyrophil cells in the orchidectomized rats in the present study may contribute to the GI function abnormality e.g. GI motility, GI calcium absorption, GI hormone production and secretion etc. frequently encountered in patients with andropausal or elderly osteoporosis. Such impairment of calcium and probably other minerals in the orx rats could be reversed by exogenous estrogen e.g estradiol benzoate (EB supplement or by phytoestrogen e.g. YCJ feeding as preliminarily detected by the numbers of argyrophil endocrine cells in this study.