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Sample records for hormone-releasing hormone therapy

  1. Alpha-adrenergic regulation of growth hormone release after electroconvulsive therapy in man.

    Science.gov (United States)

    Vigas, M; Wiedermann, V; Németh, S; Jurcovicová, J; Zigo, L

    1976-01-01

    When electroshcok therapy was administered to male psychiatric patients without anticonvulsive premedication, serum growth hormone (GH) increased; the increase was not prevented by an infusion of 20% glucose (5 ml per min) 20 min prior to electroshock. Therefore, the GH rise is not caused by muscle exercise during convulsions. Infusing 30 mg of phentolamine 40 min prior to electroshcok inhibited the GH response. Phentolamine's effect shows that the stress-induced GH release that follows electroconvulsive therapy is mediated by alpha-adrenergic neurons.

  2. Familial growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism.

    OpenAIRE

    Stirling, H F; Barr, D G; Kelnar, C J

    1991-01-01

    A mother with pseudopseudohypoparathyroidism and her short son showed poor spontaneous growth hormone secretion, and provocation tests suggested a deficiency of growth hormone releasing factor. This is the first report of growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism. The boy has responded well to growth hormone treatment over a period of three years.

  3. Luteinizing hormone-releasing hormone receptor antagonist may reduce postmenopausal flushing

    NARCIS (Netherlands)

    Gastel, P. van; Zanden, M. van der; Telting, D.; Filius, M.; Bancsi, L.; Boer, H. de

    2012-01-01

    OBJECTIVE: Hormone therapy (HT) is the most effective treatment of postmenopausal (PMP) flushing; however, its use is often contraindicated. As an alternative option, we explored the efficacy of the luteinizing hormone-releasing hormone (LHRH) receptor antagonist cetrorelix in women with severe PMP

  4. Metabolism of growth hormone releasing peptides.

    Science.gov (United States)

    Thomas, Andreas; Delahaut, Philippe; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

    2012-12-04

    New, potentially performance enhancing compounds have frequently been introduced to licit and illicit markets and rapidly distributed via worldwide operating Internet platforms. Developing fast analytical strategies to follow these new trends is one the most challenging issues for modern doping control analysis. Even if reference compounds for the active drugs are readily obtained, their unknown metabolism complicates effective testing strategies. Recently, a new class of small C-terminally amidated peptides comprising four to seven amino acid residues received considerable attention of sports drug testing authorities due to their ability to stimulate growth hormone release from the pituitary. The most promising candidates are the growth hormone releasing peptide (GHRP)-1, -2, -4, -5, -6, hexarelin, alexamorelin, and ipamorelin. With the exemption of GHRP-2, the entity of these peptides represents nonapproved pharmaceuticals; however, via Internet providers, all compounds are readily available. To date, only limited information on the metabolism of these substances is available and merely one metabolite for GHRP-2 is established. Therefore, a comprehensive in vivo (po and iv administration in rats) and in vitro (with human serum and recombinant amidase) study was performed in order to generate information on urinary metabolites potentially useful for routine doping controls. The urine samples from the in vivo experiments were purified by mixed-mode cation-exchange solid-phase extraction and analyzed by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution/high-accuracy mass spectrometry. Combining the high resolution power of a benchtop Orbitrap mass analyzer for the first metabolite screening and the speed of a quadrupole/time-of-flight (Q-TOF) instrument for identification, urinary metabolites were screened by means of a sensitive full scan analysis and subsequently confirmed by high-accuracy product ion scan experiments. Two

  5. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

    OpenAIRE

    PERONI, CIBELE N.; Cesar Y. Hayashida; Nancy Nascimento; LONGUINI, VIVIANE C.; Toledo, Rodrigo A.; Paolo Bartolini; Bowers, Cyril Y.; Toledo,Sergio P. A.

    2012-01-01

    OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormone-receptors, were compared to those ...

  6. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. (Tulane Univ. School of Medicine, New Orleans, LA (USA))

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin (cis-diamminedichloroplatinum(II)) and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  7. Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

    Directory of Open Access Journals (Sweden)

    A.-M.J. Lengyel

    2006-08-01

    Full Text Available Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a discovery of this peptide, b mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c regulation of growth hormone release in man after intravenous administration of these peptides.

  8. GH responses to growth hormone releasing factor in depression.

    Science.gov (United States)

    Thomas, R; Beer, R; Harris, B; John, R; Scanlon, M

    1989-01-01

    The growth hormone (GH), thyrotrophin (TSH) and prolactin response to growth hormone releasing factor (GRF) was investigated in 18 patients suffering from major depression with melancholia and in 18 age- and sex-matched normal controls. There was no significant difference in the GH response to GRF stimulation between the patients and controls and in neither subject group was there a demonstrable TSH or prolactin response to GRF. These findings indicate that the pathophysiology underlying the blunted GH response to pharmacological challenge, demonstrated in other studies, must lie at a suprapituitary level.

  9. Algorithmic complexity of growth hormone release in humans.

    Science.gov (United States)

    Prank, K; Wagner, M; Brabant, G

    1997-01-01

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

  10. Algorithmic complexity of growth hormone release in humans

    Energy Technology Data Exchange (ETDEWEB)

    Prank, K.; Wagner, M.; Brabant, G. [Medical School Hannover (Germany)

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  11. contribution of growth hormone-releasing hormone and ...

    African Journals Online (AJOL)

    hormone (GHRH) and increased somatostatin secretion to this phenomenon. ... negative feedback effects of IGF-1 or combinations of these factors. Studies to ..... increase in lean body mass and reduction in adipose tissue.6. Reduced GH ...

  12. Stimulation of chicken growth hormone release by phorbol esters.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1990-11-01

    Synergism between thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) has been shown in a primary (48 hr) culture of chicken adenohypophyseal cells established in this laboratory. The purpose of the present study was to determine if phorbol esters acting alone or in concert with TRH or hpGRF affect chicken GH release. Collagenase-dissociated chicken adenohypophyseal cells were treated (2 hr) with combinations of TRH, hpGRF, phorbol esters (activators of protein kinase C; PKC), and pharmacologic agents that increase cAMP. Phorbol myristate acetate (PMA) or phorbol dibutyrate (PDBu) alone stimulated GH release in a dose-dependent manner; either phorbol ester (10(-6) M) increased GH release from 100 to 390% over the value obtained in the absence of test agents (control). Similarly, hpGRF (10(-9) M), 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX, 10(-3) M) alone elevated GH release by at least 60% over the control value. The combined effects of phorbol esters (either PMA or PDBu) and hpGRF, 8 Br-cAMP, or forskolin on GH release were additive. Only one combination, phorbol esters with IBMX, exerted synergistic effects on GH release. No synergy was shown between TRH (1.3 x 10(-9) M) and either phorbol ester. These findings are the first to implicate PKC in chicken GH release in vitro. In addition, these studies, together with previous results, suggest that TRH and hpGRF synergy occurs via a pathway that arises prior to activation of PKC.

  13. Acceleration of wound healing by growth hormone-releasing hormone and its agonists

    OpenAIRE

    Dioufa, Nikolina; Schally, Andrew V.; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L.; Owens, Gary K.; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-01-01

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). ...

  14. Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1990-01-01

    It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic m......-transgenic mice, 16 to 24 months of age, develop pituitary mammosomatotroph adenomas. These findings provide conclusive evidence that protracted stimulation of secretory activity can cause proliferation, hyperplasia and adenoma of adenohypophysial cells....

  15. Dopaminergic regulation of luteinizing hormone-releasing hormone release at the median eminence level: immunocytochemical and physiological evidence in hens.

    Science.gov (United States)

    Contijoch, A M; Gonzalez, C; Singh, H N; Malamed, S; Troncoso, S; Advis, J P

    1992-03-01

    Theoretically, the most effective inhibitory control of hypophysiotropic luteinizing hormone-releasing hormone (LHRH) release might occur through a presynaptic inhibition of LHRH neuronal terminals at the median eminence (ME) level. Since: (a) we have recently reported the existence of synaptic contacts between dopamine- and LHRH-containing processes in the ewe ME, and (b) nutritional deprivation induces an ovulatory failure in both birds and mammals, we have assessed the possibility that the anovulatory state induced by feed withdrawal (FW) in laying hens, might be caused by a dopaminergic inhibition of LHRH release at the ME level. Laying hens at the start (35 weeks old) and end (75 weeks old) of their commercial egg-laying life were killed at 0, 1, 2 and 4 days after FW. Serum luteinizing hormone (LH) and progesterone (P4), in vitro release of LHRH by isolated ME, and LHRH content in ME and preoptic area (POA) were determined by RIA. ME content of dopamine (DA) and its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were assessed by LCED. The distribution of LHRH and tyrosine hydroxylase (TH)-containing processes at the ME level of the hen was determined immunocytochemically. In the hen, LHRH-containing cell bodies are localized in the anterior hypothalamus and medial POA. LHRH-containing axons project toward the ME and infundibulum through the ventral-lateral hypothalamus. TH-containing perikarya are concentrated in the arcuate nucleus and in the adjacent part of the periventricular nucleus, dorsal to the arcuate. TH-containing axons converge toward the ME and descend into the infundibulum. Dense concentrations of TH- and LHRH-containing processes are located in the lateral and mediobasal portions of the external layer of the ME, providing opportunities for synaptic interactions between them. Ovulatory failure and regression of the ovary and reproductive tract occurred 2-3 days after FW at the end, but not at the beginning of the hen's commercial egg

  16. Growth hormone-releasing hormone stimulates cAMP release in superfused rat pituitary cells.

    OpenAIRE

    Horváth, J E; Groot, K. de; Schally, A V

    1995-01-01

    The release of growth hormone (GH) and cAMP was studied in superfused rat pituitary cells by infusing growth hormone-releasing hormone (GHRH) at different doses or a combination of GHRH and somatostatin 14 (SS-14). Three-minute pulses of GHRH caused a dose-dependent GH and cAMP release (effective concentration of 50% of the maximal biological effect is 0.21 nM and 52.5 nM, respectively). The lowest effective doses of GHRH in the superfusion system were 0.03 nM for GH release and 0.3 nM for cA...

  17. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  18. Active immunization to luteinizing hormone releasing hormone to inhibit the induction of mammary tumors in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Ravdin, P.M.; Jordan, V.C.

    1988-01-01

    Immunization of female rats with a bovine serum albumin-luteinizing hormone releasing hormone conjugate results in suppression of dimethylbenzanthracene mammary tumor incidence. Tumor incidence was 1.3, and 1.29 tumors per rat in bovine serum albumin alone (n = 10) and unimmunized (n = 18) control groups, but no tumors were found in the bovine serum albumin-luteinizing hormone releasing hormone conjugate immunized animals (n = 10). In a second experiment immunization with bovine serum albumin-luteinizing hormone releasing hormone conjugates reduced tumor incidence to 0.3 tumors per rat (n = 10) from the 1.2 tumors per animal seen in the control animals (n = 10) immunized with bovine serum albumin alone. Bovine serum albumin-luteinizing hormone immunization caused the production of anti-LHRH antibodies, an interruption of estrous cycles, lowered serum estradiol and progesterone levels, and atrophy of the ovaries and uteri. Immunization BSA-hormone conjugates is a novel anti-tumor strategy.

  19. Long-term effects of human growth hormone-releasing hormone and photoperiod on hormone release and puberty in dairy heifers.

    Science.gov (United States)

    Ringuet, H; Pelletier, G; Brazeau, P; Gaudreau, P; Guilbault, L A; Morisset, J; Couture, Y; Petitclerc, D

    1994-10-01

    Forty-eight Holstein dairy heifers (98.9 kg BW; 3 mo old) were subjected for 246 d to twice-daily s.c. injections of saline (CTL) or human growth hormone-releasing hormone (GRH; 5 micrograms/kg BW) and to photoperiods of 8 h of light (L): 16 h of dark (D) or 16L:8D according to a 2 x 2 factorial arrangement of treatments. Jugular blood samples were collected from 16 heifers at 3, 4, 8, and 11 mo of age to monitor prolactin, growth hormone, and estradiol-17 beta. Plasma progesterone concentrations were monitored weekly in all heifers as an index of puberty (> 1 ng/mL). Growth hormone release was induced by GRH (P GRH heifers. However, GRH-induced GH response was less (P GRH, photoperiod, and days of treatment on GRH-induced GH response; AUC was greater in GRH-16L:8D than in GRH-8L:16D heifers at 3 mo but less at 8 mo of age. The PRL concentrations were similar for both photoperiods at 3 mo (36.4 vs 41.7 ng/mL) and 8 mo (16.2 vs 12.8 ng/mL) of age but were greater in 16L:8D vs 8L:16D heifers at 4 mo (18.4 vs 39.3 ng/mL) and 11 mo (26.3 vs 44.1 ng/mL) of age (photoperiod x day interaction, P GRH-treated heifers (271 vs 284 kg BW; GRH x photoperiod interaction, P = .10). In conclusion, GH response is maintained throughout 8 mo of GRH treatment, and a 16L:8D photoperiod will reduce age and weight at puberty in heifers. Furthermore, refractoriness to photoperiod-induced PRL changes was detected.

  20. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  1. Luteinizing hormone-releasing hormone induces thyroxine release together with testosterone in the neotenic axolotl Ambystoma mexicanum.

    Science.gov (United States)

    Jacobs, G F; Kühn, E R

    1988-09-01

    In male neotenic axolotls Ambystoma mexicanum plasma concentrations of thyroxine (T4) and testosterone were increased following intravenous injection of 10 micrograms luteinizing hormone-releasing hormone. A dose of 50 micrograms influenced only plasma T4 levels. This observation suggests for the first time that a hypothalamic hormone is capable of stimulating the thyroidal axis in the neotenic axolotl.

  2. effect of luteinizing hormone-releasing hormone analogue on the sexual behavior of sacalia quadriocellata

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    luteinizing hormone-releasing hormone (lhrh) is known to influence sexual behavior in many vertebrate taxa,but there have been no systematic studies on the role of lhrh in sexual behavior of turtles.we tested the hypotheses that exogenous lhrh analogues would induce sexual behavior of male four-eyed turtle,sacalia quadriocellata.we examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue (lhrh-a),human chorionic gonadotropin (hcg),or a combination of the two,and subsequently exposing them to sexually receptive females for behavioral observation.our data show that the injection of only hcg could not,while that of only lhrh-a could,facilitate sexual behavior along with testicular recrudescence and spermatogenesis in s.quadriocellata.the injection of both lhrh-a and hcg would induce more drastic sexual behavior of the animals than that of lhrh-a alone,indicating hcg enhances the effects of lhrh-a induced sexual behavior.however,different pharmacological dosages of lhrh-a (0.5 μg,1 μg,2 μg per 100 g bodyweight) did not correspond to different activity levels.though the mechanism of lhrh effect was not determined,this study may support that the sexual behavior ofs.quadriocellata which occurs at the beginning of the injection despite regression of the gonads.this is the first report on the exogenous lhrh-a induced sexual behavior for this species.

  3. Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells.

    OpenAIRE

    Gick, G G; Zeytin, F N; BRAZEAU, P.; Ling, N C; Esch, F S; Bancroft, C

    1984-01-01

    A peptide with high intrinsic activity for specifically stimulating the secretion of immunoreactive growth hormone (GH; somatotropin) has been characterized and reproduced by total synthesis. This peptide, human pancreatic growth hormone-releasing factor, 44-amino-acid form (hpGRF1-44-NH2), was isolated from a tumor localized in the pancreas of a patient with acromegaly. We report here the effect of this growth hormone-releasing factor (GRF) on GH release and the GH mRNA levels in monolayer c...

  4. In vivo pharmacological evaluation of a lactose-conjugated luteinizing hormone releasing hormone analogue.

    Science.gov (United States)

    Moradi, Shayli Varasteh; Varamini, Pegah; Steyn, Frederik; Toth, Istvan

    2015-11-10

    In the current study, the efficacy and pharmacokinetic profile of lactose-conjugated luteinizing hormone releasing hormone (LHRH) was examined following oral administration in male rats. A rapid and sensitive liquid chromatography/mass spectrometry technique was developed and applied for measuring the concentration of lactose[Q(1)][w(6)]LHRH (compound 1) in rat plasma in order to allow measurement of pharmacokinetic parameters. LH release was evaluated using a sandwich ELISA. Maximum serum concentration (Cmax = 0.11 μg/ml) was reached at 2h (Tmax) following oral administration of the compound at 10mg/kg. The half-life was determined to be 2.6h. The absolute bioavailability of the orally administered compound was found to be 14%, which was a remarkable improvement compared to zero-to-low oral bioavailability of the native peptide. Compound 1 was effective in stimulating LH release at 20mg/kg after oral administration. The method was validated at a linear range of 0.01-20.0 μg/ml and a correlation coefficient of r(2) ≥ 0.999. The accuracy and precision values showed the reliability and reproducibility of the method for evaluation of the pharmacokinetic parameters. These findings showed that the lactose derivative of LHRH has a therapeutic potential to be further developed as an orally active therapeutics for the treatment of hormone-dependent diseases.

  5. Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus.

    Directory of Open Access Journals (Sweden)

    Guillaume Osterstock

    Full Text Available BACKGROUND: Ghrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin. PRINCIPAL FINDINGS: Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate. CONCLUSION: Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders.

  6. Mouse hypothalamic growth hormone-releasing hormone and somatostatin responses to probes of signal transduction systems.

    Science.gov (United States)

    Sato, M; Downs, T R; Frohman, L A

    1993-01-01

    Signal transduction mechanisms involved in mouse growth hormone-releasing hormone (GRH) and somatostatin (SRIH) release were investigated using an in vitro perifusion system. Hypothalamic fragments were exposed to depolarizing agents, protein kinase A and C activators, and a calcium ionophore. The depolarizing agents, KCl (60 mM) and veratridine (50 microM), induced similar patterns of GRH and SRIH release. Somatostatin release in response to both agents was twofold greater than that of GRH. Forskolin (10 microM and 100 microM), an adenylate cyclase activator, stimulated both GRH and SRIH release, though with different secretory profiles. The SRIH response was prolonged and persisted beyond removal of the drug from the system, while the GRH response was brief, ending even prior to forskolin removal. Neither GRH nor SRIH were stimulated by 1,9-dideoxy-forskolin (100 microM), a forskolin analog with cAMP-independent actions. A23187 (5 microM), a calcium ionophore, stimulated the release of SRIH to a much greater extent than that of GRH. The GRH and SRIH secretory responses to PMA (1 microM), a protein kinase C activator, were similar, though delayed. The results suggest that 1) GRH and SRIH secretion are regulated by both protein kinase A and C pathways, and 2) depolarizing agents are important for the release of both hormones.

  7. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH).

    Science.gov (United States)

    Obayemi, J D; Dozie-Nwachukwu, S; Danyuo, Y; Odusanya, O S; Anuku, N; Malatesta, K; Soboyejo, W O

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV-Visible (UV-Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer.

  8. Growth hormone-releasing hormone (GHRH polymorphisms associated with carcass traits of meat in Korean cattle

    Directory of Open Access Journals (Sweden)

    Cheong Il-Cheong

    2006-06-01

    Full Text Available Abstract Background Cold carcass weight (CW and longissimus muscle area (EMA are the major quantitative traits in beef cattle. In this study, we found several polymorphisms of growth hormone-releasing hormone (GHRH gene and examined the association of polymorphisms with carcass traits (CW and EMA in Korean native cattle (Hanwoo. Results By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428 and five marker haplotypes (frequency > 0.1 were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA. Conclusion Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle.

  9. Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

    Science.gov (United States)

    Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-10-26

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

  10. Reproductive characteristics of grass-fed, luteinizing hormone-releasing hormone-immunocastrated Bos indicus bulls.

    Science.gov (United States)

    Hernandez, J A; Zanella, E L; Bogden, R; de Avila, D M; Gaskins, C T; Reeves, J J

    2005-12-01

    Two field trials were conducted in Brazil to evaluate LHRH immunocastration of Bos indicus bulls (d 0 = 2 yr of age). In Study I, 72 bulls were assigned randomly to one of three treatment groups: LHRH0-immunized, castrated, and intact. Immunized animals (n = 25) received a primary and two booster injections of ovalbumin-LHRH-7 and thioredoxin-LHRH-7 fusion proteins on d 0, 141, and 287. Twenty-three bulls were surgically castrated on d 141, and 24 served as intact controls. All animals were slaughtered on d 385, at approximately 3 yr of age. In Study II, 216 bulls were assigned randomly to the same three treatments as in Study I; however, because of a drought in the area, bulls were kept on pasture an additional year, and a fourth treatment was added, in which one-half the LHRH-immunized bulls received an additional booster on d 639 (fourth immunization). All animals in Study II were slaughtered on d 741 (4 yr of age). Luteinizing hormone-releasing hormone antibodies increased following each immunization for immunized bulls, but they were not detectable in castrate or intact animals in either study. Consequently, scrotal circumference was suppressed in immunized bulls compared with intact controls in both studies. By d 287, serum concentrations of testosterone in LHRH-immunized bulls were decreased compared with intact controls (P bulls (173 +/- 22 and 26 +/- 2 g, respectively) and fourth immunization bulls (78 +/- 23 and 20 +/- 2 g, respectively; Study II). At the end of each study, BW was greater (P bulls than for castrated and LHRH-immunized animals. In these two studies, the efficacy of the LHRH fusion proteins to induce an effect similar to that of surgical castration was considered 92 and 93%, respectively. These data support the concept that immunocastration of bulls at 2 yr of age was successful and that it has practical application as a tool for producing grass-fattened bulls in Brazil.

  11. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    Energy Technology Data Exchange (ETDEWEB)

    Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete, Kwara State (Nigeria); Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Electronics and Electricals Engineering, Nigerian Turkish Nile University, Abuja (Nigeria); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY 10453 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Malatesta, K. [Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States)

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement.

  12. Response of luteinizing hormone and follicle stimulating hormone to luteinizing hormone-releasing hormone in prepubertal and pubertal chidren, as measured by a highly sensitive immunradiometric assay

    OpenAIRE

    樋口,譲二

    1992-01-01

    To investigate the age-related changes in the pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), the consentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and after LH-RH administra-tion using the highly sensitive immunoradiometric assay (IRMA) in 283 normal children (161 males and 77 females) between 4 and 14 years old and in 22 patients (18 males and 4 females) with pituitary dwarfism. Then, the area of response ...

  13. Expression and purification of growth hormone-releasing factor with the aid of dihydrofolate reductase handle.

    Science.gov (United States)

    Iwakura, M; Obara, K; Kokubu, T; Ohashi, S; Izutsu, H

    1992-07-01

    Expression of a fusion protein composed of dihydrofolate reductase and a derivative of growth hormone-releasing factor resulted in the formation of inclusion bodies in Escherichia coli at 37 degrees C. Among various chemicals, such as detergents, protein denaturants, and acetic acid, tested for the ability to dissolve the inclusion bodies, acetic acid, Brij-35, deoxycholic acid sodium salts, guanidine-HCl, and urea showed a strong solubilizing effect without damaging the DHFR activity. Acetic acid was useful in terms of preparing GRF derivatives, since it could be easily removed by lyophilization, and this made it easy to perform the succeeding BrCN treatment for cutting out the GRF derivative from the fusion protein. The GRF derivative was purified by reversed phase HPLC from the BrCN digest of the acetic acid extract, and its growth hormone-releasing activity was demonstrated. However, for obtaining a highly purified fusion protein itself, solubilization of inclusion bodies by urea was preferred because urea was the only agent which did not cause serious precipitation of the regenerated fusion protein after 10-fold dilution of the extracted inclusion bodies with buffer. The fusion protein was highly purified by means of a methotrexate affinity chromatography.

  14. Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

    Science.gov (United States)

    Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

    2013-11-01

    Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep.

  15. Specific involvement of gonadal hormones in the functional maturation of growth hormone releasing hormone (GHRH) neurons.

    Science.gov (United States)

    Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G

    2010-12-01

    Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

  16. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma.

    OpenAIRE

    Frohman, L A; Downs, T. R.; Heimer, E P; Felix, A M

    1989-01-01

    The plasma enzyme responsible for primary proteolytic cleavage of growth hormone-releasing hormone (GRH) at the 2-3 amino acid bond was characterized. Native GRH[GRH(1-44)-NH2 and GRH(1-40)-OH], and COOH-terminally shortened fragments [GRH(1-32)-NH2 and GRH(1-29)-NH2] were rapidly cleaved, while GRH(2-32)-NH2 was not degraded at this site. Moreover, degradation to GRH(3-44)-NH2 was unaffected by an aminopeptidase inhibitor, indicating that this metabolite was generated from a single step clea...

  17. Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

    Science.gov (United States)

    Merchenthaler, I; Lennard, D E; López, F J; Negro-Vilar, A

    1993-01-01

    The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility--i.e., gender-specific determination of LHRH neurons coexpressing GAL--was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of

  18. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    Science.gov (United States)

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  19. Central stimulation of hormone release and the proliferative response of lymphocytes in humans.

    Science.gov (United States)

    Juránková, E; Jezová, D; Vigas, M

    1995-01-01

    The central nervous system (CNS) may communicate with the immune system by direct innervation of lymphoid organs and/or by neurotransmitters and changes in neuroendocrine functioning and hormone release. The consequences of selective transient changes in circulating hormones on immune functioning in humans have not yet been studied. To address this problem, the authors evaluated the lymphoproliferative responses to optimal and suboptimal concentrations of phytohemagglutinin (PHA) and pokeweek mitogen (PWM) under selective enhancement of circulating growth hormone, prolactin, or norepinephrine. The authors failed to demonstrate any effect of elevated growth hormone levels after clonidine challenge on the lymphoproliferative response to mitogens. Similarly, the results did not show any effect of elevated prolactin concentrations induced by domperidone administration on the immune test. Exposure of volunteers to cold resulted in elevation of plasma norepinephrine levels without changes in growth hormone, epinephrine, or cortisol secretion. Cold exposure induced elevation of plasma norepinephrine and reduction of the lymphoproliferative response to the suboptimal dosage of PHA. The reduction was significant 180 and 240 min after exposure. These results are indicative of a relationship between norepinephrine and immunity.

  20. Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1987-03-01

    A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical.

  1. Growth hormone-releasing peptide-6 inhibits cerebellar cell death in aged rats.

    Science.gov (United States)

    Pañeda, Covadonga; Arroba, Ana I; Frago, Laura M; Holm, Anne Mette; Rømer, John; Argente, Jesús; Chowen, Julie A

    2003-08-26

    Insulin-like growth factor (IGF)-I is essential for cerebellar granule neuron survival and a decline in IGF-I is implicated in various age-dependent processes. Here we show that IGF-I mRNA levels are decreased in the cerebellum of old rats compared with young rats and this was associated with increased cell death and activation of caspases 3 and 9. Growth hormone-releasing peptide (GHRP)-6, a synthetic ligand for the ghrelin receptor, increased IGF-I mRNA levels, decreased cell death and inhibited caspase 3 and 9 activation in the cerebellum of aged rats. These results suggest that increasing IGF-I expression in the cerebellum can decrease cell death in aged rats via inhibition of caspase 3 and 9 activation.

  2. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    Science.gov (United States)

    Capuco, A V; Binelli, M; Tucker, H A

    2011-10-01

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  3. Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

    Science.gov (United States)

    Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

    1999-01-01

    Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

  4. Comparison of the effects of human and chicken ghrelin on chicken ovarian hormone release.

    Science.gov (United States)

    Sirotkin, Alexander V; Harrath, Abdel Halim; Grossmann, Roland

    2016-11-01

    The aim of the present experiments was to examine the species-specific and cell-specific effects of ghrelin on chicken ovarian hormone release. For this purpose, we compared the effects of chicken and human ghrelin on the release of estradiol (E), testosterone (T), progesterone (P) and arginine-vasotocin (AVT) by cultured fragments of chicken ovarian follicles and on the release of T and AVT by cultured ovarian granulosa cells. In cultured chicken ovarian fragments, both human and chicken ghrelin promoted E release. T output was stimulated by chicken ghrelin but not by human ghrelin. No effect of either human or chicken ghrelin on P release was observed. Human ghrelin promoted but chicken ghrelin suppressed AVT release by chicken ovarian fragments. In cultured ovarian granulosa cells, human ghrelin inhibited while chicken ghrelin stimulated T release. Both human and chicken ghrelin suppressed AVT output by chicken granulosa cells. These data confirm the involvement of ghrelin in the control of ovarian secretory activity and demonstrate that the effect of ghrelin is species-specific. The similarity of avian ghrelin on avian ovarian granulosa cells and ovarian fragments (containing both granulosa and theca cells) suggests that ghrelin can influence chicken ovarian hormones primarily by acting on granulosa cells.

  5. Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis

    Institute of Scientific and Technical Information of China (English)

    Wen-Cai Qiu; Zhi-Gang Wang; Wei-Gang Wang; Jun Yan; Qi Zheng

    2008-01-01

    AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6(GHRP-6) in diabetic mice with gastric motility disorders.METHODS:A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan.Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg),and the effects on gastric emptying were measured after intragastric application of phenol red.The effect of atropine,NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg)was also investigated.The effects of ghrelin or GHRP-6(0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro,in gastric fundic circular strips taken from diabetic mice.The presence of growth hormone secretagogue receptor la transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR).RESULTS:We established a diabetic mouse model with delayed gastric emptying.Ghrelin and GHRP-6accelerated gastric emptying in diabetic mice with gastroparesis.In the presence of atropine or L-NAME,which delayed gastric emptying,ghrelin and GHRP-6(100 μg/kg) failed to accelerate gastric emptying.D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist.Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic mice.RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.CONCLUSION:Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis,perhaps by activating peripheral cholinergic pathways in the enteric nervous system.

  6. Structural study of human growth hormone-releasing factor fragment (1?29) by vibrational spectroscopy

    Science.gov (United States)

    Carmona, P.; Molina, M.; Lasagabaster, A.

    1995-05-01

    The conformational structure of fragment 1-29 of human growth hormone releasing factor, hGHRF (1-29), in aqueous solution and in the solid state is investigated by infrared and Raman spectroscopy. The polypeptide backbone is found to be unordered in the solid state. However, the spectra of the peptide prepared as 5% (w/w) aqueous solutions show that approximately 28% of the peptide is involved in intermolecular β-sheet aggregation. The remainder of the peptide exists largely as disordered and β-sheet conformations with a small portion of α-helices. Tyrosine residues are found to be exposed to the solvent. The secondary structures are quantitatively examined through infrared spectroscopy, the conformational percentages being near those obtained by HONDAet al. [ Biopolymers31, 869 (1991)] using circular dichroism. The fast hydrogen/deuterium exchange in peptide groups and the absence of any NMR sign indicative of ordered structure [ G. M. CLOREet al., J. Molec. Biol.191, 553 (1986)] support that the solution conformations of the non-aggregated peptide interconvert in dynamic equilibrium. Some physiological advantages that may derive from this conformational flexibility are also discussed

  7. L-arginine promotes gut hormone release and reduces food intake in rodents.

    Science.gov (United States)

    Alamshah, A; McGavigan, A K; Spreckley, E; Kinsey-Jones, J S; Amin, A; Tough, I R; O'Hara, H C; Moolla, A; Banks, K; France, R; Hyberg, G; Norton, M; Cheong, W; Lehmann, A; Bloom, S R; Cox, H M; Murphy, K G

    2016-05-01

    To investigate the anorectic effect of L-arginine (L-Arg) in rodents. We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  8. L‐arginine promotes gut hormone release and reduces food intake in rodents

    Science.gov (United States)

    Alamshah, A.; McGavigan, A. K.; Spreckley, E.; Kinsey‐Jones, J. S.; Amin, A.; Tough, I. R.; O'Hara, H. C.; Moolla, A.; Banks, K.; France, R.; Hyberg, G.; Norton, M.; Cheong, W.; Lehmann, A.; Bloom, S. R.; Cox, H. M.

    2016-01-01

    Aims To investigate the anorectic effect of L‐arginine (L‐Arg) in rodents. Methods We investigated the effects of L‐Arg on food intake, and the role of the anorectic gut hormones glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), the G‐protein‐coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results Oral gavage of L‐Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet‐induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L‐Arg stimulated GLP‐1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP‐1 and PYY receptors did not influence the anorectic effect of L‐Arg. L‐Arg‐mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L‐Arg suppressed food intake in rats. Conclusions L‐Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L‐Arg is unlikely to be mediated by GLP‐1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L‐Arg suppressed food intake in rats, suggesting that L‐Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L‐Arg suppresses food intake and its utility in the treatment of obesity. PMID:26863991

  9. Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans

    Directory of Open Access Journals (Sweden)

    Joanne L. Calley

    2014-01-01

    Full Text Available The kisspeptins are a family of neuropeptides which act as upstream stimulators of gonadotrophin releasing hormone (GnRH neurons. Kisspeptin signalling is prerequisite to establishing the normal human reproductive phenotype; loss of function mutations in the KISS1 or KISS1R gene produces normosmic hypogonadotrophic hypogonadism in humans and mice, whilst increased activation of KISS1R causes precocious puberty. Administration of exogenous kisspeptin to human subjects stimulates an acute gonadotrophin rise. Serum kisspeptin levels also markedly increase during pregnancy. The identification of kisspeptin has been one of the biggest discoveries in the field of reproductive endocrinology, since the isolation and sequencing of GnRH in 1977, and has generated a novel research avenue which has received much attention over the past decade. This research has delineated many properties of the KISS1-KISS1R system, but there is still further work to do. Understanding kisspeptin’s role throughout our reproductive lifetime should help us better understand—and therefore treat—disorders of reproductive function. Promisingly, the current data supports the potential to develop kisspeptin based therapies. As an outlook article this paper focusses predominantly on our groups recent investigations into the effects of kisspeptin administration to humans and the potential therapeutic role of kisspeptin.

  10. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Simona Perboni; Cyril Bowers; Shinya Kojima; Akihiro Asakawa; Akio Inui

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo-therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin ago-nist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU + GHRP-2 significantly increased com-pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P = 0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

  11. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    Science.gov (United States)

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  12. A role for central nervous growth hormone-releasing hormone signaling in the consolidation of declarative memories.

    Directory of Open Access Journals (Sweden)

    Manfred Hallschmid

    Full Text Available Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05. The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05. Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation.

  13. Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

    OpenAIRE

    Katakami, H; Downs, T. R.; Frohman, L A

    1986-01-01

    The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and...

  14. Conformational origin of a difficult coupling in a human growth hormone releasing factor analog.

    Science.gov (United States)

    Deber, C M; Lutek, M K; Heimer, E P; Felix, A M

    1989-01-01

    During the solid-phase synthesis of the human growth hormone releasing factor (GRF) analog [Ala15, Leu27, Asn28] -GRF(1-32)-OH, incorporation of Boc-Gln16 was determined to be incomplete. While aggregation of growing resin-bound peptide chains with concomitant beta-sheet formation and "precipitation" has been proposed to account in general for such "difficult coupling," no feature of sequence in the Gln16 region of this GRF analog provided an immediate rationale for this result. We now report 500 MHz 1H NMR spectra of a series of resin-bound GRF segments surrounding the Gln16 position (19-32 through 14-32), swelled in dimethylsulfoxide-d6 solutions [GRF(14-32) = Leu14-Ala-Gln-Leu-Ser(Bzl)-Ala-Arg(Tos)-Lys(CIZ)-Leu- Leu-Gln-Asp(OcHex)-Ile-Leu-Asn-Arg(Tos)-Gln-Gln-Gly32-PAM resin]. While relatively sharp spectra are observed for GRF(19-32), components with resonances broadened by an order-of-magnitude appear in spectra of the 18-32 and 17-32 peptide-resin, and the entire spectrum of 16-32 is ill-resolved and highly broadened. Subsequent spectra sharpen again (15-32, 14-32). These combined synthesis/spectroscopic experimental results, in conjunction with predictive analyses using standard Chou-Fasman 2 degrees structure parameters, suggest that the completeness of the Gln16 coupling is hindered by formation of a specific, folded beta-sheet/beta-turn structure in GRF(16-32) (with the turn located at 18-21, "upstream" of the difficult coupling site), and accompanying aggregation of peptide chains. This analysis suggests that awareness of such potential beta-sheet/beta-turn sequences can guide analog choices, and/or facilitate pre-programming of synthesis steps in anticipation of problem couplings.

  15. Identification of the growth-hormone-releasing peptide-2 (GHRP-2) in a nutritional supplement.

    Science.gov (United States)

    Thomas, Andreas; Kohler, Maxie; Mester, Joachim; Geyer, Hans; Schänzer, Wilhelm; Petrou, Michael; Thevis, Mario

    2010-03-01

    Black market products of a pharmaceutical nature and nutritional supplements have received substantial and increasing attention because of potential performance enhancement in elite and non-professional sports. In addition, improved general health is claimed for non-competing individuals. The risks and foreseeable dangers of the uncontrolled use of highly potent and non-approved pharmaceutical compounds in healthy individuals are of considerable concern. In the present case report, the emerging drug candidate GHRP-2 with verified growth-hormone-releasing properties was identified and quantified in tablets offered as an over-the-counter nutritional supplement. The impact of this orally active peptide on the hGH/IGF-axis has been established for several years and its illicit use in elite sports has been assumed. As a releasing factor for hGH, GHRP-2 belongs to the list of substances prohibited by the World Anti-Doping Agency (WADA). Unfortunately, to date there is no routinely performed assay for the determination of these peptides potentially occurring in biological fluids of competing athletes, but the present data will facilitate the implementation by providing principle analytical information on liquid chromatographic and mass spectrometric behaviour. Qualitative identification of the target analyte after extraction from the tablet matrix was performed by high resolution/high accuracy mass spectrometry after liquid chromatographic separation under consideration of the accurate masses and the ratios of the protonated molecules and their fragment ions derived from their collisionally induced dissociation. Quantitative results were obtained by means of liquid chromatography coupled to a triple quadrupole mass spectrometer and linear regression using an external calibration curve (with GHRP-2 reference compound) adjusted via internal standard (Hexarelin). Hereby, the content of GHRP-2 was determined with approximately 50 µg per tablet.

  16. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1992-01-01

    It has been shown that mice transgenic for human GH-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs, lactotrophs, and mammosomatotrophs, cells capable of producing both GH and PRL, by 8 months of age. We now report that GRH transgenic mice 10-24 months of age develop pituita...... somatotrophs or mammosomatotrophs to cells with features of the glycoprotein hormone cell line. These findings provide conclusive evidence that protracted GRH stimulation of secretory activity can result in proliferation, hyperplasia, and adenoma of adenohypophysial cells....

  17. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    Science.gov (United States)

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

  18. Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release

    OpenAIRE

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues w...

  19. Structural and functional divergence of growth hormone-releasing hormone receptors in early sarcopterygians: lungfish and Xenopus.

    Directory of Open Access Journals (Sweden)

    Janice K V Tam

    Full Text Available The evolutionary trajectories of growth hormone-releasing hormone (GHRH receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR(2 in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP receptor (PRPR. In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR(2 in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR(2 was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR(2 had the highest expression in brain, and interestingly, X. laevis(GHRHR2 also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR(2, which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP.

  20. Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

    Directory of Open Access Journals (Sweden)

    Daniele Leão Ignacio

    Full Text Available Growth hormone (GH regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1 activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60% in sham-operated animals and GH was higher (~6-fold 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response.

  1. Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

    Science.gov (United States)

    Ignacio, Daniele Leão; da S Silvestre, Diego H; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade; Carvalho, Denise P; Werneck-de-Castro, João Pedro

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response.

  2. The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro

    NARCIS (Netherlands)

    L.J. Hofland (Leo); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven); A. Beckers (Albert); J. van der Hoek (Joost); P.M. van Koetsveld (Peter); W.W. de Herder (Wouter); M. Waaijers (Marlijn); D. Sprij-Mooij (Diana); C. Bruns (Christian); G. Weckbecker (Gisbert); R.A. Feelders (Richard)

    2004-01-01

    textabstractTo determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenom

  3. Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Folkers, K.; Bowers, C.Y.; Tang, P.L.; Kubota, M.

    1986-02-01

    Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known agonist analogs of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. The authors have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and they found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: (HisV,TrpX,GlnY)LHRH; (HisV,TrpX,LeuY)LHRH; (HisV,TrpX)LHRH; (TrpX)LHRH; (HisV)LHRH. These structures are a basis for the design of antagonists without ArgY toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of ArgY and GlnY or LeuY antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas. Radioreceptor assays and radioimmunoassays were utilized.

  4. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

    Energy Technology Data Exchange (ETDEWEB)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. (Tulane Univ. School of Medicine, New Orleans, LA (USA))

    1989-08-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, (D-Mel{sup 6})LH-RH (SB-05) and (Ac-D-Nal(2){sup 1},D-Phe(pCl){sup 2},D-Pal(3){sup 3},Arg{sup 5},D-Mel{sup 6},D-Ala{sup 10})LH-RH (SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine) possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel{sup 6} analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

  5. Changes of growth hormone-releasing hormone and somatostatin neurons in the rat hypothalamus induced by genistein: a stereological study.

    Science.gov (United States)

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Nestorović, Nataša; Medigović, Ivana; Živanović, Jasmina; Milošević, Verica

    2016-12-01

    Genistein is a plant-derived estrogenic isoflavone commonly found in dietary and therapeutic supplements, due to its potential health benefits. Growth hormone-releasing hormone (GHRH) and somatostatin (SS) are neurosecretory peptides synthesized in neurons of the hypothalamus and regulate the growth hormone secretion. Early reports indicate that estrogens have highly involved in the regulation of GHRH and SS secretions. Since little is known about the potential effects of genistein on GHRH and SS neurons, we exposed rats to genistein. Genistein were administered to adult rats in dose of 30 mg/kg, for 3 weeks. The estradiol-dipropionate treatment was used as the adequate controls to genistein. Using applied stereology on histological sections of hypothalamus, we obtained the quantitative information on arcuate (Arc) and periventricular (Pe) nucleus volume and volume density of GHRH neurons and SS neurons. Image analyses were used to obtain GHRH and SS contents in the median eminence (ME). Administration of estradiol-dipropionate caused the increase of Arc and Pe nucleus volume, SS neuron volume density, GHRH and SS staining intensity in the ME, when compared with control. Genistein treatment increased: Arc nucleus volume and the volume density of GHRH neurons (by 26%) and SS neurons (1.5 fold), accompanied by higher GHRH and SS staining intensity in the ME, when compared to the orhidectomized group. These results suggest that genistein has a significant effect on hypothalamic region, involved in the regulation of somatotropic system function, and could contribute to the understanding of genistein as substance that alter the hormonal balance.

  6. Facilitation of lordosis in rats by a metabolite of luteinizing hormone releasing hormone.

    Science.gov (United States)

    Wu, T J; Glucksman, Marc J; Roberts, James L; Mani, Shaila K

    2006-05-01

    In the female rat, ovulation is preceded by a marked increase in the release of the decapeptide, LHRH, culminating in a preovulatory LH surge, which coincides with a period of sexual receptivity. The decapeptide, LHRH, is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the Tyr(5)-Gly(6) bond. We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its metabolite, LHRH-(1-5). Given the central function of LHRH in reproduction and reproductive behavior, we examined the role of the metabolite, LHRH-(1-5), in mediation of LHRH-facilitated reproductive behavior. Intracerebroventricular administration of LHRH-(1-5) facilitated sexual behavior responses, similar to those facilitated by the decapeptide LHRH, in ovariectomized estradiol-primed female rats. Furthermore, immunoneutralization of EP24.15 resulted in the inhibition of the LHRH-facilitated lordosis but had no inhibitory effects on LHRH-(1-5)-facilitated lordosis. The LHRH antagonist, Antide, was capable of inhibiting LHRH-facilitated lordosis, without affecting LHRH-(1-5)-facilitated lordosis. Collectively, these results suggest a role for LHRH metabolites in the facilitation of female receptive behavior in rats.

  7. The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release.

    Science.gov (United States)

    Kola, Blerina; Wittman, Gábor; Bodnár, Ibolya; Amin, Faisal; Lim, Chung Thong; Oláh, Márk; Christ-Crain, Mirjam; Lolli, Francesca; van Thuijl, Hinke; Leontiou, Chrysanthia A; Füzesi, Tamás; Dalino, Paolo; Isidori, Andrea M; Harvey-White, Judith; Kunos, George; Nagy, György M; Grossman, Ashley B; Fekete, Csaba; Korbonits, Márta

    2013-12-01

    This study aimed to investigate whether the growth hormone release and metabolic effects of ghrelin on AMPK activity of peripheral tissues are mediated by cannabinoid receptor type 1 (CB1) and the central nervous system. CB1-knockout (KO) and/or wild-type mice were injected peripherally or intracerebroventricularly with ghrelin and CB1 antagonist rimonabant to study tissue AMPK activity and gene expression (transcription factors SREBP1c, transmembrane protein FAS, enzyme PEPCK, and protein HSL). Growth hormone levels were studied both in vivo and in vitro. Peripherally administered ghrelin in liver, heart, and adipose tissue AMPK activity cannot be observed in CB1-KO or CB1 antagonist-treated mice. Intracerebroventricular ghrelin treatment can influence peripheral AMPK activity. This effect is abolished in CB1-KO mice and by intracerebroventricular rimonabant treatment, suggesting that central CB1 receptors also participate in the signaling pathway that mediates the effects of ghrelin on peripheral tissues. Interestingly, in vivo or in vitro growth hormone release is intact in response to ghrelin in CB1-KO animals. Our data suggest that the metabolic effects of ghrelin on AMPK in peripheral tissues are abolished by the lack of functional CB1 receptor via direct peripheral effect and partially through the central nervous system, thus supporting the existence of a possible ghrelin-cannabinoid-CB1-AMPK pathway.

  8. Antiproliferative effect of growth hormone-releasing hormone (GHRH antagonist on ovarian cancer cells through the EGFR-Akt pathway

    Directory of Open Access Journals (Sweden)

    Varga Jozsef

    2010-05-01

    Full Text Available Abstract Background Antagonists of growth hormone-releasing hormone (GHRH are being developed for the treatment of various human cancers. Methods MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR level and the phosphorylation of Akt (p-Akt, suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.

  9. Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM).

    Science.gov (United States)

    Smyth, Hugh D C; Becket, Gordon; Mehta, Samir

    2002-05-01

    A 2 x 2 factorial design was performed to determine the effect of a permeation enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination of the two treatments on the permeation enhancement of a model peptide, LHRH (luteinizing hormone releasing hormone), through human epidermal membrane (HEM). In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and sucrose (an electroosmotic flow marker) were also investigated. Structural changes in the HEM were monitored via conductance measurements, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times passive permeability, P), was greater than during iontophoresis alone (I; 14.3) and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E, indicating the mechanisms of action of the individual enhancement strategies were likely to be located at different sites in the skin. Also, no synergistic enhancement was observed with I + E for either TEAB or sucrose. For TEAB, permeability enhancement due to I (approximately 1400) was much higher than that due to E (14.9), and no additive effect could be detected. For sucrose, E had no effect on either passive or iontophoretic permeability, eliminating the possibility that electroosmosis could explain increases in LHRH permeability. Evidence of synergy between E and I was found, with conductance measurements indicating that I + E synergistically increased the membrane permeability to conducting ions (Na+ and Cl-). It appears these pathways were not available for transport for the solutes used in the current study. DSC and IR investigations showed significant changes in stratum corneum lipid structure following E treatment but not following I. These findings probably arise from the localized action of iontophoresis compared with the bulk action of enhancer. In summary, increased LHRH delivery through HEM in

  10. Discordant effects of endogenous and exogenous somatostatin on growth hormone-releasing hormone secretion from perifused mouse hypothalami.

    Science.gov (United States)

    Pecori Giraldi, F; Frohman, L A

    1995-05-01

    The role of somatostatin (SRIF) on growth hormone-releasing hormone (GRH) secretion has been controversial because of discordant findings that may be model dependent. We have examined possible explanations for these findings by altering endogenous and exogenous SRIF tone in a mouse hypothalamic perifusion system. Four mediobasal hypothalamic fragments were perifused in a single chamber for 6 h. After a 2-hour equilibration period, test substances were introduced and maintained throughout the perifusion. After an additional 2 h, fragments were submaximally stimulated with 30 mM K+. Depletion of tissue SRIF by 10(-3) M cysteamine increased K(+)-stimulated GRH release 2-fold without altering basal GRH secretion. Removal of endogenous SRIF tone by anti-SRIF serum also augmented the GRH response to K+. Perifusion of SRIF at concentrations ranging from 10(-12) to 10(-8) M significantly increased the GRH response to K+ in a dose-dependent manner. A significant increase was also observed during the perifusion of 10(-9) M octreotide. Simultaneous perifusion with anti-SRIF serum and 10(-9) M octreotide (to which the antibody does not bind) resulted in a response of GRH to K+ that was similar to that observed with anti-SRIF serum alone. Combined perifusion with cysteamine and 10(-9) M SRIF also resulted in a GRH response to K+ that did not differ from the response observed during cysteamine alone. The enhancement of GRH secretion by reduction of endogenous SRIF tone or tissue content implies an inhibitory role of endogenous SRIF on GRH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Identification of the growth hormone-releasing hormone analogue [Pro1, Val14]-hGHRH with an incomplete C-term amidation in a confiscated product.

    Science.gov (United States)

    Esposito, Simone; Deventer, Koen; Van Eenoo, Peter

    2014-01-01

    In this work, a modified version of the 44 amino acid human growth hormone-releasing hormone (hGHRH(1-44)) containing an N-terminal proline extension, a valine residue in position 14, and a C-terminus amidation (sequence: PYADAIFTNSYRKVVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 ) has been identified in a confiscated product by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Investigation of the product suggests also an incomplete C-term amidation. Similarly to other hGHRH analogues, available in black markets, this peptide can potentially be used as performance-enhancing drug due to its growth hormone releasing activity and therefore it should be considered as a prohibited substance in sport. Additionally, the presence of partially amidated molecule reveals the poor pharmaceutical quality of the preparation, an aspect which represents a big concern for public health as well.

  12. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction.

    Directory of Open Access Journals (Sweden)

    Istvan eCzikora

    2014-07-01

    Full Text Available Rationale. Antibiotic treatment of patients infected with G- or G+ bacteria promotes release of the toxins lipopolysaccharide (LPS and pneumolysin (PLY in their lungs. Growth Hormone-releasing Hormone (GHRH agonist JI-34 protects human lung microvascular cells (HL-MVEC, expressing splice variant 1 (SV-1 of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated PKA depletion.Methods. Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye incorporation. Cytokine generation in broncho-alveolar lavage fluid was measured by multiplex analysis. PKA and PKC-alpha activity were assessed by Western blotting. Results. GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-alpha activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions. GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-alpha-induced pathway in the presence of PLY, the former of which dominates the latter.

  13. Mink aging is associated with a reduction in ovarian hormone release and the response to FSH and ghrelin.

    Science.gov (United States)

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karina; Lauričik, Jozef; Morovič, Martin; Harrath, Abdel Halim; Kotwica, Jan

    2016-09-15

    The endocrine mechanisms of mink ovarian hormones release and reproductive aging are poorly investigated. The aims of our study were to: (1) identify hormones produced by mink ovaries (the steroids progesterone [P] and estradiol [E], the peptide hormone oxytocin [OT], and the prostaglandin F [PGF] and prostaglandin E [PGE]); (2) examine the effect of FSH and ghrelin on the release of the hormones listed previously; and (3) understand whether these hormones can be involved in the control of mink reproductive aging, i.e., whether aging can be associated with changes (a) in the basal release of P, E, OT, PGF, or PGE and (b) their response to FSH and ghrelin. Fragments of ovaries of young (yearlings) and old (3-5 years of age) minks were cultured with and without FSH and ghrelin (0, 1, 10, or 100 ng/mL), and the release of hormones was analyzed by EIA/RIA. We found that isolated ovaries were able to release P, E, OT, PGF, and PGE, and the levels of P produced in the ovaries of old animals were lower than those produced in the ovaries of young animals, whereas the levels of other hormones did not differ. FSH was able to stimulate P and E and suppress OT and PGF and did not affect PGE release. Aging was associated with the inhibition of the effect of FSH on ovarian P and E, the appearance of the inhibitory action of FSH on OT, and the disappearance of this action on ovarian PGF. PGE was not affected by FSH, irrespective of animal age. Ghrelin was able to promote E (but not P) and suppress OT, PGF, and PGE output. Aging was associated with the appearance of an inhibitory influence of ghrelin on ovarian OT and PGE and with the disappearance of this influence on PGF output. Aging did not affect the action of ghrelin on ovarian P and E. Our observations (1) confirm the production of P and E and show that OT, PGF, and PGE are released from mink ovaries, (2) confirm the involvement of FSH and demonstrate the involvement of ghrelin in the control of mink ovarian hormone

  14. Melatonin improves memory acquisition under stress independent of stress hormone release

    OpenAIRE

    Rimmele, U; Spillmann, M; Bärtschi, C; Wolf, O.T.; Weber, C S; Ehlert, Ulrike; Wirtz, P H

    2009-01-01

    RATIONALE: Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. OBJECTIVES: We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans. As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function. MATERIALS AND METHODS: Fifty healthy young men received a single oral dose of either 3...

  15. Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

    Science.gov (United States)

    Pueschel, Seigfried M.

    1993-01-01

    This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

  16. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus.

    OpenAIRE

    Frohman, L A; Downs, T. R.; Williams, T C; Heimer, E P; Pan, Y C; Felix, A M

    1986-01-01

    The effect of plasma on degradation of human growth hormone-releasing hormone (GRH) was examined in vitro and in vivo using high performance liquid chromatography (HPLC), radioimmunoassay (RIA), and bioassay. When GRH(1-44)-NH2 was incubated with human plasma, the t1/2 of total GRH immunoreactivity was 63 min (RIA). However, HPLC revealed a more rapid disappearance (t1/2, 17 min) of GRH(1-44)-NH2 that was associated with the appearance of a less hydrophobic but relatively stable peptide that ...

  17. Possible participation of calcium in growth hormone release and in thyrotropin-releasing hormone and human pancreatic growth hormone-releasing factor synergy in a primary culture of chicken pituitary cells.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1989-09-01

    We previously reported that thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) exert synergistic (greater than additive) effects on growth hormone (GH) release from chicken pituitary cells in primary culture. In the present studies the possible participation of calcium in GH release and in TRH and hpGRF synergy was investigated. Following dispersion with collagenase, cells were cultured for 48 hr prior to exposure (2 hr) to test agents. Cultured cells were exposed to a range of calcium concentrations (0, 0.02, 0.2, and 2.0 mM) in the presence and absence of secretagogues. These results demonstrated that basal GH release was not altered by the concentration of calcium in the medium: however, secretagogue-induced GH release required calcium. Thus, TRH, hpGRF, 8 Br-cAMP, or forskolin stimulated GH release in the absence of calcium. Furthermore, synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, or forskolin was observed only at the highest calcium concentration (2.0 mM). In other studies, ionomycin (10(-5) M), a calcium ionophore, stimulated GH release to a value about 125% over the basal (absence of test agent) value. Ionomycin-induced GH release was not affected by TRH (5.0 ng/ml); the combined effects of ionomycin (10(-7)-10(-5) M) and hpGRF (5.0 ng/ml) on GH release were less than additive. However, ionomycin (10(-5) M) further increased GH release over that resulting from the synergistic action of TRH and hpGRF (5.0 ng/ml each). Verapamil (a calcium channel blocker) did not affect GH release induced by either TRH or hpGRF (5.0 ng/ml each). However, this agent did inhibit synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, forskolin, or isobutylmethylxanthine. These results suggest that calcium participates in secretagogue-induced GH release from chicken somatotrophs in vitro.

  18. Blockade of LH release and ovulation in the rabbit with inhibitory analogues of luteinizing hormone releasing hormone.

    Science.gov (United States)

    Phelps, C P; Coy, D H; Schally, A V; Sawyer, C H

    1977-06-01

    Plasma LH levels and ovulation were studied in female rabbits following administration of several inhibitory analogues of luteinizing hormone-releasing hormone (LHRH) before and after mating with experienced males. Administration of (D-Phe2, D-Leu6)-LHRH (1.5 mg/kg sc) to does 30 min before mating did not prevent either LH release or ovulation. However, a single sc injection of (D-Phe2, L-Phe3, D-Phe6y-LHRH (6 mg/kg) given 30 min before mating in 4 rabbits resulted in a 30-60 min delay in the coitus-induced release of LH when compared with post-coital changes in the same animals injected with vehicle; however, all of the does ovulated. When multiple dosages of 4 mg/kg (D-Phe2, L-Phe3, D-Phe6)-LHRH were administered 3-5 times at half-hourly intervals beginning 30 min prior to mating there was a considerable reduction in plasma LH elevations at 0.5, 1.0, 2.0 and 4.0 h after mating and 3/5 treated rabbits showed partial or complete blockade of ovulation. Quite similar results were obtained with the same dosage of (D-Phe2, D-Trp3, D-Phe6)-LHRH. An early sharp peak in LH release and full ovulation were stimulated in 6 out of 6 does by a single iv injection of synthetic LHRH (500 ng/kg). However, in another experiment, three half-hourly sc injections (4 mg/kg) of (D-Phe2, L-Phe3, D-Phe6)-LHRH beginning 30 min before administering LHRH markedly reduced the rise in plasma LH (P less than 0.01) and completely blocked ovulation in all of the same 6 animals. An unsuccessful attempt was made to provide a test animal for LHRH analogue investigations by implanting 4 cm of silastic tubing filled with crystalline estradiol (E2) sc in ovariectomized (OVX) AND INTACT DOES. In OVX does the silastic E2 implants resulted in a progressive decline in the ability to release LH in response to mating at 6 and at 20 days after implantation. With ovaries present, the E2 implant permitted post-coital LH release and ovulation at 4 d but not at 30 d post-implantation. At 30 d after removal of

  19. Postural changes associated with public speech tests lead to mild and selective activation of stress hormone release.

    Science.gov (United States)

    Mlynarik, M; Makatsori, A; Dicko, I; Hinghofer-Szalkay, H G; Jezova, D

    2007-03-01

    We tested whether simulation of postural changes, which occur during public speech test procedures, activates cardiovascular system and stress hormone release that could interfere with the effect of psychosocial stress load. Young healthy male volunteers (n=8) underwent procedure imitating exactly all postural changes present in the psychosocial stress model based on public speech used in this laboratory (namely changes from sitting to standing and repeated sitting). Postural changes were associated with increases in heart rate, blood pressure, plasma concentrations of noradrenaline and aldosterone and elevation in plasma renin activity. In contrast to cardiovascular parameters, adrenocorticotropic hormone, cortisol and adrenaline, the main characteristics of hormonal response during mental stress, were not significantly influenced. The overall magnitude of all observed alterations was much smaller than that seen following mental stress procedures in our previous studies. This study provides evidence that changes in body posture during public speech test procedure influence hemodynamics and endocrine responses in a mild manner. Though this influence may represent a source of unspecific variance, substantial confounding effects on responses to the psychosocial component of the procedure are unlikely. In any case, models combining mental stressors and changes in body posture must be interpreted as complex stress stimuli.

  20. Aging influences steroid hormone release by mink ovaries and their response to leptin and IGF-I

    Directory of Open Access Journals (Sweden)

    Alexander V. Sirotkin

    2016-02-01

    Full Text Available The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings and old (3-5 years of age minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml. We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a reduction in basal progesterone release and (b alterations in the response of estradiol but not of progesterone to leptin and IGF-I.

  1. Aging influences steroid hormone release by mink ovaries and their response to leptin and IGF-I.

    Science.gov (United States)

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karin; Harrath, Abdel Halim; Kotwica, Jan

    2016-01-21

    The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings) and old (3-5 years of age) minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml). We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a) reduction in basal progesterone release and (b) alterations in the response of estradiol but not of progesterone to leptin and IGF-I.

  2. Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors

    NARCIS (Netherlands)

    L.J. Hofland (Leo); W.W. de Herder (Wouter); H.A. Visser-Wisselaar (Heleen); C. van Uffelen; M. Waaijers (Marlijn); J. Zuyderwijk; P. Uitterlinden (Piet); P.M. van Koetsveld (Peter); S.W.J. Lamberts (Steven); J.M. Kros (Johan)

    1997-01-01

    textabstractThe effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7

  3. Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.

    Science.gov (United States)

    Noel, G L; Dimond, R C; Earll, J M; Frantz, A G

    1976-05-01

    Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.

  4. The incretin approach for diabetes treatment: modulation of islet hormone release by GLP-1 agonism

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Ørskov, Cathrine

    2004-01-01

    Glucagon-like peptide (GLP)-1 is a gut hormone that stimulates insulin secretion, gene expression, and beta-cell growth. Together with the related hormone glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect, the augmentation of insulin secretion after oral...... improved. The natural peptide is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV), but resistant analogs as well as inhibitors of DPP IV are now under development, and both approaches have shown remarkable efficacy in experimental and clinical studies....

  5. Simultaneous measurement of hormone release and secretagogue binding by individual pituitary cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P.F.; Neill, J.D.

    1987-08-01

    The quantitative relationship between receptor binding and hormone secretion at the single-cell level was investigated in the present study by combining a reverse hemolytic plaque assay for measurement of luteinizing hormone (LH) secretion from individual pituitary cells with an autoradiographic assay of /sup 125/I-labeled gonadontropin-releasing hormone (GnRH) agonist binding to the same cells. In the plaque assay, LH secretion induces complement-mediated lysis of the LH-antibody-coated erythrocytes around the gonadotropes, resulting in areas of lysis (plaques). LH release from individual gonadotropes was quantified by comparing radioimmunoassayable LH release to hemolytic area in similarly treated cohort groups of cells; plaque area was linearly related to the amount of LH secreted. Receptor autoradiography was performed using /sup 125/I-labeled GnRH-A (a superagonist analog of GnRH) both as the ligand and as the stimulant for LH release in the plaque assay. The grains appeared to represent specific and high-affinity receptors for GnRH because (i) no pituitary cells other than gonadotropes bound the labeled ligand and (ii) grain development was progressively inhibited by coincubation with increasing doses of unlabeled GnRH-A. The authors conclude that GnRH receptor number for any individual gonadotrope is a weak determinant of the amount of LH it can secrete; nevertheless, full occupancy of all its GnRH receptors is required for any gonadotrope to reach its full LH-secretory capacity. Apparently the levels of other factors comprising the steps along the secretory pathway determine the secretory capacity of an individual cell.

  6. Bed rest suppresses bioassayable growth hormone release in response to muscle activity

    Science.gov (United States)

    McCall, G. E.; Goulet, C.; Grindeland, R. E.; Hodgson, J. A.; Bigbee, A. J.; Edgerton, V. R.

    1997-01-01

    Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P muscle activity.

  7. Bed rest suppresses bioassayable growth hormone release in response to muscle activity

    Science.gov (United States)

    McCall, G. E.; Goulet, C.; Grindeland, R. E.; Hodgson, J. A.; Bigbee, A. J.; Edgerton, V. R.

    1997-01-01

    Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P muscle activity.

  8. Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds

    Directory of Open Access Journals (Sweden)

    Yssel Mendoza Marí

    2016-01-01

    Full Text Available In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6 proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit’s ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit’s model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

  9. Diacylglycerol acyltransferase-1 (DGAT1 inhibition perturbs postprandial gut hormone release.

    Directory of Open Access Journals (Sweden)

    Hua V Lin

    Full Text Available Diacylglycerol acyltransferase-1 (DGAT1 is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1 and peptide YY (PYY only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4 inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.

  10. Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells.

    Science.gov (United States)

    Phelps, C J; Wiggins, J P; Wangsness, P J

    1988-10-01

    A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.

  11. Bed rest suppresses bioassayable growth hormone release in response to muscle activity

    Science.gov (United States)

    McCall, G. E.; Goulet, C.; Grindeland, R. E.; Hodgson, J. A.; Bigbee, A. J.; Edgerton, V. R.

    1997-01-01

    Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P < 0.05), and by 10 or 11 days the BGH response was similar to that before bed rest (1,881 +/- 75 to 4,160 +/- 315 microg/l; P < 0.05). These data demonstrate that the ambulatory state of an individual can have a major impact on the release of BGH, but not IGH, in response to a single bout of muscle activity.

  12. Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats.

    Science.gov (United States)

    Iwata, Kinuyo; Kunimura, Yuyu; Matsumoto, Keisuke; Ozawa, Hitoshi

    2017-06-01

    Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities. © 2017 Society for Endocrinology.

  13. QSAR models for predicting the activity of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A using quantum chemical properties.

    Science.gov (United States)

    Fernández, Michael; Caballero, Julio

    2007-04-01

    Multiple linear regression (MLR) combined with genetic algorithm (GA) and Bayesian-regularized Genetic Neural Networks (BRGNNs) were used to model the binding affinity (pK(I)) of 38 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A for the Human Luteinizing Hormone-Releasing Hormone (LHRH) receptor using quantum chemical descriptors. A multiparametric MLR equation with good statistical quality was obtained that describes the features relevant for antagonistic activity when the substituent at the position 3 of the erythronolide core was varied. In addition, four-descriptor linear and nonlinear models were established for the whole dataset. Such models showed high statistical quality. However, the BRGNN model was better than the linear model according to the external validation process. In general, our linear and nonlinear models reveal that the binding affinity of the compounds studied for the LHRH receptor is modulated by electron-related terms.

  14. Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

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    Yi-Ning Chao

    2016-08-01

    Full Text Available Cyclooxygenase-2 (COX-2 and interleukin-8 (IL-8 are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC activator phorbol 12, 13-didecanoate (PDD and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2. GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2 and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1 reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1 and protein phosphatase 2 (PP2A reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2 in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

  15. Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

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    Jorge Berlanga-Acosta

    2017-02-01

    Full Text Available Background: Growth hormone-releasing peptides (GHRPs constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36, which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.

  16. Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle.

    Science.gov (United States)

    Zhao, Hongqiong; Yannaing, Swe; Thanthan, Sint; Kuwayama, Hideto

    2011-11-01

    This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 μg/kg BW of [D-Lys(3)]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from -10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 μg/kg was weaker than that of 4.0 μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [D-Lys(3)]-GHRP-6; however, [D-Lys(3)]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.

  17. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.

    Directory of Open Access Journals (Sweden)

    Alexandra Mangili

    Full Text Available Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT in human immunodeficiency virus (HIV-infected patients with lipodystrophy.1 To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF or the National Cholesterol Education Program (MetS-NCEP and the Framingham Risk Score (FRS, as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2 To explore the characteristics of patients who reached a threshold of VAT 1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively. No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI and baseline VAT (95% confidence interval [CI] 2.03; 7.44.Individuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo.

  18. Effects of ionizing radiation and pretreatment with (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O' Connell, G.; Belbeck, L.

    1987-10-01

    To assess the effects of a gonadotropin-releasing hormone agonist, (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

  19. Central administration of growth hormone-releasing hormone triggers downstream movement and schooling behavior of chum salmon (Oncorhynchus keta) fry in an artificial stream.

    Science.gov (United States)

    Ojima, Daisuke; Iwata, Munehico

    2009-03-01

    Anadromous salmonids migrate downstream to the ocean (downstream migration). The neuroendocrine mechanism of triggering the onset of downstream migration is not well known. We investigated the effects of 14 chemicals, including neuropeptides, pineal hormones, neurotransmitters, and neuromodulators (growth hormone-releasing hormone: GHRH, thyrotropin-releasing hormone, corticotropin-releasing hormone: CRH, gonadotropin-releasing hormone, melatonin, N-acetyl serotonin, serotonin, beta-endorphin, enkephalin, dopamine, norepinephrine, epinephrine, acetylcholine, and histamine) on the onset of downstream migration in chum salmon (Oncorhynchus keta) fry. We defined downstream migration as a downstream movement (negative rheotaxis) with schooling behavior and counted the number of downstream movements and school size in experimental circulation tanks. An intracerebroventricular injection of GHRH, CRH, melatonin, N-acetyl serotonin, or serotonin stimulated the number of downstream movements. However, GHRH was the only chemical that also stimulated an increase in schooling behavior. These results suggest that CRH, melatonin, N-acetyl serotonin, and serotonin are involved in the stimulation of downstream movement in chum salmon, while GHRH stimulates both downstream movement and schooling behavior.

  20. Neither bST nor Growth Hormone Releasing Factor Alter Expression of Thyroid Hormone Receptors in Liver and Mammary Tissues

    Science.gov (United States)

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine, to specific nuclear receptors. It has been hypothesized that organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, target the action of thyroid hormones to the mammary...

  1. Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature.

    Science.gov (United States)

    Kuba, Sayaka; Ishida, Mayumi; Oikawa, Masahiro; Nakamura, Yoshiaki; Yamanouchi, Kosho; Tokunaga, Eriko; Taguchi, Kenichi; Esaki, Taito; Eguchi, Susumu; Ohno, Shinji

    2016-11-01

    The roles of aromatase inhibitors (AIs) and luteinizing hormone-releasing hormone (LH-RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH-RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH-RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH-RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH-RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH-RH agonist. AIs with or without an LH-RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer.

  2. Semaphorin Signaling in the Development and Function of the Gonadotropin Hormone-Releasing Hormone (GnRH System

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    Andrea eMessina

    2013-09-01

    Full Text Available The semaphorin proteins are among the best-studied families of guidance cues, contributing to morphogenesis and homeostasis in a wide range of tissue types. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors are capable to mediate signaling by semaphorins. These guidance proteins were originally identified as growth cone collapsing factors or as inhibitory signals, crucial for nervous system development. Since those seminal discoveries, the list of functions of semaphorins has rapidly grown. Over the past few years, a growing body of data indicates that semaphorins are involved in the regulation of the immune and vascular systems, in tumor growth/cancer cell metastasis and in neural circuit formation. Recently there has been increasing emphasis on research to determine the potential influence of semaphorins on the development and homeostasis of hormone systems and how circulating reproductive hormones regulate their expression and functions. Here, we focus on the emerging role of semaphorins in the development, differentiation and plasticity of unique neurons that secrete gonadotropin-releasing hormone (GnRH, which are essential for the acquisition and maintenance of reproductive competence in all vertebrates. Genetic evidence is also provided showing that insufficient semaphorin signaling contributes to some forms of reproductive disorders in humans, characterized by the reduction or failure of sexual competence.Finally, we will review some studies with the goal of highlighting how the expression of semaphorins and their receptors might be regulated by gonadal hormones in physiological and pathological conditions.

  3. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  4. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH Peptide

    Directory of Open Access Journals (Sweden)

    Pooria Mansoori

    2011-07-01

    Full Text Available Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

  5. Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS.

    Science.gov (United States)

    Knoop, Andre; Thomas, Andreas; Fichant, Eric; Delahaut, Philippe; Schänzer, Wilhelm; Thevis, Mario

    2016-05-01

    The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). The aim of the present study was to develop a method for the simultaneous detection of four different GHRHs and respective metabolites from human plasma by means of immunoaffinity purification and subsequent nano-ultrahigh performance liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The target analytes included Geref (Sermorelin), CJC-1293, CJC-1295, and Egrifta (Tesamorelin) as well as two metabolites of Geref and CJC-1293, which were captured from plasma samples using a polyclonal GHRH antibody in concert with protein A/G monolithic MSIA™ D.A.R.T.'S® (Disposable Automation Research Tips) prior to separation and detection. The method was fully validated and found to be fit for purpose considering the parameters specificity, linearity, recovery (19-37%), lower limit of detection (sports drug testing samples. Further studies are however required and warranted to account for potential species-related differences in metabolism and elimination of the target analytes.

  6. Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies.

    Science.gov (United States)

    Stanley, Takara L; Grinspoon, Steven K

    2015-04-01

    Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone-sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH-releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding the long-term efficacy and safety of this treatment modality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Seasonal differences in the parameters of luteinizing hormone release to exogenous gonadotropin releasing hormone in prepubertal Holstein heifers in Sapporo.

    Science.gov (United States)

    Kadokawa, Hiroya

    2007-02-01

    Stress due to summer heat has adverse effects on reproduction in Holstein dairy cattle. Summer suppression of reproduction of Holsteins can pose an important economic problem, even in Hokkaido prefecture located in the northern region of Japan. Hokkaido is one of the most important dairy farming areas of Japan. This study is an attempt to clarify the seasonal differences in the parameters of luteinizing hormone (LH) response to exogenous gonadotropin releasing hormone (GnRH) in Sapporo, Hokkaido, Japan. A total of 12 prepubertal heifers received an injection with GnRH analogue intramuscularly in either May (n=4, May group), July (n=4, July group), or November (n=4, November group), and serial blood samples were collected to analyze the parameters of the LH response curve after GnRH injection. The parameters were as follows: the basal LH concentration, peak LH concentration, duration from the time of GnRH injection to the time of the peak LH concentration, and area under the LH response curve (AUC). There were no significant differences in the basal and peak LH concentrations or the AUC among the three groups. The July group reached the LH peak significantly (P<0.05) faster than the May group, but there was no significant difference with the November group. Therefore, the results of the present study do not demonstrate an effect of summer heat on the LH response to the exogenous GnRH in Holstein heifers.

  8. Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.

    Science.gov (United States)

    Tarasiuk, A; Berdugo-Boura, N; Troib, A; Segev, Y

    2011-10-01

    Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (psleep and slow-wave activity was reduced (pgrowth impairment (pgrowth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

  9. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    Energy Technology Data Exchange (ETDEWEB)

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-02-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

  10. Structure and Function of Growth Hormone Releasing Peptide(Ghrelin)%生长激素释放肽的结构和功能

    Institute of Scientific and Technical Information of China (English)

    应牡英

    2006-01-01

    生长激素释放肽(growth hormone releasing peptide,Ghrelin,GHRP),是最近发现的可以促进GH分泌的肽激素,主要来源于胃,有28个氨基酸残基,其第三位氨基酸残基(一般是丝氨酸)被脂肪酸修饰,实验证明被修饰的N端是其活性核心部位.该文介绍ghrelin的主要结构和生物学功能.

  11. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Schally, A.V.; Paz-Bouza, J.I.; Schlosser, J.V.; Karashima, T.; Debeljuk, L.; Gandle, B.; Sampson, M.

    1987-02-01

    Possible protective effects of the agonist (D-Trp/sup 6/)LH-RH and antagonist N-Ac(D-Phe(pCl)/sup 1,2/,D-Trp/sup 3/,D-Arg/sup 6/,D-Ala/sup 10/)LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group give 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist (D-Trp/sup 6/)LH-RH. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist (D-Trp/sup 6/)LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

  12. Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men.

    Science.gov (United States)

    Deslypere, J P; Kaufman, J M; Vermeulen, T; Vogelaers, D; Vandalem, J L; Vermeulen, A

    1987-01-01

    The influence of aging on serum LH and testosterone (T) pulse frequency and gonadotroph sensitivity to androgen and estrogen feedback was studied in young (less than 55 yr old) and elderly (greater than 65 yr) Trappist monks. LH pulse frequency (sampling interval, 20 min) was significantly lower [0.25 +/- 0.03 (+/- SEM) vs. 0.38 +/- 0.02 pulses/h; P less than 0.01] in elderly (n = 21) than in young monks (n = 27); the pulse amplitudes were similar. Similarly, T pulse frequency was lower in the elderly than in the young monks (0.13 +/- 0.04 vs. 0.23 +/- 0.02 pulses/h; P less than 0.01). In elderly men, the hypothalamo-pituitary complex was more sensitive to 5 alpha-androstan-17 beta-ol-3-one feedback, as determined by the decrease in serum LH and T levels. Moreover, during 5 alpha-androstan-17 beta-ol-3-one (125 mg/day, percutaneously, for 10 days) administration, the LH response to LHRH (100 micrograms, iv) was significantly higher in the elderly men compared to the pretreatment response. During estradiol (1.5 mg/day, percutaneously for 10 days) administration, the LH response to LHRH was decreased in the elderly men, but unchanged in the young men, suggesting greater responsiveness to estradiol in the elderly men. We conclude that in aged men, decreased testicular androgen secretion is not exclusively the consequence of a primary testicular alteration, but that important changes occur in hypothalamo-pituitary function, specifically decreased LH pulse frequency and increased LH responsiveness to sex hormone feedback.

  13. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

    Directory of Open Access Journals (Sweden)

    Nikolaos Kyriakakis

    2017-01-01

    Full Text Available A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed.

  14. Exocytosis sensitivity to growth hormone-releasing hormone in subsets of GH cells in rats under different corticosterone conditions. Ultrastructural study using microwave irradiation for fixation and immunocytochemistry.

    Science.gov (United States)

    Ozawa, Hitoshi; Han, Fang; Kawata, Mitsuhiro

    2004-12-01

    Growth hormone (GH) cells in the rat anterior pituitary have been morphologically classified into three subtypes: type I (mature) containing large secretory granules about 350 nm in diameter, type II (intermediate) containing a mixture of large and small granules, and type III (immature) containing small granules about 150 nm in diameter. However, the functional implications of morphological heterogeneity, especially the different sensitivities to growth hormone-releasing hormone (GRH) under different corticosteroid conditions have not been elucidated to date. In the present study, by application of microwave irradiation (MWI) for fixation and immunocytochemistry, new findings of the exocytotic response have been revealed among the subsets of GH cells following adrenalectomy (ADX), corticosterone treatment and/or GRH treatment. The MWI gave effective results for fixation, especially for the permeability of the fixative, and showed good results for immunoelectron microscopy using the protein-A gold method. Moreover, the use of MWI greatly shortened the fixation, processing and immunolabeling times without compromising the quality of ultrastructural preservation and the specificity of labeling. The number of exocytotic figures was low in all subtypes of GH cells in the sham-operated control rats. GRH treatment induced a significant increase in exocytosis in each subtype of GH cells, particularly in type I (mature) and type II (intermediate) GH cells in the control rats. GRH injection to rats for 4 days after ADX also showed an increase in exocytosis, but the degree was significantly less in comparison with the GRH injection in the control group. Corticosterone replacement given to ADX rats induced a clear recovery of the exocytotic response to GRH to the control level. Serum GH content measured by radioimmunoassay correlated with these morphological results. These results suggest that the secretion of GH stimulated by GRH is closely related to corticosteroids, and

  15. Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode

    Energy Technology Data Exchange (ETDEWEB)

    Wray, S.; Grant, P.; Gainer, H. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1989-10-01

    In situ hybridization histochemistry and immunocytochemistry were used to study the prenatal expression of luteinizing hormone-releasing hormone (LHRH) cells in the mouse. Cells expressing LHRH mRNA and peptide product were first detected on embryonic day 11.5 (E11.5) in the olfactory pit. On E12.5, the majority of LHRH cells were located on tracks extending from the olfactory pit to the base of the telencephalon. From E12.5 to E15.5, LHRH cells were detected in a rostral-to-caudal gradient in forebrain areas. Prior to E12.5, cells expressing LHRH mRNA were not detected in forebrain areas known to contain LHRH cells in postnatal animals. Quantitation of cells expressing LHRH mRNA showed that the number of labeled cells on E12.5 (approximately 800) equaled the number of LHRH cells in postnatal animals, but more than 90% of these cells were located in nasal regions. Between E12.5 and E15.5, the location of LHRH cells shifted. The number of LHRH cells in the forebrain increased, while the number of LHRH cells in nasal regions decreased over this same period. These findings establish that cells first found in the olfactory pit and thereafter in forebrain areas express the LHRH gene and correspond to the position of LHRH immunopositive cells found at these developmental times. To further examine the ontogeny of the LHRH system, immunocytochemistry in combination with (3H)thymidine autoradiography was used to determine when LHRH cells left the mitotic cycle. We show that LHRH neurons exhibit a discrete time of birth, suggesting that they arise as a single neuronal population between E10.0 and E11.0. Postnatal LHRH neurons were birth-dated shortly after differentiation of the olfactory placode and before LHRH mRNA was expressed in cells in the olfactory pit.

  16. Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.

    Science.gov (United States)

    Liao, Fan; Zhang, Tony J; Mahan, Thomas E; Jiang, Hong; Holtzman, David M

    2015-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHR(lit/lit) mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHR(lit/lit) mice was significantly smaller than that in PS1APP/GHRHR(lit/+) mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition.

  17. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    Science.gov (United States)

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  18. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

    Science.gov (United States)

    Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta

    2017-01-01

    Summary A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH) and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed. Learning points: Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly. Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion

  19. Noradrenergic regulation of hypothalamic cells that produce growth hormone-releasing hormone and somatostatin and the effect of altered adiposity in sheep.

    Science.gov (United States)

    Iqbal, J; Manley, T R; Yue, Q; Namavar, M R; Clarke, I J

    2005-06-01

    The growth hormone (GH) axis is sensitive to alteration in body weight and there is evidence that central noradrenergic systems regulate neurones that produce growth hormone-releasing hormone (GHRH) and somatostatin (SRIF). This study reports semiquantitative estimates of the noradrenergic input to neuroendocrine GHRH and SRIF neurones in the sheep of different body weights. We also studied the effects of altered body weight on expression of dopamine beta-hydroxylase (DBH), the enzyme that produces noradrenalin from dopamine. Ovariectomised ewes were made Lean (39.6 +/- 2.6 kg; Mean +/- SEM) by dietary restriction, whereas Normally Fed animals (61.2 +/- 0.8 kg) were maintained on a regular diet. Brains were perfused for immunohistochemistry and in situ hybridisation. The Mean +/- SEM number of GHRH-immunoreactive (-IR) cells was lower in Normally Fed (65 +/- 7) than in Lean (115 +/- 14) animals, whereas the number of SRIF-IR cells was similar in the two groups (Normally Fed, 196 +/- 17; Lean 230 +/- 21). Confocal microscopic analysis revealed that the percentage of GHRH-IR cells (Normally Fed 36 +/- 1.5% versus Lean 32 +/- 4.6%) and percentage of SRIF-IR cells (Normally Fed 30 +/- 40.4% versus Lean 32 +/- 2.3%) contacted by noradrenergic fibres did not change with body weight. FluoroGold retrograde tracer injections confirmed that noradrenergic projections to the arcuate nucleus are from ventrolateral medulla and noradrenergic projections to periventricular nucleus arise from the ventrolateral medulla, nucleus of solitary tract, locus coeruleus (LC) and the parabrachial nucleus (PBN). DBH expressing cells were identified using immunohistochemistry and in situ hybridisation and the level of expression (silver grains/cell) quantified by image analysis. The number of DBH cells was similar in Normally Fed and Lean animals, but the level of expression/cell was lower (P < 0.02) in the PBN and LC of Lean animals. These results provide an anatomical basis for the

  20. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour.

    Science.gov (United States)

    Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta; Murray, Robert D

    2017-01-01

    A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH) and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient's acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed. Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly.Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion, mainly from neuroendocrine tumours of pancreatic or bronchial origin.Differentiating between acromegaly of pituitary origin and

  1. Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bratton, G.R.; Hiney, J.K.; Dees, W.L. (Texas A M Univ., College Station, TX (United States))

    1994-01-01

    In the present study, the authors evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E[sub 2] (PGE[sub 2]) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O[sub 2]-5% CO[sub 2]. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 [mu]M. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 [mu]M norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE[sub 2] (2.8 [mu]M) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE[sub 2] released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE[sub 2]-induced release of LHRH. Additionally, Pb did not alter basal PGE[sub 2] release; however, it significantly blocked the NE-induced release of PGE[sub 2]. Since NE-induced LHRH release is mediated by PGE[sub 2], these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE[sub 2] synthesis/release within the ME, resulting in diminished LHRH secretion.

  2. Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release

    Energy Technology Data Exchange (ETDEWEB)

    Mauras, N.; Blizzard, R.M.; Rogol, A.D.

    1989-03-01

    A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses.

  3. Regular Yoga Practice Improves Antioxidant Status, Immune Function, and Stress Hormone Releases in Young Healthy People: A Randomized, Double-Blind, Controlled Pilot Study.

    Science.gov (United States)

    Lim, Sung-Ah; Cheong, Kwang-Jo

    2015-09-01

    The aim of the present study is to highlight the beneficial effects of yoga practice on bio-parameters, such as oxidative stress, antioxidant components, immune functions, and secretion of stress hormones, in healthy young people. This study was conducted on healthy volunteers recruited from among university students, who were divided into two groups: a control (no yoga intervention, n=13) group and a yoga (n=12) group. Yoga practice was with an instructor for 90 minutes once a week spread over 12 weeks, with recommendations to practice daily at home for 40 minutes with the help of a DVD. The yoga program consisted of yoga body poses (asanas), exercises involving awareness, voluntary regulation of breath (pranayama), and meditational practices. Whole blood samples were collected when the volunteers had fasted for 8 hours at 0 and 12 weeks. The oxidative stress/antioxidant components, immune-related cytokines, and stress hormones were evaluated in serum or plasma. Serum levels of nitric oxide, F2-isoprostane, and lipid peroxide were significantly decreased by yoga practice (pyoga practice compared with the control group (pYoga practice also significantly increased immune-related cytokines, such as interleukin-12, and interferon-γ, in serum (pYoga practice significantly reduced the plasma levels of adrenalin (pyoga practice remarkably attenuated oxidative stress and improved antioxidant levels of the body. Moreover, yoga beneficially affected stress hormone releases as well as partially improved immune function.

  4. Ligand-biased regulation of PtdIns(3,4,5)P3-dependent signal transduction in GPCR control of pituitary hormone release.

    Science.gov (United States)

    Pemberton, Joshua G; Chang, John P

    2016-12-01

    Biased signaling describes the selective activation of signal transduction cascades by structurally-related ligands downstream of shared G protein-coupled receptors (GPCRs). Although class I phosphoinositide 3-kinases (PI3Ks) are important components of GPCR-controlled transduction networks, little is known regarding the potential for biased regulation of class I PI3K-dependent signaling. The full compliment of class I PI3K catalytic subunits (p110α, p110β, p110δ and p110γ) first appear in bony fishes and, despite being associated with distinct cellular functions, all class I PI3Ks produce the lipid second-messenger phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). We have previously shown that two endogenous gonadotropin-releasing hormones (GnRH2 and GnRH3), which both signal through shared Gαq/11-coupled receptors, selectively activate different subsets of class I PI3K isoforms in their control of hormone release from goldfish (Carassius auratus) pituitary cells. Here, we tested the hypothesis that the biased activation of class I PI3K isoforms results in the selective recruitment of PtdIns(3,4,5)P3-sensitive effectors downstream of GnRH-stabilized GPCRs using pharmacological mapping. Our results reveal that distinct PtdIns(3,4,5)P3-sensitive effectors are involved in the differential control of GnRH2- and GnRH3-stimulated, as well as basal, hormone release and implicate the participation of non-canonical PtdIns(3,4,5)P3-sensitive transduction elements. Furthermore, observations using a selective inhibitor of the shared Gβγ-effector interaction surface indicate a role for Gβγ-dependent signaling in the integrated control of pituitary hormone exocytosis. These novel findings add to our understanding of functional selectivity in GPCR signal transduction networks, in general, and reveal the complexity of biased signaling downstream of class I PI3K catalytic activity.

  5. Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS): studies in hypopituitary and healthy subjects

    DEFF Research Database (Denmark)

    Bach, Ermina; Møller, Andreas Buch; Jørgensen, Jens Otto Lunde

    2016-01-01

    of stress hormones. We compared the metabolic effects of LPS in hypopituitary patients (HP) (in the absence of pituitary stress hormone responses) and healthy control subjects (CTR) (with normal pituitary stress hormone responses). DESIGN: Single blind randomized. METHODS: We compared effects of LPS...... but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas...... on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic euglycemic clamp conditions with muscle biopsies and fat biopsies in each period during infusion with saline or LPS. RESULTS: LPS increased cortisol and growth hormone (GH) levels in CTR...

  6. Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

    Science.gov (United States)

    Cacabelos, R; Yamatodani, A; Fukui, H; Niigawa, H; Miyake, A; Watanabe, T; Nishimura, T; Wada, H

    1987-04-01

    Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF1-44) were studied. HA was determined by high-performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF1-44 (1-10 micrograms, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF1-44 (10 micrograms) the level of HA in the hypothalamus tended to decrease but the total amount of H-1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system.

  7. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

    Directory of Open Access Journals (Sweden)

    Sayaka Akieda-Asai

    Full Text Available BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5Kgamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268 in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5P(2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

  8. Synthesis of human pancreatic growth hormone-releasing factor and two omission analogs by segment-coupling method in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Blake, J.; Westphal, M.; Li, C.H. (Laboratory of Molecular Endocrinology, University of California, San Francisco, USA)

    1984-01-01

    The human growth hormone-releasing factor (GRF) peptides (GlyS/sup 15/)-GRF-(1-15) (IV), trifluoroacetyl-GRF-(20-44) (VI), trifluoroacetyl-GRF-(18-44) (VIII), and trifluoroacetyl-GRF-(16-44) (X) were synthesized by the solidphase method. Each of the peptides was reacted with citraconic anhydride and the trifluoroacetyl group was removed by reaction with 10% hydrazine in water. The citraconylated GRF-(1-15) peptide was coupled to the (20-44), (18-44) or (16-44) peptides by reaction with silver nitrate/N-hydroxysuccinimide to give GRF-(1-15)-(20-44) (XII), GRF-(1-15)-(18-44) (XIII), or GRF-(1-44), respectively. GRF-(1-44) was shown to stimulate the release of rat growth hormone from rat pituitary cells with an ED/sub 50/=8.8 x 10/sup -11/M. Peptides XII and XIII were inactive, either as agonists or as antagonists of the action of GRF-(1-44).

  9. Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Cicognani, A.; Cacciari, E.; Vecchi, V.; Cau, M.; Balsamo, A.; Pirazzoli, P.; Tosi, M.T.; Rosito, P.; Paolucci, G.

    1988-11-01

    To evaluate the effects of two different doses of cranial irradiation on growth and growth hormone (GH) release, we studied 61 children with acute lymphocytic leukemia who had survived at least five years in continuous complete remission. Forty-three children received 24 Gy (group 1) and 18 children received 18 Gy (group 2). Height was evaluated at diagnosis, at the end of treatment, and 6, 12, and 24 months later. Growth hormone release was evaluated by arginine and levodopa tests after the end of treatment. After diagnosis, the height SD score decreased significantly in both groups; two years after the end of treatment, only group 1 showed an SD score for height that was still significantly lower than at diagnosis. Group 1 showed impaired GH responses to the tests and, compared with controls, group 1 in fact included a percentage of subjects with a normal response to levodopa (ie, greater than 8 micrograms/L) that was significantly lower (56.4% vs 83.3%) and a percentage of nonresponders to both tests that was significantly higher (21.6% vs 0%). These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests.

  10. 腹腔注射LHRH-A对黑鲷生长激素及其受体的影响%Effects of Luteinizing Hormone-releasing Hormone Analogue Injection on Growth Hormone and Its Receptor in Black Seabream

    Institute of Scientific and Technical Information of China (English)

    邓利; 林浩然

    2003-01-01

    以海水硬骨鱼类黑鲷为研究对象,腹腔注射溶于生理盐水的促性腺激素,释放激素(gonadotropin-releasing hormone,GnRH)的类似物(analogue of luteinizing hormone- releasing hormone,LHRH-A),对照组注射生理盐水.24 h后注射LHRH-A组黑鲷血清生长激素(growth hormone,GH)水平显著高于对照组(p<0.05),于36 h又恢复到对照组水平.注射LHRH-A组肝脏生长激素受体(growth hormone receptor,GHR)及GHR mRNA均与对照组无显著差异.结果表明,腹腔注射LHRH-A刺激了处于性腺成熟期黑鲷GH的分泌,但对黑鲷肝脏GHR及其基因表达无明显影响.

  11. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  12. 聚乙二醇化生长激素释放激素的研究进展%The research of development on Pegylation of growth hormone-releasing hormone

    Institute of Scientific and Technical Information of China (English)

    王永; 刘沐荣; 万海同

    2012-01-01

    生长激素释放激素(growth hormone-releasing hormone,GHRH)又称生长激素释放因子(growth hormone-releasing factor,GRF),是由下丘脑分泌的一种肽类激素,具有促进垂体促生长素细胞合成和释放生长激素(growth hormone,GH)的作用,临床上可以用来治疗矮小症、HIV相关的脂肪营养不良、代谢综合征、艾滋病、创伤等疾病.然而GHRH应用到临床上的最大不足就是体内半衰期比较短(一般10~20 min).为了延长GHRH在体内的半衰期,减少频繁用药给患者带来的不适,须对GHRH进行修饰,以期达到半衰期显著延长,免疫原性有所降低.为此,本文主要综述了GHRH以及GHRH长效修饰的研究进展,尤其是PEG修饰GHRH的最新进展.

  13. Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

    OpenAIRE

    Frohman, L A; Szabo, M; Berelowitz, M.; Stachura, M E

    1980-01-01

    Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amount...

  14. Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study.

    Science.gov (United States)

    Pedersen, Camilla; Lefevre, Solenne; Peters, Véronique; Patterson, Michael; Ghatei, Mohammad A; Morgan, Linda M; Frost, Gary S

    2013-07-01

    Prevention of weight gain in adults is a major public health target. Animal experiments have consistently demonstrated a relationship between fermentable carbohydrate intake, such as oligofructose, anorectic gut hormones, and appetite suppression and body weight control. This study was designed to determine the dose of oligofructose which would augment the release of anorectic gut hormones and reduce appetite consistently in non-obese humans. Twelve non-obese participants were recruited for a 5-week dose-escalation study. Following a 9-14-day run-in, participants increased their daily oligofructose intake every week from 15, 25, 35, 45, to 55 g daily. Subjective appetite and side effects were monitored daily. Three-day food diaries were completed every week. Appetite study sessions explored the acute effects of 0, 15, 35, and 55 g oligofructose on appetite-related hormones, glycaemia, subjective appetite, and energy intake. In the home environment, oligofructose suppressed hunger, but did not affect energy intake. Oligofructose dose-dependently increased peptide YY, decreased pancreatic polypeptide and tended to decrease ghrelin, but did not significantly affect appetite profile, energy intake, glucose, insulin, or glucagon-like peptide 1 concentrations during appetite study sessions. In conclusion, oligofructose supplementation at ≥ 35 g/day increased peptide YY and suppressed pancreatic polypeptide and hunger; however, energy intake did not change significantly.

  15. A possible role of SchistoFLRFamide in inhibition of adipokinetic hormone release from locust corpora cardiaca.

    Science.gov (United States)

    Vullings, H G; Ten Voorde, S E; Passier, P C; Diederen, J H; Van Der Horst, D J; Nässel, D R

    1998-12-01

    The distribution and actions of FMRFamide-related peptides (FaRPs) in the corpora cardiaca of the locust Locusta migratoria were studied. Antisera to FMRFamide and SchistoFLRFamide (PDVDHVFLRFamide) label neuronal processes that impinge on glandular cells in the glandular lobe of the corpora cardiaca known to produce adipokinetic hormones. Electron microscopic immunocytochemistry revealed that these FaRP-containing processes form synaptoid contacts with the glandular cells. Approximately 12% of the axon profiles present in the glandular part of the corpus cardiacum contained SchistoFLRFamide-immunoreactive material. Retrograde tracing of the axons in the nervus corporis cardiaci II with Lucifer yellow revealed 25-30 labelled neuronal cell bodies in each lateral part of the protocerebrum. About five of these in each hemisphere reacted with the SchistoFLRFamide-antiserum. Double-labelling immunocytochemistry showed that the FaRP-containing processes in the glandular lobe of the corpora cardiaca are distinct from neuronal processes, reacting with an antiserum to the neuropeptide locustatachykinin. The effect of the decapeptide SchistoFLRFamide and the tetrapeptide FMRFamide on the release of adipokinetic hormone I (AKH I) from the cells in the glandular part of the corpus cardiacum was studied in vitro. Neither the deca- nor the tetrapeptide had any effect on the spontaneous release of AKH I. Release of AKH I induced by the phosphodiesterase inhibitor IBMX, however, was reduced significantly by both peptides. These results point to an involvement of FaRPs as inhibitory modulators in the regulation of the release of adipokinetic hormone from the glandular cells.

  16. Stress hormone release is a key component of the metabolic response to lipopolysaccharide: studies in hypopituitary and healthy subjects.

    Science.gov (United States)

    Bach, Ermina; Møller, Andreas B; Jørgensen, Jens O L; Vendelbo, Mikkel H; Jessen, Niels; Pedersen, Steen B; Nielsen, Thomas S; Møller, Niels

    2016-11-01

    Acute and chronic inflammatory and metabolic responses are generated by lipopolysaccharide (LPS) during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but whether these responses depend on intact pituitary release of hormones are not clearly identified. We compared the metabolic effects of LPS in hypopituitary patients (HPs) (in the absence of growth hormone (GH) and ACTH responses) and healthy control subjects (CTR) (with normal pituitary hormone responses). Single-blind randomized. We compared the effects of LPS on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic-euglycemic clamp conditions with muscle and fat biopsies in each period during infusion with saline or LPS. LPS increased cortisol and GH levels in CTR but not in HP. Also, it increased whole-body palmitate fluxes (3-fold) and decreased palmitate-specific activity (SA) 40-50% in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue (AT) mRNA was decreased in CTR. Although LPS increased phenylalanine fluxes significantly more in CTR, there was no difference in glucose metabolism between groups and intramyocellular insulin signaling was unaltered in both groups. LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared with HP and decreased adipocyte G0S2 mRNA only in CTR. Thus, in humans intact pituitary function and appropriate cortisol and GH release are crucial components of the metabolic response to LPS. © 2016 European Society of Endocrinology.

  17. Growth hormone release from chicken anterior pituitary cells in primary culture: TRH and hpGRF synergy, protein synthesis, and cyclic adenosine 3'5'-monophosphate.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1989-01-01

    Our earlier work showed that the effects of thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) on growth hormone (GH) release are synergistic (greater than additive) in a primary culture of chicken adenohypophyseal cells. The purpose of the present studies was to investigate the possible participation of protein synthesis and cyclic adenosine 3'5'-monophosphate (cAMP) in GH release. Following culture (48 hr), cells were incubated for 2 hr with test agents. Cycloheximide (an inhibitor of protein synthesis) had no effect on basal (absence of test agent) GH release or hpGRF-induced GH release. However, cycloheximide abolished the synergy between TRH and hpGRF. Although neither TRH nor hpGRF alone stimulated GH production (intracellular GH plus GH release) during a 2-hr incubation period, in combination these secretagogues increased total GH. These findings suggest that GH release from the chicken somatotroph under conditions of TRH and hpGRF synergy requires protein synthesis. In other studies, cells were exposed to agents inducing the formation of cAMP and either TRH or hpGRF. 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX; 10(-3) M) alone stimulated GH release to values between 30 and 50% over the basal value. The combined effects of each of these agents and TRH on GH release were synergistic. Similarly, IBMX and hpGRF exerted synergistic effects on GH release. In contrast, no synergy was shown between hpGRF and either 8 Br-cAMP or forskolin; their combined actions were less than additive.

  18. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    Science.gov (United States)

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-09-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

  19. Hormone Therapy

    Science.gov (United States)

    ... types of estrogen therapy relieve vaginal dryness. • Systemic estrogen protects against the bone loss that occurs early in menopause and helps prevent hip and spine fractures. • Combined estrogen and progestin therapy may reduce the risk of ...

  20. [Role of estrogen-sensitive neurons in the arcuate region of the hypothalamus in the mechanism of luteinizing hormone release].

    Science.gov (United States)

    Babichev, V N; Ignatkov, V Ia

    1978-01-01

    Experiments were conducted on rats; estradiol brought to the arcuate region of the hypothalamus by means of microionophoresis led to the increase of the region of the hypothalamus by means of microionophoresis led to the increase of the blood luteinizing hormone (LH) level during the following stages of the estral cycle-diestrus 1, diestrus 2, and the first half day of the proestrus; as to the second half of the proestrus day--estradiol decreased its level. Changes in the LH level in the hypophysis under the influence of the microionophoretic introduction of estradiol into the arcuate region occurred during the second half of the day of diestrus 2 (reduction), and during the estrus (elevation). In the majority of cases a rise of the blood level was combined with the neuron activation in the arcuate region under the influence of estradiol.

  1. Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness.

    Science.gov (United States)

    Louge, Pierre; Coulange, Mathieu; Beneton, Frederic; Gempp, Emmanuel; Le Pennetier, Olivier; Algoud, Maxime; Dubourg, Lorene; Naibo, Pierre; Marlinge, Marion; Michelet, Pierre; Vairo, Donato; Kipson, Nathalie; Kerbaul, François; Jammes, Yves; Jones, Ian M; Steinberg, Jean-Guillaume; Ruf, Jean; Guieu, Régis; Boussuges, Alain; Fenouillet, Emmanuel

    2016-06-01

    Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder.Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013-June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia.We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high

  2. Electromagnetic field effect or simply stress? Effects of UMTS exposure on hippocampal longterm plasticity in the context of procedure related hormone release.

    Directory of Open Access Journals (Sweden)

    Nora Prochnow

    Full Text Available Harmful effects of electromagnetic fields (EMF on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF signals of the Universal Mobile Telecommunications System (UMTS to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH and on hippocampal derived synaptic long-term plasticity (LTP and depression (LTD as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg. The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg cannot be excluded.

  3. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 2; Hypothalamic Growth Hormone-Releasing Factor, Somatostatin Immunoreactivity, and Messenger RNA Levels in Microgravity

    Science.gov (United States)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1994-01-01

    Immunohistochemical analyses of hypothalamic hormones carried out on tissue from rats flown on an earlier flight (Cosmos 1887) suggested preferential effects on hypophysiotropic principles involved in the regulation of growth hormone secretion and synthesis. We found that staining in the median eminence for peptides that provide both stimulatory (growth hormone-releasing factor, or GRF) and inhibitory (somatostatin, SS) influences on growth hormone secretion were depressed in flight animals relative to synchronous controls, while staining for other neuroendocrine peptides, cortocotropin-releasing factor and arginine vasopressin, were similar in these two groups. While this suggests some selective impact of weightlessness on the two principal central nervous system regulators of growth hormone dynamics, the fact that both GRF- and SS-immunoreactivity (IR) appeared affected in the same direction is somewhat problematic, and makes tentative any intimation that effects on CNS control mechanisms may be etiologically significant contributors to the sequelae of reduced growth hormone secretion seen in prolonged space flight. To provide an additional, and more penetrating, analysis we attempted in hypothalamic material harvested from animals flown on Cosmos 2044 to complement immunohistochemical analyses of GRF and SS staining with quantitative, in situ assessments of messenger RNAs encoding the precursors for both these hormones.

  4. Effects of growth hormone-releasing hormone treatment on milk production and plasma hormones and metabolites in lactating Japanese Black cows under negative energy balance.

    Science.gov (United States)

    Shingu, H; Hodate, K; Kushibiki, S; Touno, E; Oshibe, A; Ueda, Y; Shinoda, M; Ohashi, S

    2009-04-01

    The current study was performed to clarify the effects of GHRH treatment on milk production and plasma hormones and metabolites in lactating Japanese Black cows (a beef breed) under negative energy balance (EB). Ten multiparous lactating beef cows were offered a normal-energy diet daily (110% of ME requirements for maintenance and lactation) until 5 d in milk (DIM) to standardize the cows before dietary treatment. From 6 DIM to the final days (63 DIM) of the experiment, the cows were allotted to experimental dietary treatments: 5 cows were offered a diet formulated for 130% [high-energy diet (HED)] and the remaining 5 cows were offered a diet formulated for 80% [low-energy diet (LED)] of ME requirements for maintenance and lactation. In addition, all cows received daily subcutaneous injections of 3 mg of bovine GHRH from 36 to 56 DIM (GHRH treatment period). Differences in BW of HED- and LED-fed cows at 63 DIM were +28.4 and -7.2 kg compared with BW at 6 DIM, and HED- and LED-fed cows were under positive EB (+23.7 MJ/d) and negative EB (-11.6 MJ/d) throughout the experiment period. Treatment with GHRH increased (Pnegative EB in lactating beef cows.

  5. Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse.

    Science.gov (United States)

    Frohman, M A; Downs, T R; Chomczynski, P; Frohman, L A

    1989-10-01

    We have isolated and cloned the full length cDNA for mouse GH-releasing hormone (mGRH) from mouse hypothalamus using a recently described strategy involving the polymerase chain reaction technique (PCR). Degenerate oligonucleotide primers were selected based on short (six amino acids) conserved regions in the human and rat GRH peptides that would recognize DNA sequences encoding similar amino acids regardless of codon usage. Primer-extended cDNA was amplified by PCR on cDNA templates prepared by reverse transcribing total mouse hypothalamic RNA. After cloning and sequencing the initial product, the 3' and 5' ends of mGRH were generated using a separate PCR strategy (RACE protocol). The mGRH cDNA encodes a 103-amino acid reading frame, structurally similar to the human and rat GRH genes, containing a signal sequence, a 42-residue GRH peptide, and a 31-residue C-terminal region. Although the structures of mouse and rat GRH are highly conserved in the signal peptide and C-terminal region, there is considerable diversity in the GRH region, which exhibits nearly comparable homology with the rat (68%) and human (62%) structures. Differences between mouse and rat GRH were also found in the amino acid cleavage sites at the 5' and 3' ends of the mature peptide and at the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    QIU Wen-cai; WANG Zhi-gang; WANG Wei-gang; YAN Jun; ZHENG Qi

    2008-01-01

    Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment.In normal animals,both ghrelin and its synthetic peptide,growth hormone releasing peptide 6(GHRP-6),increase gastric emptying.Thus,we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.Methods A diabetic guinea pig model was produced by intraperitoneal(i.p.)injection of streptozotocin(STZ,280 mg/kg).Diabetic guinea pigs were injected i.p.with ghrelin or GHRP-6(10-100 pg/kg),and the effects on gastric emptying were measured after intragastric application of phenol red.The effect of atropine or a growth hormone secretagogue receptor(GHS-R)antagonist,D-Lys3-GHRP-6,on the gastroprokinetic effects of ghrelin or GHRP-6(100 μg/kg)was also investigated.Further,the in vitro effects of ghrelin or GHRP-6(0.01-10 μmol/L)on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined.Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction(RT-PCR).Results We established a guinea pig model of delayed gastric emptying.Ghrelin(20,50,or 100 μg/kg)and GHRP-6 (20,50,or 1 00 μg/kg)accelerated gastric emptying in diabetic guinea pigs with gastroparesis(n=-6,P<0.05).In the presence of atropine,which delayed gastric emptying,ghrelin and GHRP-6(100 μg/kg)failed to accelerate gastric emptying(n=6,P<0.05).D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist(n=6,P<0.05).Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs(n=6,P<0.05).RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis,potentially,by activating the

  7. β-Hydroxybutyric acid inhibits growth hormone-releasing hormone synthesis and secretion through the GPR109A/extracellular signal-regulated 1/2 signalling pathway in the hypothalamus.

    Science.gov (United States)

    Fu, S-P; Liu, B-R; Wang, J-F; Xue, W-J; Liu, H-M; Zeng, Y-L; Huang, B-X; Li, S-N; Lv, Q-K; Wang, W; Liu, J-X

    2015-03-01

    β-Hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA-mediated hormone regulation or the detailed mechanisms by which BHBA regulates growth hormone-releasing hormone (GHRH) synthesis and secretion. In the present study, we examined the expression of the BHBA receptor GPR109A in primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via GPR109A and its downstream signals. Initial in vivo studies conducted in rats demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely correlated with BHBA levels in the cerebrospinal fluid during postnatal development (r = -0.89, P hypothalamus in both in vivo and in vitro, and this effect was also inhibited by PTX in vitro. In primary hypothalamic cells, BHBA activated the extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) kinases, as shown by western blot analysis. Moreover, inhibition of ERK1/2 with U0126 attenuated the BHBA-mediated reduction in Gsh-1 expression and GHRH synthesis and secretion. These results strongly suggest that BHBA directly regulates GHRH synthesis and secretion via the GPR109A/ERK1/2 MAPK pathway, and also that Gsh-1 is essential for this function. © 2015 British Society for Neuroendocrinology.

  8. Effect of growth hormone-releasing peptide on ardiac cholinergic nerve fiber density distribution in a rat model of heart failure

    Institute of Scientific and Technical Information of China (English)

    Guozhong Tian; Xiuqin Ni; Yong Zhao; Jia Feng; Yanjun Li; Zhenya Zhong; Shuling Bai

    2009-01-01

    BACKGROUND: Changes in the cardiac autonomic nerve are considered to be important factors in the mechanisms of heart failure. It is possible to reduce or slow down nerve degeneration and necrosis, provided that patients take effective neuroprotectants during the early stages of heart failure. Moreover, it is possible to relieve the pathological process and reduce the risk of death.OBJECTIVE: To study the effect of growth hormone releasing peptide (GHRP) on cardiac cholinergic nerve fiber density distribution in a rat model of heart failure, and verify whether GHRP can ameliorate denervation.DESIGN, TIME AND SETTING: A randomized controlled study was performed at the Key Laboratory of Anatomy, Harbin Medical University, between June and October 2009.MATERIALS: Fifty adult, healthy, female, Wistar rats, weighing (200±20) g, were randomly divided into GHRP (n=30), model (n=10), and sham operation (n=10) groups. GHRP-2 was made in Shanghai, China (batch No. z071212-03).METHODS: Acute myocardial infarction was established by ligating the left anterior descending coronary artery in the GHRP and model groups. Five weeks later, myocardial function was detected using color ultrasound electrocardiograph. Ejection fraction < 60% was considered to be a successful marker of chronic heart failure models. However, the left anterior descending coronary artery was not ligated in the sham operation group. The GHRP group was injected with 100μg/kg GHRP-2, and the other two groups were injected with the same volume of physiological saline, once per day.MAIN OUTCOME MEASURES: After 4 weeks, pathological changes in cardiac cholinergic nerve fibers were detected under optic microscopy following hematoxylin/eosin staining. In addition, density distribution was measured using a multi-function color pathological image system.RESULTS: In the sham operation group, myocardial cells were regular, uniformly stained, and no inflammatory cells were present. In the model group, myocardial cells

  9. Interleukin-8 production from human somatotroph adenoma cells is stimulated by interleukin-1β and inhibited by growth hormone releasing hormone and somatostatin

    DEFF Research Database (Denmark)

    Vindeløv, Signe Diness; Hartoft-Nielsen, Marie-Louise; Rasmussen, Åse Krogh;

    2011-01-01

    Pituitary adenomas cause morbidity and mortality due to their localization and influence on pituitary hormone secretion. Although the pathogenesis of pituitary adenomas is unclear, studies have indicated that cytokines are involved. We investigated the role of cytokines, in particular interleukin...... (IL)-8, in the pathogenesis of growth hormone (GH) producing tumours.......Pituitary adenomas cause morbidity and mortality due to their localization and influence on pituitary hormone secretion. Although the pathogenesis of pituitary adenomas is unclear, studies have indicated that cytokines are involved. We investigated the role of cytokines, in particular interleukin...

  10. Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

    Science.gov (United States)

    Adoption of the hybrid catfish (channel catfish, Ictalruus punctatus, female x blue catfish, I. furcatus, male) is increasing in the catfish industry. The most effective way to produce fry is hormone induced spawning of females coupled with hand stripping and in vitro fertilization. The success of...

  11. Leptin alters the response of the growth hormone releasing factor- growth hormone--insulin-like growth factor-I axis to fasting.

    Science.gov (United States)

    LaPaglia, N; Steiner, J; Kirsteins, L; Emanuele, M; Emanuele, N

    1998-10-01

    Proper nutritional status is critical for maintaining growth and metabolic function, playing an intimate role in neuroendocrine regulation. Leptin, the recently identified product of the obese gene, may very well be an integral signal which regulates neuroendocrine responses in times of food deprivation. The present study examines leptin's ability to regulate hormonal synthesis and secretion within the GRF-GH-IGF axis in the adult male rat during almost 3 days of fasting. Serum levels of GH and IGF-I were drastically suppressed by fasting. Daily leptin administration was able to fully prevent the fasting-induced fall in serum GH. Leptin failed to restore IGF-I to control levels, however, suggesting possible GH resistance. Fasting caused an insignificant increase in GH mRNA, while leptin injections significantly increased steady-state levels of this message. The GRF receptor (GRFr) message was not altered with fasting or leptin treatment. Leptin also exhibited effects at the hypothalamic level. Fasting induced a sharp fall in GRF mRNA expression and leptin injections partially prevented this fall. However, there were no observed changes in the hypothalamic GRF content. These results provide evidence that leptin may function as a neuromodulator of the GRF-GH-IGF axis communicating to this hormonal system the nutritional status of the animal.

  12. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  13. Differential sensitivity of growth hormone-releasing hormone and somatostatin release from perifused mouse hypothalamic fragments in response to glucose deficiency.

    Science.gov (United States)

    Sato, M; Frohman, L A

    1993-06-01

    The effects of glucose deficiency on growth hormone (GH)-releasing hormone (GRH) and somatostatin (SRIH) release from mouse hypothalamic fragments were investigated using an in vitro perifusion system. Fragments were perifused with Krebs-Ringer bicarbonate solution (KRB) containing 5.6 mM glucose for 3 h followed by reduced glucose concentrations in KRB for the next 2 h. GRH release was simulated by 0.7-2.8 mM glucose in an inverse concentration-dependent manner. In contrast, SRIH release was not stimulated by glucose at concentrations of 2.8 and 1.4 mM; only at 0.7 mM was there a modest stimulation of SRIH release that was comparable to the effect of 2.8 mM glucose on GRH release. The maximal stimulation of GRH and SRIH release by 0.7 mM glucose was 221 and 150%, respectively, of controls. Glucose concentrations of 11.2 and 22.4 mM inhibited GRH release but did not alter SRIH release. The glucose analog 2-deoxy-D-glucose (2-DG; 5.6-39.2 mM) also stimulated GRH release in a dose-dependent manner, and SRIH release was less sensitive to 2-DG than was GRH. The maximal stimulation of GRH and SRIH release by 39.2 mM 2-DG was 190 and 147%, respectively, of controls. Increases in GRH and SRIH release stimulated by 30 mM KCl 1 h after exposure to low glucose or 2-DG were not significantly different from those after exposure to 5.6 mM glucose. However, the SRIH response to K(+)-induced depolarization was much greater than that of GRH. The glucose intermediate pyruvate (4.9 and 9.8 mM) partially inhibited both GRH and SRIH release induced by 0.7 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Damber, Jan-Erik; Malmberg, Anders

    2016-01-01

    hazards regression model and a conditional logistic regression model was used for a case-control analysis of odds ratios (ORs). RESULTS: Patients received degarelix monotherapy (n = 972) or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific antigen progression-free survival....../ml in the LHRH agonist + AA group, a case-control analysis using a conditional logistic regression model was utilized. This resulted in an OR for PSA PFS of 0.42 (95% CI 0.20-0.89; p = 0.023) in the overall population, and 0.35 (95% CI 0.13-0.96; p = 0.042) in patients with PSA >50 ng/ml at baseline, when...... protection therapy in patients with prostate cancer when a case-control analysis was used to compensate for differences between treatment groups....

  15. The effect of short-term cortisol changes on growth hormone responses to the pyridostigmine-growth-hormone-releasing-hormone test in healthy adults and patients with suspected growth hormone deficiency

    DEFF Research Database (Denmark)

    Andersen, M; Støving, R K; Hangaard, J

    1998-01-01

    BACKGROUND AND AIMS: The interaction between cortisol and growth hormone (GH)-levels may significantly influence GH-responses to a stimulation test. In order to systematically analyse the interaction in a paired design, it is necessary to use a test, which has been proven safe and reliable such a...

  16. The effect of short-term cortisol changes on growth hormone responses to the pyridostigmine-growth-hormone-releasing-hormone test in healthy adults and patients with suspected growth hormone deficiency

    DEFF Research Database (Denmark)

    Andersen, M; Støving, R K; Hangaard, J

    1998-01-01

    BACKGROUND AND AIMS: The interaction between cortisol and growth hormone (GH)-levels may significantly influence GH-responses to a stimulation test. In order to systematically analyse the interaction in a paired design, it is necessary to use a test, which has been proven safe and reliable such a...... (30 mg/day for 1 and 3 days). However, peak GH-responses to PD in combination with GHRH were reduced during HC (80 mg/day for 1 day) compared to no glucocorticoid pretreatment in all patients. Short-term hypocortisolism did not significantly affect peak GH-responses. CONCLUSION: The GH...

  17. Características testiculares de touros imunizados com vacina anti-hormônio liberador do hormônio luteinizante Testicular characteristics of bulls immunosterilized with anti-luteinizing hormone-releasing hormone vaccine

    Directory of Open Access Journals (Sweden)

    Ricardo Zanella

    2009-10-01

    Full Text Available O objetivo deste trabalho foi avaliar a ação imunoesterilizadora de uma vacina anti-hormônio liberador de hormônio luteinizante (LHRH, composta por ovalbumina-LHRH-7 e tiorredoxina-LHRH-7, em touros mestiços Nelore. Vinte e seis touros, com dois anos de idade, foram distribuídos aleatoriamente em dois grupos de 13 animais. No grupo I, os animais receberam uma dose e dois reforços da vacina nos dias 0, 141, e 287 do experimento. No grupo II, os animais não receberam nenhum tratamento (controle. Para avaliar o efeito da vacina nos touros, foi realizada a mensuração da circunferência escrotal no início do experimento e no dia do abate, 741 dias depois. Por ocasião do abate, também foi coletada uma amostra dos testículos para avaliação histológica. O grupo imunizado apresentou circunferência escrotal ao abate de 22±5,98 cm, menor do que a do grupo controle que foi de 35,6±2,4 cm. Na análise histológica dos animais do grupo imunizado, foi observada degeneração testicular com ausência de espermatozoides em 85% dos animais avaliados, os outros 15% apresentaram redução no número de espermatozoides, em comparação aos animais do grupo controle. A vacina anti-LHRH, com fusão de proteínas, é efetiva na castração imunológica de touros e deve ser considerada como alternativa para utilização na produção bovina extensiva no Brasil.The objective of this study was to evaluate the immunosterilization action of the anti-luteinizing hormone-releasing hormone (LHRH vaccine, composed with ovalbumin-LHRH-7 and thioredoxin-LHRH-7, in Nelore-cross bulls. Twenty-six 2-year old bulls were randomly assigned in two groups of 13 animals each. The animals of group I received a primary and two booster injections of the vaccine on days 0, 141, and 287 of the experiment. In group II, the control group, the bulls did not receive any type of treatment. Scrotal circumference was measured in the beginning of the experiment and at slaughter

  18. Butyrate Increases Intracellular Calcium Levels and Enhances Growth Hormone Release from Rat Anterior Pituitary Cells via the G-Protein-Coupled Receptors GPR41 and 43

    OpenAIRE

    Maria Consolata Miletta; Vibor Petkovic; Andrée Eblé; Ammann, Roland A; Flück, Christa E.; Primus-E Mullis

    2014-01-01

    Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous...

  19. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43

    OpenAIRE

    Miletta, Maria Consolata; Petkovic, Vibor; Eblé, Andrée; Ammann, Roland; Flück, Christa; Mullis, Primus-Eugen

    2014-01-01

    Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous...

  20. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.

    Directory of Open Access Journals (Sweden)

    Maria Consolata Miletta

    Full Text Available Butyrate is a short-chain fatty acid (SCFA closely related to the ketone body ß-hydroxybutyrate (BHB, which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR, GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

  1. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.

    Science.gov (United States)

    Miletta, Maria Consolata; Petkovic, Vibor; Eblé, Andrée; Ammann, Roland A; Flück, Christa E; Mullis, Primus-E

    2014-01-01

    Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR), GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH)-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

  2. Effect of a hormone-releasing intrauterine system (Mirena® on aromatase and Cox-2 expression in patients with adenomyosis submitted or not, to endometrial resection

    Directory of Open Access Journals (Sweden)

    Maia R

    2012-04-01

    Full Text Available Hugo Maia Jr1,2, Clarice Haddad1, Julio Casoy1, Rebeca Maia1, Nathanael Pinheiro3, Elsimar M Coutinho11Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH, 2Itaigara Memorial Day Hospital, 3IMAGEPAT, Salvador, Bahia, BrazilObjective: To investigate the effect of a levonorgestrel-releasing intrauterine system (Mirena® on aromatase and cyclooxygenase-2 (Cox-2 expression in the endometrium of patients with adenomyosis who were submitted to endometrial resection at the time of insertion, compared to a group not submitted to endometrial resection and a group of controls with adenomyosis not submitted to any previous hormonal treatment.Patients and methods: Patients with adenomyosis (n = 89 were included in this study. Twenty-two patients had been using Mirena® for 5 years but had not been submitted to endometrial resection prior to insertion of the device. Twenty-four patients were submitted to endometrial resection at the time of Mirena® insertion. The remaining 43 patients with adenomyosis had undergone no previous hormonal treatment and served as a control group. Cox-2 and aromatase expression were determined in the endometrium by immunohistochemistry.Results: Use of Mirena® for 5 years reduced aromatase expression in the endometrium; however, this reduction was significantly greater in the uteri previously submitted to endometrial resection. The reduction in Cox-2 expression was significant only in the uteri submitted to endometrial resection followed by the insertion of Mirena®.Conclusion: Endometrial resection followed by the insertion of Mirena® was associated with greater rates of amenorrhea in patients with adenomyosis, which in turn were associated with a more effective inhibition of aromatase and Cox-2 expression in the endometrium.Keywords: aromatase, Mirena®, adenomyosis, Cox-2, endometrium, levonorgestrel

  3. Parenteral versus early intrajejunal nutrition: Effect on pancreatitic natural course, entero-hormones release and its efficacy on dogs with acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Huan-Long Qin; Zhen-Dong Su; Lei-Guang Hu; Zai-Xian Ding; Qing-Tian Lin

    2003-01-01

    AIM: To evaluate the effect of early intrajejunal nutrition (EIN) on the natural course, entero-hormone secretion and its efficacy on dogs with acute pancreatitis.METHODS: An acute pancreatitis model was induced by injecting 1 ml/kg of combined solution (2.5% sodium taurocholate and 8 000-10 000 BAEE units trypsin/mi) into the pancreas via pancreatic duct. Fifteen dogs were divided into parenteral nutrition (PN) group and EIN group. Two groups were isonitrogenous and isocaloric. EIN was used at postoperative 24 h. Serum glucose, calcium, amylase and lysosomal enzymes were determined before and 1, 4, 7 d after acute pancreatitis was induced. All the dogs were injected 50 uCi 125I-BSA 4 h before sacrificed on the 7th day.The 125I -BSA index of the pancreas/muscle, pancreas/blood,and pancreas pathology score (PPS) were determined. The peripheral plasma cholecystokinin (CCK), secretin (SEC) and gastrin were measured by ELISA and RIA, and was quantitative analysis of pancreatic juice and amylase,pancreatolipase and HCO3-, Cl-, Na+ and K+ performed by an autochemical analyzer at 30, 60, 120 and 180 min after beginning PN or EIN on the first day.RESULTS: There was no difference between two groups in the contents of serum calcium, amylase and lysosomal enzymes, 125I-BSA index of pancreas/muscle and pancreas/blood and PPS. The contents of CCK and gastrin in EIN were higher than those in PN group at 60 and 120 min (P<0.05).The content of SEC post-infusion of nutrition solution was higher than that of pre-infusion of nutrition solution in both groups, and only at 60 min SEC in EIN group was higher than that in PN group. The content of gastrin in EIN was higher than that in PN group at 120 and 180 min (P<0.05).The changes of pancreatic juice, amylase, pancreatolipase and HCO3-, Cl-, Na+ and K+ between two groups did not reach significantly statistical difference (P>0.05).CONCLUSION: EIN does not stimulate entero-hormone and pancreatic juice secretion, and enzyme

  4. JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

    Science.gov (United States)

    Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

    2011-10-01

    Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

  5. Heterogeneity of rat FSH by chromatofocusing: studies on serum FSH, hormone released in vitro and metabolic clearance rates of its various forms.

    Science.gov (United States)

    Blum, W F; Gupta, D

    1985-04-01

    Rat pituitary FSH was fractionated by chromatofocusing between pH 6 and 3. Ten components were resolved having apparent isoelectric points between 3.1 and 5.1. A comparative study of pituitary FSH and FSH secreted in vitro by quartered pituitary glands in the presence and in the absence of gonadotrophin-releasing hormone (GnRH) revealed similar patterns of charged species of intracellular and released FSH. Although GnRH increased FSH secretion about fourfold, no influence on the pattern of charged species was observed. Utilizing exclusion chromatography and chromatofocusing, pituitary FSH was compared to serum FSH which had been extracted by immuno-affinity chromatography. The results demonstrate for serum FSH a larger molecular size and a relative shift to more acidic components. Metabolic clearance rates of eight FSH components separated by chromatofocusing were measured in adult male rats. Half-lives varied between 13 min and several hours. A correlation existed between decrease of isoelectric points and decrease of metabolic clearance rates. These findings suggest that all hypophysial FSH components are secreted into the circulation at similar rates and the more acidic FSH components which appear to contain increased sialic acid, have a longer circulatory half-life and are more abundant in serum. It is concluded that sialylation may be involved in modulating serum FSH levels.

  6. Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin.

    Directory of Open Access Journals (Sweden)

    Lara Pena-Bello

    Full Text Available Metabolic substrates and nutritional status play a major role in growth hormone (GH secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG administration in normal and obese patients is a pending issue.The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity.We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed.The AUC of GH (μg/L•min was lower in obese (249.8±41.8 than in healthy women (490.4±74.6, P=0.001. The AUC of total ghrelin (pg/mL•min was lower in obese (240995.5±11094.2 than in healthy women (340797.5±37757.5, P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.

  7. Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices.

    Science.gov (United States)

    Glanowska, Katarzyna M; Venton, B Jill; Moenter, Suzanne M

    2012-10-17

    Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for the central regulation of fertility. There is no method allowing real-time GnRH detection in brain slices. We developed fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFME) to detect GnRH release and validated it using a biologically relevant system. FSCV parameters (holding potential, switching potential, and scan rate) were determined for stable GnRH detection in vitro, then optimized for GnRH detection in mouse brain slices. Placement of CFMEs in the median eminence (ME) near GnRH terminals allowed detection of both KCl-evoked and spontaneous GnRH release. GnRH release was also detected from GnRH fibers passing near GnRH soma and near fiber-fiber appositions in the preoptic area. No GnRH signal was detected from CFMEs in the ME of hpg mice, which lack GnRH, or in regions not containing GnRH neurons in wild-type mice; application of exogenous GnRH produced a signal similar to that observed for spontaneous/evoked endogenous GnRH release. Using an established mouse model that produces diurnal variations in GnRH neuron activity, we demonstrated corresponding changes in spontaneous GnRH release in the median eminence. These results validate FSCV to detect GnRH in brain slices and provide new information on the sites and amounts of GnRH release, providing insight into its neuromodulatory functions.

  8. Different effects of growth hormone-releasing hormone (GRH) and somatostatin on growth hormone and stable metabolite of prostaglandin E2, 13, 14-dihydro-15-keto-prostaglandin E2 (PGE2-M) in normal subjects.

    Science.gov (United States)

    Zacharieva, S; Muchá, I; Popova, J; Andonova, K

    1992-01-01

    Twenty four healthy subjects were placed in two treatment groups: 1. The first group consisted of twelve subjects in whom growth releasing hormone (GRH) (1 microgram/kg.BW) resulted in a marked and sustained elevation of serum growth hormone (GH) and a slight and delayed increase in plasma prostaglandin E2-M. In the second group, consisting also of twelve subjects, somatostatin infusion (500 micrograms/250 ml) was initiated and maintained for 60 min. Serum GH significantly decreased at 30 and 60 min during infusion and 15 min thereafter. We did not observe any changes in plasma prostaglandin E2-M during or after somatostatin infusion. The results obtained confirm previous in vitro studies and suggest a possible link between growth releasing hormone and prostaglandin E2 in their action on growth hormone secretion. It seems that somatostatin does not play a role in the control of prostaglandin E2 release.

  9. Hormone therapy for transgender patients

    Science.gov (United States)

    2016-01-01

    Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients. Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. PMID:28078219

  10. Types of Cancer Treatment: Hormone Therapy

    Science.gov (United States)

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  11. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  12. Deciding about hormone therapy

    Science.gov (United States)

    ... your risk for endometrial cancer. Taking progestin with estrogen seems to protect against this cancer. So if you have a ... menopause without taking hormones. They can also help protect your bones, improve your heart health , and help you stay ...

  13. Effects of antagonists of growth hormone-releasing hormone (GHRH) on GH and insulin-like growth factor I levels in transgenic mice overexpressing the human GHRH gene, an animal model of acromegaly.

    Science.gov (United States)

    Kovacs, M; Kineman, R D; Schally, A V; Zarandi, M; Groot, K; Frohman, L A

    1997-11-01

    Transgenic mice overexpressing the human GH-releasing hormone (hGHRH) gene, an animal model of acromegaly, were used to investigate the effects of potent GHRH antagonists MZ-4-71 and MZ-5-156 on the excessive GH and insulin-like growth factor I (IGF-I) secretion caused by overproduction of hGHRH. Because metallothionein (MT)-GHRH mice express the hGHRH transgene in various tissues, including the pituitary and hypothalamus, initial experiments focused on the effectiveness of the GHRH antagonists in blocking basal and stimulated GH secretion from pituitary cells in vitro. Both MZ-4-71 and MZ-5-156 suppressed basal release of GH from superfused MT-GHRH pituitary cells, apparently by blocking the action of endogenously produced hGHRH. In addition, these antagonists effectively eliminated the response to stimulatory action of exogenous hGHRH(1-29)NH2 (30 and 100 nM). To ascertain whether MZ-4-71 and MZ-5-156 could antagonize the effect of hGHRH hyperstimulation in vivo, each antagonist was administered to MT-GHRH transgenic mice in a single iv dose of 10-200 microg. Both compounds decreased serum GH levels in transgenic mice by 39-72% at 1 h after injection. The inhibitory effect of 50 microg MZ-5-156 was maintained for 5 h. Twice daily ip administration of 100 microg MZ-5-156 for 3 days suppressed the highly elevated serum GH and IGF-I concentrations in transgenic mice by 56.8% and 39.0%, respectively. This treatment also reduced IGF-I messenger RNA levels in the liver by 21.8% but did not affect the level of GH messenger RNA in the pituitary. Our results demonstrate that GHRH antagonists MZ-4-71 and MZ-5-156 can inhibit elevated GH levels caused by overproduction of hGHRH. The suppression of circulating GH concentrations induced by the antagonists seems to be physiologically relevant, because both IGF-I secretion and synthesis also were reduced. Our findings, showing the suppression of GH and IGF-I secretion with GHRH antagonists, suggest that this class of analogs

  14. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  15. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  16. Progestogens in menopausal hormone therapy

    Directory of Open Access Journals (Sweden)

    Małgorzata Bińkowska

    2015-06-01

    Full Text Available Progestogens share one common effect: the ability to convert proliferative endometrium to its secretory form. In contrast, their biological activity is varied, depending on the chemical structure, pharmacokinetics, receptor affinity and different potency of action. Progestogens are widely used in the treatment of menstrual cycle disturbances, various gynaecological conditions, contraception and menopausal hormone therapy. The administration of progestogen in menopausal hormone therapy is essential in women with an intact uterus to protect against endometrial hyperplasia and cancer. Progestogen selection should be based on the characteristics available for each progestogen type, relying on the assessment of relative potency of action in experimental models and animal models, and on the indirect knowledge brought by studies of the clinical use of different progestogen formulations. The choice of progestogen should involve the conscious use of knowledge of its benefits, with a focus on minimizing potential side effects. Unfortunately, there are no direct clinical studies comparing the metabolic effects of different progestogens.

  17. Alterations of serum levels of three kinds of promote hormone releasing hormones in patients with fibromyalgia%纤维肌痛患者血清中三种促激素释放激素含量的改变

    Institute of Scientific and Technical Information of China (English)

    虞金霞; 陈贵海

    2011-01-01

    ObjectiveTo explore alterations of serum levels and clinical significance of corticotropin releasing hormone (CRH), thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) in patients with fibromyalgia (FM). Methods A total of 55 subjects participated in this study: 29 healthy volunteers and 26 patients with FM recruited from Department of Neurology, the First Affiliated Hospital of Anhui Medical University from June 2009 to October 2010. The depression rate was assessed by Hamilton Depression Rating Scale-17. ELISA was used for the detection of the serum levels of CRH, TRH and GnRH. Normal distribution quantitative data were described by the (-x) ± s and tested by independent sample t-test. Non-normal quantitative data were described by interquartile range and tested by independent Mann-Whitney. The diagnostic specificity and sensitivity of 3 kinds of hormones test were analyzed by receiver operator characteristic ( ROC ) curve, and the Spearman correlation was used for analysis of hormone levels and age, gender, tenderness, pain degree and depression severity. Results Compared with the control (70. 0(48.7,78.0) ng/L), the fibromyalgia patients had obviously increased CRH (271.9 (210.9,326.5) rg/L, x2 =6.408, P<0. 01) , and significantly higher TRH ((82.7 ±6. 9 ) ng/L vs ( 87. 2 ± 6. 8 ) ng/L, t = 2. 560, P < 0. 05, respectively) and GnRH ( ( 18. 2 ± 0. 9 ) ng/L vs ( 19. 9 ± 1.6)ng/L,t =5. 324, P <0. 01, respectively). The serum concentrations of the CRH, TRH and GnRH were positively correlated with pain intensity and numbers of tenderness respectively, and those of the CRH and GnRH were positively correlated with depressive degree either. The areas under the ROC curve in the CRH, TRH and GnRH, evaluating the sensitivity and specificity for diagnosis of fibromyalgia, were respectively 1. 000, 0. 684 and 0. 854. Conclusions The FM patients had an increased secretion of CRH,TRH and GnRH. CRH might serve as the adjunctive criteria for

  18. Estrogen receptor immunoreactivity is present in the majority of central histaminergic neurons: evidence for a new neuroendocrine pathway associated with luteinizing hormone-releasing hormone-synthesizing neurons in rats and humans.

    Science.gov (United States)

    Fekete, C S; Strutton, P H; Cagampang, F R; Hrabovszky, E; Kalló, I; Shughrue, P J; Dobó, E; Mihály, E; Baranyi, L; Okada, H; Panula, P; Merchenthaler, I; Coen, C W; Liposits, Z S

    1999-09-01

    The central regulation of the preovulatory LH surge requires a complex sequence of interactions between neuronal systems that impinge on LH-releasing hormone (LHRH)-synthesizing neurons. The reported absence of estrogen receptors (ERs) in LHRH neurons indicates that estrogen-receptive neurons that are afferent to LHRH neurons are involved in mediating the effects of this steroid. We now present evidence indicating that central histaminergic neurons, exclusively located in the tuberomammillary complex of the caudal diencephalon, serve as an important relay in this system. Evaluation of this system revealed that 76% of histamine-synthesising neurons display ERalpha-immunoreactivity in their nucleus; furthermore histaminergic axons exhibit axo-dendritic and axo-somatic appositions onto LHRH neurons in both the rodent and the human brain. Our in vivo studies show that the intracerebroventricular administration of the histamine-1 (H1) receptor antagonist, mepyramine, but not the H2 receptor antagonist, ranitidine, can block the LH surge in ovariectomized estrogen-treated rats. These data are consistent with the hypothesis that the positive feedback effect of estrogen in the induction of the LH surge involves estrogen-receptive histamine-containing neurons in the tuberomammillary nucleus that relay the steroid signal to LHRH neurons via H1 receptors.

  19. Postmenopausal hormone therapy and cognition.

    Science.gov (United States)

    McCarrey, Anna C; Resnick, Susan M

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Prior to the publication of findings from the Women's Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the 'critical window hypothesis', which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as lower global cognition or diabetes. Lastly, we point towards implications for future research and clinical treatments. Published by Elsevier Inc.

  20. Postmenopausal hormone therapy and cognition

    Science.gov (United States)

    McCarrey, Anna C.; Resnick, Susan M.

    2015-01-01

    Prior to the publication of findings from the Women’s Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the ‘critical window hypothesis’, which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as cerebrovascular disease or diabetes. Lastly, we point towards implications for future research and clinical treatments. PMID:25935728

  1. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

    Ravn, S H; Rosenberg, J; Bostofte, E

    1994-01-01

    in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin....... Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke...... suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular...

  2. Postmenopausal hormone therapy in clinical perspective.

    Science.gov (United States)

    Hodis, Howard N; Mack, Wendy J

    2007-01-01

    Although many of the risks and benefits of postmenopausal hormone therapy are known, only recently has the magnitude of these effects and their perspective to other therapies become more fully understood. Careful review of randomized controlled trials indicates that the risks of postmenopausal hormone therapy including breast cancer, stroke and venous thromboembolism are similar to other commonly used agents. Overall, these risks are rare (less than 1 event per 1,000 women) and even rarer when initiated in women less than 60 years of age or within 10 years of menopause. In addition, the literature indicates similar benefit of postmenopausal hormone therapy, in women who initiate hormone therapy in close proximity to menopause, to other medications used for the primary prevention of coronory heart disease in women.

  3. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    , including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women......Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers...

  4. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...

  5. Therapy for obesity based on gastrointestinal hormones

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Christensen, Mikkel; Knop, Filip K;

    2011-01-01

    It has long been known that peptide hormones from the gastrointestinal tract have significant impact on the regulation of nutrient metabolism. Among these hormones, incretins have been found to increase insulin secretion, and thus incretin-based therapies have emerged as new modalities...

  6. Menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Ali Baziad

    2001-12-01

    Full Text Available The global population in the 21st century has reached 6.2 billion people, by the year 2025 it is to be around 8.3-8.5 billion, and will increase further. Elderly people are expected to grow rapidly than other groups. The fastest increase in the elderly population will take place in Asia. Life expectancy is increasing steadily throughout developed and developing countries. For many  menopausal women, increased life expectancy will accompanied by many health problems. The consequences of estrogen deficiency are the menopausal symptoms. The treatment of menopause related complaints and diseases became an  important socioeconomic and medical issue. Long term symptoms, such as the increase in osteoporosis fractures, cardio and cerebrovascular disesses and dementia, created a large financial burden on individuals and society. All these health problems can be lreated or prevented by hormone replacement therapy (HRT. Natural HRT is usually prefened. Synthetic  estrogen in oral contraceptives (oc are not recommended for HRT. Many contra-indications for oc, but now it is widely usedfor HRT. The main reasons for discontinuing HRT are unwanted bleeding, fear of cancer, and negative side effects. Until now there are sill debates about the rebrtonship between HRT and the incidence of breast cancer. Many data showed that there were no clear relationship between the use of HRT and breast cancer. ThereÎore, nwny experts advocate the use of HRTfrom the first sign of climacteric complaints until death. (Med J Indones 2001;10: 242-51Keywords: estrogen deficiency, climacteric phases, tibolone.

  7. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh;

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

  8. Effects of leptin on gonadotropin-releasing hormone release from hypothalamic-infundibular explants and gonadotropin release from adenohypophyseal primary cell cultures: further evidence that fully nourished cattle are resistant to leptin.

    Science.gov (United States)

    Amstalden, M; Harms, P G; Welsh, T H; Randel, R D; Williams, G L

    2005-01-01

    In rodents and pigs, leptin stimulates the release of gonadotropin-releasing hormone (GnRH) from hypothalamus, gonadotropins from adenohypophyseal (AP) explants and cells, and luteinizing hormone (LH) from full-fed animals. In the current studies, we investigated whether leptin could stimulate the release of GnRH from bovine hypothalamic-infundibular (HYP) explants and gonadotropins from bovine adenohypophyseal cells. In Experiment 1A, HYP explants collected from 17 bulls and seven steers were incubated with Krebs-Ringer bicarbonate buffer (KRB) containing 0, 10, 100, or 1000 ng/ml recombinant ovine leptin (oleptin) for 30 min after a 3-h period of equilibration. None of the doses of leptin affected (P > 0.05) GnRH release into the media. In Experiment 1B, HYP explants collected from six steers were incubated with KRB containing 0 or 1000 ng/ml oleptin for two consecutive 30-min periods and challenged with 60 mM K(+) afterwards. Leptin did not affect (P > 0.05) basal or K(+)-stimulated release of GnRH. In Experiment 2, adenohypophyses from steers were collected at slaughter and cells dispersed and cultured for 4 days. On day 5, cells were treated with media alone (control) or media containing 10(-11), 10(-10), 10(-9), and 10(-8)M oleptin. Three independent replications were performed. None of the doses of leptin stimulated (P > 0.05) the release of LH. Although leptin at 10(-11), 10(-10), and 10(-9)M increased (P release of FSH compared to control-treated cells in one replicate, this effect was not confirmed in the other two replicates. Results support the hypothesis that leptin has limited effects on the release of GnRH and gonadotropins in full-fed cattle and reiterate important species differences in responsiveness to leptin.

  9. Menopausal Hormone Therapy and Cancer

    Science.gov (United States)

    ... Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  10. [Hormone replacement therapy: curse or blessing?].

    Science.gov (United States)

    Schmidt, M; Fink, D; Lang, U; Kimmig, R

    2006-01-01

    There is a controversial discussion on the risks and benefits of hormonal replacement therapy (HRT), and many women and doctors have revised their opinions of HRT over the last few years. Complementary and alternative therapies can be considered an option to treat menopausal symptoms. The following issue summarizes the actual knowledge of treatment options of menopausal symptoms.

  11. Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.

    Science.gov (United States)

    Carlson, Robert W; Henderson, I Craig

    2003-01-01

    The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that

  12. Growth hormone therapy in progeria.

    Science.gov (United States)

    Sadeghi-Nejad, Ab; Demmer, Laurie

    2007-05-01

    Catabolic processes seen in Hutchinson-Gilford progeria resemble those of normal aging and, in the affected children, usually result in death at an early age. In addition to its growth promoting effects, growth hormone (GH) has potent anabolic properties. Administration of GH ameliorates some of the catabolic effects of normal aging. We report the results of GH treatment in a young child with progeria.

  13. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    Science.gov (United States)

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  14. Growth hormone replacement therapy in Costello syndrome.

    Science.gov (United States)

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  15. Hormone replacement therapy and risk of glioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper;

    2013-01-01

    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  16. Ionic channels and hormone release from peptidergic nerve terminals.

    Science.gov (United States)

    Lemos, J R; Nordmann, J J

    1986-09-01

    Although there is considerable evidence that depolarization of nerve cell terminals leads to the entry of Ca2+ and to the secretion of neurohormones and neurotransmitters, the details of how ionic currents control the release of neuroactive substances from nerve terminals are unknown. The small size of most nerve terminals has precluded direct analysis of membrane ionic currents and their influence on secretion. We now report that it is possible, using patch-clamp techniques, to study stimulus--secretion coupling in isolated peptidergic nerve terminals. Sinus gland terminals from Cardisoma are easily isolated following collagenase treatment and appear morphologically and electrically very similar to non-dissociated nerve endings. We have observed two types of single-channel currents not previously described. The first ('f') channel is activated by intracellular Na+ and the second ('s') by intracellular Ca2+. Both show little selectivity between Na+ and K+. In symmetrical K+, these cation channels have mean conductances of 69 and 213 pS, respectively. Furthermore, at least three types of Ca2+ channels can be reconstituted from nerve terminal membranes prepared from sinus glands. Nerve terminals can also be isolated from the rat neural lobe. These neurosecretosomes release oxytocin and vasopressin, in response to membrane depolarization, only in the presence of external Ca2+. The depolarization of the nerve endings is associated with an increase in intracellular free Ca2+ concentration and this increase, measured using a fluorescent indicator, is abolished by Ca2+ channel blockers. Channels similar in their properties to the f and s channels also exist in rat neural lobe endings. Since these channels have not been found in other neurones or neuronal structures they may be unique to peptidergic nerve terminals.

  17. Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

    Science.gov (United States)

    Hormone replacement therapy: Can it cause vaginal bleeding? I'm taking hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from Shannon K. Laughlin- ...

  18. Effect of acute retrograde gastric electrical stimulation on gastric accommodation, emptying and gastrointestinal hormones releasing in obese patients%急性逆行胃电刺激对肥胖患者胃容受性、胃排空和胃肠激素释放的影响

    Institute of Scientific and Technical Information of China (English)

    房龙; 杜时雨; 姚树坤; 张艳丽; 李艳梅

    2011-01-01

    Objective To observe the effect of acute retrograde gastric electrical stimulation (RGES) on gastric accommodation,emptying and gastrointestinal hormones releasing in obese patients. Methods Sixteen obese patients were examined. On the first day,a pair of mucosal gastric electrodes was placed under endoscope. The liquid meal load test and the standard solid meal gastric emptying test were carried out on the second day. RGES was performed starting at 30 minutes before each test and through the whole testing process. The serum leptin,ghrelin,resistin and peptide YY were examined before and after the standard solid meal gastric emptying test. On the third day,sham stimulation was given. The effect of acute RGES on related index was compared by self-control.Results BMI of the 16 patients was (32. 90±2. 99) kg/m2. Acute RGES significantly reduced the liquid meal volume of fullness [(460±148) ml and (630±219) ml,t=-7. 200,P<0. 01] and the maximal tolerable meal volume [(699±215) ml and (926±295) ml,t=- 5. 390,P<0. 01]. The effects of RGES and sham RGES on half-emptying time of standard solid meal was (109±26) min and (103±31) min (t=1. 009,P= 0. 329);on the retention rate of standard solid meal at one hour and two hour was (63. 37±9. 75)% and (59. 73±12.87)% (t=1. 834,P= 0. 087),(42.22±13.97)%and (38. 33±16. 87)% (t= 1.780,P= 0. 095),respectively. The ratio of gastrointestinal hormones after and before the stimulation also of the sham stimulation,leptin was 1. 03±0. 34 and 1. 08±0. 38(t=-0.386,P=0. 705),ghrelin was 0. 99±0. 11 and 0. 98±0. 12 (t= 0. 413,P=0.685),resistin was 1. 11±0. 25 and 0. 99±0. 24 (t= 1. 753,P= 0. 100),and peptide YY was 1. 56±0. 71 and 1. 33±0. 61 (t=1. 402,P= 0. 181). Conclusions In obese patients,acute RGES significantly reduce the liquid meal volume by lower gastric accommodation,to certain extent which will delay gastric emptying. There is no significant influence on gastrointestinal hormones releasing.%目的 观察急

  19. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

    Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

  20. Growth hormone therapy for people with thalassaemia.

    Science.gov (United States)

    Ngim, Chin Fang; Lai, Nai Ming; Hong, Janet Yh; Tan, Shir Ley; Ramadas, Amutha; Muthukumarasamy, Premala; Thong, Meow-Keong

    2017-09-18

    Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. To assess the benefits and safety of growth hormone therapy in people with thalassaemia. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively. Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria. One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes

  1. Abnormal Bleeding During Menopause Hormone Therapy: Insights for Clinical Management

    OpenAIRE

    2013-01-01

    Objective Our objective was to review the involved mechanisms and propose actions for controlling/treating abnormal uterine bleeding during climacteric hormone therapy. Methods A systemic search of the databases SciELO, MEDLINE, and Pubmed was performed for identifying relevant publications on normal endometrial bleeding, abnormal uterine bleeding, and hormone therapy bleeding. Results Before starting hormone therapy, it is essential to exclude any abnormal organic condition, identify women a...

  2. 促性腺激素释放激素及多巴胺对斜带石斑鱼生长激素分泌及其mRNA表达的调控%Stimulatory effects of gonadotropin-releasing hormone and dopamine on growth hormone release and growth hormone mRNA expression in Epinephelus coioides

    Institute of Scientific and Technical Information of China (English)

    冉雪琴; 李文笙; 林浩然

    2004-01-01

    研究斜带石斑鱼生长激素分泌及其mRNA表达的调控规律对于性别分化的控制、临床药物的选择,以及石斑鱼的增养殖等均具有重要的理论意义和实践意义.本文应用静态孵育系统,采用放射免疫测定法和化学发光液相杂交实验,研究GnRH和DA对斜带石斑鱼GH分泌、GH mRNA合成的调控作用.100 nmol/L sGnRH作用斜带石斑鱼脑垂体碎片1~24 h,明显促进GH的释放和GH mRNA的合成,并具有时间依存性;10 nmol/L~1μmol/L sGnRH作用1 h能明显促进斜带石斑鱼脑垂体释放GH,促进GH mRNA的合成,表现出明显的剂量效应.100 nmol/L、1μmol/L mGnRH作用1 h以一定的剂量依存方式促进GH的释放、促进GH mRNA的合成,但mGnRH的效应比相应剂量的sGnRH的作用弱.APO为DA受体的非选择性激动剂,不同剂量APO对斜带石斑鱼脑垂体碎片的作用结果显示,10 nmol/L~lμmol/L APO以剂量依存方式促进斜带石斑鱼脑垂体碎片释放GH、促进GH mRNA的合成;1μmol/L APO作用12 h以上明显促进GH的释放和GH mRNA的合成,并随时间的延长而增加.与sGnRH对斜带石斑鱼GH释放、GH mRNA合成的作用相比,APO的作用较弱.本文研究结果证实GnRH和DA能促进斜带石斑鱼脑垂体GH释放和GH mRNA合成.%Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth hormone (GH) release, but their effects on GH mRNA synthesis are controversial and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a hermaphroditic marine fish with sex reversal. Few data are available concerning the regulation of GH in grouper. In the present study, the effects of GnRH and DA on GH release and GH mRNA expression were determined using pituitary fragments of orange-spotted grouper under static culture conditions. After incubation from 1 h to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and increased the level of GH mRNA time-dependently. The minimum duration of s

  3. [Localized lipohypertrophy during growth hormone therapy].

    Science.gov (United States)

    Mersebach, Henriette; Feldt-Rasmussen, Ulla F

    2002-04-01

    Accumulation of subcutaneous fat is described in a 51-year-old woman with panhypopituitarism treated on all insufficient pituitary axes, including growth hormone (GH). Malnutrition and alcoholic liver disease caused reduced synthesis of hepatic insulin-like growth factor I (IGF-I), and the function of IGF-I as biochemical marker of the GH effect was compromised. Peripheral levels of GH and IGF-I in tissues may have reached supra physiological levels and induced localised lipohypertrophy. Adjustment of GH treatment should not rest in all cases on IGF-I alone, but also depend on the clinical effect. Adjustment should follow suspected adverse events, such as lipohypertrophy, which is, however, an unusual complication of GH therapy.

  4. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

    DEFF Research Database (Denmark)

    Vestergaard, P; Hermann, A P; Gram, J

    1997-01-01

    To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

  5. Risk of Stroke With Various Types of Menopausal Hormone Therapies

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Nielsen, Lars Hougaard; Keiding, Niels

    2017-01-01

    BACKGROUND AND PURPOSE: Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of reg...

  6. Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Alexander L. Pan

    2012-01-01

    Full Text Available Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.

  7. Growth Hormone Therapy in Adults with Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Karen S. Vogt

    2015-04-01

    Full Text Available Prader-Willi syndrome (PWS is characterized by hyperphagia, obesity if food intake is not strictly controlled, abnormal body composition with decreased lean body mass and increased fat mass, decreased basal metabolic rate, short stature, low muscle tone, cognitive disability, and hypogonadism. In addition to improvements in linear growth, the benefits of growth hormone therapy on body composition and motor function in children with PWS are well established. Evidence is now emerging on the benefits of growth hormone therapy in adults with PWS. This review summarizes the current literature on growth hormone status and the use of growth hormone therapy in adults with PWS. The benefits of growth hormone therapy on body composition, muscle strength, exercise capacity, certain measures of sleep-disordered breathing, metabolic parameters, quality of life, and cognition are covered in detail along with potential adverse effects and guidelines for initiating and monitoring therapy.

  8. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Coakley, J H; Moorcraft, J; Hipkin, L J; Smith, C S; Griffiths, R D; Edwards, R H

    1988-12-01

    Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

  9. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

    OpenAIRE

    Coakley, J. H.; Moorcraft, J; Hipkin, L J; Smith, C. S.; R.D. Griffiths; Edwards, R H

    1988-01-01

    Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

  10. Hormones for therapy of climacteric afflictions

    Directory of Open Access Journals (Sweden)

    Greiner, Wolfgang

    2007-03-01

    Full Text Available Background: In Western countries hormone replacement therapy (HT is widely used in the treatment of climacteric women who are affected with hot flashes and night sweats. Besides, long-term HT was frequently used to manage the higher risks for osteoporosis and heart attack in postmenopause. Estrogens alone or combined with progestin feature most frequently in HT. Objectives: This HTA report addresses the questions on medical efficacy and cost-effectiveness of HT as a treatment of hot flashes and night sweats as well as in the primary prevention of osteoporosis and cardiovascular disease in postmenopause in general healthy women. Methods: The literature search for articles published after 1998 was conducted in March 2004 in standard medical and economic databases. The analysis included randomised controlled trials, systematic reviews, meta-analysis and economic evaluations considering relevant clinical endpoints in English or German language. The quality of the studies was assessed using checklists corresponding to the study type. Results: HT is highly effective in treating hot flashes in climacteric women. The question of economical efficiency cannot be answered due to the scarce database. As the positive effects (lower risk for fractures and endometrial cancer do not outweigh the negative effects (higher risk for breast cancer and general cardiovascular risk estrogen-progestin combination HT cannot be recommended for primary prevention of osteoporosis and cardiovascular disease in postmenopausal women. Discussion: The observation period of most of the studies regarding therapy of hot flashes and night sweats were too short to evaluate possible risks of long-term HT. The economic publications assessing HT for this indication varied vastly in terms of applied methods and were not carried out with respect to the German health care system. Conclusions: HT can be recommended in the short-term treatment of hot flashes and night sweats in climacteric

  11. Hormone replacement therapy in Denmark, 1995-2004

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Lidegaard, Ojvind; Møller, Lisbeth Nørgaard;

    2007-01-01

    Recently, the Danish National Register of Medicinal Product Statistics (NRM) was opened for research purposes, and therefore, on an individual basis, can merge with other national registers. The aim of this study was to analyse the use of hormones based on the individual data of the entire Danish...... female population, with the focus on a detailed evaluation of specific hormone regimens and factors associated with systemic hormone replacement therapy (HRT)....

  12. Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

    Science.gov (United States)

    According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

  13. Endocrine therapy use among elderly hormone receptor-pos...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Clinical guidelines recommend that women with hormone-receptor positive breast cancer receive endocrine therapy (selective estrogen receptor modulators or aromatase...

  14. Hormone Therapy Not Advised for Preventing Disease After Menopause

    Science.gov (United States)

    ... Hormone Therapy Not Advised for Preventing Disease After Menopause Benefits of treatment don't outweigh the risks, ... attack, stroke and blood clots. Women typically enter menopause around the age of 50. Following menopause, women's ...

  15. Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

    OpenAIRE

    2012-01-01

    Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year...

  16. Effects of hormone therapy on brain structure

    Science.gov (United States)

    Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay; Miller, Virginia M.

    2016-01-01

    Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42–56 years, within 5–36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Results: Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = −0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Conclusions: Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. Classification of evidence: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. PMID:27473135

  17. Hormone Replacement Therapy After Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mueck AO

    2008-01-01

    Full Text Available So far, patient samples in all studies investigating hormone replacement therapy (HRT after breast cancer have been small.Therefore, HRT should only be used if alternatives such as specifically not contraindicated phytopreparations or selective sero-tonin reuptake inhibitors (SSRIs are not effective. This is primarily due to forensic reasons since clinical data on the risk ofalternatives (based on present evidence are even more sparse. Regarding HRT, four prospective randomized studies and at least15 observational studies after breast cancer are available. Only the HABITS study shows an increased risk of relapse. The authorssuggest that this is probably associated with the relatively high number of patients with HRT treatment after ER-positive cancersas well as due to the preferred use of estrogen/progestin-combined preparations. Based on the results of the randomized pla-cebo-controlled study Women’s Health Initiative (WHI as well as of at least 12 observational studies, the progestin componentseems to be mainly responsible for the probability of increased diagnosis frequency of primary breast cancer. However, no dataare available on the impact of progestin on the use of combined HRT after breast cancer. However, also with estrogen only anincreased risk of relapse must be expected and patients should be informed about it. This has to be concluded due to biologicalplausibility and observational studies although the estrogen-only arm in WHI did not show any increased primary risk. Thus, anyform of HRT should only be performed in exceptional cases, and treatment duration should be as short as possible with thelowest effective dose.

  18. Increased survival in men with metastatic prostate cancer receiving chemo and hormone therapy

    Science.gov (United States)

    Men with hormone-sensitive metastatic prostate cancer who received the chemotherapy drug docetaxel given at the start of standard hormone therapy lived longer than patients who received hormone therapy alone, according to early results from a NIH-supporte

  19. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. In children, GH has growth-promoting effects on the body. It stimulates the ...

  20. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    DEFF Research Database (Denmark)

    Comasco, Erika; Frøkjær, Vibe; Sundström-Poromaa, Inger

    2014-01-01

    The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuat......The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone...... fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri......-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain....

  1. Optimization of growth hormone therapy in growth hormone deficient children

    NARCIS (Netherlands)

    S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1991-01-01

    textabstractIt is obvious that the results published so far as well as the present preliminary data do not answer many questions regarding the optimal therapeutic regimen in GH deficiency. In particular, long-term follow-up must be organized to evaluate efficacy and safety of GH therapy not only in

  2. Hormone Therapy for Breast Cancer in Men

    Science.gov (United States)

    ... of testosterone and other androgens (male hormones). Most male breast cancers have androgen receptors that may cause the cells ... into estrogens in the body. Orchiectomy shrinks most male breast cancers, and may help make other treatments like tamoxifen ...

  3. Hormone therapy in hypospadias surgery: a systematic review.

    Science.gov (United States)

    Netto, Jose Murillo B; Ferrarez, Carlos Eduardo P F; Schindler Leal, Anucha Andrade; Tucci, Silvio; Gomes, Carlos Augusto; Barroso, Ubirajara

    2013-12-01

    Surgical correction of hypospadias is proposed to improve the aesthetic and functional quality of the penis. Hormone therapy preceding surgical correction is indicated to obtain better surgical conditions. However, there is divergence in the literature regarding the hormone therapy of choice, time of its use before surgery, appropriate dose, and route of application. To try to elucidate this matter, an electronic survey of the databases PubMed and Cochrane Central Library was conducted, limited to articles in English published since 1980. Search strategy identified 14 clinical trials that matched the inclusion criteria. Analysis was made in terms of study design, classification of hypospadias, association with chordee and cryptorchidism, type of hormone, route of application, dose and duration of treatment, penile length before and after hormone therapy, glans circumference before and after hormone therapy, adverse effects, and surgical complications. From the trials evaluated it was not possible to determine the ideal neoadjuvant treatment. A preference for use of testosterone was observed. Intramuscular administration seems to have fewer adverse effects than topical treatment. Side effects were seldom described, and treated patients were not followed on a long-term basis. The scarcity of randomized and controlled clinical trials regarding the topic impairs the establishment of a protocol. In conclusion, although preoperative hormone therapy is currently used before hypospadias surgery, its real benefit in terms of improvement of the penis and surgical results has not been defined.

  4. Thyroid hormone and the heart.

    Science.gov (United States)

    Moolman, J A

    2002-01-01

    Thyroid hormone has important cardiovascular effects, and abnormalities of its production cause cardiovascular morbidity. The role of both excessive and insufficient thyroid hormone production in the pathogenesis of clinical cardiac diseases can be deduced from thyroid hormone-induced molecular changes. Thyroid hormone regulates the expression of myocardial genes regulating the handling of calcium, which affects both systolic and diastolic myocardial function. Thyroid hormone also has indirect and direct effects on peripheral vascular smooth muscle tone, and alters the coupling of the left ventricle and arterial system. Excessive production of thyroid hormone results in an increased cardiac output as well as increased cardiac work efficiency, but reduced cardiac reserve. Amiodarone therapy for cardiac rhythm can cause both hyper- and hypothyroidism. Amiodarone-induced thyrotoxicosis (AIT) can be due to either excessive thyroid hormone production (type I AIT) or thyroid hormone release due to an inflammatory condition (type II AIT). Classification of AIT is helpful in guiding therapy. Amiodarone causes changes in the thyroid function tests of euthyroid patients on therapy--it inhibits the conversion of T(4) and T(3), which results in decreased T(3) and slightly increased T(4) serum levels in euthyroid patients. Baseline thyroid functions should therefore be determined before starting amiodarone therapy, and at 6-monthly intervals thereafter.

  5. Cloning and bioinformatics analysis of a fragment cDNA encoding growth hormone-releasing hormone in Tibetan sheep%草地藏系绵羊生长激素释放激素基因部分 cDNA 的克隆及生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    王金玲; 王永; 刘鲁蜀; 陶永平

    2015-01-01

    为了克隆草地藏系绵羊生长激素释放激素基因,采用Trizol法从草地藏系绵羊下丘脑组织中提取总RNA,用反转录-聚合酶链式反应( RT-PCR)进行cDNA扩增并克隆测序,获得长度为207 bp的促生长激素释放激素基因( GHRH)的部分cDNA序列。结果表明获得的草地藏系绵羊GHRH部分cDNA序列与GenBank中注册的绵羊GHRH基因编码起始位置(86位)到292位区域高度同源,仅有1个碱基的差异,该cDNA序列编码69个氨基酸残基,其内含有信号肽序列,该氨基酸序列的31~57位具有典型胰高血糖素类似激素特征的GLUCA结构域。%Total RNA was extracted from the hypothalamus tissues of Tibetan sheep using Trizol method and cDNA was amplified by reverse transcription polymerase chain reaction ( RT-PCR) . The cDNA of Tibetan sheep GHRH gene was cloned from the amplified PCR product and sequenced. The cDNA was 207 bp in length and showed 99% homology with that of com-mon sheep registered in GenBank from the starting position (86) to 292 bp. The cDNA sequence encodes 69 amino acid resi-dues and contains a signal peptide sequence which has a GLUCA domain characterizing glucagon-like hormone at amino acid 31 to 57.

  6. Hormone replacement therapy and risk of non-fatal stroke

    DEFF Research Database (Denmark)

    Pedersen, A T; Lidegaard, O; Kreiner, S;

    1997-01-01

    BACKGROUND: The effect of postmenopausal hormone replacement therapy (HRT) on the risk of subtypes of stroke is as yet unclear. To investigate the effect of oestrogen and combined oestrogen-progestagen therapy on the risk of non-fatal haemorrhagic and thromboembolic stroke, we carried out a case-...

  7. Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

    Directory of Open Access Journals (Sweden)

    Peter C. Hindmarsh

    2010-01-01

    Full Text Available Background/Aims. 20 Kilodalton-hGH (20 K-hGH is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29NH2 bolus (0.5 μg/kg (n=20 or 1.0 μg/kg (n=20, preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received 0.5 μg/kg GHRH(1–29NH2 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29NH2 doses. Repetitive stimulation reduced the amount of 22 K-hGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH (P=.05. Half-life of 20 and 22 K-hGH were not significantly different (P=.55. Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.

  8. Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

    Directory of Open Access Journals (Sweden)

    Robinson IainCAF

    2010-05-01

    Full Text Available Background/Aims. 20 Kilodalton-hGH (20 K-hGH is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29 bolus   ( or   (, preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received   GHRH(1–29 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29 doses. Repetitive stimulation reduced the amount of 22 K-hGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH . Half-life of 20 and 22 K-hGH were not significantly different . Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.

  9. Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Wang, Bin; Qin, Chaobin; Zhang, Cong; Jia, Jirong; Sun, Caiyun; Li, Wensheng

    2014-02-15

    Somatostatin is the most effective inhibitor of GH release, and GHRH was recently identified as one of the primary GH-releasing factors in teleosts. In this study, we analyzed the possible intracellular transduction pathways that are involved in the mechanisms induced by SRIF and GHRH to regulate GH release. Using a pharmacological approach, the blockade of the PLC/IP/PKC pathway reversed the SRIF-induced inhibition of GH release but did not affect the GHRH-induced stimulation of GH release. Furthermore, SRIF reduced the GH release induced by two PKC activators. Inhibitors of the AC/cAMP/PKA pathway reversed both the SRIF- and GHRH-induced effects on GH release. Moreover, the GH release evoked by forskolin and 8-Br-cAMP were completely abolished by SRIF. The blockade of the NOS/NO pathway attenuated the GHRH-induced GH release but had minimal effects on the inhibitory actions of SRIF. In addition, inhibitors of the sGC/cGMP pathway did not modify the SRIF- or GHRH-induced regulation of GH release. Taken together, these findings indicate that the SRIF-induced inhibition of GH release is mediated by both the PLC/IP/PKC and the AC/cAMP/PKA pathways and not by the NOS/NO/sGC/cGMP pathway. In contrast, the GHRH-induced stimulation of GH secretion is mediated by both the AC/cAMP/PKA and the NOS/NO pathways and is independent of the sGC/cGMP pathway and the PLC/IP/PKC system.

  10. Therapy of hypoparathyroidism by replacement with parathyroid hormone

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

    2014-01-01

    Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (Qo......L) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses...

  11. Menopausal depression:comparison of hormone replacement therapy and hormone replacement therapy plus fiuoxetine

    Institute of Scientific and Technical Information of China (English)

    刘平; 何方方; 白文佩; 郁琦; 史蔚; 吴宜勇; 贺丹军; 肖计划; 郑晔; 廖秦平

    2004-01-01

    Background To compare the efficacy and safety of hormone replacement therapy (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women suffering from depression.Methods A randomized, open-label, parallel trial was applied. HRT was administered to all patients for 2 cycles, with ]4 days of estrogen therapy and 14 days of estrogen plus progesterone. Patients who were randomly assigned to the HRT plus fluoxetine group were given fluoxetine in combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman Menopausal Index (KMI), and Clinical Global Impressions scale were used to measure the efficacy. Results One hundred and twenty-three post-menopausal patients with depression were enrolled in the study. Among them, 120 had at least one post-treatment visit and entered into the statistical analysis. The mean total HAMD scores were significantly lower, and the percentages of HAMD score reductions were higher in the HRT plus fluoxetine Group compared with the HRT Group, after at least 3 weeks of treatment, with an average difference of 5 points at the endpoint. The Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were significantly different in the 2 groups, in favor of the combination therapy. The mean total KMI was significantly lower in the Combination Group compared with the HRT Group, after at least 6 weeks of treatment, with an average 4. 5-point difference between the groups. No statistically significant differences were found in most of the adverse events reported in the Combination Group compared with the HRT group, with the exception of 3 symptoms, i. e., dry mouth, loss of appetite, and abdominal distention. They were mild to moderate in severity. Two patients in the HRT group, but none in the combination group, dropped out due to adverse events. Conclusion HRT plus fluoxetine therapy was effective in the treatment of menopausal depression with a satisfactory safety profile.

  12. Hormone therapy for patients with advanced or recurrent endometrial cancer.

    Science.gov (United States)

    Lee, Wen-Ling; Yen, Ming-Shyen; Chao, Kuan-Chong; Yuan, Chiou-Chung; Ng, Heung-Tat; Chao, Hsiang-Tai; Lee, Fa-Kung; Wang, Peng-Hui

    2014-05-01

    The "gold standard" treatment for endometrial cancer is completely staged surgery, followed by radiation or chemotherapy, based on the final pathological surgical stage and requirements. In the primary treatment of endometrial cancers, hormones are rarely taken into consideration after primary surgery. Primary treatment with hormones to preserve fertility in younger women with endometrial cancer is an attractive option, and many successful cases have been reported, although the majority of them finally received definite therapy, including total hysterectomy. The role of hormone therapy is often delayed in recurrent disease; response rates to progestins and tamoxifen or aromatase inhibitors in advanced/recurrent endometrial cancers are approximately 15-20% and nearly ≤ 10%, respectively. This review is focused on updated information and recent knowledge on the use of hormones in the management of women with advanced or recurrent endometrial cancers.

  13. The influence of hormone therapies on colon and rectal cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels;

    2016-01-01

    followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression...... analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0......Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were...

  14. Cognitive effects of hormonal therapy in older adults.

    Science.gov (United States)

    Mitsiades, Nicholas; Correa, Denise; Gross, Cary P; Hurria, Arti; Slovin, Susan F

    2008-12-01

    There is ample preclinical evidence that gonadal steroids (estrogens and androgens) play an important role in central nervous system development and function. The abrupt decline of estrogen levels in women after menopause, and the slower, subtler decline in total and bioavailable testosterone serum levels that occurs in aging men ("andropause," "male menopause," partial androgen deficiency in ageing males [PADAM]), have been implicated in the pathogenesis of cognitive dysfunction prevalent in elderly adults. However, the current clinical evidence supporting hormonal replacement as a neuroprotective therapy is at best inconclusive. Anti-estrogen and anti-androgen hormonal therapies are used in the treatment of breast and prostate carcinomas, respectively. Although generally considered less toxic than conventional cytotoxic chemotherapy, these hormonal manipulations have side effects that are not trivial. This review will summarize the available evidence regarding the impact of these hormonal therapies on cognitive function in older adults. Additional clinical research in this field is needed to confirm the existence and severity of such a possible cognitive impact, which may then need to be considered prior to initiating hormonal therapies in the elderly, as many patients may be in the prodromal phase or early stages of a neurodegenerative disorder, such as Alzheimer's disease, and this information may influence treatment decision-making and subsequent management.

  15. The adverse effects of hormonal therapy.

    Science.gov (United States)

    Bush, T L

    1986-02-01

    Estrogen therapy must be cycled with progestin therapy in women with intact uteri in order to prevent uterine cancer. However, these women cannot be expected to benefit (with regard to cardiovascular disease) from any estrogen-induced changes in the lipoprotein profile, as progestins will either negate or overwhelm any estrogen effects. However, such women will definitely benefit from estrogen's effects with regard to menopausal symptoms and bone loss. These clearly beneficial effects of estrogen-progestin therapy are not outweighed by any known risks. However, in women without uteri (approximately 30 per cent of women), unopposed estrogen therapy in the menopause may protect against cardiovascular disease, as well as have beneficial effects on bone metabolism and menopausal symptoms. In this special case, the beneficial effects of unopposed estrogen therapy clearly outweigh any known risk.

  16. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Erika eComasco

    2014-12-01

    Full Text Available The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. This review summarizes the findings of thirty-four studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women’s brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

  17. Abnormal Bleeding During Menopause Hormone Therapy: Insights for Clinical Management

    Science.gov (United States)

    de Medeiros, Sebastião Freitas; Yamamoto, Márcia Marly Winck; Barbosa, Jacklyne Silva

    2013-01-01

    Objective Our objective was to review the involved mechanisms and propose actions for controlling/treating abnormal uterine bleeding during climacteric hormone therapy. Methods A systemic search of the databases SciELO, MEDLINE, and Pubmed was performed for identifying relevant publications on normal endometrial bleeding, abnormal uterine bleeding, and hormone therapy bleeding. Results Before starting hormone therapy, it is essential to exclude any abnormal organic condition, identify women at higher risk for bleeding, and adapt the regimen to suit eachwoman’s characteristics. Abnormal bleeding with progesterone/progestogen only, combined sequential, or combined continuous regimens may be corrected by changing the progestogen, adjusting the progestogen or estrogen/progestogen doses, or even switching the initial regimen to other formulation. Conclusion To diminish the occurrence of abnormal bleeding during hormone therapy (HT), it is important to tailor the regimen to the needs of individual women and identify those with higher risk of bleeding. The use of new agents as adjuvant therapies for decreasing abnormal bleeding in women on HT awaits future studies. PMID:24665210

  18. The Physiology of Growth Hormone-Releasing Hormone (GHRH) in Breast Cancer

    Science.gov (United States)

    2003-06-01

    E., Billestrup, 5813. N., Gonzalez-Manchon, C., and Vale, W. (1992). Endocrino !- 28. Jungwirtb, A., Schally, A. V., Pinski, J., H-almos, G., Groot... Endocrino !. Metab. 82,690-696. Sc!. USA 88, 8749-8753. 33. Barinaga, M., Yamamoto, G., Rivier, C., Vale, W. W., Evans, 10. Berry, S. A., Srivastava, C. H...Matsubara, S., Sato, M., Mizobuchi, M., Niimi, M., and Docherty, K. (1986). J. Endocrino !. 110, 5 1-57. Takahara, J. (1997). Endocrinology 136, 4147-4150

  19. Homologous and heterologous regulation of pituitary receptors for ghrelin and growth hormone-releasing hormone.

    Science.gov (United States)

    Luque, Raúl M; Kineman, Rhonda D; Park, Seungjoon; Peng, Xiao-Ding; Gracia-Navarro, Francisco; Castaño, Justo P; Malagon, María M

    2004-07-01

    Secretion of GH by pituitary somatotropes is primarily stimulated by the hypothalamic GHRH through the activation of a specific G protein-coupled receptor, GHRH receptor (GHRH-R). GH is also released in response to ghrelin, a peptide produced in the stomach, hypothalamus, and pituitary that activates somatotropes via a distinct G protein-coupled receptor, referred to as the GH secretagogue receptor (GHS-R). Here, we have analyzed the expression of both GHRH-R and GHS-R (by multiplex RT-PCR) in porcine pituitary cell cultures, after acute (4 h) treatment with GHRH or ghrelin as well as with other regulators of somatotropes (somatostatin, dexamethasone). Exposure of cultures to GHRH decreased GHRH-R mRNA content and also diminished GHS-R transcript levels. Likewise, ghrelin down-regulated both GHS-R and GHRH-R expression. Interestingly, administration of the activator of adenylate cyclase, forskolin, decreased GHRH-R mRNA levels but had no effect on GHS-R, thus suggesting a distinct contribution of the various intracellular signals operating in somatotropes to the regulation of the expression of these receptors. Accordingly, an atypical activator of adenylate cyclase in the pig somatotrope is low-dose (10(-13) m) somatostatin, which also suppressed GHRH-R mRNA levels without altering GHS-R expression. Finally, dexamethasone did not modify GHRH-R or GHS-R expression. In summary, our data show for the first time that ghrelin, as well as GHRH, mediates homologous and heterologous down-regulation of their own receptor synthesis. However, our results also indicate that the expression of porcine GHRH-R and GHS-R is regulated by distinct signals that may differ from those reported in other mammalian species.

  20. Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born.

    Science.gov (United States)

    Schweizer, Michael T; Antonarakis, Emmanuel S

    2012-08-01

    The number of life-prolonging therapies proven effective in the treatment of metastatic castrate-resistant prostate cancer (CRPC) has been limited until recently. In the past 2 years several such therapies have come to market. In 2010, the autologous immunotherapy sipuleucel-T and the next-generation taxane cabazitaxel were approved in this setting. However, abundant evidence has shown that CRPC growth continues to be driven through androgen-dependent signaling. Both of these drugs fail to take advantage of this targetable oncogenic pathway. Potent specific inhibitors of cytochrome P450-17 have been engineered with the aim of suppressing androgen synthesis beyond that seen with the luteinizing hormone-releasing hormone agonists/antagonists. Abiraterone acetate was developed by rational design based on a pregnenolone parent structure. Its approval by the US Food and Drug Administration (FDA) was granted in 2011 based on phase III data demonstrating an overall survival advantage compared with placebo. More recently, other drugs that act along the androgen signaling pathway, such as orteronel (TAK-700), galeterone (TOK-001), enzalutamide (MDV3100) and ARN-509, have shown promise in clinical trials. Some of these are expected to gain FDA approval in the near future. Here, we review abiraterone and other novel androgen-directed therapeutic strategies for the management of advanced prostate cancer.

  1. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...... or placebo; and after a 12-month open phase of GH therapy. In the placebo group, insulin sensitivity and fat mass increased and lipid oxidation decreased, whereas glucose oxidation increased (p...

  2. Concomitant therapies (glucocorticoids and sex hormones) in adult patients with growth hormone deficiency.

    Science.gov (United States)

    Scaroni, C; Ceccato, F; Rizzati, S; Mantero, F

    2008-09-01

    Adult-onset GH deficiency (GHD), mostly due to organic lesions of the pituitary-hypothalamic region, is frequently associated with multiple anterior pituitary deficiencies that need long-term substitutive treatment. The GH-IGF-I axis may play an important role in modulating peripheral metabolism of hormones (adrenal, thyroid, and sex hormones) and these interactions may have clinically significant implications on the phenotypes of adult GHD patients and on the effects of the combined replacement hormonal treatment of this condition. By accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients; estrogen replacement blunts the response to GH in women whereas in men with androgen substitution the responsivity increases over time. Endocrinologists should be mindful of these phenomena when starting patients with hypopituitarism on GH replacement therapy.

  3. [Hormonal therapy for prostatic cancer--state of the art].

    Science.gov (United States)

    Miyakita, Hideshi

    2005-02-01

    Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

  4. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

  5. Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Charlotte Guyader

    Full Text Available Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR antagonists (bicalutamide or flutamide. Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration, but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR as compared to continuous castration (RR(intermittent: 14.5, RR(complete blockade: 6.5 and 1.35. All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17 and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent

  6. Therapy for obesity based on gastrointestinal hormones

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Christensen, Mikkel; Knop, Filip K;

    2011-01-01

    for the treatment of type 2 diabetes. In contrast to other antidiabetic treatments, these agents have a positive outcome profile on body weight. Worldwide there are 500 million obese people, and 3 million are dying every year from obesity-related diseases. Recently, incretin-based therapy was proposed...... for the treatment of obesity. Currently two different incretin therapies are widely used in the treatment of type 2 diabetes: 1) the GLP-1 receptor agonists which cause significant and sustained weight loss in overweight patients, and 2) dipeptidyl peptidase 4 (DPP-4) inhibitors being weight neutral. These findings...... have led to a greater interest in the physiology of intestinal peptides with potential weight-reducing properties. This review discusses the effects of the incretin-based therapies in obesity, and provides an overview of intestinal peptides with promising effects as potential new treatments for obesity....

  7. Type of hormone therapy and risk of misclassification at mammography screening

    DEFF Research Database (Denmark)

    Njor, Sisse H; Hallas, Jesper; Schwartz, Walter;

    2011-01-01

    Current users of hormone therapy (HT) are known to have a lower accuracy of mammography screening than do never users. We studied whether the risk of misclassification depends on type of hormone, administration, regimen, and dose of the therapy.......Current users of hormone therapy (HT) are known to have a lower accuracy of mammography screening than do never users. We studied whether the risk of misclassification depends on type of hormone, administration, regimen, and dose of the therapy....

  8. Growth hormone deficiency in adults--an indication for therapy?

    Science.gov (United States)

    Preece, M A; Round, J M; Jones, D A

    1987-01-01

    Case studies are presented for two patients, one with isolated hGH deficiency and one with multiple hormone deficiencies. The patients were studied 3 months before, and 3 and 9 months after discontinuing hGH therapy, at 19 and 18 years of age, respectively. Strength in the quadriceps femoris, cross-sectional area of the quadriceps muscles and cross-sectional muscle fibre area were measured. In the patient with multiple hormone deficiencies, clear decreases in all three parameters were evident after discontinuing hGH treatment. There were no significant changes in the other patient. Reasons for these differences are discussed.

  9. Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis.

    Science.gov (United States)

    Augustine, Marilyn; Horwitz, Mara J

    2013-12-01

    Osteoporotic fractures result in significant morbidity and mortality. Anabolic agents reverse the negative skeletal balance that characterizes osteoporosis by stimulating osteoblast-dependent bone formation to a greater degree than osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP) are peptide hormones, which have anabolic actions when administered intermittently. The only FDA-approved anabolic bone agent for the treatment of osteoporosis in the United States is PTH 1-34, or teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog, BA058, have also been shown to increase lumbar spine bone density. These agents and several other PTH and PTHrP analogs, including some which are not administered as injections, continue to be investigated as potential anabolic therapies for osteoporosis.

  10. Hormonal therapy for acne: why not as first line therapy? facts and controversies.

    Science.gov (United States)

    Katsambas, Andreas D; Dessinioti, Clio

    2010-01-01

    Standard systemic therapeutic agents used in acne include oral antimicrobials, isotretinoin, and hormonal agents. Appropriate patient selection is the key to decide when to use hormonal agents as first-line therapy as well as to achieve optimal results. Indications of hormonal therapy in acne in girls and women include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to repeated courses of oral isotretinoin, acne tarda, polycystic ovary syndrome, or the presence of clinical signs of hyperandrogenism such as androgenic alopecia or the presence of the seborrhea, acne, hirsutism, alopecia syndrome. We describe the hormonal agents currently available for acne treatment, discuss their indications and contraindications, and address the question of whether they may be used as a first-line therapy in acne.

  11. Hormone replacement therapy and risk of non-fatal stroke

    DEFF Research Database (Denmark)

    Pedersen, A T; Lidegaard, O; Kreiner, S

    1997-01-01

    BACKGROUND: The effect of postmenopausal hormone replacement therapy (HRT) on the risk of subtypes of stroke is as yet unclear. To investigate the effect of oestrogen and combined oestrogen-progestagen therapy on the risk of non-fatal haemorrhagic and thromboembolic stroke, we carried out a case......-control study. METHODS: From the Danish National Patient Register we identified all Danish women aged 45-64 years who had a non-fatal, first-ever cerebrovascular attack during 1990-92. Two age-matched controls were randomly selected for each case from the Danish National Person Register. Important correlates...... of hormone use and stroke, on which information was obtained from postal questionnaires, were controlled for by multivariate analyses based on log-linear graphical models. The analyses included data on 1422 cases classified in four subtypes of stroke (160 subarachnoid haemorrhage, 95 intracerebral...

  12. Hormone replacement therapy and the prevention of postmenopausal osteoporosis

    OpenAIRE

    Marco Gambacciani; Marco Levancini

    2014-01-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a ...

  13. Adherence to hormone therapy among women with breast cancer.

    Science.gov (United States)

    Brito, Claudia; Portela, Margareth Crisóstomo; de Vasconcellos, Mauricio Teixeira Leite

    2014-06-03

    Despite the excellent results obtained with hormone therapy, the long treatment period and the side effects associated with its use make patient adherence difficult. Moreover, certain aspects of health care can mitigate or exacerbate non-adherence. This study aimed to identify the factors associated with adherence to hormone therapy for breast cancer, with the goal of contributing to the reformulation of the care process and to improvements in outcomes. This was a retrospective longitudinal study based on secondary data. The study integrated and analyzed data from a cohort of 5,861 women with breast cancer who were identified in the databases of the Brazilian National Cancer Institute [Instituto Nacional de Câncer - INCA] and the Unified Health System [Sistema Único de Saúde - SUS]. All of the patients were treated at INCA, which dispenses free medication, and the follow-up period lasted from 01/01/2004 to 10/29/2010. The outcome of interest was hormone treatment adherence, which was defined as the possession of medication, and a logistic regression model was employed to identify the socio-demographic, behavioral, clinical, and health care variables that were independently associated with the variations in this outcome. The proportion of women who adhered to hormone therapy was 76.3%. The likelihood of adherence to hormone therapy increased with each additional year of age, as well as among women with a secondary or higher level education, those with a partner, those who underwent surgery, those who had more consultations with a breast specialist and clinical oncologist, and those who underwent psychotherapy; the effect for the latter increased with each additional consultation. Conversely, the likelihood of adherence was lower among patients at a non-curable stage, those who were alcohol drinkers, those who received chemotherapy, those who had undergone more tests and had more hospitalizations, and those who used tamoxifen and combined aromatase inhibitors

  14. Adherence and discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer.

    Science.gov (United States)

    Ayres, Lorena Rocha; Baldoni, André de Oliveira; Borges, Anna Paula de Sá; Pereira, Leonardo Régis Leira

    2014-02-01

    Oral treatment in women with breast cancer has been increasingly used. However, a potentially negative side of oral medication is poor patient adherence and/or discontinuation, which reduces the treatment effectiveness, accelerating progression of the disease and reducing the patient survival rate. To compare the rates of adherence and/or discontinuation and the methodologies used to assess these outcomes. It was conducted an integrative review of original articles published from 2000 to 2012, in which their primary outcome was to quantify medication adherence and/or discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer. Original studies were searched in the PubMed/MEDLINE, Scopus, Embase and SciELO databases. The Medical Subject Heading was used to define descriptors. The descriptor "breast neoplasms" was used in all combinations. Each of the descriptors "medication adherence" and "patient compliance" were combined with each of the following descriptors "tamoxifen", "aromatase inhibitors", "selective estrogen receptor modulators", or the terms "letrozole", "anastrozole", and "exemestane". Twenty-four original articles were included. Our study showed a wide range of adherence and discontinuation rates, ranging from 45-95.7 and 12-73 %, respectively. Regarding the methodological development of the selected articles, a high prevalence (87.5 %) of prospective and/or retrospective longitudinal studies was found. In addition, there was a high prevalence of studies using a database (70.8 %). Among some of the studies, it was shown that patient adherence to hormonal therapy gradually reduces, while discontinuation increases during the treatment. It was observed a great diversity among rates of adherence and/or discontinuation of hormonal therapy for breast cancer, which may be due to a lack of methodology standardization. Therefore, adequate and validated methods to ensure reliability of the results and allow comparison in the

  15. Hormone therapy in transgender adults is safe with provider supervision; A review of hormone therapy sequelae for transgender individuals

    OpenAIRE

    Jamie D. Weinand, BS, BA; Joshua D. Safer, MD

    2015-01-01

    Introduction: Some providers report concern for the safety of transgender hormone therapy (HT). Methods: This is a systematic literature review of HT safety for transgender adults. Results: Current literature suggests HT is safe when followed carefully for certain risks. The greatest health concern for HT in transgender women is venous thromboembolism. HT among transgender men appears to cause polycythemia. Both groups experienced elevated fasting glucose. There is no increase in cancer...

  16. Ghrelin: much more than a hunger hormone

    Science.gov (United States)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  17. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  18. Both radical prostatectomy following treatment with neoadjuvant LHRH agonist and estramustine and radiotherapy following treatment with neoadjuvant hormonal therapy achieved favorable oncological outcome in high-risk prostate cancer: a propensity-score matching analysis.

    Science.gov (United States)

    Koie, Takuya; Ohyama, Chikara; Yamamoto, Hayato; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Yoneyama, Tohru; Tobisawa, Yuki; Aoki, Masahiko; Takai, Yoshihiro

    2014-04-30

    To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70 to 76 Gy administered at 2 Gy/fraction. Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival rates were 98.3% and 92.1% in the RP and RT groups, respectively (P=0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P=0.878). Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have an important impact on decision making in treatment of high-risk Pca.

  19. Isolated growth hormone deficiency type 2: from gene to therapy.

    Science.gov (United States)

    Miletta, Maria Consolata; Lochmatter, Didier; Pektovic, Vibor; Mullis, Primus-E

    2012-01-01

    Isolated growth hormone deficiency type-2 (IGHD-2), the autosomal-dominant form of GH deficiency, is mainly caused by specific splicing mutations in the human growth hormone (hGH) gene (GH-1). These mutations, occurring in and around exon 3, cause complete exon 3 skipping and produce a dominant-negative 17.5 kD GH isoform that reduces the accumulation and secretion of wild type-GH (wt-GH). At present, patients suffering from IGHD-2 are treated with daily injections of recombinant human GH (rhGH) in order to reach normal height. However, this type of replacement therapy, although effective in terms of growth, does not prevent toxic effects of the 17.5-kD mutant on the pituitary gland, which can eventually lead to other hormonal deficiencies. Considering a well-known correlation between the clinical severity observed in IGHD-2 patients and the increased expression of the 17.5-kD isoform, therapies that specifically target this isoform may be useful in patients with GH-1 splicing defects. This chapter focuses on molecular strategies that could represent future directions for IGHD-2 treatment.

  20. Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

    Science.gov (United States)

    Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

    2012-01-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established

  1. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

    Science.gov (United States)

    Giannoulis, Manthos G; Martin, Finbarr C; Nair, K Sreekumaran; Umpleby, A Margot; Sonksen, Peter

    2012-06-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.

  2. Primary prevention of cardiovascular disease with hormone replacement therapy

    DEFF Research Database (Denmark)

    Schierbeck, L

    2015-01-01

    Many peri- and postmenopausal women suffer from a reduced quality of life due to menopausal symptoms and preventable diseases. The importance of cardiovascular disease in women must be emphasized, as it is the leading cause of mortality and morbidity in women. It is well known that female hormones...... contribute to the later onset of cardiovascular disease in women. The effect of estrogens has for decades been understood from observational studies of postmenopausal women treated with hormone replacement therapy (HRT). Later, treatment with HRT was disregarded due to the fear of side......-effects and an ambiguity of the cardiovascular advantages. Accumulating knowledge from the large number of trials and studies has elucidated the cause for the disparity in results. In this paper, the beneficial effects of HRT, with emphasis on cardiovascular disease are explained, and the relative and absolute risks...

  3. Stroke in women - oral contraception, pregnancy, and hormone replacement therapy.

    Science.gov (United States)

    Rantanen, Kirsi; Tatlisumak, Turgut

    2013-01-01

    Stroke is a devastating disease affecting millions of people worldwide every year. Female stroke victims have higher mortality rates and they do not re-cover as well as men. Women's longevity and different vascular risk factor burden like a larger prevalence of atrial fibrillation play a role. Women also have unique risk factors such as oral contraception, pregnancy, estrogen decrease after the menopause and hormone replacement therapy, which should all be evaluated and taken into consideration in treatment decisions both in the acute phase of stroke and in secondary prevention. In this review, the evidence regarding these hormonal aspects and the risk of stroke in women are evaluated. The relevant guidelines are studied and research gaps identified. Future topics for research are recommended and current treatment possibilities and their risks discussed.

  4. Postmenopausal hormone therapy and the risk of breast cancer: a contrary thought.

    Science.gov (United States)

    Speroff, Leon

    2008-01-01

    The most important unanswered question regarding postmenopausal hormone therapy and the risk of breast cancer is whether hormone therapy initiates the growth of new breast cancers or whether the epidemiologic data reflect a hormonal impact on preexisting tumors. In this perspective I review the evidence favoring hormonal effects on preexisting tumors and suggest that exposure to combined estrogen and progestin is beneficial, causing greater differentiation and earlier detection of breast cancers.

  5. Effectiveness and adverse effects of hormonal therapy for prostate cancer: Japanese experience and perspective

    Institute of Scientific and Technical Information of China (English)

    Mikio Namiki; Satoru Ueno; Yasuhide Kitagawa; Takashi Fukagai; Hideyuki Akaza

    2012-01-01

    Recently,novel anti-androgens and inhibitors of androgen biosynthesis have been developed through the elucidation of mechanisms of castration resistance of prostate cancer.We believe that these new developments will improve hormonal therapy.On the other hand,there has been an increase in criticism of hormonal therapy,because hormonal therapy is supposed to induce adverse effects such as cardiovascular disease.In this review,we have introduced the Japanese experience of hormonal therapy,because we believe that there may be ethnic differences between Caucasians and Asian people in the efficacy and adverse effects of hormonal therapy.First,we showed that primary hormonal therapy can achieve long-term control of localized prostate cancer in some cases and that quality of life of patients receiving hormonal therapy is rather better than previously thought.Neoadjuvant and adjuvant hormonal therapy in cases undergoing radical prostatectomy or radiotherapy are very useful for high-risk or locally advanced prostate cancer.Further clinical trials are required to confirm the efficacy of neoadjuvant or adjuvant hormonal therapy.We showed that the death from cardiovascular diseases in Japanese patients receiving hormonal therapy was not higher than that in the general population.However,efforts should be made to decrease the adverse effects of hormonal therapy,because life-style change may increase the susceptibility to adverse effects by hormonal therapy even in Japan.Managements of endocrine and metabolic dysfunction,such as diabetes mellitus,are essential.New hormonal compounds such as selective androgen receptor modulators capable of specifically targeting prostate cancer are expected to be developed.

  6. Growth hormone therapy and craniofacial bones: a comprehensive review.

    Science.gov (United States)

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth.

  7. Magnetic resonance imaging in infantile spasms: effects of hormonal therapy.

    Science.gov (United States)

    Konishi, Y; Yasujima, M; Kuriyama, M; Konishi, K; Hayakawa, K; Fujii, Y; Ishii, Y; Sudo, M

    1992-01-01

    Magnetic resonance imaging (MRI) was performed on five patients with infantile spasms who were treated with relatively low doses of adrenocorticotrophic hormone (ACTH) to study the extent of brain shrinkage induced by ACTH therapy. MRI prior to ACTH therapy revealed periventricular hyperintensity (PVH) areas and poor myelination in four patients. In one case, MRI performed 2 days after initiation of ACTH therapy also showed PVH and poor myelination. Brain shrinkage was observed 2 weeks after initiation of ACTH therapy. The most impressive follow-up finding upon MRI was the decrease in PVH found in four patients. The differentiation between myelinated white matter and surrounding cortex became poorer in three cases. Cortical atrophy progressed in all patients but ventricular dilation progressed in only one patient. At the end of ACTH therapy, ventricular dilation progressed in all cases. These findings suggest that loss of water not only from periventricular white matter but also from cortex is the main etiological factor of brain shrinkage induced by ACTH.

  8. Postoperative pituitary hormonal disturbances and hormone replacement therapy time and dosage in children with craniopharyngiomas

    Institute of Scientific and Technical Information of China (English)

    LI Gui-mei; SUN Xiao-jun; SHAO Peng

    2008-01-01

    BackgroundThe proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas (CP) often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency (MPHD). This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy (HRT) time and dosage in children with CP.Methods Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of (10.63 3.18) years (Group A) and 10 male patients of group A aged >10 years (Group B) were entailed. Thirty age-, sex- and Tanner stage-matched normal children (control Group A), and 44 male older children >10 years (control Group B) served as controls. The serum concentrations of insulin-like growth factor-1 (IGF-1), growth hormone (GH), free thyroxine (FT4), thyroid-stimulating hormone (TSH), adrenocorticortropic hormone (ACTH), cortisol (COR), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine (L-T4) dosage and primary FT4 in CP patients after resection. Results All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased (P <0.001); however, E2 and PRL were significantly increased (P <0.001) in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus (Dl) by water deprivation test and MRI. There was a significant negative linear regression (r= -0.8, P <0.001) between L-T4 and primary FT4 in Group A patients with CP

  9. Hormone replacement therapy and the risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sjögren, Lea; Mørch, Lina S; Løkkegaard, Ellen

    2016-01-01

    progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only......BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus......, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone...

  10. A retrospective study: osteoporosis and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    H. June Kuczynski

    1989-09-01

    Full Text Available The purpose of this stud y was to determine i f women who undergo hormone replacement therapy postmenopausally, will demonstrate less osteoporosis than women who do not undergo H R T. The osteoporosis subjects were 195 women who volunteered to participate in an NIHsponsored double-blind clinical trial entitled Safely and Efficacy of Fluoride Therapy in Osteoporosis. A convenience sample of 78 controls was obtained by inviting women seeking regular medical attention to join an epidemiological investigation of osteoporosis. The data were analyzed using Chisquare and Student’s t-ratio. The study concludes that future retrospective and prospective analyses appreciate the com plexity of the problem in terms of individual risk for osteoporosis.

  11. Fibromyalgic syndromes: could growth hormone therapy be beneficial?

    Science.gov (United States)

    Cuatrecasas, Guillem

    2009-06-01

    Fibromyalgia is a chronic, idiopathic condition in which patients experience pain, asthenia and fatigue. The pathogenesis of the condition is unknown, and numerous mechanisms have been postulated, including neural hypersensitivity and autoimmunity. Symptoms of fibromyalgia are broadly similar to those of growth hormone deficiency (GHD), and there is evidence of decreased GH secretion and functional GHD in a subset of patients with fibromyalgia. Use of GH therapy in this patient population therefore represents a rational treatment strategy. Preliminary placebo-controlled trials have shown that GH therapy can significantly improve signs and symptoms of fibromyalgia and quality of life in patients receiving the current standard of care. Despite the use of relatively high doses of GH in these patients, treatment is well tolerated. Several mechanisms of action for GH in fibromyalgia have been suggested, including both central and peripheral effects.

  12. Alzheimer's disease, apolipoprotein E and hormone replacement therapy.

    Science.gov (United States)

    Depypere, H; Vierin, A; Weyers, S; Sieben, A

    2016-12-01

    Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.

  13. The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors

    Directory of Open Access Journals (Sweden)

    Fernando Cordido

    2010-01-01

    Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD when peak GH after stimulation with GHRH was ≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R=−0.650, P=.012, HOMA-IR (R=−0.846, P=.001, total cholesterol (R=−0.532, P=.034, and LDL cholesterol (R=−0.692, P=.006 and positively associated with HDL cholesterol (R=0.561, P=.037. These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome.

  14. Risk of Breast Cancer in Relation to Combined Effects of Hormone Therapy, Body Mass Index, and Alcohol Use, by Hormone-receptor Status

    DEFF Research Database (Denmark)

    Hvidtfeldt, Ulla Arthur; Tjonneland, Anne; Keiding, Niels;

    2015-01-01

    BACKGROUND: Alcohol consumption, increased body mass index (BMI), and hormone therapy are risk factors for postmenopausal breast cancer, but their combined effects are not well understood. Because hormone therapy is effective for the relief of menopausal symptoms, the identification of "high...... therapy users across all BMI strata (P for interaction = 0.003). A markedly higher risk of breast cancer was also observed for alcohol combined with hormone therapy use compared with abstinent nonusers (P for interaction = 0.02). These effects were primarily restricted to ER-positive cases. Combined...... effects of hormone therapy/high BMI and hormone therapy/alcohol on serum estradiol and testosterone supported the hypothesis of a hormonal pathway linking these exposures to breast cancer. CONCLUSION: These analyses suggest an increased risk of breast cancer associated with hormone therapy use-a risk...

  15. Menopausal Women's Access Path to Bioidentical Hormone Replacement Therapy: An Exploratory.

    Science.gov (United States)

    Moro, Doris; Young, Wendy; Stein, Richard; Isaac, Winston; Goodman, Deborah

    2010-01-01

    The objective of this exploratory qualitative study was to describe (1) the key factors affecting women's initial decision to explore the use of bioidentical hormone, (2) where women gather their information on bioidentical hormones, (3) the enablers and barriers to obtaining bioidentical hormones, and (4) how to improve the bioidentical hormone replacement therapy access path. The study was conducted in a compounding pharmacy located in a large urban area in southern Ontario, Canada. The participants included four postmenopausal women between the ages of 46 and 72 who self-identified as users of bioidentical hormone replacement therapy and with comprehensive provincial healthcare coverage. Participants were recruited at a compounding pharmacy with the use of tri-fold brochures, tear-sheets, and posters. The women participated in an audio-taped mini focus group. Discussion was guided by six open-ended questions. Verbatim quotes were analyzed using an affinity diagram. Participants identified three key factors related to their initial decision: (1) symptoms unalleviated by synthetic hormone replacement therapy, (2) side effects from synthetic hormone replacement therapy, and (3) personal preference. They obtained information and support from many sources, including: family/friends, publications, and specialists in menopausal health. Once participants had made a decision, they obtained a prescription and accessed bioidentical hormone replacement therapy at a compounding pharmacy. Knowledgeable primary care physicians and compounding pharmacists were seen as enablers. Lack of support/Information and costs were identifies as barriers. Improvements to bioidentical hormone replacement therapy access path were suggested. The results of this study suggest that there may be value in implementing strategies to further encourage family physicians and other specialists in menopausal health to discuss options regarding hormone replacement therapy with patients. For example, the

  16. Conversion from latent to symptomatic Sheehan's syndrome by pegylated interferon therapy for chronic hepatitis C.

    Science.gov (United States)

    Kanda, Keitaro; Kayahara, Takahisa; Seno, Hiroshi; Yamashita, Yukitaka; Chiba, Tsutomu

    2008-01-01

    A 58-year-old woman with chronic hepatitis C was admitted to our hospital to receive interferon (IFN) therapy. Twenty years earlier she had received blood transfusion because of obstetric hemorrhage. Blood test showed mild hypothyroidism and a relatively elevated eosinophil count. Therapy with pegylated IFNalpha-2a was started, and two days later she complained of nausea and severe malaise. Blood test showed hyponatremia, and plasma prolactin, growth hormone and cortisol levels were all decreased. A simultaneous administration test of lutenizing hormone releasing-, corticotrophin releasing-, growth hormone releasing- and thyrotropin releasing-hormones revealed that only adrenocorticotropic hormone was responsive. Magnetic resonance imaging showed atrophy of anterior lobe of pituitary gland. We diagnosed that IFN therapy disclosed latent Sheehan's syndrome due to previous obstetric hemorrhage. Following supplementation of thyroid and adrenal cortical hormones, we were able to complete IFN therapy. Thus, before IFN therapy for woman patients it is important to suspect latent Sheehan's syndrome when the patient had a history of obstetric hemorrhage.

  17. Emerging potential of parenteral estrogen as androgen deprivation therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Syed Imran Ali Shah

    2015-01-01

    Full Text Available Androgen deprivation therapy (ADT is a key management strategy for prostate cancer (PC, achieved commonly by administration of luteinizing hormone-releasing hormone agonist (LHRHa, ADT markedly suppresses both male and female sex hormones which results in "castration syndrome", a constellation of adverse events such as muscle weakness, impairment of glucose and lipid metabolism, impotence, osteoporosis, and fractures. Recent evidence suggests that estrogen, in the parenteral form, may emerge as an alternative to LHRHa as it offers potential benefits of arresting PC growth as well as avoiding some of the estrogen deficiency related toxicities of LHRHa by maintaining endogenous levels of estrogen.

  18. Role of Sleep and Sleep Loss in Hormonal Release and Metabolism

    OpenAIRE

    Leproult, Rachel; Van Cauter, Eve

    2009-01-01

    Compared to a few decades ago, adults, as well as children, sleep less. Sleeping as little as possible is often seen as an admirable behavior in contemporary society. However, sleep plays a major role in neuroendocrine function and glucose metabolism. Evidence that the curtailment of sleep duration may have adverse health effects has emerged in the past 10 years. Accumulating evidence from both epidemiologic studies and well-controlled laboratory studies indicates that chronic partial sleep l...

  19. Role of sleep and sleep loss in hormonal release and metabolism.

    Science.gov (United States)

    Leproult, Rachel; Van Cauter, Eve

    2010-01-01

    Compared to a few decades ago, adults, as well as children, sleep less. Sleeping as little as possible is often seen as an admirable behavior in contemporary society. However, sleep plays a major role in neuroendocrine function and glucose metabolism. Evidence that the curtailment of sleep duration may have adverse health effects has emerged in the past 10 years. Accumulating evidence from both epidemiologic studies and well-controlled laboratory studies indicates that chronic partial sleep loss may increase the risk of obesity and weight gain. The present chapter reviews epidemiologic studies in adults and children and laboratory studies in young adults indicating that sleep restriction results in metabolic and endocrine alterations, including decreased glucose tolerance, decreased insulin sensitivity, increased evening concentrations of cortisol, increased levels of ghrelin, decreased levels of leptin and increased hunger and appetite. Altogether, the evidence points to a possible role of decreased sleep duration in the current epidemic of obesity. Bedtime extension in short sleepers should be explored as a novel behavioral intervention that may prevent weight gain or facilitate weight loss. Avoiding sleep deprivation may help to prevent the development of obesity, particularly in children.

  20. Glucose absorption, hormonal release and hepatic metabolism after guar gum ingestion

    Science.gov (United States)

    Simoes Nunes, C.; Malmlof, K.

    1992-01-01

    Six non-anaesthetized Large White pigs (mean body weight 59 +/- 1.7 kg) were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein and with electromagnetic flow probes around the portal vein and the hepatic artery. The animals were provided a basal none-fibre diet (diet A) alone or together with 6% guar gum (diet B) or 15% purified cellulose (diet C). The diets were given for 1 week and according to a replicated 3 x 3 latin-square design. On the last day of each adaptation period test meals of 800 g were given prior to blood sampling. The sampling was continued for 8 h. Guar gum strongly reduced the glucose absorption as well as the insulin, gastric inhibitory polypeptide (GIP) and insulin-like growth factor-1 (IGF-1) production. However, the reduction in peripheral blood insulin levels caused by guar gum was not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly produced by the gut. The liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut produced IGF-1. Guar gum ingestion also appeared to decrease pancreatic glucagon secretion. Cellulose at the level consumed had very little effect on the parameters considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the latter internal metabolic effects.

  1. Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor

    DEFF Research Database (Denmark)

    Stefaneanu, L; Kovacs, K; Horvath, E

    1989-01-01

    The effect of protracted GH-releasing factor (GRF) stimulation on adenohypophysial morphology was investigated in six mice transgenic for human GRF (hGRF). All animals had significantly higher plasma levels of GH and GRF and greater body weights than controls. Eight-month-old mice were killed...

  2. Growth hormone-releasing factor induces c-fos expression in cultured primary pituitary cells

    DEFF Research Database (Denmark)

    Billestrup, Nils; Mitchell, R L; Vale, W;

    1987-01-01

    GH-releasing factor (GRF) and somatostatin regulates the secretion and biosynthesis of GH as well as the proliferation of GH-producing cells. In order to further characterize the mitogenic effect of GRF, we studied the expression of the proto-oncogene c-fos in primary pituitary cells. Maximal...

  3. Inhibition of Thyroid Hormone Release from Cultured Amphibian Thyroid Glands by Methimazole, 6-Propylthiouracil, and Perchlorate

    Science.gov (United States)

    The research presented here is the development of an in vitro thyroid gland culture system to test the effect of chemicals directly on the gland without influence of other parts of the HPT axis. . . This information can then be used to select chemicals for further evaluation in v...

  4. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    . This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese...... and perpetuate the obese state....

  5. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD...

  6. Hormone therapy for postmenopausal women—An unanswered issue

    Directory of Open Access Journals (Sweden)

    Wen-Ling Lee

    2013-02-01

    Full Text Available Menopause is a biological and natural process that occurs as part of aging in women and is secondary to ovarian failure with resultant estrogen deficiency; therefore, menopause should not be considered as a disease. However, there is no doubt that estrogen deficiency induces general psychological and physical changes, and that postmenopausal women will experience many health-related issues and problems, including osteoporotic fractures, coronary heart disease (CHD, and most importantly for the quality of life (QOL and vasomotor symptoms (VMS such as hot flashes and night sweats. Hormone therapy (HT is very effective in the management of postmenopausal women with symptoms. With the large number of patients being treated with HT, especially the combination of estrogen and progestin therapy (EPT in the Women's Health Initiative (WHI study, clinicians now recognize the potential adverse effects of EPT. Although this concept is much clearer now, some women might still benefit from short-term HT, especially for young postmenopausal women. In this review, some health issues of postmenopausal women, especially alternative therapies are discussed.

  7. Bioidentical hormone therapy: An assessment of provider knowledge.

    Science.gov (United States)

    Files, Julia A; Kransdorf, Lisa N; Ko, Marcia; Kling, Juliana M; David, Paru S; Pruthi, Sandhya; Sood, Richa; Creedon, Douglas; Chang, Yu-Hui H; Mayer, Anita P

    2016-12-01

    Bioidentical hormone therapy (BHT) is available in the United States in formulations that have been approved by the Food and Drug Administration (FDA) but also in formulations that have not been so approved. The aim of this study was to evaluate the knowledge, beliefs, and prescribing practices of BHT among healthcare providers. A cross-sectional self-selected responder survey was conducted of health care providers attending primary care Continuing Medical Education (CME) conferences in the United States from May 2012 to April 2013. The questionnaire consisted of 26 items assessing knowledge, beliefs, and current practice around BHT. A total of 366 survey responses were analyzed. Though 69.8% of respondents accurately identified the definition of BHT, only 45.3% were aware that BHT is available in FDA-approved products and 34.2% of respondents incorrectly identified that BHT is available only in custom-compounded formulations. Of those who had prescribed CC-BHT, less than half agreed with the statement "I am comfortable prescribing BHT" (45.4%). Our study showed that many practitioners are unaware that bioidentical hormones are available in FDA-approved products. Knowledge gaps identified by this survey highlight the need for and importance of education to further dispel misinformation surrounding the topic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Breast density changes associated with postmenopausal hormone replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Mads; Pettersen, Paola; Alexandersen, P

    2010-01-01

    Objective: The aim of this study was to assess the impact of oral hormone therapy (HT) on breast density in postmenopausal women and to compare the use of computer-based automated approaches for the assessment of breast density with reference to traditional methods. Methods: Low-dose oral estrogen...... (1 mg) continuously combined with drospirenone (2 mg) was administered to postmenopausal women for up to 2 years (26 treatment cycles, 28 d/cycle) in a randomized, placebo-controlled trial. This post hoc analysis assessed the changes in breast density measured from digitized images by two radiologist.......01) but not in the placebo group. Conclusions: HT for 2 years in postmenopausal women significantly increased radiologist-assessed breast density compared with placebo, in addition to significant changes in estrogen levels, markers of bone metabolism, and bone mineral density. Computer-automated techniques may be comparable...

  9. [Molecular-targeted therapy for hormone-refractory prostate cancer].

    Science.gov (United States)

    Nishimura, Kazuo; Takayama, Hitoshi; Nakayama, Masashi; Nonomura, Norio; Okuyama, Akihiko

    2006-06-01

    Molecular-targeted therapy is to treat pathologic pathways specifically in tumor cell or tumor microenvironment. Specific molecular-targeted therapeutic agents for hormone-refractory prostate cancer (HRPC) include endothelin-A receptor antagonist, EGF receptor (EGFR) inhibitor, platelet derived growth factor receptor (PDGFR) inhibitor, nuclear factor of kappaB (NF-kappaB) inhibitor, cyclooxygenase-2 (COX2) inhibitor, and active form of Vitamin D. These agents have been investigated in clinical trials. So far, none of the above-mentioned agent has shown a sufficient clinical efficacy alone. However, docetaxel-based combinations with thalidomide or calcitriol have promising clinical activities. Further investigations are needed to optimize the molecular-targeted agents in the combinations with chemotherapeutic agents for the treatment of HRPC.

  10. Safety and efficacy of growth hormone therapy in childhood.

    Science.gov (United States)

    Bowlby, Deborah A; Rapaport, Robert

    2004-11-01

    Growth hormone (GH) has been used for more than 40 years. GH improves height velocity in many conditions associated with impaired growth and corrects metabolic deficits attributable to GH deficiency (GHD). Many studies and surveillance programs exist to collect efficacy and safety data. GH has been demonstrated to have a relatively wide safety margin. Reported side effects, including pseudotumor cerebri, edema, slipped capital femoral epiphysis (SCFE), worsening of scoliosis, gynecomastia, and hyperglycemia require careful monitoring. Currently, there are no data suggesting that GH therapy increases the risk of developing de novo, recurrent, or secondary malignancies. Patients who have a high intrinsic risk factor for the development of an adverse event need more vigilant surveillance.

  11. Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events

    DEFF Research Database (Denmark)

    Bretler, Ditte-Marie; Hansen, Peter Riis; Sørensen, Rikke;

    2012-01-01

    To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue.......To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue....

  12. Relation between hormone replacement therapy and ischaemic heart disease in women

    DEFF Research Database (Denmark)

    Løkkegaard, E; Pedersen, A T; Heitmann, B L

    2003-01-01

    To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors.......To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors....

  13. Experimental Benefits of Sex Hormones on Vascular Function and the Outcome of Hormone Therapy in Cardiovascular Disease

    OpenAIRE

    Ross, Reagan L.; Serock, Michelle R; Khalil, Raouf A.

    2008-01-01

    Cardiovascular disease (CVD) is more common in men and postmenopausal women than premenopausal women, suggesting vascular benefits of female sex hormones. Experimental data have shown beneficial vascular effects of estrogen including stimulation of endothelium-dependent nitric oxide, prostacyclin and hyperpolarizing factor-mediated vascular relaxation. However, the experimental evidence did not translate into vascular benefits of hormone replacement therapy (HRT) in postmenopausal women, and ...

  14. Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

    OpenAIRE

    2016-01-01

    Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age...

  15. Effects of menopausal hormonal therapy on occult breast tumors.

    Science.gov (United States)

    Santen, Richard J; Song, Yan; Yue, Wei; Wang, Ji-Ping; Heitjan, Daniel F

    2013-09-01

    An estimated 7% of 40-80 year old women dying of unrelated causes harbor occult breast tumors at autopsy. These lesions are too small to be detected by mammography, a method which requires tumors to be approximately 1cm in diameter to be diagnosed. Tumor growth rates, as assessed by "effective doubling times" on serial mammography range from 10 to >700 days with a median of approximately 200 days. We previously reported two models, based on iterative analysis of these parameters, to describe the biologic behavior of undiagnosed, occult breast tumors. One of our models is biologically based and includes parameters of a 200 day effective doubling time, 7% prevalence of occult tumors in the 40-80 aged female population and a detection threshold of 1.16 cm and the other involves computer based projections based on age related breast cancer incidence. Our models facilitate interpretation of the Women's Health Initiative (WHI) and anti-estrogen prevention studies. The biologically based model suggests that menopausal hormone therapy with conjugated equine estrogens plus medroxyprogesterone acetate (MPA) in the WHI trial primarily promoted the growth of pre-existing, occult lesions and minimally initiated de novo tumors. The paradoxical reduction of breast cancer incidence in women receiving estrogen alone is consistent with a model that this hormone causes apoptosis in women deprived of estrogen long term as a result of the cessation of estrogen production after the menopause. Understanding of the kinetics of occult tumors suggests that breast cancer "prevention" with anti-estrogens or aromatase inhibitors represents early treatment rather than a reduction in de novo tumor formation. Our in vivo data suggest that the combination of a SERM, bazedoxifene (BZA), with conjugated equine estrogen (CEE) acts to block maturation of the mammary gland in oophorectomized, immature mice. This hormonal combination is defined by the generic term, tissue selective estrogen complex or

  16. Prescribing menopausal hormone therapy: an evidence-based approach

    Directory of Open Access Journals (Sweden)

    Sood R

    2014-01-01

    Full Text Available Richa Sood, Stephanie S Faubion, Carol S Kuhle, Jacqueline M Thielen, Lynne T Shuster Division of General Internal Medicine, Women's Health Clinic, Mayo Clinic, Rochester, MN, USA Abstract: The constantly changing landscape regarding menopausal hormone therapy (MHT has been challenging for providers caring for menopausal women. After a decade of fear and uncertainty regarding MHT, reanalysis of the Women's Health Initiative data and the results of recent studies have provided some clarity regarding the balance of risks and benefits of systemic MHT. Age and years since menopause are now known to be important variables affecting the benefit-risk profile. For symptomatic menopausal women who are under 60 years of age or within 10 years of menopause, the benefits of MHT generally outweigh the risks. Systemic MHT initiated early in menopause appears to slow the progression of atherosclerotic disease, thereby reducing the risk of cardiovascular disease and mortality. During this window of opportunity, MHT might also provide protection against cognitive decline. In older women and women more than 10 years past menopause, the risk-benefit balance of MHT is less favorable, particularly with regard to cardiovascular risk and cognitive impairment. For women entering menopause prematurely (<40 years, MHT ameliorates the risk of cardiovascular disease, osteoporosis, and cognitive decline. Nonoral administration of estrogen offers advantages due to the lack of first-pass hepatic metabolism, which in turn avoids the increased hepatic synthesis of clotting proteins, C-reactive protein, triglycerides, and sex hormone-binding globulin. The duration of combined MHT use is ideally limited to less than 5 years because of the known increase in breast cancer risk after 3–5 years of use. Limitations to use of estrogen only MHT are less clear, since breast cancer risk does not appear to increase with use of estrogen alone. For women under the age of 60 years, or

  17. Growth hormone therapy in heart failure: a novel therapy worthy of further consideration?

    Science.gov (United States)

    Demers, Catherine; McKelvie, Robert S

    2005-08-01

    Despite the improvements in survival with angiotensin-converting enzyme inhibitors and beta-blockers, the clinical events for patients with heart failure remain elevated. New therapies for heart failure are required to improve the functional capacity, quality of life and prognosis. Growth hormone exerts both direct and indirect effects on cardiac structure and function. Experimental models of heart failure and small studies have demonstrated significant improvements in cardiac function, haemodynamical parameters, functional capacity and quality of life. The results from randomised controlled studies have been mixed with others showing benefit and some that do not. The randomised studies showing benefit consistently used growth hormone every other day. Further studies are needed to assess the potential role of this adjuvant therapy in patients with heart failure.

  18. Terapia hormonal y calidad del hueso Hormone therapy and bone quality

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available La osteoporosis se reconoce como uno de los problemas de salud de la población femenina posmenopáusica, y la terapia hormonal de reemplazo (THR como una de las medidas terapéuticas efectivas para evitar la fractura. Nos propusimos mostrar la experiencia acumulada en relación con el efecto de la terapia hormonal de reemplazo sobre la calidad del hueso. En un estudio retrospectivo realizado en 42 mujeres con edades entre 40 y 59 años que asistieron a la Clínica de Climaterio y Osteoporosis y a la consulta multidisciplinaria de climaterio del Hospital Ginecoobstétrico “Ramón González Coro” entre enero de 1997 y diciembre del año 2003, se determinó la calidad ósea mediante absorciometría dual de rayos X en región lumbar (L2-L4 o por ultrasonido del calcáneo (USCAL y recibieron tratamiento continuado con terapia estrogénica (E o con estrógenos progestagenos (EP durante no menos de un año (n = 30. Las mujeres que no pudieron recibir THR fueron agrupadas y evaluadas como grupo control (n =12. Durante el tiempo de observación promedio de 2 años, las mujeres que recibieron THR mejoraron su calidad ósea en el 16,8 %, mientras que las del grupo control empeoraron en el 8 % de los casos. Estos resultados iniciales, aunque son modestos, muestran la utilidad de la THR para mejorar la calidad del hueso y la necesidad de continuar estudios que permitan definir en nuestro medio la persistencia de la mejoría ósea, así como la magnitud de la osteoporosis posmenopáusica.Osteoporosis is recognized as one of the health problems of the female postmenopausic population and the replacement hormone therapy (RHT as one of the effective therapeutical measures to prevent fracture. We proposed ourselves to show the experience accumulated in relation to the effect of the replacement hormone therapy on the bone quality. In a retrospective study conducted among 42 women aged 30-59 that attended the Climacteric and Osteoporosis Clinic and the

  19. Advances in hormone replacement therapy: making the menopause manageable

    Directory of Open Access Journals (Sweden)

    Palacios Santiago

    2008-11-01

    Full Text Available Abstract The importance of the results of some large, randomized controlled trials (RCTs on Hormone Replacement Therapy (HRT has modified the risk/benefit perception of HRT. Recent literature review supports a different management. The differences in age at initiation and the duration of HRT are key points. HRT appears to decrease coronary disease in younger women, near menopause; yet, in older women, HRT increases risk of a coronary event. Although HRT is a recognized method in the prevention and treatment of osteoporosis, it is not licensed for the prevention of osteoporosis as a first-line treatment. The effectiveness of low and ultra-low estrogen doses has been demonstrated for the treatment of vasomotor symptoms, genital atrophy and the prevention of bone loss, with fewer side-effects than the standard dose therapy. Further research, however, is needed to determine the effect both on fractures, as well as on cardiovascular and breast diseases. Newer progestins show effects that are remarkably different from those of other assays. The effectiveness of testosterone at improving both sexual desire and response in surgically and naturally postmenopausal women is shown by the testosterone patch. The intention, dose and regimen of HRT need to be individualized, based on the principle of choosing the lowest appropriate dose in relation to the severity of symptoms and the time and menopause age.

  20. Breast cancer and post-menopausal hormone therapy.

    Science.gov (United States)

    Kenemans, P; Bosman, A

    2003-03-01

    From the introduction of post-menopausal hormone replacement therapy (HRT) there has been great concern that HRT could possibly increase the risk of breast cancer. Prolonged exposure to endogenous oestrogens undeniably increases the risk of breast cancer. Questions that are important and until now only partly answered, are the following. Are oestrogens tumour promoters, as they induce mitosis, lead to proliferation and, therefore, accelerated growth of clinically occult pre-existing tumours? In addition to this, are they genotoxic mutagenic carcinogens, or could they initiate tumours by way of accumulation of incessant DNA-replication damage mechanism? Opinions vary as to the effect of the addition of a progestogen. There is a multitude of different progestogens which could bind with differing affinity to progesterone receptor PR-A or PR-B, and which have different physiological functions via differential gene regulation. The action of a progestogen on the oestrogen-induced cellular mitotic activity could be synergistic or antagonistic (by different pathways: oestrogen receptor downregulation, activating of metabolic pathways within the breast or stimulation of apoptosis)? Over 60 observational studies and two randomized trials provide evidence that the small but significant increase in risk appears with long-term current post-menopausal hormone use. The addition of a progestogen does not decrease the risk as seen with oestrogens alone and might increase the risk further. It is not clear whether there is a difference in risk with sequentially combined versus continuously combined HRT. Many questions nevertheless still remain. Is the risk increase limited to lean women only? What about risk-modifying factors such as alcohol use and a positive family history for breast cancer? Are tumours detected under HRT less aggressive, is there a better prognosis and is the mortality not increased while morbidity is? And is HRT contraindicated for women with a positive family

  1. A nonpeptidyl growth hormone secretagogue.

    Science.gov (United States)

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  2. Enhanced Neuroactivation during Verbal Memory Processing in Postmenopausal Women Receiving Short Term Hormone Therapy

    Science.gov (United States)

    Persad, Carol C.; Zubieta, Jon-Kar; Love, Tiffany; Wang, Heng; Tkaczyk, Anne; Smith, Yolanda R.

    2012-01-01

    Capsule Using a randomized, double-blind placebo-controlled cross-over design, we showed that short-term hormone replacement therapy increases brain activation in parietal and prefrontal areas during verbal memory tasks in postmenopausal women. Objective To study the effects of hormone therapy on brain activation patterns during verbal memory in postmenopausal women. Design A randomized, double-blind placebo-controlled cross-over study was performed. Setting A tertiary care university medical center. Participants Ten healthy postmenopausal women (age range 50-60 years) were recruited from the local community. Interventions Women were randomized to the order they received combined hormone therapy, 5 ug ethinyl estradiol and 1 mg norethindrone acetate, and placebo. Volunteers received hormone therapy or placebo for 4 weeks, followed by a one month washout period, and then received the other treatment for 4 weeks. An fMRI was performed at the end of each 4 week treatment utilizing a verbal memory task. Main Outcome Measure Brain activation patterns were compared between hormone therapy and placebo. Results Hormone therapy was associated with increased activation in left middle/superior frontal cortex (BA 6,9), medial frontal cortex and dorsal anterior cingulate (BA 24,32), posterior cingulate (BA 6), and left inferior parietal (BA 40) during memory encoding. All regions were significant at p ≤ 0.05 with correction for multiple comparisons. Conclusions Hormone therapy increased neural activation in frontal and parietal areas in postmenopausal women during a verbal memory task. PMID:18692790

  3. Sexual healing in patients with prostate cancer on hormone therapy.

    Science.gov (United States)

    Schover, Leslie R

    2015-01-01

    Since prostate cancer becomes more common with age, at least one-third of men have sexual problems at diagnosis. All localized treatments for prostate cancer greatly increase the prevalence of sexual dysfunction, which include loss of desire, erectile dysfunction, and changes in orgasm. Even men on active surveillance have a higher rate of problems than matched peers without prostate cancer. However, men given androgen deprivation therapy (ADT) have the worst rates of sexual dysfunction. Even after 3 to 4 months of ADT, men's desire for sex is decreased and irreversible damage may occur to the erectile tissue in the penis. Erections do not recover in about one-half of men, even if ADT is discontinued. Although intermittent ADT allows some recovery of sexual function, serum testosterone requires 9 to 12 months off ADT to recover. Again, one-half of men have permanent erectile dysfunction. If ADT causes atrophy of the erectile tissue, blood leaks out of the venous system during erection. This syndrome is difficult to treat except with surgery to implant a penile prosthesis. Despite the high rate of sexual problems in men on ADT, a small group stays sexually active and is able to have reliable erections. To improve men's sexual satisfaction on ADT, it may be important to educate them about getting extra mental and physical sexual stimulation, as well as using penile rehabilitation during hormone therapy. Information on reaching orgasm and coping with problems such as dry orgasm, pain with orgasm, and urinary incontinence during sex also should be provided.

  4. Hormone replacement therapy diminishes hearing in peri-menopausal mice.

    Science.gov (United States)

    Price, Katharine; Zhu, Xiaoxia; Guimaraes, Patricia F; Vasilyeva, Olga N; Frisina, Robert D

    2009-06-01

    We recently discovered that progestin in hormone replacement therapy (HRT) for post-menopausal women has detrimental effects on the ear and central auditory system [Guimaraes, P., Frisina, S.T., Mapes, F., Tadros, S.F., Frisina, D.R., Frisina, R.D., 2006. Progestin negatively affects hearing in aged women. Proc. Natl. Acad. Sci. - PNAS 103, 14246-14249]. To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen+progestin) and estrogen alone on hearing in peri-menopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion-product otoacoustic emissions (DPOAEs-cochlear outer hair cell system) were employed. Middle age female CBA mice received either a time-release, subcutaneous implanted pellet of estrogen+progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen+progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen+progestin treatment group in the high and middle frequency ranges (15-29 and 30-45 kHz) after as early as 2 months of treatment (p<0.01 and p<0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen+progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen+progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

  5. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

    2002-06-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  6. Plant derived alternatives for hormone replacement therapy (HRT).

    Science.gov (United States)

    Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

    2013-12-01

    Abstract Hormone replacement therapy (HRT) has undisputable positive effects on climacteric complaints, in the bone and on body weight but also several undesired side effects. Therefore, plant-derived alternatives are currently promoted. Phytoestrogens - primarily the isoflavones genistein, daidzein and coumestrol, stemming from soy (Glycine max) or red clover (Trifolium pratense) - were suggested to have the desired but not the undesired effects of estrogens. Most recently published placebo-controlled studies question the beneficial effects. When taken at the time of puberty however, phytoestrogens appear to protect against mammary cancer later in life. Extracts from the rhizome of Cimicifuga racemosa (black cohosh) have no estrogenic effects. In a narrow dose range they have beneficial effects on climacteric complaints, which are due to several compounds with dopaminergic, noradrenergic, serotoninergic and GABAergic actions that act together in the hypothalamus. Ecdysone is produced by several plants, including spinach (Spinacia oleracea) and was very early on shown to increase muscle mass. Later it became apparent that spinach extracts containing ecdysone decreased body fat load, thereby reducing secretion of proinflammatory cytokines by visceral adipocytes and oxidative stress. This had beneficial effects on body weight and serum lipids not only in obese postmenopausal but also in premenopausal women and in men. For the above-described plant extracts, solid placebo-controlled clinical trials are available. For other plant extracts claiming beneficial effects on climacteric complaints or postmenopausal diseases, no solid data are available.

  7. Low-dose hormone therapy in postmenopausal women in China.

    Science.gov (United States)

    Zang, H; Shi, H; Speroff, L

    2010-12-01

    To review the experience of menopausal symptoms and low-dose hormone therapy (HT) in postmenopausal women in China. Literature review and critical summaries of available prospective, clinical trials (randomized, controlled trials, RCTs). Chinese women experience menopausal symptoms less frequently compared with women in developed countries, and the prevalence of menopausal symptoms is less in women of southern China than in women of northern China. The majority of postmenopausal Chinese women lack knowledge about HT, and the usage rate of HT is low in these women compared to that in women of developed countries. Some RCTs investigated the efficacy and safety of low- or ultra-low-dose HT, including conjugated equine estrogen, estradiol valerate, transdermal estradiol, nylestriol alone or in combination with progesterone, and tibolone in postmenopausal Chinese women. These RCTs reported that low- or ultra-low-dose HT relieved menopausal symptoms and prevented bone loss as well as standard-dose HT and was less likely to induce side-effects, including irregular vaginal bleeding and breast tenderness; there may be dose-dependent effects of HT. No study evaluated the effects of low-dose HT on cardiovascular events or breast mammographic density/risk of breast cancer. More RCTs are required to confirm efficacy and to assess the safety of low- or ultra-low-dose HT for a long-term period in a large group of postmenopausal women.

  8. Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

    Science.gov (United States)

    de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Willem Redeker, Egbert Johan; Eduard Santen, Gijs Willem; Henriëtta Verkerk, Annemieke Johanna Maria; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

    2017-06-07

    Cornelia de Lange Syndrome (CdLS) is a heterogeneous syndrome, both clinically and genetically, in its classical form characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the Cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge there are no reports on the effect of recombinant human GH (r-hGH) treatment in CdLS patients. We present a patient born small for gestational age (SGA) with persistent severe growth retardation (height -3.4 SDS) and mild dysmorphic features, who was treated with GH from 4.3 years of age onward, and diagnosed 6 years later with CdLS using whole exome sequencing. Treatment led to a height gain of 1.6 standard deviation score (SDS) over 8 years. Treatment was interrupted shortly due to high serum IGF-1 serum values. We conclude that GH therapy appears effective and safe for short children with CdLS.

  9. Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies.

    Science.gov (United States)

    Esbrit, Pedro; Herrera, Sabina; Portal-Núñez, Sergio; Nogués, Xavier; Díez-Pérez, Adolfo

    2016-04-01

    The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)-either its N-terminal 1-34 fragment or the whole molecule of 1-84 aminoacids-whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N-terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies.

  10. Hormone replacement therapy and the prevention of postmenopausal osteoporosis.

    Science.gov (United States)

    Gambacciani, Marco; Levancini, Marco

    2014-09-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  11. Effects of hormone therapy on cognition and mood.

    Science.gov (United States)

    Fischer, Barbara; Gleason, Carey; Asthana, Sanjay

    2014-04-01

    Results of the Women's Health Initiative (WHI) and Women's Health Initiative Memory Study (WHIMS) suggested that hormone therapy (HT) may be detrimental to cognitive health. This article reviews clinical studies that address issues relevant to those results. Literature review. A search of Pubmed and Web of Science was conducted using the search terms HT and cognition, HT and mood. Clinical and observational studies were selected if they were published after the year 2000. Theories of HT mechanisms of action, pharmacology, biology, and observational and clinical trials are discussed. Although observational and clinical trials show conflicting findings, methodologic considerations must be acknowledged. HT formulation and dose, route of administration, timing of initiation, length of treatment, and health of participants all contribute to inconsistencies in results. Transdermal estradiol and micronized progesterone administered at time of menopause are generally associated with cognitive and affective benefit. At the present time, results from existing studies are equivocal regarding the benefits of HT on cognition and affect. Future studies, such as the Kronos Early Estrogen Prevention Study (KEEPS), should address methodologic inconsistencies to provide clearer answers to this important question. Published by Elsevier Inc.

  12. Hormone replacement therapy: real concerns and false alarms.

    Science.gov (United States)

    Bluming, Avrum Z; Tavris, Carol

    2009-01-01

    From 2002 to 2008, reports from the Women's Health Initiative (WHI) claimed that hormone replacement therapy (HRT) significantly increased the risks of breast cancer development, cardiac events, Alzheimer disease, and stroke. These claims alarmed the public and health professionals alike, causing an almost immediate and sharp decline in the numbers of women receiving HRT. However, the actual data in the published WHI articles reveal that the findings reported in press releases and interviews of the principal investigators were often distorted, oversimplified, or wrong. This review highlights the history of research on HRT, including a timeline of studies that have or have not found a link between HRT and breast cancer; discusses how to distinguish important, robust findings from those that are trivial; closely examines the WHI findings on HRT and breast cancer, most of which are weak or statistically insignificant; reviews the current thinking about possible links of HRT with cardiovascular disease and cognitive functioning; and reports research on the benefits of HRT, notably relief of menopausal symptoms, that affect a woman's quality of life. On these complicated matters, physicians and the public must be cautious about accepting "findings by press release" in determining whether to prescribe or take HRT.

  13. Hormone replacement therapy and the prevention of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Marco Gambacciani

    2014-09-01

    Full Text Available Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT at different doses rapidly normalizes turnover, preserves bone mineral density (BMD at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR, is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC, is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  14. Manufacturing heterosexuality: hormone replacement therapy and menopause in urban Oaxaca.

    Science.gov (United States)

    Ramirez, Michelle

    2006-01-01

    For several decades, hormone replacement therapies have been prescribed to women, not only to prevent disease but to improve the sexual functioning of menopausal women. The medical promotion of continued sexual activity in a woman's post-reproductive years is exported to locations outside of North America and Europe, which provides an opportunity to critically examine the cultural roots that have informed expert biomedical representations. This ethnographic study examined menopause and social class in Oaxaca de Juarez, Mexico using interviews, questionnaires, and textual analysis. The research found that biomedicine in conjunction with the pharmaceutical industry promoted culturally constructed gender hierarchies under the guise of optimal menopausal health. However, women's actual experience of gender and sexuality in mid-life diverged significantly from these expert representations. Themes that emerged in interviews and questionnaires included the importance of motherhood in old age, diminished sexual desire as not problematic, and greater sexual freedom at a post-reproductive age. Ultimately, biomedical discourse was not the sole arbiter of appropriate menopausal womanhood and femininity.

  15. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy

    Directory of Open Access Journals (Sweden)

    Bedimo R

    2011-07-01

    Full Text Available Roger BedimoInfectious Disease section, VA North Texas Health Care System, TX, USAAbstract: HIV-infected patients on highly active antiretroviral therapy (HAART develop a complex of body composition changes known, including peripheral fat loss (lipoatrophy and central fat accumulation (lipohypertrophy. These changes may cause significant patient distress, which could in turn interfere with adherence to antiretroviral therapy. Treatment options – including antiretroviral switch, insulin sensitizers, and surgical approaches – have been associated with limited success and potential complications. The observation that low growth hormone levels are associated with central fat accumulation among HIV patients has led to the development of tesamorelin (a growth hormone releasing hormone analog for the management of central fat accumulation. Randomized controlled trials have shown that administration of tesamorelin is safe and effective in reducing central fat accumulation among HIV-infected patients. This effect is transient, however, and its association with improved cardiovascular risk remains unclear.Keywords: HAART, HIV, tesamorelin, lipodystrophy

  16. Difference in signalling between various hormone therapies in endometrium, myometrium and upper part of the vagina

    NARCIS (Netherlands)

    P. Hanifi-Moghaddam (Payman); B. Boers-Sijmons (Bianca); A.H.A. Klaassens (Anet); F.H. van Wijk (Heidy); W.F.J. van IJcken (Wilfred); P.J. van der Spek (Peter); H.A.M. Verheul (Herman); H.J. Kloosterboer (Helenius); C.W. Burger (Curt); L.J. Blok (Leen)

    2008-01-01

    textabstractBACKGROUND: Combined hormone treatments in post-menopausal women have different clinical responses on uterus and vagina; therefore, we investigated differences in steroid signalling between various hormone therapies in these tissues. METHODS: A total of 30 post-menopausal women scheduled

  17. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  18. Thyroid hormone therapy and procurement of livers from brain-dead donors.

    Science.gov (United States)

    Novitzky, Dimitri; Mi, Zhibao; Videla, Luis A; Collins, Joseph F; Cooper, David K C

    2016-08-01

    Hormonal therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63,593 donors in whom information on T3/T4 therapy was available. In 40,124 donors, T3/T4 and all other hormonal therapy was recorded. The percentages of all organs procured, except livers, were greater in T3/T4-treated donors. Nevertheless, if T3/T4 therapy had been administered to the donor, liver transplantation was associated with significantly increased graft and recipient survival at 1 month and 12 months. The potential reasons for the lack of effect of T3/T4 therapy on the number of livers procured are discussed.

  19. An automatic framework for assessing breast cancer risk due to various hormone replacement therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal; Brandt, Sami; Nielsen, Mads

    It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone(...... features describing the local elongatedness or stripiness, especially trained to see the effect of HRT (Hormone Replacement Therapy ) thereby providing a non-subjective and reproducible measure and compare it to the BIRADS and percentage density measure....

  20. Current attitudes on self-use and prescription of hormone therapy among New York City gynaecologists

    DEFF Research Database (Denmark)

    Devi, Gayatri; Sugiguchi, Fumitaka; Pedersen, Anette Tønnes

    2013-01-01

    The results of the Women's Health Initiative studies dramatically altered hormone therapy use around the world. In countries outside the United States, self-use in physicians remained unaltered while prescription use declined, implying that physicians may not concur with the findings. We wished t...... to explore prevailing attitudes among American physicians by examining New York City obstetrician-gynaecologists' self-use and prescription use of hormone therapy....

  1. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, Henrik Enghusen; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  2. Prescription drug coverage: implications for hormonal therapy adherence in women diagnosed with breast cancer.

    Science.gov (United States)

    Bradley, Cathy J; Dahman, Bassam; Jagsi, Reshma; Katz, Steven; Hawley, Sarah

    2015-11-01

    In spite of its demonstrated benefits, many women do not initiate hormonal therapy, and among those who do, many discontinue it prematurely. We examined whether differences in hormonal therapy adherence may be at least partially explained by the availability of prescription drug coverage. Women aged 20-79 years diagnosed with stage I-III breast cancer between June 2005 and February 2007 were enrolled in the study. Women completed a mailed survey, on average 9 months after diagnosis, and again approximately 4 years later (N = 712). Adjusted logistic regression was used to predict the likelihood of initiating hormonal therapy and hormonal therapy continuation. Women who had prescription drug coverage were more likely to initiate hormonal therapy relative to women without prescription drug coverage (OR 2.91, 95 % CI 1.24-6.84). Women with prescription drug coverage were also more likely to continue hormonal therapy (OR 2.23; 95 % CI 0.99-5.05, p = 0.0543). The lowest income women were also less likely to continue hormonal therapy relative to women with annual household income that exceeded $70,000 (OR 0.55; 95 % CI 0.29-1.04) with a borderline significance of (p = 0.08). This study demonstrates the critical role of prescription drug coverage in hormonal therapy initiation and continuation, independent of health insurance coverage. These findings add to the body of literature that addresses medication adherence. Financial factors must be considered along with behavioral factors that influence adherence, which is becoming increasingly relevant to oncology as treatments are shifted to oral medications, many of which are very expensive.

  3. Understanding Breast Cancer Survivors' Beliefs and Concerns About Adjuvant Hormonal Therapy: Promoting Adherence.

    Science.gov (United States)

    Hurtado-de-Mendoza, Alejandra; Jensen, Roxanne E; Jennings, Yvonne; Sheppard, Vanessa B

    2017-02-15

    Adjuvant hormonal therapy is recommended for women with hormone receptor (HR)-positive breast cancer. Though critical, many patients are non-adherent to this therapy. Few scales have been developed to specifically address beliefs about adjuvant hormonal therapy. This study explores the clarity and relevance of the Beliefs about Medicine Questionnaire (BMQ) in the context of adherence behaviors to hormonal therapy in Black and White breast cancer survivors. We recruited women diagnosed with HR-positive cancer from the Washington, DC, area. An interviewer administered a standardized survey and conducted a cognitive interview. Participants rated the BMQ across three areas: relevance, difficulty, and clarity. We coded whether the comments identified item level issues: limited applicability, unclear reference, unclear perspective, or wording or tone. In-depth interviews were conducted with women who prematurely discontinued hormone therapy. The sample (n = 30) was equally split between Black and White survivors. On average, women were 57.9 years old (SD = 9.0). Overall 77% rated scale as relevant. Cognitive interviews revealed areas of perceived limited acceptability such as the notion of becoming too dependent or the notion of becoming worse if not taking the medication. Women who discontinued hormonal therapy (n = 2) felt ambivalent towards hormonal therapy as they reported having both positive and negative beliefs about the medication. Our study findings suggest new areas for further research and instrument development to accurately measure self-reported beliefs about hormonal therapy by HR-positive breast cancer survivors.

  4. Postmenopausal hormone therapy and the risk of breast cancer. A clinician's view.

    Science.gov (United States)

    Speroff, Leon

    2004-09-24

    Reports from the Women's Health Initiative (WHI) and the Million Women Study have indicated that postmenopausal hormone therapy increases the risk of breast cancer. At this point in time, it is not certain whether these data reflect a small increase in risk or an impact of hormone therapy on pre-existing tumors. The purpose of this review is to provide an analysis of the epidemiologic data that can help the clinician inform patients and assist patients in their decision-making.

  5. Impact of hormone therapy on quality of life after menopause.

    Science.gov (United States)

    Utian, Wulf H; Woods, Nancy Fugate

    2013-10-01

    Given the complexity of the literature on quality of life (QOL) and hormone therapy (HT) among women in the menopausal transition and postmenopause, the purposes of this integrative review were to (1) define QOL as a multidimensional construct; (2) review validated instruments for measurement of QOL; (3) review results of HT and QOL clinical trials that have used validated instruments; and (4) assess the effectiveness of HT on QOL, including health-related QOL (HRQOL), menopause-specific QOL (MSQOL), and global QOL (GQOL). The literature on HT and QOL was searched for definitions of QOL and validated instruments for measuring QOL, and the results were summarized. The purposes of this integrative review were to evaluate the effects of HT on HRQOL, differentiating the effects of HT on GQOL, HRQOL, and MSQOL. As a basis for this review, we searched for published controlled clinical trials in which the effects of HT on QOL were studied using validated QOL instruments, in particular menopause-specific validated instruments. Clear definitions are elucidated. Validated instruments for the measurements of HRQOL, GQOL, and MSQOL are summarized, and the necessity of their incorporation into future research and clinical practice is emphasized. The published effects on QOL of estrogens and progestogens administered to symptomatic and nonsymptomatic women in the menopausal transition and beyond are reviewed. The impact of various health state-related symptoms on HRQOL and GQOL is now an integral component of contemporary health care. Effects of HT include GQOL and HRQOL and should be menopause-specific. There is clearly a need for further studies on menopause and menopause-related therapies using appropriate and validated instruments. Literature review shows that HT provides a significant benefit for MSQOL in midlife women, mainly through relief of symptoms, but treatment also may result in a global increase in sense of well-being (GQOL). HRQOL benefits are contingent on

  6. Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist.

    Science.gov (United States)

    Carter, D A; Saridaki, E; Lightman, S L

    1988-04-01

    The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sex-typical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.

  7. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    Energy Technology Data Exchange (ETDEWEB)

    Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

    1988-03-01

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

  8. Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Kawa, S; Ueno, T; Iijima, A; Midorikawa, T; Fujimori, Y; Tokoo, M; Oguchi, H; Kiyosawa, K; Imai, Y; Kaneko, G; Kuroda, T; Hashizume, K; Osamura, R Y; Katakami, H

    1997-07-01

    The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

  9. Immunoreactive neuronal pathways of growth hormone-releasing hormone (GRH) in the brain and pituitary of the teleost Gadus morhua.

    Science.gov (United States)

    Pan, J X; Lechan, R M; Lin, H D; Jackson, I M

    1985-01-01

    Using an antiserum directed against the C-terminus of hGRH(1-44)NH2 and another recognizing the mid portion to C-terminal of hGRH(1-40)OH, we identify two immunocytochemically distinct GRH-immunoreactive systems in the brain of the codfish, Gadus morhua. The antiserum directed against GRF(1-44)NH2 stains cell bodies exclusively in the rostral pars distalis. The other antiserum immunoreactive with GRF(1-40)OH reacts with a population of parvocellular and magnocellular neuronal cell bodies in the hypothalamus and with two major axonal pathways which project toward the median eminence and terminate primarily in the pars nervosa. These results indicate the presence of at least two forms of hGRH-like peptides in the teleost which may have different roles in the regulation of pituitary function.

  10. Growth Hormone Therapy in Children with Chronic Renal Failure

    OpenAIRE

    Cayir, Atilla; Kosan, Celalettin

    2014-01-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant huma...

  11. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

    Science.gov (United States)

    Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H

    2016-03-17

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration.

  12. Growth Hormone Therapy Is Safe and Effective in Patients with Lysinuric Protein Intolerance

    OpenAIRE

    Niinikoski, Harri; Lapatto, Risto; Nuutinen, Matti; Tanner, Laura; Simell, Olli; Näntö-Salonen, Kirsti

    2011-01-01

    Background: Lysinuric protein intolerance (LPI) is an autosomal recessive cationic amino acid transport defect characterized by episodes of postprandial hyperammonemias and spontaneous protein aversion. Subnormal growth is common in spite of appropriate nutritional therapy. Growth hormone (GH) therapy promotes appetite, protein synthesis and accretion, but its possible growth-promoting effects and safety in patients with LPI are poorly known.

  13. Postmenopausal hormone therapy and breast cancer: a clinician's message for patients.

    Science.gov (United States)

    Speroff, Leon

    2004-08-01

    The Women's Health Initiative agrees with some but not all case-control and cohort studies that current use of postmenopausal estrogen-progestin therapy is associated with a small increase in the risk of breast cancer. It is not known whether this is because of new tumor growth or an effect of hormonal therapy on preexisting tumors. Many studies indicate that women who develop breast cancer while using postmenopausal hormone therapy have a reduced risk of dying from breast cancer; this is consistent with an effect on preexisting tumors so that tumors appear at a less virulent and aggressive stage.

  14. Behavioral interventions to enhance adherence to hormonal therapy in breast cancer survivors: A systematic literature review

    Science.gov (United States)

    Hurtado-de-Mendoza, Alejandra; Cabling, Mark L.; Lobo, Tania; Dash, Chiranjeev; Sheppard, Vanessa B.

    2016-01-01

    Adjuvant hormonal therapy contributes to reductions in recurrence and mortality for women with hormone receptor positive breast cancer. However, adherence to hormonal therapy is suboptimal. This is the first systematic literature review examining interventions aimed at improving hormonal therapy adherence. Researchers followed the PRISMA guidelines. PubMed-Medline, CINAHL, PsychInfo, Ovid-Medline, and EMBASE were searched for behavioral interventions that aimed to enhance adherence to adjuvant hormonal therapy in breast cancer survivors. There were 376 manuscripts screened for eligibility. Five articles met criteria. All interventions presented adherence outcomes after one-year follow-up. None significantly enhanced adherence compared to the usual care in the primary analysis (OR ranged from 1.03 to 2.06 for adherence and from 1.11 – 1.18 for persistence). All targeted patients and three only included post-menopausal breast cancer patients. Three tested the same intervention consisting of educational materials. Only one was conducted in the US. Only one reported participants' ethnicity. Overall it was unclear whether the studies contained bias. The use of different terminology and operationalization of adherence made comparisons challenging. Interventions to improve adherence to adjuvant hormonal therapy in US breast cancer populations that includes survivors who are ethnically diverse, premenopausal, and taking tamoxifen are necessary to inform future interventions. Adoption of consistent adherence definitions/measurements will provide a clearer framework to consolidate aggregate findings. Given the limited efficacy of tested interventions, it is important to engage oncologists and academics to develop approaches that target different components associated with hormonal therapy adherence, such as doctor-patient communication or social support. PMID:27133733

  15. Psychosocial factors in adjuvant hormone therapy for breast cancer: an emerging context for adherence research.

    Science.gov (United States)

    Van Liew, Julia R; Christensen, Alan J; de Moor, Janet S

    2014-09-01

    For patients with hormone receptor positive breast cancer, survivorship entails prolonged self-management of adjuvant treatment in the form of daily hormone therapy. Although sustained daily adherence across the 5-year course of therapy is associated with improved recurrence-free survival outcomes, adherence is suboptimal and many women discontinue hormone therapy prematurely. Factors associated with breast cancer survivors' nonadherence and nonpersistence are not comprehensively understood. Furthermore, psychosocial variables have only received limited research attention, despite their documented relationships with adherence in other chronic illness populations. A systematic literature review identified 14 studies that analyzed relationships between psychosocial factors and breast cancer survivors' adherence and/or persistence with adjuvant hormone therapy. Although identified relationships were complex and at times inconsistent, salient conclusions emerged. Interpersonal factors, in the form of positive social support and patient-centered interactions with medical providers, as well as intrapersonal factors, such as anxiety and beliefs about the relative benefits of medication use, were reliably associated with better adherence and persistence. Depression did not demonstrate the negative impact on adherence that has been observed in other medical populations. No relationships between quality of life and adherence were identified. Adjuvant hormone therapy appears to be a unique context for medication adherence, which warrants further attention and more rigorous analysis in future research. Individual patients' psychosocial characteristics and health care preferences should be considered when striving to optimize medication adherence.

  16. Low dose hormone therapy in reproductive endocrinology in China

    Institute of Scientific and Technical Information of China (English)

    葛秦生; 肖碧莲; 乌毓明; 李晓红

    2003-01-01

    @@ The human endocrine system normally functions in a balanced physiological state. Any excess or deficiency will cause an endocrine imbalance and result in hyper-or hypo-function, requiring readjustment by hormone suppression or supplementation in order to reestablish a normal physiological balance.

  17. [Hormone therapy in prostate cancer; a pharmacotherapeutic challenge

    NARCIS (Netherlands)

    Westdorp, H.; Benoist, G.E.; Schers, H.J.; Erp, P.H. van; Gerritsen, W.R.; Mulders, P.F.A.; Kramers, C.

    2015-01-01

    Prostate cancer is the most common form of cancer in men in the Western world. One-third of the patients with localised prostate cancer will develop recurrent disease, localised disease spread or distant metastases. The presence of distant metastases is an indication for primary palliative hormone

  18. Effects of hormone replacement therapy on depressive and anxiety symptoms after oophorectomy

    Directory of Open Access Journals (Sweden)

    Danijela D. Ðoković

    2015-02-01

    Full Text Available Aim To assess the effect of hormone replacement therapy on postoperative depression and anxiety symptoms. Methods In observational prospective study 80 women divided into two groups were evaluated: women who received estrogen and androgen replacement therapy after hysterectomy with bilateral oophorectomy before onset of menopause (35-45 years old and a control group that consisted of perimenipausal women (45-55 years old. Hormone replacement therapy began one week after surgery. The severity of depression and anxiety was evaluated through the use of Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale. Subjects from the study group were interviewed right after the surgical treatment, one, two and three months later. Subjects from the control group were interviewed only once. Results The women who underwent surgery had a statistically significantly higher score in Hamilton Depression Scale (p<0.001 and Hamilton Anxiety Scale (p=0.002 compared to the control perimenopausal women. There was a significant reduction of depressive and anxiety symptoms during hormone replacement therapy. Statistically significant difference in depressive score was found immediately after one month of hormone replacement therapy (first week/one month later: p=0.0057. Statistically significant difference in anxiety score appeared three months after the introduction of hormone therapy (first week/one month later: p=0.309; first week/two months later: p=0.046; first week/three months later: p<0.001. Level of serum luteinizing hormone was in correlation with depressive and anxiety score. Conclusion Estrogen-androgen replacement therapy may reduce the risk of psychiatric disorders developing in women with bilateral oophorectomy (indication for hysterectomy with oophorectomy was leiomyomata uteri.

  19. Risk of Stroke With Various Types of Menopausal Hormone Therapies: A National Cohort Study.

    Science.gov (United States)

    Løkkegaard, Ellen; Nielsen, Lars Hougaard; Keiding, Niels

    2017-08-01

    Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of regimens and routes of administration. A national historical cohort of women aged 51 to 70 years from 1995 to 2010 was established by linking 5 Danish registries. The National Registry of Medicinal Product Statistics provided information on hormone therapy exposure and the National Patient or Cause of Death Registries supplied data regarding stroke diagnoses (ischemic/hemorrhagic/subarachnoid hemorrhage). Multiply adjusted rate ratios with time-varying covariates were fitted in Poisson regression models. Of the 980 003 included women, 20 199 suffered a stroke (78% ischemic, 12% hemorrhagic, and 10% subarachnoid hemorrhage). In total, 36% of women used hormone therapy. Current use conferred a relative rate of 1.16 (95% confidence interval, 1.12-1.22). Compared with never users, the increased rate ratio of all stroke with continuous, cyclic combined estrogen/progestin, and estrogen only oral therapies were 1.29 (95% confidence interval, 1.21-1.37), 1.11 (95% confidence interval, 1.04-1.20), and 1.18 (95% confidence interval, 1.10-1.26), respectively. The increased risk was because of ischemic stroke, but not hemorrhagic stroke. Transdermal application of hormone therapy was not associated with risk of stroke. Vaginal estrogen was associated with a decreased risk of stroke. In a national setting, we found an increased risk of stroke, based on ischemic stroke, with oral hormone therapies that was comparable to findings from randomized studies. We found no risk of stroke with transdermal application and a reduced risk with vaginal estrogen. © 2017 American Heart Association, Inc.

  20. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review.

    Science.gov (United States)

    Murphy, Caitlin C; Bartholomew, L Kay; Carpentier, Melissa Y; Bluethmann, Shirley M; Vernon, Sally W

    2012-07-01

    Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). This systematic review aims to: (1) determine the prevalence of adherence and persistence to adjuvant hormonal therapy among breast cancer survivors in clinical practice, and (2) identify correlates of adherence and persistence. We searched Medline, PubMed, PsycINFO, and CINAHL for studies that measured rates and/or correlates of adherence and/or persistence to adjuvant hormonal therapy. Studies were reviewed in a multi-step process: (1) the lead author screened titles and abstracts of all potentially eligible studies; (2) each coauthor reviewed a random 5 % sample of abstracts; and (3) two sets of coauthors each reviewed half of all "maybe" abstracts. Any disagreements were discussed until consensus was reached. Twenty-nine studies met inclusion criteria. Prevalence of adherence ranged from 41 to 72 % and discontinuation (i.e., nonpersistence) ranged from 31 to 73 %, measured at the end of 5 years of treatment. Extremes of age (older or younger), increasing out-of-pocket costs, follow-up care with a general practitioner (vs. oncologist), higher CYP2D6 activity, switching from one form of therapy to another, and treatment side effects were negatively associated with adherence and/or persistence. Taking more medications at baseline, referral to an oncologist, and earlier year at diagnosis were positively associated with adherence and/or persistence. Adherence and persistence to adjuvant hormonal therapy among breast cancer survivors is suboptimal. Many of the correlates of adherence and persistence studied to date are not modifiable. Our review reveals a critical need for further research on modifiable factors

  1. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Directory of Open Access Journals (Sweden)

    Marco Antonio Botelho

    2014-02-01

    Full Text Available OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10% combined with estriol (0.1% + estradiol (0.25% for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05 after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

  2. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan, E-mail: marcobotelho@pq.cnpq.br [Universidade Potiguar, Natal, RN (Brazil). Lab. de Nanotecnologia; Fechine, Pierre [Universidade Federal do Ceara (GQMAT/UFCE), Fortaleza, CE (Brazil). Dept. de Quimica Analitica. Grupo Avancado de Biomateriais em Quimica; Queiroz, Danilo Caldas de [Instituto Federal de Ciencia e Tecnologia (IFCT), Fortaleza, CE (Brazil). Lab. de Biotecnologia; Ruela, Ronaldo [Instituto de Biotecnologia Aplicada (INBIOS), Fortaleza, CE (Brazil); Almeida, Jackson Guedes [Universidade Federal do Vale de Sao Francisco (UNIVALE), Petrolina, PE (Brazil). Fac. de Ciencias Farmaceuticas; Quintans Junior, Lucindo [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Fisiologia

    2014-06-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  3. Lipoproteína a, aterosclerosis y terapia hormonal de reemplazo Lipoprotein a, atherosclerosis and replacement hormone therapy

    Directory of Open Access Journals (Sweden)

    Miguel Lugones Botell

    2005-08-01

    Full Text Available Se realizó una revisión sobre la lipoproteína plasmática, Lp(a, cuyo papel fisiológico es poco conocido. Se ha descrito una asociación entre las concentraciones aumentadas de Lp(a y el proceso aterosclerótico. Además, su exceso podría inducir una disminución de la actividad fibrinolítica y, por tanto, favorecer la trombosis. También analizamos la terapia hormonal de reemplazo. En relación con los efectos positivos, mejora los síntomas climatéricos y previene la osteoporosis, aunque entre los efectos adversos en las mujeres que la siguen, se ha descrito un ligero aumento del riesgo del tromboembolismo venoso, y más recientemente, en estudios realizados en EE.UU. en los años 2002 y 2004, en el ya conocido estudio (Women´s Health Initiative Study, se reportó mayor incidencia de eventos cardiovasculares para la terapia combinada con estrógenos conjugados equinos y medroxiprogesterona, y de stroke para la terapia estrogénica. Estos estudios pusieron en su lugar los efectos de esta terapia, que no es totalmente inocua. Se precisan estudios más amplios para definir el papel de la terapia hormonal de reemplazo y otras medidas terapéuticas sobre el sistema hemostático, el metabolismo lipídico y la enfermedad cardiovascular.A review of plasmatic lipoprotein, Lp(a, whose physiological role is little known, was made. An association between the augmented concentrations of Lp(a and the atherosclerotic proccess has been described. Besides, its excess may lead to a reduction of the fibrinolytic activity and, therefore, favor thrombosis. The replacement hormone therapy was also analyzed. In relation to its positive effects, it improves the climacteric symptoms and prevents osteoporosis. Among its adverse effects, it has been observed a mild increase of the risk for venous thromboembolism and, more recently, in the aleady known Women's Health Initiative Study, it was reported a higher incidence of cardiovascular events for the combined

  4. Efeitos da terapia hormonal na menopausa sobre o sistema imune Effects of the menopause hormone therapy on the immune system

    Directory of Open Access Journals (Sweden)

    Sebastião Freitas de Medeiros

    2007-11-01

    be altered during pregnancy, gonadectomy, menopause and hormone therapy. Estrogen depresses the cellular immunity, suppresses the natural killer cell activity and increases the production of antibodies. Progesterone/progestogen suppresses the cellular immune system. Androgens, after metabolization in estrogens, might stimulate the humoral immune response. Hormone therapy is still broadly used in post-menopause women with the purpose of decreasing climacteric symptoms, as well as preventing genital atrophy and bone loss. Its use to attenuate the risk of cardiovascular and neurodegenerative diseases remains in debate. A few studies have been carried out to examine the effect of post-menopause hormone therapy on the immune system. There is evidence that the hypoestrogenic state, following menopause, could result in less resistance to infections. The present review examines the interaction between sexual steroids and the immune system and, based on epidemiological and clinical studies, evaluates the effects of hormone therapy on the immune responses. It was concluded that the hormone therapy normalizes the cellular immune response in post-menopausal women.

  5. The selection of hormonal therapy in prostate cancer: who, when, and for how long?

    Science.gov (United States)

    Ryan, Charles J; Small, Eric J

    2004-05-01

    Androgen deprivation is the foundation for the systemic therapy of advanced prostate cancer. Multiple trials have tested combined androgen blockade versus androgen deprivation alone in patients with advanced disease. These studies suggest a slight advantage to the combined approaches that contain flutamide and bicalutamide, but the lack of dramatic differences in outcome makes monotherapy reasonable, especially in patients with more indolent disease. Intermittent androgen deprivation is an alternative that may allow patients to reduce the total time on androgen suppression as well as possibly delay the onset of androgen independence. A number of secondary hormonal therapies, including deferred and secondary antiandrogens, ketoconazole, and estrogens have shown modest response proportions. Patients with less advanced disease such as a rising prostate-specific antigen have varied outcomes, and no standard approach exists. In this group, noncastrating forms of hormonal therapy are being evaluated. Patients undergoing definitive local therapy who have high-risk features may benefit from early, as opposed to deferred, androgen deprivation. This review examines the evidence for the current state of the art in hormonal therapy in patients with prostate cancer and focuses, in particular, on treatment composition and timing as well as the rationale for the use of hormonal therapy in early stage disease.

  6. Usefulness of MRI in evaluation of hormonal therapy for the ovarian chocolate cysts

    Energy Technology Data Exchange (ETDEWEB)

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kono, Michio; Yamasaki, Katsuhito.

    1988-09-01

    We evaluated the diagnostic capability of MRI in ovarian chocolate cysts treated by Danazol (analogue of testosterone). Both inversion recovery as T1-weighted image and long TE and TR spin echo as T2-weighted image were performed before and during hormonal therapy. Temporal change of signal intensity and size was evaluated in three ovarian chocolate cysts (stage II: 2 cases, stage III: 1 case by Beecham classification, 1966) using the 0.15-T MR system. The high intense signal from all of the cysts was seen on both T1 and T2 weighted images before treatment. There was marked decrease in size of the chocolate cysts during hormonal therapy, and they were of considerably lower signal intensity than initially on T2-weighted image. We concluded that MRI was useful to evaluate hormonal therapy for ovarian chocolate cysts.

  7. Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency

    OpenAIRE

    Kim, Ja Hye; Cho, Ja Hyang; Yoo, Han-Wook; Choi, Jin-Ho

    2014-01-01

    Purpose Growth hormone (GH) plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD). This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters. Methods A total of 45 patients (17 females and 28 males) diagnosed with childhood-onset GHD (CO-GHD) were investigated and al...

  8. Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

    Science.gov (United States)

    Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

    2015-12-01

    Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

  9. Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer

    Science.gov (United States)

    Sekiguchi, Atsushi; Sato, Chiho; Matsudaira, Izumi; Kotozaki, Yuka; Nouchi, Rui; Takeuchi, Hikaru; Kawai, Masaaki; Tada, Hiroshi; Ishida, Takanori; Taki, Yasuyuki; Ohuchi, Noriaki; Kawashima, Ryuta

    2016-01-01

    Cancer survivors are exposed to several risk factors for cognitive dysfunction, such as general anesthesia, surgical trauma, and adjuvant therapies. In our recent study we showed that thalamic volume reduction and attentional dysfunction occurred shortly after surgery. Here, we examined the 6-month prognosis of the 20 patients with breast cancer who underwent surgery. Seven patients did not receive any adjuvant therapy after the surgery and 13 patients received a hormonal therapy after the surgery. We assessed their attentional functions, and thalamic volumes shortly after and 6 months after surgery. We found a significant group x time interaction in the attentional functions (p = 0.033) and the right thalamus (p <  0.05, small volume correction), suggesting the thalamic volume reduction and attentional dysfunction recovered in patients without adjuvant therapy. Our findings provide a better understanding of the potential role of hormonal therapy in relation to the cognitive dysfunction of cancer survivors. PMID:27708377

  10. Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy

    DEFF Research Database (Denmark)

    Lee, Peter A; Ross, Judith L; Pedersen, Birgitte Tønnes

    2015-01-01

    BACKGROUND: Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS) or the A......BACKGROUND: Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS...

  11. Hormone Therapy Plus Chemotherapy for Metastatic Prostate Cancer

    Science.gov (United States)

    A trial of androgen deprivation therapy (ADT) plus six cycles of docetaxel versus ADT alone found that after a median follow-up of nearly 29 months, median overall survival was 13.6 months longer with the combination therapy than with ADT alone.

  12. Slipped Capital Femoral Epiphysis as a Complication of Growth Hormone Therapy

    Directory of Open Access Journals (Sweden)

    Shuo-Yu Wang

    2007-01-01

    Full Text Available Slipped capital femoral epiphysis (SCFE is a rare complication of growth hormone (GH therapy. Here, we report three patients who developed SCFE during GH therapy. The first two patients had hypopituitarism and had started GH therapy at the age of 15 years 6 months and 13 years 9 months, respectively. SCFE developed 4 years and 1 year after GH therapy, respectively. The third patient had Prader-Willi syndrome with obesity and hypogonadism and began GH therapy at the age of 12 years and 11 months. SCFE developed 2 months after starting GH therapy. Pain over the hip joints or over the knees is an early sign of SCFE. Despite recommendation, none of the three patients continued GH therapy. A high index of suspicion during GH therapy in patients at high risk of SCFE is important for early diagnosis and appropriate management. [J Formos Med Assoc 2007;106(2 Suppl:S46-S50

  13. Long-term hormone therapy for perimenopausal and postmenopausal women.

    Science.gov (United States)

    Marjoribanks, Jane; Farquhar, Cindy; Roberts, Helen; Lethaby, Anne; Lee, Jasmine

    2017-01-17

    BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use

  14. Adjuvant Hormonal Therapy in Postmenopausal Women with Breast Cancer: Physician’s Choices

    Directory of Open Access Journals (Sweden)

    Asim Jamal Shaikh

    2012-01-01

    Full Text Available The choice of adjuvant hormonal therapy in postmenopausal women with hormone receptor positive breast cancer has remained a matter of controversy and debate. The variety of agents is available, with each claiming to be superior. This clinical survey was undertaken to get an impression of the physician’s first choice of therapy in an attempt to find out what questions still need to be answered in the making of “standard of care.” A web-based clinical survey was sent to the cancer physicians around the world, and 182 physicians responded to the survey. Most were medical oncologists in a tertiary care hospital. 36.3% preferred Anastrozole, 35.2% Tamoxifen, and 22.2% Letrozole as their first choice. Data support (67.8% and safety concerns (30% were given as the main reasons for the choice, 63.7% switched their therapy, and 24% had to switch because of side effects. 73.6% used 5 years of adjuvant hormonal therapy, 6.6% for 7 years, and 4.4% for 10 years. 61.5% follow their patients 3 times monthly, and 73.2% used laboratory and radiological assessment at each followup. Conclusion. Physicians show disagreement over the choice and duration of hormonal therapy in this patient population. Clinical trials leading to firm recommendations to set standards from which patients benefit the most are needed.

  15. Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study.

    Science.gov (United States)

    Gorin-Lazard, Audrey; Baumstarck, Karine; Boyer, Laurent; Maquigneau, Aurélie; Gebleux, Stéphanie; Penochet, Jean-Claude; Pringuey, Dominique; Albarel, Frédérique; Morange, Isabelle; Loundou, Anderson; Berbis, Julie; Auquier, Pascal; Lançon, Christophe; Bonierbale, Mireille

    2012-02-01

    Although the impact of sex reassignment surgery on the self-reported outcomes of transsexuals has been largely described, the data available regarding the impact of hormone therapy on the daily lives of these individuals are scarce. The objectives of this study were to assess the relationship between hormonal therapy and the self-reported quality of life (QoL) in transsexuals while taking into account the key confounding factors and to compare the QoL levels between transsexuals who have, vs. those who have not, undergone cross-sex hormone therapy as well as between transsexuals and the general population (French age- and sex-matched controls). This study incorporated a cross-sectional design that was conducted in three psychiatric departments of public university teaching hospitals in France. The inclusion criteria were as follows: 18 years or older, diagnosis of gender identity disorder (302.85) according to the Diagnostic and Statistical Manual, fourth edition text revision (DSM-IV TR), inclusion in a standardized sex reassignment procedure following the agreement of a multidisciplinary team, and pre-sex reassignment surgery. QoL was assessed using the Short Form 36 (SF-36). The mean age of the total sample was 34.7 years, and the sex ratio was 1:1. Forty-four (72.1%) of the participants received hormonal therapy. Hormonal therapy and depression were independent predictive factors of the SF-36 mental composite score. Hormonal therapy was significantly associated with a higher QoL, while depression was significantly associated with a lower QoL. Transsexuals' QoL, independently of hormonal status, did not differ from the French age- and sex-matched controls except for two subscales of the SF-36 questionnaire: role physical (lower scores in transsexuals) and general health (lower scores in controls). The present study suggests a positive effect of hormone therapy on transsexuals' QoL after accounting for confounding factors. These results will be useful for

  16. Influence of estrogen receptor alpha and progesterone receptor polymorphisms on the effects of hormone therapy on mammographic density.

    NARCIS (Netherlands)

    Duijnhoven, F.J.B. van; Peeters, P.H.; Warren, R.M.; Bingham, S.; Uitterlinden, A.G.; Noord, P.A.H. van; Monninkhof, E.M.; Grobbee, D.E.; Gils, C.H. van

    2006-01-01

    Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch

  17. Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

    DEFF Research Database (Denmark)

    Birch-Johansen, Fatima; Jensen, Allan; Olesen, Anne Braae

    2012-01-01

    We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women.......We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women....

  18. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    Science.gov (United States)

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-06-26

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  19. Estrogen receptor activation by tobacco smoke condensate in hormonal therapy-resistant breast cancer cells.

    Science.gov (United States)

    Niwa, Toshifumi; Shinagawa, Yuri; Asari, Yosuke; Suzuki, Kanae; Takanobu, Junko; Gohno, Tatsuyuki; Yamaguchi, Yuri; Hayashi, Shin-Ichi

    2017-01-01

    The relationship between tobacco smoke and breast cancer incidence has been studied for many years, but the effect of smoking on hormonal therapy has not been previously reported. We investigated the effect of smoking on hormonal therapy by performing in vitro experiments. We first prepared tobacco smoke condensate (TSC) and examined its effect on estrogen receptor (ER) activity. The ER activity was analyzed using MCF-7-E10 cells into which the estrogen-responsive element (ERE)-green fluorescent protein (GFP) reporter gene had been stably introduced (GFP assay) and performing an ERE-luciferase assay. TSC significantly activated ERs, and upregulated its endogenous target genes. This activation was inhibited by fulvestrant but more weakly by tamoxifen. These results suggest that the activation mechanism may be different from that for estrogen. Furthermore, using E10 estrogen depletion-resistant cells (EDR cells) established as a hormonal therapy-resistant model showing estrogen-independent ER activity, ER activation and induction of ER target genes were significantly higher following TSC treatment than by estradiol (E2). These responses were much higher than those of the parental E10 cells. In addition, the phosphorylation status of signaling factors (ERK1/2, Akt) and ER in the E10-EDR cells treated with TSC increased. The gene expression profile induced by estrogenic effects of TSC was characterized by microarray analysis. The findings suggested that TSC activates ER by both ligand-dependent and -independent mechanisms. Although TSC constituents will be metabolized in vivo, breast cancer tissues might be exposed for a long period along with hormonal therapy. Tobacco smoke may have a possibility to interfere with hormonal therapy for breast cancer, which may have important implications for the management of therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Hormone-refractory prostate cancer and the skeleton

    NARCIS (Netherlands)

    Soerdjbalie-Maikoe, Vidija

    2006-01-01

    Prostate cancer is the second most common cancer in men in the UK. Androgen ablation with luteinising hormone-releasing hormone agonists (LHRH agonists) alone, or in combination with anti-androgens is the standard treatment for men with metastatic prostate cancer. Unfortunately, despite maximal andr

  1. Failure of growth hormone-suppressing agents to affect TSH-releasing hormone- and LH-releasing hormone-induced growth hormone release in acromegaly.

    Science.gov (United States)

    Nakagawa, K; Obara, T

    1977-01-01

    In patients with acromegaly whose basal plasma GH levels were suppressed with 9 mg/day of dexamethasone for 2 days, TRH-(6 cases) and LHRH-(1 case) induced GH release were unaffected when the responses were compared to the basal levels. Phentolamine infusion, 70 mg in 150 min, or hyperglycemia induced by iv infusion of 700 ml of 50% glucose solution also did not suppress TRH-induced GH release in 2 acromegalic patients whose basal GH levels were lowered with these agents alone. These results seem to indicate that dexamethasone does not affect TRH- or LHRH-induced GH release per se, but affects the basal state which determines the absolute level of response. They also support the concept that TRH and LHRH act directly on pituitary tumor cells to release GH in acromegaly.

  2. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized, double-blin

  3. Breast cancer incidence and use of hormone therapy in Denmark 1978-2007

    DEFF Research Database (Denmark)

    von Euler-Chelpin, My

    2011-01-01

    Internationally, there have recently been reports of declining incidence rates for breast cancer. Decreased use of hormone therapy and decreased use of mammography has been put forward as possible reasons for this decline. The aim of this study was to analyse breast cancer incidence trends in Den...

  4. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.;

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  5. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women

    DEFF Research Database (Denmark)

    Mosekilde, Leif; Beck-Nielsen, H.; Sørensen, O.H.

    2000-01-01

    OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual...... and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention....

  6. Replacing hormone therapy-is the decline in prescribing sustained, and are nonhormonal drugs substituted?

    NARCIS (Netherlands)

    Vegter, Stefan; Kolling, Pieternel; Toben, Marjolijn; Visser, Sipke T.; de Jong-van den Berg, Lolkje T. W.

    2009-01-01

    Objectives: After two cautioning landmark studies in 2002 and 2003, a dramatic decrease in hormonal therapy (HT) prescribing for menopausal symptoms was seen. Our objectives were to (1) determine whether this decline in HT prescribing sustained until 2007 and (2) investigate nonhormonal drug prescri

  7. Attitude of German women towards hormone therapy : results of a lay survey

    NARCIS (Netherlands)

    Buhling, K. J.; Daniels, B.; Studnitz, F. S. G.; Eulenburg, C.; Mueck, A. O.

    2013-01-01

    Objective: Hormone therapy (HT) use has experienced a substantial change since publication of Women's Health Initiative (WHI) controlled trial. We aimed to investigate the attitude towards HT in German women aged 45-60 years. Study design: A questionnaire was sent to 9785 randomly selected women in

  8. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

    2004-01-01

    Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...

  9. Attitude of German women towards hormone therapy : results of a lay survey

    NARCIS (Netherlands)

    Buhling, K. J.; Daniels, B.; Studnitz, F. S. G.; Eulenburg, C.; Mueck, A. O.

    Objective: Hormone therapy (HT) use has experienced a substantial change since publication of Women's Health Initiative (WHI) controlled trial. We aimed to investigate the attitude towards HT in German women aged 45-60 years. Study design: A questionnaire was sent to 9785 randomly selected women in

  10. Use of postmenopausal hormone replacement therapy and risk of non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Nørgaard, M; Poulsen, A H; Pedersen, L;

    2006-01-01

    Use of postmenopausal hormone replacement therapy (HRT) has been hypothesised to be associated with a reduced risk of non-Hodgkin's lymphoma (NHL), but the epidemiologic evidence is conflicting. To examine the risk of NHL in HRT users aged 40 and older, we conducted a cohort study in the County...

  11. The validity of self-reported use of hormone replacement therapy among Danish nurses

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen Christine Leth; Johnsen, Søren Påske; Heitmann, Berit Lillienthal

    2004-01-01

    Recent findings from randomized clinical trials on the effects of hormone replacement therapy (HRT) among postmenopausal women contradict findings from observational studies indicating a protective effect on the development of cardiovascular disease. Most observational studies on HRT are based...... on self-reported data, although data on the validity of HRT in postmenopausal women are sparse....

  12. Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review

    NARCIS (Netherlands)

    Hemelaar, M.; Mooren, M.J. van der; Rad, M.; Kluft, C.; Kenemans, P.

    2008-01-01

    Objective: To review the effects of non-oral administration of postmenopausal hormone therapy (HT) on risk markers for atherosclerotic and venous thromboembolic disease.Non-oral postmenopausal HT appears not to increase venous thromboembolic risk, whereas the effect on coronary heart disease risk is

  13. The Miracle Drug : Hormone Replacement Therapy and Labor Market Behavior of Middle-Aged Women

    NARCIS (Netherlands)

    Meltem Daysal, N.; Orsini, C.

    2012-01-01

    Abstract: In an aging society, determining which factors contribute to the employment of older individuals is increasingly important. This paper sheds light on the impact of medical innovation in the form of Hormone Replacement Therapy (HRT) on employment of middle-aged women. HRT are drugs taken by

  14. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  15. Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency?

    NARCIS (Netherlands)

    ter Maaten, JC

    2000-01-01

    During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated

  16. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers

    NARCIS (Netherlands)

    A. Eisen (Andrea); J. Lubinski (Jan); J. Gronwald (Jacek); P. Moller (Pal); H. Lynch (Henry); J.G.M. Klijn (Jan); C. Kim-Sing (Charmaine); S.L. Neuhausen (Susan); L. Gilbert (Lucy); P. Ghadirian (Parviz); S. Manoukian (Siranoush); G. Rennert (Gad); E. Friedman (Eitan); C. Isaacs (Claudine); B. Rosen (Barry); M.J. Daly (Mark); P. Sun (Ping); S. Narod (Steven); O.I. Olopade (Olofunmilayo); S. Cummings (Shelly); N. Tung (Nadine); F.J. Couch (Fergus); W.D. Foulkes (William); S.M. Domchek (Susan); D. Stoppa-Lyonnet (Dominique); R. Gershoni-Baruch (Ruth); D. Horsman (David); H. Saal (Howard); E. Warner (Ellen); W. Meschino (Wendy); K. Offit (Kenneth); A. Trivedi (Amber); M. Robson (Mark); M. Osborne (Michael); D. Gilchrist (Dawna); J.N. Weitzel (Jeffrey); W. McKinnon (Wendy); M. Wood (Marie); C. Maugard (Christine); B. Pasini (Barbara); T. Wagner (Teresa); K. Sweet; B. Pasche (Boris); T. Fallen (Taya); B.Y. Karlan (Beth); C. Eng (Charis); R.N. Kurz; S. Armel (Susan); A. Tulman (Anna); P.J. Ainsworth (Peter); E. Lemire (Edmond); J. McLennan; G. Evans (Gareth); T. Byrski (Tomas); T. Huzarski (Tomas); L. Shulman (Lee)

    2008-01-01

    textabstractBackground: Hormone therapy (HT) is commonly given to women to alleviate the climacteric symptoms associated with menopause. There is concern that this treatment may increase the risk of breast cancer. The potential association of HT and breast cancer risk is of particular interest to wo

  17. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy

    DEFF Research Database (Denmark)

    Sørensen, M B; Rosenfalck, A M; Højgaard, L

    2001-01-01

    OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional ......, which in turn, prevents disease in the elderly....

  18. The future of postmenopausal hormone therapy: It's time to move forward.

    Science.gov (United States)

    Speroff, Leon

    2007-05-20

    There are good reasons why the use of postmenopausal hormone therapy is at a contemporary low level. But an analysis of these factors provides explanations that offer a basis for appropriate and renewed use. A more optimistic position is supported by an up-to-date appraisal of clinical studies.

  19. The association between early menopause and risk of ischaemic heart disease: Influence of Hormone Therapy?

    DEFF Research Database (Denmark)

    Løkkegaard, E; Andersen, Zorana Jovanovic; Heitmann, B L

    2006-01-01

    Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether...... HT reduces this risk associated with early menopause....

  20. Carotid Artery Distensibility and Hormone Therapy and Menopause: The Los Angeles Atherosclerosis Study (LAAS)

    Science.gov (United States)

    Shufelt, Chrisandra; Elboudwarej, Omeed; Johnson, B. Delia; Mehta, Puja; Bittner, Vera; Braunstein, Glenn; Berga, Sarah; Stanczyk, Frank; Dwyer, Kathleen; Merz, C. Noel Bairey

    2015-01-01

    Objective Observational studies suggest that arterial distensibility decreases during menopause; however, the relation to hormone therapy use is controversial. We prospectively studied distensibility and hormone therapy use during different menopause stages. Methods 161 women between 42–61 years of age without cardiovascular disease had carotid artery measurements by ultrasound to calculate the distensibility index at baseline and 3 years later. Menopause stage was classified at each visit as premenopausal, perimenopausal, and postmenopausal. Over 3 years of prospective observation, women were classified as remaining premenopausal, remaining postmenopausal, or transitioning, defined as change from premenopausal-to-perimenopausal, premenopausal-to-postmenopausal, perimenopausal-to-perimenopausal, or perimenopausal-to-postmenopausal. Results Distensibility declined over time in all menopause stages (pmenopause transition is associated with reduced vascular compliance. Hormone therapy is associated with better arterial distensibility only during menopause transition. Additional prospective studies are needed to confirm these findings and to determine if hormone therapy use beyond menopause transition is related to distensibility. PMID:26308234

  1. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk

    DEFF Research Database (Denmark)

    Rudolph, Anja; Hein, Rebecca; Lindström, Sara

    2013-01-01

    Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...

  2. Radiation therapy alone for growth hormone-producing pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Plataniotis, G.A.; Kouvaris, J.R.; Vlahos, L.; Papavasiliou, C. [Athens Univ. (Greece). Dept. of Radiology

    1998-09-01

    We present our experience in the treatment of growth hormone (GH)-producing pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients suffering from GH-secreting pituitary adenomas were treated with radiotherapy alone. Two bilateral opposing coaxial fields were used in 10 patients and in the remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2 Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was given using a cobalt unit. Four patients treated with somatostatin prior to and 14 patients treated after the end of radiotherapy experienced symptom relief for 6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%) patients. Whereas RT alone is effective in the treatment of microadenomas, this is not true for large infiltrative macroadenomas. (orig.)

  3. Growth hormones therapy in immune response against Trypanosoma cruzi.

    Science.gov (United States)

    Frare, Eduardo Osório; Santello, Fabricia Helena; Caetano, Leony Cristina; Caldeira, Jerri C; Toldo, Míriam Paula Alonso; Prado, José Clóvis do

    2010-04-01

    Growth hormone (GH) is an important hypophyseal hormone that is primarily involved in body growth and metabolism. In mammals, control of Trypanosoma cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. To explore the possibility that GH might be effective in the treatment of Chagas' disease, we investigated its effects on the course of T. cruzi infection in rats, focusing our analyses on its influences on parasitemia, NO, TNF-alpha and IFN-gamma concentration and on histopathological alterations and parasite burden in heart tissue. T. cruzi-infected male Wistar rats were intraperitoneally treated with 5 ng/10 g body weight/day of GH. Animals treated with GH showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection compared with untreated animals (P<0.05). For all experimental days (7, 14 and 21 post infection) of the acute phase, infected and GH treated animals reached higher concentrations of TNF-alpha, IFN-gamma and nitric oxide as compared to untreated and infected counterparts (P<0.05) Histopathological observations of heart tissue revealed that GH administration also resulted in fewer and smaller amastigote burdens, and less inflammatory infiltrate and tissue disorganization, indicating a reduced parasitism of this tissue. These results show that GH can be considered as an immunomodulator substance for controlling parasite replication and combined with the current drug used may represent in the future a new therapeutic tool to reduce the harmful effects of Chagas' disease.

  4. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status : a large prospective cohort study

    NARCIS (Netherlands)

    Ritte, Rebecca; Lukanova, Annekatrin; Berrino, Franco; Dossus, Laure; Tjonneland, Anne; Olsen, Anja; Overvad, Thure Filskov; Overvad, Kim; Clavel-Chapelon, Francoise; Fournier, Agnes; Fagherazzi, Guy; Rohrmann, Sabine; Teucher, Birgit; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Ramon Quiros, Jose; Buckland, Genevieve; Sanchez, Maria-Jose; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Sund, Malin; Lenner, Per; Bueno-de-Mesquita, Bas; van Gils, Carla H.; Peeters, Petra H. M.; Krum-Hansen, Sanda; Gram, Inger Torhild; Lund, Eiliv; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E.; Key, Timothy J.; Romieu, Isabelle; Rinaldi, Sabina; Siddiq, Afshan; Cox, David; Riboli, Elio; Kaaks, Rudolf

    2012-01-01

    Introduction: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement

  5. Diagnóstico clínico e laboratorial da deficiência isolada do hormônio do crescimento em crianças e adolescentes portadores da mutação no gene do receptor do hormônio liberador do hormônio de crescimento em Itabaianinha, Sergipe Clinical and laboratorial diagnosis isolated deficiency of growth hormone in children and adolescents with mutation in receptor gene of growth hormone-releasing hormone in Itabaianinha, SE, Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Menezes

    2004-12-01

    central adiposity. CONCLUSION: The results showed that the IDGH patients from Itabaininha presented a growth hormone isolated Type IB deficiency. In addition, the lower height was not associated with pituitary alterations or other non-hormone pathologies.

  6. Ductal carcinoma In-Situ in turner syndrome patient undergoing hormone replacement therapy: A case report

    Directory of Open Access Journals (Sweden)

    Rashmi Bawa

    2016-03-01

    Full Text Available Turner’s syndrome is a rare congenital disease which affects about 1 in every 2500-3000 live-born females. This happens due to chromosomal abnormalities in a phenotypic female, causing increased gonadotropin concentrations and low concentrations of estrogens from infancy. As a result, hormone replacement therapy is started in most adolescent Turner syndrome patients to initiate and sustain sexual maturation. Accordingly, most Turner’s syndrome patients undergo several decades of estrogen replacement therapy, from puberty to post-menopausal age. The highly publicized findings of the Women’s Health Initiative have called into question the appropriateness of hormone replacement therapy in adolescents with Turner’s syndrome. Those concerns were mostly theoretical extrapolations, as few prospective studies of cancer occurrence in women with Turner syndrome have been reported. Consequently, several recent publications have challenged those extrapolations, based on the assertion that the levels of hormone replacement in Turner syndrome patients are well below the physiologic levels observed in normal menstruating women, as well as the fact that these women are significantly younger than those studied by the Women’s Health Initiative. In discord to those reports, we present a case of ductal carcinoma in-situ in a 40-year-old Turner patient, who had undergone over two decades of combined hormone replacement therapy. The patient underwent an elective excisional biopsy for a palpable mass, with histopathology revealing a complex fibroadenoma with a nidus of ductal carcinoma in-situ. The lesion was noted to be estrogen receptor positive and progesterone receptor negative, with heavy staining for HER-2/Neu receptor. The patient was treated with tamoxifen. While a rare case, it is imperative for the astute clinician to keep in mind the consequences of long-term hormone replacement therapy in Turner’s syndrome patients in order to avoid missed

  7. Psychological functioning after growth hormone therapy in adult growth hormone deficient patients: endocrine and body composition correlates

    OpenAIRE

    Lašaitė, Lina; Bunevičius, Robertas; Lašienė, Danutė Teresė; Lašas, Liudvikas

    2004-01-01

    Growth hormone replacement in adult growth hormone deficient patients improves psychological well-being and the quality of life. The aim of this study was to investigate relationship between changes in mood, cognitive functioning, quality of life, changes in body composition and hormone concentration at baseline and six months after treatment with human recombinant growth hormone. Eighteen adult patients with growth hormone deficiency syndrome were recruited to the study. Growth hormone was a...

  8. Abiraterone acetate for prostate cancer: a new era of hormonal therapies

    Institute of Scientific and Technical Information of China (English)

    Emmanuel S Antonarakis

    2011-01-01

    @@ Therapies targeting the androgen receptor (AR) axis have constituted the Holy Grail in the management of advanced prostate cancer for seven decades.1 These hormonal therapies have traditionally taken two main forms: those that suppress gonadal androgen synthesis (e.g.,the gonadotropin releasing hormone agonists/antagonists,such as leuprolide),and those that inhibit the AR directly (e.g.,the anti-androgens,such asbicalutamide).However,although the vast majority of patients with prostate cancer initially respond favorably to androgen-ablative therapies (manifested by tumor regressions and symptomatic improvements),all patients will eventually develop further disease progression after a median of 18-24 months.This transformed disease state,known as castration-resistant prostate cancer (CRPC),is invariably fatal.

  9. Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; Jensen, Rikke; Sundberg, Karin

    2014-01-01

    OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls.DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born...... SGA.SETTING: Not applicable.PATIENT(S): A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS).INTERVENTION(S): One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated).MAIN OUTCOME MEASURE...... normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed...

  10. Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women.

    Science.gov (United States)

    Kabat, Geoffrey C; Miller, Anthony B; Rohan, Thomas E

    2008-02-01

    Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk. We used data from a large cohort study of Canadian women enrolled in a randomized controlled trial of breast cancer screening to assess the association of oral contraceptive use, hormone replacement therapy and reproductive factors with risk of colorectal cancer, overall and by subsite within the colorectum. Cancer incidence and mortality were ascertained by linkage to national databases. Among 89,835 women aged 40-59 at enrollment and followed for an average of 16.4 years, we identified 1,142 incident colorectal cancer cases. Proportional hazards models were used to estimate the associations between the exposures of interest and risk of colorectal cancer. Ever use of oral contraceptives at baseline was associated with a modest reduction in the risk of colorectal cancer (hazard ratio 0.83, 95% confidence interval 0.73-0.94), with similar effects for different subsites within the colorectum. No trend was seen in the hazard ratios with increasing duration of oral contraceptive use. No associations were seen with use of hormone replacement therapy (ever use or duration of use) or reproductive factors. Our results are suggestive of an inverse association between oral contraceptive use and colorectal carcinogenesis. However, given the lack of a dose-response relationship and the potential for confounding, studies with more complete assessment of exogenous hormone use throughout the life course are needed to clarify this association. (c) 2007 Wiley-Liss, Inc.

  11. Promotion and marketing of bioidentical hormone therapy on the internet: a content analysis of websites.

    Science.gov (United States)

    Yuksel, Nese; Treseng, Laetitia; Malik, Bushra; Ogbogu, Ubaka

    2017-10-01

    To evaluate the quality of information presented and claims made on websites offering bioidentical hormone therapy (BHT) products or services. A quantitative content analysis was completed on 100 websites promoting or offering BHT products or services. Websites were identified through Google search engine from September to October 2013. Search terms included "bioidentical hormone therapy" or "bioidentical progesterone," accompanied by "purchase or buy," "service," or "doctors." The Brief DISCERN instrument was used to determine the quality of the health information. Websites were from Canada (59%), United States (38%), and other countries (3%). Almost half of the websites originated from medical clinics (47%), and healthcare professionals offering BHT services included physicians (50%), pharmacists (19%), and naturopaths (16%). Majority of websites promoted BHT as custom-compounded formulations (62%), with only 27% indicating that BHT is also commercially available. Websites overall claimed that BHT had less risk compared with conventional hormone therapy (62%). BHT was described as having less breast cancer risk (40%), whereas over a quarter of websites described BHT as "protective" for breast cancer. Websites mainly targeted women (99%), with males mentioned in 62% of websites. Product descriptors used to promote BHT included individualization (77%), natural (70%), hormone imbalance (56%), and antiaging (50%). The mean Brief DISCERN score was 15, indicating lower quality of information. Claims made about BHT on the internet are misleading and not consistent with current professional organizations' recommendations. Understanding how BHT may be promoted on the internet can help healthcare professionals when educating patients.

  12. Hormonal changes during GnRH analogue therapy in children with central precocious puberty

    DEFF Research Database (Denmark)

    Müller, J; Juul, A; Andersson, A M

    2000-01-01

    Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypoth......Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both...... the hypothalamopituitary-gonadal axis as well as on growth hormone (GH) secretion. Gonadal activity is increased in children with CPP; during GnRHa therapy secretion of gonadal hormones is suppressed as reflected by measurements of LH, FSH, and estradiol/testosterone. More recently, studies of levels of inhibin A and B...... as well as markers of androgen action such as SHBG and prostate specific antigen have demonstrated marked suppression of gonadal function possibly to infra-physiological levels. The possible long-term consequences of these observations have yet to be determined. Detailed analyses of the GH-IGF-I axis have...

  13. The Efficacy of Neoadjuvant Androgen Deprivation Therapy as a Prostate Volume Reduction before Brachytherapy for Clinically Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Miki,Kenta

    2007-12-01

    Full Text Available From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH agonist, 49 patients with anti-androgen (bicaltamide/flutamide, and 48 patients with maximum androgen blockade (MAB. The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml, and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction. The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume.

  14. Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

    Science.gov (United States)

    Baumgärtner, A K; Häusler, A; Seifert-Klauss, V; Schuster, T; Schwarz-Boeger, U; Kiechle, M

    2011-10-01

    Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (pprognosis in perimenopausal women only (TTP: HR=1.16; OS: HR=1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.

  15. Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.

    Science.gov (United States)

    Christ, Emanuel R; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

    2016-01-21

    Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

  16. Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia.

    Science.gov (United States)

    Stanosz, Staniaław; Zochowska, Ewa; Safranow, Krzysztof; Sieja, Krzysztof; Stanosz, Małgorzta

    2009-01-01

    The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 +/- 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17beta-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E(1)) was increased about 11-fold in the group of women receiving orally given HST (P hormone was

  17. Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

    Directory of Open Access Journals (Sweden)

    Nathan W Kopper

    2008-10-01

    Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

  18. Impacto da terapia hormonal sobre o peso corpóreo Impact of hormone replacement therapy on body weight

    Directory of Open Access Journals (Sweden)

    Joana Palmira Martins Almeida

    2011-10-01

    Full Text Available OBJETIVO: avaliar o efeito da terapêutica hormonal (TH no peso de mulheres na peri-menopausa, assim como o efeito de diferentes regimes terapêuticos no referido parâmetro. MÉTODOS: estudo retrospectivo de 139 mulheres, com menopausa há menos de 2 anos, acompanhadas na consulta de climatério do nosso departamento. Obtiveram-se dois grupos: mulheres a quem se iniciou TH (n=89 e outro, grupo controle, sem terapia hormonal (n=50. Em cada grupo, foi avaliada a modificação ponderal no intervalo de 1 ano após a primeira consulta. Nas submetidas a TH, avaliou-se esse mesmo parâmetro em função de diferentes regimes terapêuticos preconizados: estrogênio isolado vs estroprogestagênio e dose standard vs baixa dosagem. A análise estatística foi realizada com recurso ao programa SPSS®, adotando-se como nível de significância valores pPURPOSE: to evaluate the effect of hormone replacement therapy (HT on the weight on perimenopausal women as well as the effect of different treatment regimens on this parameter. METHODS: a retrospective study of 139 women with menopause for less than 2 years, who were monitored with periodical visits in our department. We compared two groups: women who started HT (n=89 with women who had no hormonal treatment (n=50 and in the two groups, we evaluated the changes in body weight over a 1-year period. In the first group, we assessed the same parameter as a function of different treatment regimens: estrogen alone versus estrogen combined with progestin and standard dose versus low dose. The SPSS® program was used for statistical analysis, with the level of significance set at p<0.05. RESULTS: the groups were similar with respect to demographic and baseline characteristics; weight gain was higher in the untreated group (434 vs 76 g, but the difference observed was not significant (p = 0.406; among HT users, those taking estrogen alone had an increased weight gain compared to women taking estrogen with progestin

  19. Phytoestrogens as alternative hormone replacement therapy in menopause: What is real, what is unknown.

    Science.gov (United States)

    Moreira, Ana C; Silva, Ana M; Santos, Maria S; Sardão, Vilma A

    2014-09-01

    Menopause is characterized by an altered hormonal status and by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, with increasing life span, women spend one-third of their lifetime under menopause. Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important topic in the clinic. This review describes physiological and hormone alterations observed during menopause and therapeutic strategies used during this period. We critically address the benefits and doubts associated with estrogen/progesterone-based hormone replacement therapy (HRT) and discuss the use of phytoestrogens (PEs) as a possible alternative. These relevant plant-derived compounds have structural similarities to estradiol, interacting with cell proteins and organelles, presenting several advantages and disadvantages versus traditional HRT in the context of menopause. However, a better assessment of PEs safety/efficacy would warrant a possible widespread clinical use.

  20. Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

    Directory of Open Access Journals (Sweden)

    Alun L Edwards

    1996-01-01

    Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

  1. Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles.

    Directory of Open Access Journals (Sweden)

    Adriane Fugh-Berman

    2011-03-01

    Full Text Available BACKGROUND: Even after the Women's Health Initiative (WHI found that the risks of menopausal hormone therapy (hormone therapy outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. METHODS AND FINDINGS: We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1 Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2 acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement

  2. Hepatic adenomatosis associated with hormone replacement therapy and hemosiderosis: A case report

    Institute of Scientific and Technical Information of China (English)

    Satoshi Hagiwara; Hiroyuki Kuwano; Masatomo Mori; Hitoshi Takagi; Daisuke Kanda; Naondo Sohara; Satoru Kakizaki; Kenji Katakai; Teruo Yoshinaga; Tsugio Higuchi; Kenichi Nomoto

    2006-01-01

    We have reported a case of hepatic adenomatosis associated with hormone replacement therapy (estrogen and progesterone) and hemosiderosis caused by excessive blood transfusion for the treatment of chronic myeloid leukemia. A 34-year-old woman was found to have several hepatic tumors on a routine medical examination. The general condition was good.Laboratory studies showed iron overload. Abdominal computed tomography and selective hepatic angiography showed several hypervascular tumors in the right lobe of the liver (up to 20 mm in diameter). Since hepatocellular carcinoma could not be ruled out, subsegmental hepatectomy was performed. Histopathological examination of the surgical specimen showed hepatic adenomatosis with hemosiderosis. Both hormone replacement therapy and iron overload could be the cause of hepatic adenomatosis.

  3. Use and discontinuation of hormone replacement therapy in women with myocardial infarction: a nationwide study

    DEFF Research Database (Denmark)

    Bretler, Ditte-Marie; Hansen, P. R.; Abildstrom, S. Z.

    2011-01-01

    center dot General use of hormone replacement therapy (HRT) dropped drastically after 2002 when pivotal randomized trials showed increased risk of coronary artery disease and other complications with HRT. center dot HRT is not recommended for primary or secondary prevention of coronary heart...... disease and guidelines recommend discontinuation of HRT after myocardial infarction (MI). center dot It is unknown whether women actually discontinue HRT after MI. WHAT THIS STUDY ADDS center dot Women who use HRT when they experience their MI generally continue using HRT. center dot We found a remarkably...... low increase in discontinuation after 2002, in contrast to the general drop in use of HRT. AIM To characterize the pattern of use and discontinuation of postmenopausal hormone replacement therapy (HRT) in women with myocardial infarction (MI) before and after 2002, where the general use of HRT dropped...

  4. How Should Physicians Help Gender-Transitioning Adolescents Consider Potential Iatrogenic Harms of Hormone Therapy?

    Science.gov (United States)

    Steensma, Thomas D; Wensing-Kruger, S Annelijn; Klink, Daniel T

    2017-08-01

    Counseling and treatment of transgender youth can be challenging for mental health practitioners, as increased availability of gender-affirming treatments in recent years raises ethical and clinical questions. Is a gender identity diagnosis helpful? What is the right time to treat, and should the adolescent's age matter in decision making? In this article, we discuss these questions in light of a case in which an adolescent wishes to pursue hormone therapy. Our analysis focuses on the importance of balanced decision making when counseling and treating adolescents with nonconforming gender identities. We argue that clinicians' communicating appropriate expectations about the effectiveness and limitations of hormone therapy and the risks of psychological and physical iatrogenic effects is critical. © 2017 American Medical Association. All Rights Reserved.

  5. Development of a growth-hormone-conjugated nanodiamond complex for cancer therapy.

    Science.gov (United States)

    Chu, Hsueh-Liang; Chen, Hung-Wei; Tseng, Shin-Hua; Hsu, Ming-Hua; Ho, Li-Ping; Chou, Fu-Hsuan; Li, Md Phd Hsing-Yuan; Chang, Yu-Chuan; Chen, Pei-Hsin; Tsai, Li-Yun; Chou, Ching-Chung; Chen, Jyh Shin; Cheng, Tsai-Mu; Chang, Chia-Ching

    2014-05-01

    It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.

  6. Effect of electroconvulsive therapy without anticonvulsive premedication on serum growth hormone in man.

    Science.gov (United States)

    Vigas, M; Stowasserová, N; Németh, S; Jurcovicová, J

    1975-01-01

    Serum concentrations of human growth hormone (HGH) were measured in psychiatric patients during the first, third and sixth electroconvulsive therapy (ECT) without anticonvulsive premedication. Serum HGH increased 30 min after the application of current and no differences were found between responses to 1st, 3rd, or 6th ECT. Maximal increase of serum glucose was seen after the first ECT and gradual decreases after the 3rd and 6th ECT were observed

  7. Impact of recent studies on attitudes and use of hormone therapy among Scandinavian gynaecologists

    DEFF Research Database (Denmark)

    Pedersen, Anette Tønnes; Iversen, Ole-Erik; Løkkegaard, Ellen

    2007-01-01

    Climacteric medicine has been in focus during the last 2 decades, and an intensive debate has been ongoing regarding the positive and negative aspects of postmenopausal hormone therapy (HT). Recent randomised controlled studies have been unable to confirm data from observational studies of primar...... of the present study was to re-assess the same parameters concerning HT among Scandinavian gynaecologists in 2002-2003, and compare the results with the data collected in 1995-1997....

  8. The Miracle Drug : Hormone Replacement Therapy and Labor Market Behavior of Middle-Aged Women

    OpenAIRE

    Meltem Daysal, N.; Orsini, C.

    2012-01-01

    Abstract: In an aging society, determining which factors contribute to the employment of older individuals is increasingly important. This paper sheds light on the impact of medical innovation in the form of Hormone Replacement Therapy (HRT) on employment of middle-aged women. HRT are drugs taken by middle-aged women to soften symptoms related to menopause. Before 2002, HRT products were among the most popular prescription drugs in America. We use the timing of the release of information of t...

  9. Natural products and no-hormone therapy for the treatment of vasomotor symptoms affecting menopause women

    Directory of Open Access Journals (Sweden)

    Jaime Urdinola

    2005-08-01

    Full Text Available Among menopausal women receiving hormone therapy, whether combinedor with estrogens alone, there has always been a great worryabout the side effects or the potential development of cancer.This is especially true among women that have survived breastcancer, in the event the disease may reoccur. However there arealternatives for women not willing to take these standard therapiesfor their estrogen deficiency. This revision presents the up-to-dateevidence about the efficiency and safety of these compounds usedto treat this problem.

  10. Vaginal estrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy.

    Science.gov (United States)

    Sulaica, Elisabeth; Han, Tiffany; Wang, Weiqun; Bhat, Raksha; Trivedi, Meghana V; Niravath, Polly

    2016-06-01

    Atrophic vaginitis represents a major barrier to compliance with aromatase inhibitor (AI) therapy in breast cancer (BC) survivors. While local estrogen therapy is effective for postmenopausal vaginal dryness, the efficacy of such therapies has not been evaluated systematically in hormone receptor-positive (HR+) BC patients on AI therapy. Furthermore, the potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for the patients with HR + BC. Unfortunately, there is no standardized assay to measure very low concentrations of estradiol (E2) in these women being treated with AI therapy. This makes it difficult to evaluate even indirectly the potential risk of BC recurrence with vaginal estrogen therapy in HR + BC patients on AI therapy. In this review, we describe available assays to measure very low concentrations of E2, discuss the Food and Drug Administration-approved vaginal estrogen products on the market, and summarize published and ongoing clinical trials evaluating the safety and efficacy of vaginal estrogen in HR + BC patients on AI therapy. In the absence of any randomized controlled clinical trials, this review serves as a summary of available clinical data and ongoing studies to aid clinicians in selecting the best available option for their patients.

  11. Growth hormone inhibition causes increased selenium levels in Duchenne muscular dystrophy: a possible new approach to therapy.

    Science.gov (United States)

    Collipp, P J; Kelemen, J; Chen, S Y; Castro-Magana, M; Angulo, M; Derenoncourt, A

    1984-08-01

    Nine children with Duchenne muscular dystrophy were given Sanorex (mazindol), a growth hormone inhibitor, daily for 6 months. There was no significant change in their muscle function, but there was a significant reduction in weight gain and in levels of growth hormone, somatomedin C, hair zinc, serum zinc, and serum LDH. Selenium and glutathione peroxidase in the serum increased significantly. Thirteen other children with growth hormone deficiency had a significant reduction in hair selenium following growth hormone administration. These results show a significant relationship between growth hormone and selenium nutritional status and confirm our previous reports indicating an effect of growth hormone on zinc nutritional status. It is possible that prolonged therapy with a growth hormone inhibitor would attenuate the course and improve the longevity of patients with muscular dystrophy.

  12. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study.

    Science.gov (United States)

    Ruiz, Andres D; Daniels, Kelly R

    2014-01-01

    Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy; however, clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking. The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor, mood, and other quality-of-life symptoms in post-menopausal women. This was a prospective, observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1, 2003 and October 1, 2010 in a community pharmacy. Data collection included patient demographics, comorbidities, hormone regimens, and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of-life symptoms as absent, mild, moderate, or severe at baseline, at one to three months follow-up, and three to six months follow-up. Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test. A total of 200 patients met study criteria; 160 received topical bioidentical hormone replacement therapy, and 40 received sublingual bioidentical hormone replacement therapy. Most sublingually-treated patients (70%) received an estrogen combination and 100% received progesterone. Nearly half (43%) of the topically treated patients received an estrogen combination (43%) and 99% received progesterone. The percentage of sublingually treated patients reporting "moderate" or "severe" symptoms was significantly reduced at one to three months follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night sweats (38%, P sublingual bioidentical hormone

  13. [Hormone replacement therapy among Norwegian women. Self-reported use and sales of estrogen preparations].

    Science.gov (United States)

    Søgaard, A J; Fønnebø, V; Magnus, J H; Tollan, A

    1998-02-10

    In order to analyse the use of hormone replacement therapy (HRT) and the predicting factors for its use, two random samples of Norwegian women (30-79 years) were interviewed by the Central Bureau of Statistics in 1994 (n = 565) and in 1996 (n = 470). The extent of use of HRT was compared with statistics for sales of oestrogen in Norway and the Nordic countries. In the age group 45-69 years the use of hormone replacement therapy increased from 16.3% in 1994 to 19.1% in 1996. The proportion of users did not increase with a higher level of education. In addition to information received, and after adjusting for other variables, attitudes towards oestrogen and knowledge about it were the most important contributing factors for using HRT. Sales figures show that the use of systemic oestrogen in Norway has increased more than 280% since 1990. None of the Nordic countries have had a corresponding increase, but the Norwegian figures are still low compared to most other Nordic countries. In 1996 14.5% of Norwegian women (50-79 years) used oestrogen for urogenital disorders. Norwegian women need to be better informed and more knowledgeable to enable them to make conscious choice regarding use of hormone replacement therapy.

  14. Second-line hormonal therapy with the enzalutamid in patients with castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2016-01-01

    Full Text Available Prostate cancer (PC is an actual problem of modern oncourology due to the continuing high rates of this disease morbidity and mortality. Despite improvements in diagnostic techniques, incidence of common forms of the disease remain to be high. Metastatic castrate-resistant prostate cancer (mCRPC is a disease with an extremely poor prognosis, in which standard methods of hormonal treatment are ineffective. Heterogeneity of CRPC patient population requires differentiated approach to the administration of therapy based on the availability of various prognostic factors. Not so long ago chemotherapy with docetaxel was the main treatment for this group of patients. Second-line hormonal therapy was introduced into clinical practice in 2011 with the advent of new drugs aimed at the complete suppression of testosterone production. Enzalutamid, a new drug for second-line hormonal therapy, has essentially different mechanism of action. It is able to block androgen receptors selectively and disrupt translocation of the signal from the receptor into the cell and into the cell nucleus. Large randomized trials that studied the effectiveness of this drug allowed to register it for clinical use, including our country. An article presents a review of the literature on clinical trials devoted to the use of a drug in CRPC patients. 

  15. The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

    Science.gov (United States)

    Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

    2001-01-01

    Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

  16. Effects of growth hormone deficiency and recombinant growth hormone therapy on postprandial gallbladder motility and cholecystokinin release.

    NARCIS (Netherlands)

    Moschetta, A.; Twickler, M.; Rehfeld, J.F.; Ooteghem, N.A. van; Castro Cabezas, M.; Portincasa, P.; Berge-Henegouwen, G.P. van; Erpecum, K.J. van

    2004-01-01

    In addition to cholecystokinin, other hormones have been suggested to be involved in regulation of postprandial gallbladder contraction. We aimed to evaluate effects of growth hormone (GH) on gallbladder contractility and cholecystokinin release. Gallbladder and gastric emptying (by ultrasound) and

  17. Effect of dietary macronutrients on postprandial incretin hormone release and satiety in obese and normal-weight women.

    Science.gov (United States)

    Wikarek, Tomasz; Chudek, Jerzy; Owczarek, Aleksander; Olszanecka-Glinianowicz, Magdalena

    2014-01-28

    The aim of the present study was to assess the effect of dietary macronutrients on postprandial incretin responses and satiety and hunger sensation in obese and normal-weight women. A total of eleven obese and nine normal-weight women were recruited for the assessment of plasma concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and insulin and the sensation of satiety and hunger using a visual analogue scale before and during a 6 h period after administration of three different macronutrient test meals. The AUCtotal GLP-1 and AUCtotal GIP values were decreased in obese women after the consumption of a fatty meal and all the test meals, respectively. However, the AUCtotal insulin value after a carbohydrate meal was greater in the obese group. The AUCtotal satiety value was decreased only after the intake of the protein meal in obese women when compared with normal-weight women. After the consumption of the fatty meal, a significant positive correlation between maximum satiety sensation and the AUCtotal GLP-1 value in the obese group and that between minimum hunger sensation and the AUCtotal GLP-1 value in the normal-weight group were observed. In conclusion, the findings of the present study suggest that: (1) satiety sensation after consumption of carbohydrate and protein meals in the obese group is related to the postprandial insulin response, while after consumption of a fatty meal, it is related to the postprandial GLP-1 release; (2) the postprandial GIP response does not influence the sensation of satiety and hunger; (3) the reduced GLP-1 release after the intake of a fatty meal in obese individuals may explain impaired satiety sensation; (4) the impaired postprandial GIP response is not related to the consumption of macronutrients and may be the early indicator of incretin axis dysfunction in obese women.

  18. Effects of guar gum and cellulose on glucose absorption, hormonal release and hepatic metabolism in the pig

    Science.gov (United States)

    Nunes, C. S.; Malmlof, K.

    1992-01-01

    Six Large White pigs (mean body-weight 59 (SE 1.7) kg) were surgically fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein, as well as with electromagnetic flow probes around the portal vein and the hepatic artery, and allowed to recover. The non-anaesthetized animals were given a basal non-fibre diet (diet A) alone or together with 60 g guar gum/kg (diet B) or 150 g purified cellulose/kg (diet C) by substitution for mica. The diets were given for weekly periods and according to a replicated 3 x 3 Latin square design. On the last day of each such adaptation period, test meals of 800 g were given before blood sampling. Sampling was continued for 8 h. Guar gum strongly reduced glucose apparent absorption without changing the absorption and the hepatic uptake profiles. Production rates of insulin, gastric inhibitory polypeptide and insulin-like growth factor-1 (IGF-1) were lowest after guar gum ingestion. However, the reductions in peripheral blood insulin levels caused by guar gum were not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly secreted by the gut, whereas the liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut-produced IGF-1. Guar gum ingestion appeared also to decrease glucagon secretion. Cellulose at the level consumed had very few effects on the variables considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the metabolic effects described.

  19. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice

    DEFF Research Database (Denmark)

    Gunnarsson, P Thomas; Winzell, Maria Sörhede; Deacon, Carolyn F

    2006-01-01

    -1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P

  20. ATP-modulated K+ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release

    OpenAIRE

    Bernardi, H; de Weille, J.R.; Epelbaum, J; Mourre, C; Amoroso, S.; Slama, A; Fosset, M; Lazdunski, M

    1993-01-01

    The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+ channels. The binding protein has a M(r) of 145,000 +/- 5000. The presence of ATP-sensitive K+ channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+ channels induces a large hyperpolarization (approximately 30 mV) that is antagonized by an...

  1. A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor.

    Science.gov (United States)

    Asa, S L; Scheithauer, B W; Bilbao, J M; Horvath, E; Ryan, N; Kovacs, K; Randall, R V; Laws, E R; Singer, W; Linfoot, J A

    1984-05-01

    We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.

  2. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy

    NARCIS (Netherlands)

    J.B. Madalinska; M. van Beurden; E.M.A. Bleiker; H.B. Valdimarsdottir; J. Hollenstein; L.F. Massuger; K.N. Gaarenstroom; M.J.E. Mourits; R.H.M. Verheijen; E.B.L. van Dorst; H. van der Putten; K. van der Velden; H. Boonstra; N.K. Aaronson

    2006-01-01

    Purpose Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined t

  3. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.

    NARCIS (Netherlands)

    Madalinska, J.B.; Beurden, M. van; Bleiker, E.M.A.; Valdimarsdottir, H.B.; Hollenstein, J.; Massuger, L.F.A.G.; Gaarenstroom, K.N.; Mourits, M.J.E.; Verheijen, R.H.; Dorst, E.B.L. van; Putten, H. van der; Velden, K. van der; Boonstra, H.; Aaronson, N.K.

    2006-01-01

    PURPOSE: Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined

  4. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.

    NARCIS (Netherlands)

    Madalinska, J.B.; Beurden, M. van; Bleiker, E.M.A.; Valdimarsdottir, H.B.; Hollenstein, J.; Massuger, L.F.A.G.; Gaarenstroom, K.N.; Mourits, M.J.E.; Verheijen, R.H.; Dorst, E.B.L. van; Putten, H. van der; Velden, K. van der; Boonstra, H.; Aaronson, N.K.

    2006-01-01

    PURPOSE: Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined

  5. Acromegaly caused by a growth hormonereleasing hormone secreting carcinoid tumour of the lung : the effect of octreotide treatment

    NARCIS (Netherlands)

    De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.

    2007-01-01

    in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the

  6. Acromegaly caused by a growth hormonereleasing hormone secreting carcinoid tumour of the lung : the effect of octreotide treatment

    NARCIS (Netherlands)

    De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.

    2007-01-01

    in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the lun

  7. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy

    DEFF Research Database (Denmark)

    Würtz, Anne Mette Lund; Tjønneland, Anne; Christensen, Jane Hvarregaard;

    2012-01-01

    Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT.......Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT....

  9. Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

    Science.gov (United States)

    Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

    2013-11-01

    Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

  10. Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure.

    Science.gov (United States)

    Krul, Inge M; Opstal-van Winden, Annemieke W J; Aleman, Berthe M P; Janus, Cécile P M; van Eggermond, Anna M; De Bruin, Marie L; Hauptmann, Michael; Krol, Augustinus D G; Schaapveld, Michael; Broeks, Annegien; Kooijman, Karen R; Fase, Sandra; Lybeert, Marnix L; Zijlstra, Josée M; van der Maazen, Richard W M; Kesminiene, Ausrele; Diallo, Ibrahima; de Vathaire, Florent; Russell, Nicola S; van Leeuwen, Flora E

    2017-07-18

    Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction: .06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: a case of localised urticarial vasculitis following anastrozole therapy and a review of the literature.

    Science.gov (United States)

    Bock, Vanessa L; Friedlander, Michael; Waring, Dale; Kossard, Steven; Wood, Glenda K

    2014-11-01

    Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer.

  12. An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

    Science.gov (United States)

    2008-10-01

    hormone therapy in breast cancer risk.” Kerryn W. Reding, Chu Chen, Christopher I. Li, Christopher S. Carlson, Jasmine Wilkerson, Frederico M...therapy in breast cancer risk.” Kerryn W. Reding, Chu Chen, Christopher I. Li, Christopher S. Carlson, Jasmine Wilkerson, Frederico M. Farin, Kenneth E...Chen, Christopher I. Li, Christopher S. Carlson, Jasmine Wilkerson, Frederico M. Farin, Kenneth E. Thummel, Janet R. Daling, and Kathleen E. Malone

  13. Hormone replacement therapy and menopause%绝经期激素替代疗法

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    SUMMARY Hormone replacement therapy (HRT) was initiated almost half a century ago to treat menopausal symptoms. Initially, its use remained limited even among symptomatic women and the move toward postmenopausal hormone use for disease prevention came later. Improved treatment schedules and delivery systems expanded the use of HRT worldwide. However, large trials of postmenopausal hormones with disease outcomes were even later in coming and today HRT has become a specialized, multidisciplinary area of research. As the population continues to grow older, there has been an increased focus on the effects of ageing. HRT may affect length and quality of life through disease prevention. It may have possible beneficial effects on cognition, on the incidence of hip fracture, myocardial infarction and stroke, and adverse effects on the incidence of breast cancer, endometrial cancer, and venous thromboembolism.Today's attitudes about the hormonal treatments for the menopausal transition have moved from expansive optimism to contracting disappointment amidst safety concerns and equivocal results and faces greater skepticism and scrutiny. The health and well being of large numbers of women are at stake, and researchers, clinicians and the general public are watching and weighing the options.

  14. The role of hormone replacement therapy in the intensive care management of deceased organ donors: a primer for nurses.

    Science.gov (United States)

    Smetana, Keaton S; Kimmons, Lauren A; Jones, G Morgan

    2015-01-01

    Donation after brain death remains the primary contributor to the supply of organs available for transplantation in the United States. After brain death, both a surge of catecholamines and a dysregulation of the neurohormonal axis may result in hypotension, decreased organ perfusion, and reduced viability of organs to be transplanted. Hormone replacement therapy is widely used to maintain organ perfusion and has been shown to increase the number of organs procured. This article reviews the literature and mechanisms supporting the use of hormone replacement therapy in brain-dead organ donors and provides clinicians with information regarding the administration, monitoring, and preparation of thyroid hormone, arginine vasopressin, and corticosteroids.

  15. Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine.

    Science.gov (United States)

    Rigamonti, A E; Marazzi, N; Cella, S G; Cattaneo, L; Müller, E E

    1998-02-01

    Using unanesthetized young male and female beagle dogs, before and after a 2-day fast, we studied the effect of an i.v. infusion of 0.9% saline (5 ml/h), somatostatin (SS, 4 or 8 micrograms/kg/h), or pretreatment with pirenzepine (PZ, 0.6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS, on the GH release evoked by acute administration of GHRH (2 micrograms/kg i.v.), hexarelin (HEXA), a member of the GH-releasing peptide family (250 micrograms/kg i.v.) or GHRH plus HEXA. In fasted dogs, GHRH delivered during saline infusion induced a clear-cut rise in plasma GH levels, significantly higher than that which it induced in fed dogs. In contrast, HEXA, although very effective in causing the release of GH, only slightly increased GH secretion in fasted dogs over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into fed dogs induced a synergic GH response that further increased with fasting. The action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at either dose was ineffective in suppressing the GH-releasing effect during fasting. Infusion of the lower dose of SS failed to counter the action of HEXA, either before or during fasting, whilst the higher SS dose partially reduced it in both conditions. In contrast to SS, PZ reduced the GH-releasing effect of GHRH and HEXA, both in the fed state and, though to a lesser extent, during fasting. Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA in fed dogs. The suppressive effect of PZ on the GH response to combined administration of the peptides was lowest in fasted dogs. These data show that: (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA; (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted state; (3) only the higher dose of SS partially reduced the GH stimulation by HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5) PZ did not modify the GH release due to the combined administration of GHRH and HEXA. It is suggested that: (1) during fasting the greatly enhanced GH response to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion; (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion in states of calorie deprivation; (3) in contrast to a general belief, muscarinic cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but probably also through inhibition of GHRH function.

  16. Peak Growth Hormone-Releasing Hormone-Arginine-Stimulated Growth Hormone Is Inversely Associated with Intramyocellular and Intrahepatic Lipid Content in Premenopausal Women with Obesity

    OpenAIRE

    Bredella, Miriam A.; Torriani, Martin; Thomas, Bijoy J.; Ghomi, Reza Hosseini; Brick, Danielle J.; Gerweck, Anu V.; Miller, Karen K

    2009-01-01

    Context: Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity.

  17. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial

    Directory of Open Access Journals (Sweden)

    Veerus Piret

    2012-04-01

    Full Text Available Abstract Background For postmenopausal women, the main reason to start hormone therapy (HT is to reduce menopausal symptoms and to improve quality of life (QOL. The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a randomised trial. A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy (EPHT trial in 1999–2001. Women were randomised to blind HT, open-label HT, placebo or non-treatment arm. After one year in the trial, a questionnaire was mailed and 1359 women (75% responded, 686 in the HT arms and 673 in the non-HT arms. Mean age at filling in the questionnaire was 59.8 years. The questionnaire included Women's Health Questionnaire (WHQ to assess menopause specific QOL of middle-aged women together with a 17-item questionnaire on symptoms related to menopause, a question about painful intercourse, and a question about women's self-rated health. Results After one year in the trial, fewer women in the HT arms reported hot flashes, trouble sleeping, and sweating on the symptom questionnaire. According to WHQ, women in the HT arms had fewer vasomotor symptoms, sleep problems, and problems with sexual behaviour, but more menstrual symptoms; HT had no effect on depression, somatic symptoms, memory, attractiveness, or anxiety. A smaller proportion of women reported painful intercourse in the HT arms. There were no significant differences between the trial arms in women’s self-rated subjective health. Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms, other than vasomotor symptoms, among postmenopausal women. WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women.

  18. Progressive pituitary hormone deficiency following radiation therapy in adults; Deficiencia progressiva dos hormonios adeno-hipofisarios apos radioterapia em adultos

    Energy Technology Data Exchange (ETDEWEB)

    Loureiro, Rafaela A.; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia]. E-mail: rafaela_loureiro@hotmail.com

    2004-10-01

    Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

  19. What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

    Directory of Open Access Journals (Sweden)

    Eli Marcelo Lakryc

    2015-02-01

    Full Text Available OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol, Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate and Group C received a placebo (control. The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels.

  20. Prostate cancer: what are the news in hormonal therapy? The role of GnRH antagonists.

    Science.gov (United States)

    Zattoni, Filiberto

    2012-09-01

    The latest EAU guidelines on the evidence based-management of prostate cancer (P.Ca.), with regard to pharmacological androgen deprivation therapy (ADT), reiterate that the primary objective of hormonal therapy is to slow down the progression of the disease to the greatest possible extent. Degarelix a new product for the treatment of hormone-dependent P.Ca. has recently become available in Italy. This product is classified as a GnRH antagonist and provides safe and effective ADT. It completely blocks the synthesis and release of gonadotropins (LH and FSH), thus rapidly reducing the testosterone levels without causing clinical flare. The results of the clinical trials (36 months) demonstrate that degarelix, compared to high-dose leuprorelin (7.5 mg), suppresses levels of testosterone and PSA (Prostate-Specific Antigen) more rapidly and reduces levels of FSH and musculoskeletal events associated with treatment (pain, muscle weakness, spasms, oedema/joint stiffness, arthralgia, osteoporosis and osteopoenia) to a greater extent. In addition, these results demonstrate a significant increase in the probability of PSA progression-free survival, suggesting a possible delay in the onset of the "castration-resistant" stage. The information available to date supports the use of this new molecule as a valid alternative to GnRH agonists in the treatment of hormone-sensitive P.Ca.

  1. Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

    Science.gov (United States)

    Espeland, Mark A; Rapp, Stephen R; Manson, JoAnn E; Goveas, Joseph S; Shumaker, Sally A; Hayden, Kathleen M; Weitlauf, Julie C; Gaussoin, Sarah A; Baker, Laura D; Padula, Claudia B; Hou, Lifang; Resnick, Susan M

    2017-06-01

    Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age. Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos. Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase. CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years.

  2. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  3. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic;

    2004-01-01

    The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...... of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2...

  4. Managing the menopause - British Menopause Society Council consensus statement on hormone replacement therapy.

    Science.gov (United States)

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Stevenson, John; Williamson, Jennifer

    2003-09-01

    The British Menopause Society Council aims to aid health professionals to inform and advise women about the menopause. The oestrogen plus progestogen arm of the Women's Health Initiative was stopped in July 2002. This guidance regarding hormone replacement therapy (HRT) use responds to the results and analysis that have been published since then. Because there are few effective alternatives to HRT for vasomotor and urogenital symptoms, oestrogen-based treatments still have a major role. HRT is also most effective for prevention of osteoporosis. Unopposed oestrogens are contraindicated in women with an intact uterus, and hence a range of oestrogen and progestogen combinations, with differing routes of delivery, now exists under the title of "HRT". Treatment choice should be based on up to date information and targeted to individual women's needs. Hormone replacement still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  5. An evidence-based approach to hormonal therapies for premenopausal women with fibroids.

    Science.gov (United States)

    Lethaby, Anne E; Vollenhoven, Beverley J

    2008-04-01

    Ovarian steroids, particularly oestrogen, are important factors for fibroid growth. This has provided a rationale for the investigation of hormonal therapies for women with fibroids. This chapter will assess the role of hormonal therapies for pre-menopausal women with fibroids. A comprehensive search of MEDLINE and EMBASE was undertaken in December 2006. Twenty-nine relevant randomized controlled trials and two systematic reviews were found. The included studies assessed gonadotrophin-releasing hormone analogues (GnRHa) alone, GnRHa plus add-back (with either progestagen, tibolone, combined oestrogen and progestagen, or raloxifene) and GnRHa given for at least 3 months prior to surgery for fibroids. Two trials assessed the effects of raloxifene alone. One trial assessed the effects of low-dose mifepristone, and a pilot study assessed the role of the selective progesterone receptor modulator, asoprisinil. GnRHa reduce fibroid and uterine volume and heavy bleeding but are associated with menopausal symptoms and bone loss, which limit long-term use. There is some evidence that add-back therapy, either progestagen, tibolone, combined oestrogen and progestagen, or raloxifene, can reduce the menopausal symptoms associated with GnRHa and/or loss of bone density, but there is insufficient good-quality research to make definitive conclusions. GnRHa given for at least 3 months before fibroid surgery improve pre-operative haemoglobin concentration and haematocrit, reduce uterine and pelvic symptoms, and reduce the rate of vertical incisions during laparotomy. Women undergoing hysterectomy are more likely to have a vaginal than an abdominal procedure. Limited evidence suggests that raloxifene may be useful in older premenopausal women with lower concentrations of background oestradiol. Limited short-term evidence of two progestogenic therapies indicates that low-dose mifepristone may improve quality of life and bleeding in the short term, and asoprisinil may improve bleeding

  6. Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review.

    Science.gov (United States)

    Streed, Carl G; Harfouch, Omar; Marvel, Francoise; Blumenthal, Roger S; Martin, Seth S; Mukherjee, Monica

    2017-08-15

    Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.

  7. Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

    Science.gov (United States)

    Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

    2016-11-01

    To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

    Directory of Open Access Journals (Sweden)

    Piotr Milecki

    2010-10-01

    Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

  9. A Mathematical Model of Prostate Tumor Growth Under Hormone Therapy with Mutation Inhibitor

    Science.gov (United States)

    Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

    2010-04-01

    This paper extends Jackson’s model describing the growth of a prostate tumor with hormone therapy to a new one with hypothetical mutation inhibitors. The new model not only considers the mutation by which androgen-dependent (AD) tumor cells mutate into androgen-independent (AI) ones but also introduces inhibition which is assumed to change the mutation rate. The tumor consists of two types of cells (AD and AI) whose proliferation and apoptosis rates are functions of androgen concentration. The mathematical model represents a free-boundary problem for a nonlinear system of parabolic equations, which describe the evolution of the populations of the above two types of tumor cells. The tumor surface is a free boundary, whose velocity is equal to the cell’s velocity there. Global existence and uniqueness of solutions of this model is proved. Furthermore, explicit formulae of tumor volume at any time t are found in androgen-deprived environment under the assumption of radial symmetry, and therefore the dynamics of tumor growth under androgen-deprived therapy could be predicted by these formulae. Qualitative analysis and numerical simulation show that controlling the mutation may improve the effect of hormone therapy or delay a tumor relapse.

  10. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art.

    Science.gov (United States)

    Milecki, Piotr; Martenka, Piotr; Antczak, Andrzej; Kwias, Zbigniew

    2010-10-11

    Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT-EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

  11. Effects of substitution and high-dose thyroid hormone therapy on deiodination, sulfoconjugation, and tissue thyroid hormone levels in prolonged critically ill rabbits.

    Science.gov (United States)

    Debaveye, Yves; Ellger, Björn; Mebis, Liese; Visser, Theo J; Darras, Veerle M; Van den Berghe, Greet

    2008-08-01

    To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3'-diiodothyronine (T(2)) and T(4)S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T(4) and T(3), either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T(3) (P=0.006), hepatic T(3) (P=0.02), and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T(4) (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T(3) and tissue T(3)/reverse T(3) ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T(2). Plasma T(4)S was increased only by T(4) in high dose. We conclude that in prolonged critically ill rabbits, low plasma T(3) levels were associated with low liver and kidney T(3) levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation.

  12. Behavioral Interventions to Enhance Adherence to Hormone Therapy in Breast Cancer Survivors: A Systematic Literature Review.

    Science.gov (United States)

    Hurtado-de-Mendoza, Alejandra; Cabling, Mark L; Lobo, Tania; Dash, Chiranjeev; Sheppard, Vanessa B

    2016-08-01

    Adjuvant hormone therapy contributes to reductions in recurrence and mortality for women with hormone receptor-positive breast cancer. However, adherence to hormone therapy is suboptimal. This is the first systematic literature review examining interventions aimed at improving hormone therapy adherence. Researchers followed the PRISMA guidelines. PubMed-Medline, CINAHL, PsychInfo, Ovid-Medline, and EMBASE were searched for behavioral interventions that aimed to enhance adherence to adjuvant hormone therapy in breast cancer survivors. A total of 376 articles were screened for eligibility. Five articles met the study criteria. All interventions presented adherence outcomes after 1-year follow-up. None significantly enhanced adherence compared to the usual care in the primary analysis (odds ratios ranged from 1.03 to 2.06 for adherence and from 1.11 to 1.18 for persistence). All studies targeted patients, and only 3 studies included postmenopausal breast cancer patients. Three tested the same intervention consisting of educational materials. Only one was conducted in the United States. Only one reported participants' ethnicity. Overall, it was unclear whether the studies contained bias. The use of different terminology and operationalization of adherence made comparisons challenging. Interventions to improve adherence to adjuvant hormone therapy in US breast cancer populations that include survivors who are ethnically diverse, premenopausal, and receiving tamoxifen therapy are necessary to inform future interventions. Adoption of consistent adherence definitions/measurements will provide a clearer framework to consolidate aggregate findings. Given the limited efficacy of tested interventions, it is important to engage oncologists and researchers to develop approaches that target different components associated with hormone therapy adherence, such as doctor-patient communication or social support. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The relationship between breast density and bone mineral density in never users of postmenopausal hormone therapy.

    Science.gov (United States)

    Seckin, Berna; Pekcan, Meryem Kuru; Inal, Hasan Ali; Gulerman, Cavidan

    2017-06-01

    Estrogen is known to affect both mammographic breast density and bone mineral density (BMD), but there are inconsistent results about the association of these density measurements in postmenopausal women. Furthermore, there are scarce data on the relationship between breast density and BMD in never users of postmenopausal hormone therapy. In this study, we examined the relationship between mammographic breast density and BMD in postmenopausal women who were never hormone replacement therapy users. A total of 293 postmenopausal women were enrolled in this cross-sectional study. Mammograms and BMD measurements for screening purposes were obtained. Assessment of mammographic breast density was performed by using breast imaging reporting and data system classification. The BMD was measured using dual-energy X-ray absorptiometry of the lumbar spine and femoral neck. Grade 1 breast density was observed in 64 women (21.8 %), grade 2 in 113 women (38.6 %) and grades 3 and 4 in 116 (39.6 %) women. Breast density decreased with increasing age and body mass index (BMI). Meanwhile, no significant differences were detected in BMD measures of the hip (p = 0.14) and lumbar spine (p = 0.29) among the breast density categories. After adjusting for age and BMI, the differences in the mean BMD at the hip and lumbar spine across the breast density categories remained insignificant (p = 0.26 and 0.11, respectively). There is no evidence of a relationship between mammographic breast density and BMD in postmenopausal women who had never used hormone replacement therapy.

  14. Incremental value of hormonal therapy for deep vein thrombosis prediction: an adjusted Wells score for women.

    Science.gov (United States)

    Barros, Márcio Vinícius Lins de; Arancibia, Ana Elisa Loyola; Costa, Ana Paula; Bueno, Fernando Brito; Martins, Marcela Aparecida Corrêa; Magalhães, Maria Cláudia; Silva, José Luiz Padilha; Bastos, Marcos de

    2016-04-01

    Deep venous thrombosis (DVT) management includes prediction rule evaluation to define standard pretest DVT probabilities in symptomatic patients. The aim of this study was to evaluate the incremental usefulness of hormonal therapy to the Wells prediction rules for DVT in women. We studied women undertaking compressive ultrasound scanning for suspected DVT. We adjusted the Wells score for DVT, taking into account the β-coefficients of the logistic regression model. Data discrimination was evaluated by the receiver operating characteristic (ROC) curve. The adjusted score calibration was assessed graphically and by the Hosmer-Lemeshow test. Reclassification tables and the net reclassification index were used for the adjusted score comparison with the Wells score for DVT. We observed 461 women including 103 DVT events. The mean age was 56 years (±21 years). The adjusted logistic regression model included hormonal therapy and six Wells prediction rules for DVT. The adjusted score weights ranged from -4 to 4. Hosmer-Lemeshow test showed a nonsignificant P value (0.69) and the calibration graph showed no differences between the expected and the observed values. The area under the ROC curve was 0.92 [95% confidence interval (CI) 0.90-0.95] for the adjusted model and 0.87 (95% CI 0.84-0.91) for the Wells score for DVT (Delong test, P value < 0.01). Net reclassification index for the adjusted score was 0.22 (95% CI 0.11-0.33, P value < 0.01). Our results suggest an incremental usefulness of hormonal therapy as an independent DVT prediction rule in women compared with the Wells score for DVT. The adjusted score must be evaluated in different populations before clinical use.

  15. Influence of hormone substitution therapy on postmenopausal uterus; Einfluss einer Hormonsubstitution auf den postmenopausalen Uterus

    Energy Technology Data Exchange (ETDEWEB)

    Otte, A.; Ruedisueli, A.; Goetze, M.; Leibundgut, U.; Mueller-Brand, J. [Inst. fuer Nuklearmedizin, Kantonsspital, Universitaetskliniken, Basel (Switzerland); Nitzsche, E.U. [Abt. Nuklearmedizin, Radiologische Universitaetsklinik, Freiburg (Germany)

    1997-12-01

    In a 58-year-old postmenopausal woman blood flow and blood pool images of bone scintigraphy showed a focus of increased activity in the right pelvic region. Computed tomography and ultrasound exhibited no abnormalities in the abdomen; especially the uterus and ovaries were normal. Careful anamnestic evaluation revealed that the patient received a long-term peroral estrogen/gestagen replacement therapy for the prevention of osteoporosis, but did not have menstruation-like bleedings for the last twelve months of therapy. At time of admission, the patient was on day 25 of hormone replacement therapy, and the uterus wash, therefore, in a premenstrual stage. Hence, despite cessation of bleedings in postmenopausal women, one should think of hormone replacement therapy as an explanation for vascular pelvic tumors seen by the first two phases of bone scintigraphy, before further diagnostic steps are undertaken. (orig.) [Deutsch] Bei der Skelettszintigraphie einer 58jaehrigen postmenopausalen Frau erkannte man in der Perfusions- und Blood-pool-Phase einen unklaren Fokus erhoehter Aktivitaet im rechten Becken. Computertomographie und Sonographie des Abdomens, insbesondere des Uterus und der Ovarien, waren unauffaellig. Nach eingehender anamnestischer Befragung stellte sich heraus, dass die Patientin unter einer mehrjaehrigen peroralen Oestrogen-/Gestagen-Hormonsubstitutionstherapie zur Osteoporose-Prophylaxe stand, jedoch seit den letzten zwoelf Monaten der Therapie ueber keine menstruationsaehnlichen Abbruchblutungen mehr berichten konnte. Bei ihrer Zuweisung befand sich die Patientin am 25. Tag der Hormonsubstitutionstherapie und ihr Uterus somit in einem praemenstruellen Stadium. Trotz Ausbleibens der Blutung bei postmenopausalen Frauen sollte somit an die Moeglichkeit der Hormonsubstitution gedacht und danach gefragt werden, wenn in den ersten beiden Phasen der Skelettszintigraphie eine unklare, gut vaskularisierte Struktur im kleinen Becken gefunden wird, bevor weitere

  16. Hormone replacement therapy and risk of breast cancer: the role of progestins

    DEFF Research Database (Denmark)

    Stahlberg, Claudia Irene; Pederson, Anette Tønnes; Lynge, Elsebeth;

    2003-01-01

    Epidemiological studies have shown an increased risk of breast cancer associated with the use of hormone replacement therapy (HRT). This notion is mostly based on studies from the USA. During the last decades unopposed estrogen treatment has been used to a lesser extent, whereas the combined...... estrogen-progestin treatment regime is now prescribed worldwide. In the USA the predominant compounds are conjugated estrogens and medroxyprogesterone-acetate, whereas oestradiol combined with testosterone-like progestins is commonly used in Europe. These differences are largely the result of traditions...

  17. Long-term hormone replacement therapy preserves bone mineral density in Turner syndrome

    DEFF Research Database (Denmark)

    Cleemann, Line; Hjerrild, Britta E; Lauridsen, Anna L;

    2009-01-01

    at baseline and follow-up (5.9+/-0.7 years). SETTING: Tertiary hospital. PARTICIPANTS: Fifty-four women with TS (43.0+/-9.95 years). Interventions Hormone replacement therapy (HRT) and calcium and vitamin D supplementation. Main outcome measures BMD (g/cm(2)) measured at lumbar spine, hip, and the non.......010+/-0.144, PTestosterone, IGF1, and maximal oxygen uptake was significantly reduced in TS. CONCLUSION: Longitudinal changes in BMD in TS were slight. BMD can be maintained at most sites in well...

  18. A randomized, controlled pilot trial of hormone therapy for menopausal insomnia.

    Science.gov (United States)

    Silva, Betania Huber; Martinez, Denis; Wender, Maria Celeste Osório

    2011-12-01

    Insomnia is a frequent climacteric symptom. This pilot, double-blind, randomized placebo-controlled trial compared estradiol associated with trimegestone or placebo in 12 women with perimenopausal insomnia. The Pittsburgh Sleep Quality Index (PSQI) was administered, and polysomnography was performed at baseline and after 28 days. Sleep efficiency and median score of the PSQI improved significantly in the hormone therapy group (HT) (p=0.041 and p=0.027, respectively) and not in placebo group. Perimenopausal insomnia improved after short-term HT.

  19. Effects of hormone replacement therapy on endothelial function in menopausal women

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To observe the effects of hormone replacement therapy (HRT) on endothelial function in menopausal women. Methods A total of 30 menopausal women were treated with 2.5 mg of Tibolone (Livial) daily. At the same time,30 women with natural menopause without any treatment served as the control group. Endothelium-dependent (EDD),endothelium-independent (NID) vasodilatation function,and estradiol (E2) were examined by the non-invasive high-resolution ultrasonography before the treatment and at 12th,24th,...

  20. Medicare D Subsidies and Racial Disparities in Persistence and Adherence With Hormonal Therapy

    Science.gov (United States)

    Shi, Yushu; Charlson, John; Smith, Elizabeth C.; Smallwood, Alicia J.; Nattinger, Ann B.; Laud, Purushottam W.; Neuner, Joan M.

    2016-01-01

    Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially

  1. Managing the menopause: British Menopause Society Council consensus statement on hormone replacement therapy.

    Science.gov (United States)

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Marsden, Jo; Stevenson, John; Williamson, Jennifer

    2005-12-01

    The British Menopause Society Council aims to help health professionals inform and advise women about the menopause. This guidance regarding estrogen-based hormone replacement therapy (HRT), including tibolone, which is classified in the British National Formulary as HRT, responds to the results and analysis of the randomized Women's Health Initiative studies and the observational Million Women Study. Treatment choice should be based on up-to-date information and targeted to individual women's needs. HRT still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  2. Menopausia, hipertensión arterial y terapia de reemplazo hormonal Menopause, blood hypertension and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Daysi Navarro Despaigne

    2003-04-01

    Full Text Available Para evaluar la influencia de la terapia de reemplazo hormonal (THR sobre el síndrome climatérico (SC y los niveles de tensión arterial en mujeres posmenopáusicas con hipertensión arterial (HTA, se realizó un ensayo terapéutico abierto, el cual incluyó 45 mujeres no obesas con HTA ligera/moderada. En cada mujer se evaluó la evolución de los síntomas climatéricos y de los niveles de tensión arterial, así como los efectos indeseables a la THR. Como medicamento las pacientes recibieron Estradiol 2mg + Levonorgestrel 1 mg por día durante 12 meses. Durante la THR disminuyeron los síntomas climatéricos, en particular los vasomotores (de 86,6 a 10 % y los genitourinarios (de 56,7 a 15 %. En la totalidad de las mujeres existió estabilidad en los niveles de tensión arterial. En 5 mujeres hubo necesidad de incrementar la dosis de medicamentos antihipertensivos. En el resto esta se mantuvo o disminuyó. Como efectos indeseables se reportó sangramiento vaginal, mastodinia, cefalea, vasculitis e isquemia del quinto dedo del pie. Las dos últimas pacientes debieron suspender el tratamiento y se presentaron al sexto mes de haber iniciado la THR. En conclusión, en mujeres de edad mediana con hipertensión arterial la THR mejora el síndrome climatérico sin empeorar los niveles de tensión arterial.To evaluate the influence of hormone replacement therapy on the climateric syndrome (CS and the blood pressure values in postmenopausal women with hypertension, an open therapeutic assay was carried out, which included 45 non-obese women with slight/moderate hypertension. The course of the climateric symptoms and the blood pressure levels as well as the adverse effects of HRT were evaluated in every woman. The patients took Estradiol 2mg plus Levonorgestrel 1 mg per day for 12 months as drug therapy. During the application of the HRT, the climateric symptoms, particularly vasomotor (from 86,6 to 10% and genitourinary (from 56,7 to 15% decreased

  3. Use of Menopausal Hormone Therapy and Bioidentical Hormone Therapy in Australian Women 50 to 69 Years of Age: Results from a National, Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Louiza S Velentzis

    Full Text Available Menopausal Hormone Therapy (MHT use in Australia fell by 55% from 2001 to 2005, following the release of large-scale findings on its risks and benefits. Comprehensive national data, including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004-5 National Health Survey, when 11% of women aged 45+ years were estimated to be current MHT users. No national data are available on prevalence of use of "bioidentical" hormone therapy (BHT. The objective of this study was to determine recent prevalence of MHT and BHT use. A cross-sectional, national, age-stratified, population survey was conducted in 2013. Eligible women, aged 50-69 years, resident in Australia were randomly sampled in 5-year age groups from the Medicare enrolment database (Australia's universal health scheme. The response rate was 22% based on return of completed questionnaires, and analyses were restricted to 4,389 women within the specified age range. The estimated population-weighted prevalence of current use of MHT was 13% (95%CI 12-14, which was broadly similar to the previously reported national figures in 2004-5, suggesting that the use of MHT in Australia has largely stabilised over the past decade. A total of 39% and 20% of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT, respectively, whereas 77% of hysterectomised current-users used oestrogen-only MHT. Almost three-quarters of current-users [population-weighted prevalence 9% (95%CI 8-10] had used MHT for ≥5 years. In regard to BHT, estimated population-weighted prevalence of ever use was 6% (95%CI 6-7 and 2% (95%CI 2-3 for current use. The population-weighted prevalence of MHT and BHT combined, in current users in their fifties and sixties was 15% (95%CI 14-16. These data provide a recent national "snapshot" of Australian women's use of both conventional MHT and of BHT.

  4. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    Science.gov (United States)

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

  5. Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage.

    Science.gov (United States)

    Chew, Fiona; Wu, Xianwei

    2017-01-01

    Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002-2003, 2008-2009 and 2012-14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians' HT recommendations from 2002 to 2009, and 2012 to 2014. Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap.

  6. Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage

    Science.gov (United States)

    Wu, Xianwei

    2017-01-01

    Objective Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). Methods We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002–2003, 2008–2009 and 2012–14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians’ HT recommendations from 2002 to 2009, and 2012 to 2014. Results Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Conclusion Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap. PMID:28158240

  7. Efficacy of Drospirenone-Containing Hormone Replacement Therapy to Reduce Vasomotor Symptoms of Menopause

    Directory of Open Access Journals (Sweden)

    Dana A. Brown

    2013-10-01

    Full Text Available Hormone replacement therapy has been proven efficacious for controlling vasomotor symptoms such as hot flushes associated with menopause. Drospirenone is a progestin with antiandrogenic and antimineralocorticoid activity that may be used in combination with estrogen to control hot flushes and offers the potential benefit of minimizing breast tenderness, blood pressure elevations and weight gain. Six clinical trials were reviewed. Of these, four trials explicitly listed hot flushes as a primary outcome. Efficacy with regards to hot flushes was found to range from modest to large (i.e., 37.5% to 94.6%, and four of the studies utilized diary cards to assess hot flushes. Results from these studies must be interpreted cautiously as quite a few limitations existed such as small population sizes involving specific ethnic groups, lack of p values with regards to baseline characteristics lending question to homogeneity, and inclusion of mostly healthy participants. Additionally, while the studies were long enough to see an effect, the long term effects of drospirenone-containing hormone replacement therapy (HRT is unknown. The available data supports the use of drospirenone-containing HRT for the treatment of hot flushes associated with menopause.

  8. Management of acne vulgaris with hormonal therapies in adult female patients.

    Science.gov (United States)

    Husein-ElAhmed, Husein

    2015-01-01

    Acne vulgaris is a very common condition affecting up of 93% of adolescents. Although rare, this disease may persist in adulthood. In adult women with acne (those older than 25 years old), this condition is particularly relevant because of the refractory to conventional therapies, which makes acne a challenge for dermatologists in this group of patients. In order to its potential risk for chronicity and the involvement of visible anatomical sites such as face and upper torso, acne has been associated with a wide spectrum of psychological and social dysfunction such as depression, anxiety, suicidal ideation, somatization, and social inhibition. In particular, adult women with acne have been shown to be adversely impacted by the effect of acne on their quality of life. For the last four decades, dermatologists have used hormonal therapies for the management of acne vulgaris in adult women, which are considered a rational choice given the severity and chronicity of this condition in this group of patients. The aim of this work is to review the hormonal drugs for management of acne.

  9. RETRACTION: Challenges of combined everolimus/endocrine therapy in hormone receptor-positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Camillo Porta

    2014-06-01

    Full Text Available To our readers:With deep regrets, we inform our Readers that the article Challenges of combined everolimus/endocrine therapy in hormone receptor-positive metastatic breast cancer (DOI: http://dx.doi.org/10.4081/oncol.2014.236, which has been published Ahead of Print in the first issue of Oncology Reviews (2014, contains verbatim text plagiarized from another paper.1The manuscript must be considered as retracted. On behalf of the Editorial Board of Oncology Reviews, I apologize to the Author of the manuscript whose text was plagiarized by Y. Abubakr and Y. Albushra that this was not picked up in the peer review process. I also apologize to the affected journal for the violation of copyright due to plagiarism. Oncology Reviews is uncompromising in its commitment to scientific integrity. When credible evidence of misconduct is brought to our attention, our commitment to the scientific record and to our readership requires immediate notification. Oncology Reviews is increasingly employing sophisticated software to detect plagiarism. Other journals use similar tools. Authors should be aware that most journals routinely employ plagiarism detection software, and that any plagiarism is likely to be detected.Camillo Porta, Editor-in-Chief Oncology Reviews Reference 1. André F. Enhancing effectiveness of endocrine therapy in hormone receptor-positive advanced breast cancer. Medscape Education Oncology. CME Released: 05/24/2013; Valid for credit through 05/24/2014. http://www.medscape.org/viewarticle/804496

  10. Modification of blood pressure in postmenopausal women: role of hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Cannoletta M

    2014-08-01

    Full Text Available Marianna Cannoletta, Angelo Cagnacci Institute of Obstetrics and Gynecology, Department of Medical and Surgical Sciences of the Mother, Child and Adult, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Emilia-Romagna, Italy Abstract: The rate of hypertension increases after menopause. Whether estrogen and progesterone deficiency associated with menopause play a role in determining a worst blood pressure (BP control is still controversial. Also, studies dealing with the administration of estrogens or hormone therapy (HT have reported conflicting evidence. In general it seems that, despite some negative data on subgroups of later postmenopausal women obtained with oral estrogens, in particular conjugated equine estrogens (CEE, most of the data indicate neutral or beneficial effects of estrogen or HT administration on BP control of both normotensive and hypertensive women. Data obtained with ambulatory BP monitoring and with transdermal estrogens are more convincing and concordant in defining positive effect on BP control of both normotensive and hypertensive postmenopausal women. Overall progestin adjunct does not hamper the effect of estrogens. Among progestins, drospirenone, a spironolactone-derived molecule, appears to be the molecule with the best antihypertensive properties. Keywords: hormone replacement therapy, estrogen, progestin, blood pressure, menopause, hypertension 

  11. Paraneoplastic Dermatomyositis with Cutaneous and Myopathic Disease Responsive to Adrenocorticotropic Hormone Therapy

    Science.gov (United States)

    Mancuso, Christopher; Lal, Karan; Dicostanzo, Damian; Gropper, Charles

    2017-01-01

    Dermatomyositis is a myopathic or amyopathic autoimmune connective tissue disease that presents with classic dermatologic findings ranging from: poikilodermatous photosensitivity (shawl sign), eyelid edema and violaceous-pigmentation (heliotrope sign), lichenoid eruptions on the knuckles and elbows (Gottron’s sign), periungual telangiectasias, and ragged cuticles (Samitz sign). Up to 30 percent of adult-onset cases of dermatomyositis may represent a paraneoplastic syndrome warranting a thorough work-up for malignancy. The authors present a case report of paraneoplastic dermatomyositis associated with triple negative, BRCA-1 positive, invasive intraductal carcinoma of the breast, whose myopathic and cuteanous symptoms were recalcitrant to high-dose corticosteroid therapy. Herein, the authors describe the first reported case of the use of an injectable adrenocorticotropic hormone agonist gel in a patient with myopathic paraneoplastic disease that achieved clinical resolution of both myopathic and cutaneous symptoms, but subseuqently developed significant hyperpigmentation of her face suspected to be secondary to a chemotherapeutic-induced pigmentary change which was augmented by adrenocorticotropic hormone therapy. PMID:28210382

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

    Science.gov (United States)

    2017-06-22

    The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees.Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT.For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision making and periodic reevaluation. For bothersome GSM symptoms not

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

    Science.gov (United States)

    2017-07-01

    The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees.Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT.For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision making and periodic reevaluation. For bothersome GSM symptoms not

  14. Using predictors of hormone therapy use to model the healthy user bias: how does healthy user status influence cognitive effects of hormone therapy?

    Science.gov (United States)

    Gleason, Carey E; Dowling, N Maritza; Friedman, Elliot; Wharton, Whitney; Asthana, Sanjay

    2012-05-01

    This study investigated the phenomenon known as the healthy user bias by equating hormone therapy (HT) use (past or current) with healthy user status. Data from the Survey of Midlife in the United States were used to identify the predictors of HT use. The unique Survey of Midlife in the United States data include psychological, demographic, health-related, and behavioral variables as well as history of HT use. Predictors of HT use were combined to derive propensity scores, describing the likelihood that a woman was an HT user, based on her psychological, demographic, physical, and behavioral profile (ie, likelihood of being a healthy user) as opposed to her actual use of HT. Finally, cognitive performance on an executive function test was examined in women stratified by propensity score. Using a multiple logistic regression model, nine variables emerged as predictors of HT use. The nine variables were used to estimate the propensity or conditional probability of using HT for each subject; resultant propensity scores were ranked and divided into tertiles. Women in the highest tertile demonstrated shorter median response latencies on a test of executive function than did women who did not use HT. From an array of psychological, medical, and behavioral variables, nine emerged as predictors of HT use. If validated, these features may serve as a means of estimating the phenomenon known as healthy user bias. Moreover, these data suggest that the degree to which a woman fits a model of a healthy user may influence cognitive response to HT.

  15. Sindrom pomanjkanja rastnega hormona pri odraslem - učinki nadomestnega zdravljenja: Syndrome of growth hormone deficiency in adults - effects of growth hormone replacement therapy:

    OpenAIRE

    Pfeifer, Marija

    2001-01-01

    Background. After the cessation of longitudinal growth, growth hormone (GH) continues to subserve an important role in the regulation of body metabolism (stimulation of lipolysis and lipid oxidation, protein synthesis, insulin antagonism, and sodium and water retention) to optimise body composition and function. Most patients with hypopituitarism exhibit the syndrome of GH deficiency with a number of abnormal features which can be reversed with recombinant GH replacement therapy. Conclusions....

  16. Risks and benefits of hormone replacement therapy in older men Riscos e benefícios da terapia de reposição hormonal em homens idosos

    Directory of Open Access Journals (Sweden)

    Fábio Firmbach Pasqualotto

    2004-02-01

    Full Text Available The use of testosterone in older men, known as male hormonal replacement therapy or androgen replacement therapy, has become of increasing interest to both the medical and lay communities over the past decade. Even though the knowledge of the potential benefits and risks of male Androgen Replacement Therapy has increased dramatically, there is still much that needs to be determined. Although there are a number of potential benefits of male Androgen Replacement Therapy and data concerning clinical effects of such replacement have accumulated, as yet there have not been any large multicenter randomized controlled trials of this therapy. It is the purpose of this article to review what is currently known about the possible risks and benefits of male Androgen Replacement Therapy by discussing the clinical trials to date.O uso da testosterona em homens idosos, conhecido como Terapia de Reposição Hormonal no homem ou Terapia de Reposição com Androgênios, têm aumentado o interesse para as comunidades médica e leiga na última década. Muito embora o conhecimento a respeito dos potenciais benefícios e riscos da Terapia de Reposição Hormonal nos homens tem aumentado dramaticamente, ainda existe muito que precisa ser determinado. Embora existam vários benefícios potenciais da Terapia de Reposição com Androgênios e dados clínicos relacionados com o uso de tal terapia, não existem ainda nenhum estudo controlado, randomizado e multicêntrico avaliando o uso de tal terapia. O objetivo deste artigo é revisar os aspectos atuais sobre os possíveis riscos e benefícios da Terapia de Reposição com Androgênios discutindo os estudos clínicos publicados sobre o assunto.

  17. Serum uric acid levels and hormone therapy type: a retrospective cohort study of postmenopausal women.

    Science.gov (United States)

    Jung, Jae H; Song, Gwan G; Lee, Young H; Kim, Jae-Hoon; Hyun, Myung H; Choi, Sung J

    2017-08-07

    Serum uric acid levels increase in postmenopausal women, but decrease when hormone therapy (HT) is administered. No study has, however, evaluated the effects of different types of HT on serum uric acid levels. We therefore examined whether estrogen therapy (ET), estrogen plus progestogen therapy (EPT), and tibolone use affected serum uric acid levels in this population. We performed a retrospective cohort study of postmenopausal women. From 2005 to 2015, postmenopausal women who had undergone blood uric acid-level testing at least twice were enrolled. Participants were grouped according to HT regimen: ET, EPT, or tibolone. The nonhormone therapy group did not receive HT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual participants. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, estimated glomerular filtration rate, alcohol consumption, smoking status, and comedications were also adjusted. After adjusting for multiple variables, the serum uric acid level increased to 0.87 ± 0.27 mg/dL (least squares mean ± standard error) in the nonhormone therapy group, and serum uric levels in the EPT group were found to be significantly lower (-0.38 ± 0.29 mg/dL, P uric acid levels in the ET and tibolone groups did not, however, differ significantly from the nonhormone therapy group level. We attribute our findings to the effects of progestogen, rather than estrogen.

  18. Transdermal hormone therapy and the risk of stroke and venous thrombosis.

    Science.gov (United States)

    Speroff, L

    2010-10-01

    Recent case-control and cohort studies have indicated that the transdermal administration of postmenopausal estrogen therapy is not associated with an increased risk of cardiovascular complications, specifically stroke and venous thrombosis. These studies have prompted the clinical promotion of transdermal treatment as 'safer'. There are reasons, however, to be cautious regarding postmenopausal transdermal hormone therapy, especially in regard to stroke. Previous reports linking postmenopausal estrogen therapy and the risk of stroke have not yielded consistent results, finding it difficult to adjust for all confounding factors, including compliance with treatment. Age of the population studies may be a critical issue. Notably, the risk of stroke with oral estrogen was not increased in the Women's Health Initiative when women with prior cardiovascular disease or those older than 60 years were excluded. There does appear to be a dose-response relationship with stroke, similar to that observed with estrogen-progestin contraceptives, and this may be a problem when studying standard doses of transdermal treatment, in that many women receiving transdermal estrogen display lower estrogen blood levels when compared with oral treatment. Clinicians should administer low doses of estrogen to women with risk factors for stroke, and the transdermal route of administration is indicated for women at high risk for venous thrombosis and for older postmenopausal women, especially for women with stroke risk factors. In a recent study, Renoux and colleagues from McGill University in Montreal performed a nested case-control study deriving the data from a cohort of women in the UK General Practice Research Database (GPRD). Current use of oral and transdermal hormone therapy, based on recorded prescriptions, was compared to no use in 15 710 cases and 59 958 controls. The adjusted rate ratio (RR) for stroke for current use of transdermal estrogens, with or without a progestin, was not

  19. Contracepção hormonal e anti-retrovirais em mulheres infectadas pelo HIV Hormonal contraception and antiretroviral therapy among HIV-infected women

    Directory of Open Access Journals (Sweden)

    Eliana Amaral

    2006-11-01

    Full Text Available Há controvérsia sobre a relação entre o uso de contraceptivos hormonais e o risco de adquirir o vírus da imunodeficiência humana (HIV, e pouco se sabe sobre os efeitos da contracepção hormonal em mulheres infectadas (efeitos colaterais, distúrbios menstruais, progressão da doença, interações com terapias anti-retrovirais. O objetivo deste artigo foi revisar os dados disponíveis quanto à vulnerabilidade ao HIV e à sua transmissibilidade na vigência do uso de contraceptivos hormonais bem como as conseqüências potenciais do uso desses contraceptivos por mulheres HIV-positivas sob terapia anti-retroviral (TARV, com ênfase nas interações medicamentosas. Concluiu-se que ainda não é possível elaborar recomendações, baseadas em evidências, sobre a contracepção hormonal em mulheres portadoras do HIV sob TARV. Assim, os infectologistas e os ginecologistas devem estar atentos às interações potenciais que possam representar aumento de efeitos adversos, individualizando a orientação sobre os esteróides contraceptivos, suas doses e vias de administração, considerando a TARV em uso.There is much controversy regarding the realtionship between the use of hormonal contraceptives and the risk of acquiring human immunodeficiency virus (HIV, and little is known about the effects of hormonal contraception in HIV-infected women (adverse events, menstrual disorders, disease progression, antiretroviral therapy interactions. The aim of the present study was to review available data regarding HIV vulnerability and transmission associated with hormonal contraceptives and the use of these contraceptives by women on antiretroviral therapy, with emphasis on drug interactions. In conclusion, it was not possible to offer evidence-based recommendations for the use of hormonal contraceptives among HIV-infected women under antiretroviral therapy. Infectious disease specialists and gynecologists providing care should be cautious about potential

  20. Standard and Low-dose Hormone Therapy for Postmenopausal Women—Focus on the Breast

    Directory of Open Access Journals (Sweden)

    Peng-Hui Wang

    2007-06-01

    Full Text Available Menopause occurs naturally when the ovary ceases folliculogenesis, or artificially by surgical and/or medical ablation of the ovarian function. Menopause is a hypoestrogenic state, which may adversely affect estrogen target tissues, such as the brain, skeleton and skin, as well as the cardiovascular and genitourinary systems, with resultant frequency and severity of climacteric symptoms. The climacteric symptoms, however, vary significantly among women. For decades, hormone therapy (HT has been the mainstay and is considered the most effective for managing menopausal symptoms. The prolonged use of either single estrogen therapy or a combination therapy of estrogen and progestogen (EPT might be associated with a slightly increased risk of breast cancer and many resultant adverse events, such as coronary heart disease, stroke and venous thromboembolism. Perhaps because the clear benefits are limited to these end points of HT in treating menopausal women, the relatively significant adverse event profiles of these women may not be enough to trigger primary care physicians to be more aggressive than they have been to date in treating climacteric symptoms of postmenopausal women. However, severe climacteric symptoms really disturb the woman's life. Some epidemiologic studies have shown that the increased risk for breast cancer after 5 years of combined EPT is similar in magnitude to other lifestyle variables, such as 10-year delayed menopause, fewer pregnancies and reduced breastfeeding, postmenopausal obesity, excessive alcohol or cigarette use, and lack of regular exercise. Furthermore, elevated serum concentrations of either endogenous or exogenous (replaced by HT sex hormone in either pre- or postmenopausal women are associated with an increased risk of breast cancer. Finally, the increased breast cancer risk diminishes soon after discontinuing hormones, and largely disappears by 5 years after cessation. Taken together, low-dose conventional HT

  1. Invited commentary: hormone therapy and risk of coronary heart disease why renew the focus on the early years of menopause?

    Science.gov (United States)

    Manson, JoAnn E; Bassuk, Shari S

    2007-09-01

    After the initial report from the Women's Health Initiative estrogen-progestin trial, which found that menopausal hormone therapy was associated with an increased risk of coronary heart disease in the overall cohort (age range: 50-79 years; mean age: 63 years), researchers took a closer look at the data from this and other studies, focusing on the timing of initiation of such therapy. The results suggest that hormone therapy may have a beneficial effect on the heart if started in early menopause, when a woman's arteries are still likely to be relatively healthy, but a harmful effect if started in late menopause, when advanced atherosclerosis may be present. The implication of the timing hypothesis for clinical practice is not that recently menopausal women be given hormone therapy for coronary heart disease prevention but rather that clinicians can be reassured about cardiac risks when considering short-term use of hormone therapy for vasomotor symptom relief in such women. The reduction in vasomotor symptoms must be weighed against other risks and benefits of treatment, but coronary disease is typically not a major factor in the equation for women who are recently menopausal.

  2. Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis.

    Science.gov (United States)

    Sheanon, Nicole M; Backeljauw, Philippe F

    2015-01-01

    Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome. Turner syndrome effects 1 in every 2000 live births. Short stature is a cardinal feature of Turner Syndrome and the standard treatment is recombinant human growth hormone. When growth hormone is started at an early age a normal adult height can be achieved. With delayed diagnosis young women with Turner Syndrome may not reach a normal height. Adjuvant therapy with oxandrolone is used but there is no consensus on the optimal timing of treatment, the duration of treatment and the long term adverse effects of treatment. The objective of this review and meta-analysis is to examine the effect of oxandrolone on adult height in growth hormone treated Turner syndrome patients. Eligible trials were identified by a literature search using the terms: Turner syndrome, oxandrolone. The search was limited to English language randomized-controlled trials after 1980. Twenty-six articles were reviewed and four were included in the meta-analysis. A random effects model was used to calculate an effect size and confidence interval. The pooled effect size of 2.0759 (95 % CI 0.0988 to 4.0529) indicates that oxandrolone has a positive effect on adult height in Turner syndrome when combined with growth hormone therapy. In conclusion, the addition of oxandrolone to growth hormone therapy for treatment of short stature in Turner syndrome improves adult height. Further studies are warranted to investigate if there is a subset of Turner syndrome patients that would benefit most from growth hormone plus oxandrolone therapy, and to determine the optimal timing and duration of such therapy.

  3. Survival improvement in hormone-responsive young breast cancer patients with endocrine therapy.

    Science.gov (United States)

    Yoon, Tae In; Hwang, Ui-Kang; Kim, Eui Tae; Lee, SaeByul; Sohn, Guiyun; Ko, Beom Seok; Lee, Jong Won; Son, Byung Ho; Kim, Seonok; Ahn, Sei Hyun; Kim, Hee Jeong

    2017-09-01

    We investigated the oncologic outcomes by intrinsic subtype and age in young breast cancer patients and whether survival differences were related to treatment changes over time. A retrospective analysis was performed on 9633 invasive breast cancer patients treated at Asan Medical Center from January 1989 to December 2008. We also enrolled a matched cohort adjusting for tumor size, lymph node metastasis, subtypes, and tumor grade. Patients aged <35 years were included in the younger group (n = 602) and those aged ≥35 years were included in the older group (n = 3009). The younger patients showed a significantly higher T stage, a more frequent axillary node presentation, higher histologic grade, and higher incidence of triple-negative subtype tumors than older patients and also received more chemotherapy and were less likely to undergo hormone therapy. The younger patients with hormone receptor (HR)-positive tumors showed significantly poorer disease-free survival (DFS), loco-regional recurrence-free survival, distant metastasis-free survival, and breast cancer-specific survival outcomes than older patients. Younger patients with HR-positive and human epidermal growth factor receptor 2 (HER2)-negative tumor subtypes had a significantly improved DFS over time (p = 0.032). Within the HR-positive/Her2-negative subtype, more women received gonadotropin-releasing hormone agonist and tamoxifen treatment from 2003 to 2008 compared with 1989 to 2002 (p = 0.001 and p = 0.075, respectively). HR-positive young breast cancer patients have a poorer survival compared with older patients, even with more frequent chemotherapy, but more recent use of tamoxifen and ovarian suppression might improve this outcome in these patients.

  4. Low-dose growth hormone therapy reduces inflammation in HIV-infected patients

    DEFF Research Database (Denmark)

    Lindboe, Johanne Bjerre; Langkilde, Anne; Eugen-Olsen, Jesper

    2016-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) has drastically increased the life expectancy of HIV-infected patients. However, HIV-infected patients exhibit increased inflammation and 33-58% exhibit a characteristic fat re-distribution termed HIV-associated lipodystrophy syndrome (HALS...... to investigate the impact of low-dose rhGH therapy on inflammation in HIV-infected patients. METHODS: Forty-six cART-treated HIV-infected men were included in the HIV-GH low-dose (HIGH/Low) study: a randomized, placebo-controlled, double-blinded trial. Subjects were randomized 3:2 to 0.7 mg/day rhGH, or placebo......). Recombinant human growth hormone (rhGH) has been tested as treatment of HALS. Low-dose rhGH therapy improves thymopoiesis and fat distribution in HIV-infected patients and appears to be well tolerated. However, since high-dose rhGH is associated with adverse events related to inflammation, we wanted...

  5. Pharmaceutical intervention in menopausal patients with hormone replacement therapy in a community pharmacy from Antofagasta

    Directory of Open Access Journals (Sweden)

    Alejandrina Alucema

    2015-02-01

    Full Text Available Context: Hormone replacement therapy (HRT is the most widely used treatment for controlling the effects of menopause. This type of therapy causes some drug-related problems (DRP, which requires monitoring to control the negative effects and ensure patient adherence to therapy. Aims: Perform a pharmacotherapeutic monitoring and educate to menopausal patients in HRT of a community pharmacy from the city of Antofagasta. Methods: A 98-menopausal patients underwent a pharmaceutical intervention to identify the PRM and its resolution. It was applied to them a survey before and after educational activities about this disease and HRT to determine the knowledge on the subject. Results: During the pharmacotherapeutic monitoring was determined that 55% of patients using combined HRT. 62 DRPs were detected, of which 43 were resolved (69%; the most were Patient-Pharmacist (73%. The better resolution DRP were DRP 4(b “frequency of inadequate administration” and DRP 2(a “no medical indication”. At baseline, 90% had an inadequate level of knowledge about the disease and THR, 8% intermediate, and only 2% adequate. After the implementation of the education strategy, the level of knowledge increased, achieving at the end of the study only intermediate (10% and adequate (90% levels. Conclusions: The results confirm the importance of pharmaceutical intervention for the identification and resolution of DRP and the requirement to establish educational strategies to increase the knowledge about menopause and HRT in menopausal patients.

  6. Menopausal hormone therapy and lung cancer-specific mortality following diagnosis: the California Teachers Study.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available Previous results from research on menopausal hormone therapy (MHT and lung cancer survival have been mixed and most have not studied women who used estrogen therapy (ET exclusively. We examined the associations between MHT use reported at baseline and lung cancer-specific mortality in the prospective California Teachers Study cohort. Among 727 postmenopausal women diagnosed with lung cancer from 1995 through 2007, 441 women died before January 1, 2008. Hazard Ratios (HR and 95% Confidence Intervals (CI for lung-cancer-specific mortality were obtained by fitting multivariable Cox proportional hazards regression models using age in days as the timescale. Among women who used ET exclusively, decreases in lung cancer mortality were observed (HR, 0.69; 95% CI, 0.52-0.93. No association was observed for estrogen plus progestin therapy use. Among former users, shorter duration (15 years was associated with a decreased risk (HR, 0.60; 95% CI, 0.38-0.95. Smoking status modified the associations with deceases in lung cancer mortality observed only among current smokers. Exclusive ET use was associated with decreased lung cancer mortality.

  7. Adherence to hormone therapy in women with breast cancer: a quantitative study.

    Science.gov (United States)

    Iacorossi, Laura; Gambalunga, Francesca; Fabi, Alessandra; Giannarelli, Diana; Facchinetti, Gabriella; Piredda, Michela; De Marinis, Maria Grazia

    2016-01-01

    The majority of patients with hormone receptor-positive breast cancer are treated with oral endocrine therapies, which are administered in periods ranging from 5 to 10 years. Adherence, ie the degree a subject's behavior corresponds to the agreed recommendations, then becomes a significant problem, which can also affect distress levels. The aim of this study is to evaluate the level of adherence to endocrine therapy and distress in a sample of Italian women. The study is a descriptive cross sectional survey. Adherence was measured with the Morisky Medication Adherence 8-item Scale and distress was measured by the Distress Thermometer. Socio-demographic and clinical data were also collected and then processed. Adherence measured with MMAS-8 items scored 6.18 corresponding to an average level of adherence in the 151 patients examined. The only factors affecting adherence signi- ficantly were: level of education, marital status and, among the side effects of therapy, poor concentration and memory. The data analysis obtained from the Distress Thermometer showed a degree of discomfort equal to 4.71,For example, in younger patients' levels of distress are greater in relationships, whereas in married/defacto women and workers distress levels are greater in practical areas. Results from this study can be useful to identify patients at risk for non-adhe- rence and distress, and consequently to help, the oncology team. Despite this, the study of adherence and related-factors needs further investigation.

  8. The 2012 Hormone Therapy Position Statement of The North American Menopause Society

    Science.gov (United States)

    2012-01-01

    Objective This position statement aimed to update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2010 regarding recommendations for hormone therapy (HT) for postmenopausal women. This updated position statement further distinguishes the emerging differences in the therapeutic benefit-risk ratio between estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) at various ages and time intervals since menopause onset. Methods An Advisory Panel of expert clinicians and researchers in the field of women’s health was enlisted to review the 2010 NAMS position statement, evaluate new evidence, and reach consensus on recommendations. The Panel’s recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. Results Current evidence supports the use of HT for perimenopausal and postmenopausal women when the balance of potential benefits and risks is favorable for the individual woman. This position statement reviews the effects of ET and EPT on many aspects of women’s health and recognizes the greater safety profile associated with ET. Conclusions Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms and to prevent osteoporosis in women at high risk of fracture. The more favorable benefit-risk ratio for ET allows more flexibility in extending the duration of use compared with EPT, where the earlier appearance of increased breast cancer risk precludes a recommendation for use beyond 3 to 5 years. PMID:22367731

  9. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients

    Directory of Open Access Journals (Sweden)

    Ravaioli Laura

    2011-02-01

    Full Text Available Abstract Background In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available. Methods To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route, we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol, pain (VAS and other pain questionnaires, andrological (Ageing Males' Symptoms Scale - AMS and psychological (POMS, CES-D and SF-36 parameters were evaluated at baseline (T0 and after 3, 6 and 12 months (T3, T6, T12 respectively. Results The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID progressively improved from T3 to T12 while the other pain parameters (VAS, Area% remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time. Conclusions In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management.

  10. Effects of hormone replacement therapy on endothelial function in menopausal women

    Institute of Scientific and Technical Information of China (English)

    Jin-rn Yang; Fen Li

    2009-01-01

    Objective To observe the effects of hormone replacement therapy (HRT) on endothelial function in menopausal women. Methods A total of 30 menopausal women were treated with 2.5 mg of Tibolone (Livial) daily. At the same time, 30 women with natural menopause without any treatment served as the control group. Endothelium-dependent (EDD), endothelium-independent (NID) vasodilatation function, and estradiol (E2) were examined by the non-invasive high-resolution ultrasonography before the treatment and at 12th, 24th, 36th and 48th week of treatment, respectively. Results After hormone treatment, E2 increased significantly and EDD was improved significantly (P<0.05), and E2 was positively related with EDD (r=0.8092, P<0.001). No change of EDD was observed in the control group whereas a significant increase was observed in the treatment group. Conclusion Endothelium-dependent vasodilatation dysfunction is prominent in menopausal women. Tibolone can help improve the condition.

  11. Beliefs about bioidentical hormone therapy: a cross-sectional survey of pharmacists.

    Science.gov (United States)

    Siyam, Tasneem; Yuksel, Nesé

    2013-02-01

    The aim of this study was to assess pharmacists' beliefs about bioidentical hormone therapy (BHT) and to identify factors influencing these beliefs. This was a cross-sectional survey of pharmacists. An email invitation to participate in the online survey was sent to a random sample of 2000 pharmacists in Alberta. The survey was accessible for a six-week period from May to July, 2011. A 54-item questionnaire was used to capture knowledge and beliefs about, and confidence in BHT. Summary statistics and multivariate regression were used for analyses. Overall, 401 pharmacists completed the survey (response rate 20%). Respondents were mainly female (64%), above 30 years of age (81%) and in practice for more than 10 years (63%). Only 35% of respondents correctly classified BHT as including both compounding and commercial products. In regards to beliefs, 68% of respondents agreed that BHT is as effective as non-bioidentical hormones for vasomotor symptoms, while 60% agreed BHT had equal risk. Beliefs on estriol, progesterone, and saliva testing however, were more diverse with many "do not know" responses (40%). In multivariate analysis, pharmacists who worked in pharmacies that compounded BHT were more likely to believe in BHT safety (pBHT (pBHT. In addition, beliefs on the safety of BHT were associated with pharmacists' practice, specifically working in a pharmacy that compounds BHT. This study helps identify areas for targeted education. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Hormone replacement therapy: will it affect seizure control and AED levels?

    Science.gov (United States)

    Harden, Cynthia L

    2008-03-01

    Interest in the years of reproductive changes for women with epilepsy (WWE), specifically perimenopause, menopause and postmenopause has been emerging in the epilepsy community. This article discusses evidence for changes in seizure frequency during perimenopause and postmenopause. Further, a catamenial epilepsy pattern during the reproductive years may be a hallmark for the observed seizure frequency change during these years; that is, an increase at perimenopause but a decrease at menopause. This finding implies that a subset of WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in questionnaires, and was later borne out in a clinical trial. The laboratory counterpart of this human trial, HRT in ovariectomized rodent seizure models, shows that estrogen and progesterone are neuroprotective and do not uniformly increase seizure frequency. Possible reasons for the discrepancy between "the lab and the clinic" are presented. Strategies for managing HRT in symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that may be less likely to promote seizures are discussed.

  13. Effect of hormone therapy on exercise capacity in early postmenopausal women.

    Science.gov (United States)

    Mercuro, Giuseppe; Saiu, Francesca; Deidda, Martino; Mercuro, Silvia; Vitale, Cristiana; Rosano, Giuseppe M C

    2007-10-01

    To compare the exercise capacity of postmenopausal women with matched premenopausal controls, as well as postmenopausal women before and after 3 months of hormone therapy (HT). This study examined the response to strenuous isotonic exercise in 30 women with recently developed menopause (age, mean+/-standard deviation, 50.6+/-1.1 years) without cardiovascular risk factors or diseases. Thirty premenopausal subjects, matched one-to-one for age and biophysical characteristics, were the control group. Postmenopausal women underwent examination before (T(0)) and 3 months after (T(1)) HT (oral 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone acetate/day) with high-resolution ultrasound determination of peripheral flow-mediated vasodilation and an integrative cardiopulmonary test. Postmenopausal women showed an impairment of flow-mediated vasodilation (Pexercise intolerance, and there are benefits in introducing HT.

  14. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian

    2017-01-01

    OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy...... birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0...

  15. Hormone Replacement Therapy: An Increased Risk of Recurrence and Mortality for Breast Cancer Patients?

    Science.gov (United States)

    Lupo, Molly; Dains, Joyce E.; Madsen, Lydia T.

    2015-01-01

    Historically, randomized controlled trials (RCTs) have shown an increased risk of recurrence and mortality among women who have used primarily oral HRT after breast cancer. However, many of these studies have had design flaws that may impact the findings. Numerous investigators have concluded that additional RCTs should be performed, but because of ethical issues and logistic challenges, large-scale RCTs are unlikely. Thus, the authors conducted an integrative review investigating recurrence and mortality data among breast cancer survivors who have used hormone replacement therapy (HRT). They recommend a stepwise algorithm for treating vaginal symptoms in breast cancer survivors: (1) start with nonhormonal treatments; (2) progress to a detailed discussion among patients and health-care professionals about the current known risks and benefits of vaginal estrogen; and (3) conclude with mutual decision-making between health-care providers and patients regarding the use of vaginal estrogen treatment. PMID:26705493

  16. Changing pattern of thyroid and adrenal function in postmenopausal women after hormone replacement therapy

    Institute of Scientific and Technical Information of China (English)

    Lu Shu-lan; Yu Shan-shan; Cao Zuan-sun

    2005-01-01

    Objective:To investigate the changing pattern of thyroid and adrenal function in postmenopausal women; and the relationship between hormone replacement therapy (HRT) and thyroid and adrenal function. Methods:The levels of tT3, tT4, fT3, fT4, TSH and cortisol were measured in 60 postmenopausal women (30 cases in HRT group; 30 cases in control group) before and 12 months after HRT.Results:The serum levels of tT3, tT4, fT3, fT4, TSH and cortisol had no significant difference before and 12 months after HRT in postmenopausal women. The values of them were all in normal ranges.Conclusion:Changing pattern of thyroid and adrenal function was not as significant as that of gonads in postmenopausal women and the impact of HRT on it was not so significantly evident.

  17. Description of women's personality traits and psychological vulnerability prior to choosing hormone replacement therapy

    DEFF Research Database (Denmark)

    Loekkegaard, E; Eplov, L F; Køster, A

    2002-01-01

    INTRODUCTION: Data suggest that women using hormone replacement therapy (HRT) represent a special subgroup of the general population regarding, for instance, cardiovascular risk factors and education. OBJECTIVE: To analyse if women who choose HRT are characterised a priori by high neuroticism score...... included Eysencks personality questionnaire concerning intro/extroversion and neuroticism. At the age of 45, the re-examination of the women included a test for psychological vulnerability. The participants reported whether or not they used HRT at the age of 40, 45, 51 and 60 years. The analyses comprised...... "never users" of HRT and "future users", defined as women who started HRT subsequent to baseline registration during the observation period. The groups were compared by multivariate statistical methods to adjust for confounding factors. RESULTS: Women with high neuroticism score at the age of 40 were...

  18. The influence of hormone therapies on type I and II endometrial cancer

    DEFF Research Database (Denmark)

    Mørch, Lina S.; Kjær, Susanne K.; Keiding, Niels

    2016-01-01

    The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes...... of administration and about the influence of tibolone. We followed all Danish women aged 50–79 years without previous cancer or hysterectomy (n = 914,595) during 1995–2009. From the National Prescription Register, we computed HT exposures as time-dependent covariates. Incident endometrial cancers (n = 6,202) were...... identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1...

  19. Hormone replacement therapy and age-related brain shrinkage: regional effects.

    Science.gov (United States)

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Acker, James D

    2004-11-15

    Neuroprotective properties of estrogen have been established in animal models, but clinical trials of hormone replacement therapy (HRT) produced contradictory results. We examined the impact of HRT on age-related regional changes in human brain volume. Six brain regions were measured twice, five years apart, in 12 healthy women who took HRT and in matched controls who did not. The controls showed a typical pattern of differential brain shrinkage in the association cortices and the hippocampus with no change in the primary visual cortex. In contrast, women who took HRT showed comparable shrinkage of the hippocampus but no significant shrinkage of the neocortex. Future large scale studies may benefit from applying regional rather than global measures in assessment of brain integrity.

  20. [Puberty-delaying hormone therapy in adolescents with gender identity disorder].

    Science.gov (United States)

    Nakatsuka, Mikiya

    2013-01-01

    The guideline for the treatment of people with gender identity disorder (GID) of the Japanese Society of Psychiatry and Neurology was revised in January 2012. The guideline eased restrictions for the endocrine treatment of transsexual adolescents. A medical specialist can start treating transsexual adolescents at the age of 15 after the diagnosis of GID. It recommends that transsexual adolescents (Tanner stage 2 [mainly 12-13 years of age]) are treated by endocrinologists to suppress puberty with gonadotropin-releasing hormone (GnRH) agonists until the age of 15 years old, after which cross-sex hormones may be given. Female-to-male transsexuals do not necessarily want to start androgen therapy before presenting female secondary sexual characteristics because androgen can easily stop menstruation, cause beard growth, and lower the voice. On the contrary, male-to-female transsexuals want to start estrogen therapy before presenting male secondary sexual characteristics because estrogen cannot alter the beard and low voice. It is important to identify children with gender dysphoria in school and help them receive medical advice. However, approximately half of school teachers think that children with gender dysphoria are very rare and they do not know of the notification from Ministry of Education, Culture, Sports, Science and Technology, JAPAN, which aims to help children with gender dysphoria. The revision of the guideline for the treatment of transsexual people and endocrine treatment of transsexual adolescents by medical specialists may prevent them from attempting suicide, being depressive, and refusing to attend school. Furthermore, the treatment may help avoid mental disorders, aid being employed with the desired sexuality, and, subsequently, getting married and having children.