Significant Increase In Follicle-stimulating Hormone Research Articles

Aphrodisiac Potential of Tiger Nut (Cyperus esculentus L.) Powder in Male Wistar Albino Rat

This study aimed to assess the aphrodisiac potential of tiger nuts (Cyperus esculentus L.) powder in male Wistar albino rats. Twenty-five male and twenty-five female rats were used for the experiment. The male rats were selected into five groups of 5 rats/group. Two groups served as normal and positive controls. Three groups were fed with feed supplemented with varying concentrations of Cyperus esculentus powder (5%, 10%, and 20%) for fourteen (14) days. After the treatment, sexual behaviors, fasting blood glucose, lipid profile, nitric oxide, and some sex hormone levels were assayed. The results showed a significant variation in mount frequencies, while significant increases were observed in intromission frequency and intromission ratio as compared to the normal control. Significant increases in the body weight of both the normal control and treated groups were observed. However, the fasting blood glucose level was not altered significantly. Lipid profile levels were increased in rats fed a 20% tiger nut supplementary diet when compared with the control, whereas low-density lipoprotein was not changed significantly. Nitric oxide concentration significantly increased in the testes but decreased in the kidneys of the treated groups. The results of sex hormone levels showed a significant increase in follicle-stimulating hormone and testosterone with no variation in luteinizing hormone. These results showed that Cyperus esculentus powder can improve the sexual behavior of male rats, hence giving credence to the aphrodisiac potential of Cyperus esculentus.

Hormono-metabolic disorders in women with hypothalamic syndrome in the ontogenetic aspect

Introduction. The rising incidence of obesity among children and adolescents has become a major public health problem. Problems of female reproductive function associated with obesity include menstrual irregularities, complications of pregnancy and childbirth, and infertility.Aim. To conduct a prospective analysis of carbohydrate, lipid metabolism, neuroendocrine regulation in women with primary infertility and hypothalamic syndrome of puberty.Materials and methods. Prospective, longitudinal study of adolescent girls (n=170) with hypothalamic dysfunction for 14.2±1.6 years, mean age was 14.41±0.26 years. The second stage of the study included an assessment of the hormonal status and metabolic changes in 86 women, of which 46 were fertile, 26 had primary infertility and 14 had secondary infertility, mean age was 21.89±1.15 years. Clinical and laboratory methods were used to study the indicators of lipid and carbohydrate metabolism, pituitary-ovarian and adrenal hormonal regulation systems, instrumental and functional research methods, as well as statistical analysis methods were carried out.Results. Among adolescent girls with hypothalamic dysfunction a high proportion of secondary amenorrhea − 31% (p=0.042) and metabolic syndrome − 86% was revealed, as well as a significant increase in follicle-stimulating hormone, testosterone, cortisol and a decrease in the concentration of progesterone, inhibin B, an increase in cholesterol, low density lipoproteins, triglycerides, the HOMA index, insulin and a decrease in high density lipoprotein cholesterol. We found a high proportion of polycystic ovary syndrome − 19.8%, polymenorrhea − 18.6%, oligomenorrhea − 19.8%, primary infertility − 30.2%, (p=0.001) in women with a history of hypothalamic obesity in the pubertal period. We determined a set of primary infertility predictors: the presence of triglyceridemia and hyperlipidemia in the puberty period (OR 9.5; 95%CI [1.7–51.9]) and hormone-dependent diseases in the reproductive period (OR 5.6; 95%CI [2.5–18.2]).Conclusion. In our opinion, timely prevention and correction of lipid metabolism disorders in adolescents, as well as early detection of hormone-dependent diseases in the reproductive period are promising for the prevention of reproductive disorders.

Nesfatin-1, Dopamine, and NADPH levels in Infertile Women with Polycystic Ovary Syndrome: Is There a Relationship Between Their Levels and Metabolic and Hormonal Variables.

Polycystic ovary syndrome (PCOS) is commonest endocrine disease occurring in women of reproductive age. This study conducted to clarify altered concentrations of Nesfatin-1, nicotinamide adenine dinucleotide phosphate (NADPH), and dopamine in PCOS women and controls. Also, to assess their role in PCOS pathophysiology and their correlation with measured biochemical parameters. In this observational study, 60 PCOS patients and 24 controls included. Medical history was recorded and full examinations were done. Serum concentrations of lipid profile, fasting blood glucose (FBG), fasting insulin (FSI), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone, progesterone, estradiol, Nesfatin-1, dopamine, and NADPH were measured by ELISA kits. Values were analyzed using unpaired t-test and Pearson Chi-square test. The p<0.05 was considered statistically significant. In this study, there was significantly elevated waist hip ratio (WHR) and body mass index (BMI) in PCOS patients versus controls (p<0.0001 and p=0.014). There was significant increase in FSH, LH, prolactin, estradiol, testosterone, Nesfatin-1, and dopamine (p=0.021, p=0.015, p<0.0001, p<0.0001, p=0.006, p=0.017, p< 0.0001) and decrease of NADPH (p<0.0001) in PCOS patients. There were significant positive correlations between Nesfatin-1, prolactin, and dopamine levels. Also, there was significant positive correlation between dopamine and BMI, FSI, FSH, LH, estradiol, and prolactin levels; however, significant negative correlations observed between NADPH and BMI, FSI, estradiol, and prolactin levels. Elevated serum Nesfatin-1 concentrations and their association with hyperprolactinemia indicate that they have a role in PCOS pathophysiology. Moreover, elevated dopamine and decreased NADPH concentrations could play role in PCOS pathogenesis.

Harmful Consequences of Proton Pump Inhibitors on Male Fertility: An Evidence from Subchronic Toxicity Study of Esomeprazole and Lansoprazole in Wistar Rats.

Proton pump inhibitors (PPIs) are frequently prescribed as gastric acid-suppressing agents. Nevertheless, there is limited evidence supporting the risk of detrimental effects of PPIs on male fertility. The purpose of the current study was to evaluate the effect of subchronic use of proton pump inhibitors on male fertility. Seventy adult male Wistar rats were assigned into seven groups. The normal control group orally received solvent only. Groups 2, 3, and 4 were orally given esomeprazole while groups 5, 6, and 7 received lansoprazole at 2.5, 5, and 10 mg/kg/day, respectively. After 45 days of treatment, blood samples, epididymis, and testis were collected. Sperm count, motility, and morphology were determined. The level of hormones such as testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) and oxidative status of testis tissue, such as superoxide dismutase, catalase, reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were estimated. Results demonstrated a significant decline in sperm count, motility, morphology, testosterone, and catalase at 10 mg/kg/day and GSH at 2.5 mg/kg/day. A significant increase in FSH, LH, and MDA at 10 mg/kg/day and NO at 2.5 mg/kg/day was found as compared to the control group. The pathological alterations specifically dilation of Leydig cells, vacuolization, and degeneration of the seminiferous tubules were also evident. It is concluded that PPIs had caused male reproductive toxicity in Wistar rats due to altered levels of hormones such as testosterone, FSH, and LH, elevated levels of NO, and oxidative stress.

ОСОБЕННОСТИ ИЗМЕНЕНИЯ УРОВНЯ ГОРМОНОВ ПРИ ПАТОЛОГИИ ЭНДОМЕТРИЯ В ПОСТМЕНОПАУЗАЛЬНОМ ПЕРИОДЕ

Background. In recent decades, the increase in life expectancy has led to a significant increase in the duration of the postmenopausal period. Prolonged estrogen deficiency contributes to an increase in the incidence of chronic somatic diseases, including neurovegetative, metabolic-endocrine, and psycho-emotional disorders that define the menopausal syndrome. Aim. To study the prognostic and diagnostic significance of hormone parameters in endometrial abnormalities in the postmenopausal period. Material and methods. Forty-seven women with various clinical manifestations of endometrial pathology in the postmenopausal period were examined. The mean age of the examined women was (58,43±1,1) years. All the patients had luteinizing hormone, follicle-stimulating hormone, progesterone, testosterone, estradiol, dehydroepiandrosterone sulfate, and serum sex hormone-binding globulin measured by enzyme immunoassay. The results obtained were subjected to statistical processing using standard computer programs «Statgraph» designed for parametric and nonparametric methods of calculating mean values. We calculated mean and standard deviation (M±Se), as well as minimum-maximum values for the sample. Differences were considered significant at p&lt;0,05. Results and discussion. As a result of the study the abnormality of the endometrium in the postmenopausal period was determined. Endometritis was observed in 4 (8,5%) of 47 patients, atrophic endometrium in 7 (14,9%) patients, diffuse endometrial hyperplasia in 3 (6,4%) cases, endometrial polyp in 29 (61,7%) cases, and endometrial carcinoma in 3 (6,4%) cases. A significant increase in follicle-stimulating hormone [(65,39±1,27) mmE/ mL], luteinizing hormone [(34,85±0,15] mmE/mL), estradiol [(88,73±2,1) pg/mL], and testosterone [(2,29±0,08) ng/mL] values was registered in the postmenopausal patients, which is an important prognostic and diagnostic criterion in this patient population. Conclusion. The study of hormone parameters in the postmenopausal period is one of the most important methods of early detection of various endometrial abnormalities, allowing timely implementation of appropriate therapeutic and preventive measures.

Effects of Xylopia aethiopica Pod Extract on Reproductive Hormones in Female Wistar Rats

Plants and their metabolites have been used in the treatment of various disease conditions from time immemorial. This study investigated the effect of hydro-ethanolic extract of pods of Xylopia aethiopica on reproductive hormone (follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone) in female Wistar rats. Thirty female wistar rats were randomly divided into 5 groups of six animals per group, per cage (n=6). Group A served as the normal control group and was administered distilled water while group B served as positive control and was administered 5 mg of standard drug (Clomid-Clomiphene Citrate). Groups C, D and E served as the treatment group and was administered 50 mg/kg, 100 mg/kg and 200 mg/kg extract of X. aethiopica respectively for seven days. Administration of drugs and extract was done via oral route. The rats were thereafter copulated with their male counterparts for 72 hours and the female rats were observed throughout their gestation and the numbers of litters produced were recorded. The hormonal assay was carried out using Enzyme Linked Immunosorbent Assay. Result showed a significant increase in FSH and Progesterone level (p&lt;0.05) in treated group when compared with the control group while no significant difference (p&gt;0.05) was observed for the luteinizing hormone in the treated groups. The work thus showed that the plant could exert a positive effect on female fertility by enhancing levels of female reproductive hormones.

The effect of lipid disturbance and vitamin D on the fertility in male albino rats

ABSTRACT Background: Vitamin D has multiple biological effects on male reproductive system. Vitamin D deficiency (VD−) and disturbance of lipid metabolism can induce changes in testicular hormone production and seminal parameters that relate to male infertility. Objective: To investigate the role of vitamin D and lipid metabolism on fertility in male albino rats. Methods: The study was performed on 60 male rats, divided into 6 groups; GI: control group, GII: orlistat group, GIII: orlistat and vitamin D group, GIV: hyperlipidemic group, GV: hyperlipidemic orlistat group and GVI: hyperlipidemic orlistat and vitamin D group. Serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c), 25-hydroxyvitamin D (25(OHD), testosterone (T), inhibin B, follicle-stimulating hormone (FSH) and estradiol (E) levels were determined. Sperm count and viability were also analyzed. Results: Administration of orlistat in GII caused significant alterations of the serum lipid profile, compared to control group. There was interaction between dietary fat and VD− on serum 25 (OHD). A significant VD− was occurred in both GII and GIV, compared to GI. VD− in these groups consequently caused significant decrease in serum T, inhibin B, sperm count and viability and significant increase in FSH and E levels. Administration of orlistat in GV caused significant changes in serum lipid profile, a decrease in E, increase in 25(OHD) and inhibin B, compared to IV. On the other hand, administration of vitamin D with orlistat in GIII and GVI caused significant increase in HDL-c, 25(OHD), T, sperm count and viability and significant decrease in TC, TG, LDL-c, FSH and E. Conclusion: Both hyperlipidemia and hypolipidemia were associated with vitamin D deficiency. Moreover, vitamin D has a positive potential effect on male fertility in either hyperlipidemic or hypolipidemic rats.

Ethanolic extract of Moringa oleifera leaves alleviate cyclophosphamide-induced testicular toxicity by improving endocrine function and modulating cell specific gene expression in mouse testis

Ethnopharmacological relevanceMoringa oleifera Lam. is known for its nutritional and ethno medicinal values due to the presence of wide array of phytochemicals with multiple biological activities. We have previously reported that ethanolic extract of Moringa oleifera leaves (MOE) ameliorated cyclophosphamide (CP)-induced testicular toxicity and improved functional integrity of spermatozoa as well as spermatogenic cells. Aim of the studyThe present study was planned to investigate whether the mitigation of CP-induced testicular toxicity by MOE is mediated via modulation of endocrine profile, genes associated with function of different cell types and enhancement of DNA repair response in spermatogonial cells. Materials and methodsAdult Swiss albino mice (8 week) were injected with CP (100 mg/kg, one dose in a week for 3 weeks) and MOE (100 mg/kg, 5 doses in a week for 4 weeks) either alone or in combination intraperitoneally. At 35 day post CP injection (first dose), the functional characteristics such as count, motility, head morphology and DNA integrity were assessed in epididymal spermatozoa. Key reproductive hormones like testosterone, follicle stimulating hormone (FSH) and Inhibin B concentration were analyzed in serum and testis. In addition, mRNA expression of genes pertaining to the function of Leydig, Sertoli and spermatogonial cells as well as antioxidant enzymes were evaluated in the testis. To understand the DNA damage and repair process in germ cells, prepubertal (2 week) mice were administered with single dose of CP (200 mg/kg) and/or MOE (100 mg/kg) and analyzed for expression of DNA damage (γ-H2AX, P53 and Caspase3) and repair genes (Rad51 and Ku80) in isolated spermatogonial cells at various time points after treatment. ResultsCP administration resulted in decrease in count, motility and increase in morphological defects and DNA damage in spermatozoa. Testosterone level was marginally decreased while there was a significant increase in FSH (p < 0.001) and decrease in inhibin B (p < 0.05) observed in CP treated mice. Administration of MOE prior to CP, improved sperm functional characteristics, decreased FSH and increased inhibin B levels. Expression of Abp was down-regulated while Transferrin, Fshr and Gata4 (Sertoli cell specific genes) were up-regulated in testis treated with CP. Administration of CP down-regulated the expression of Oct4 and Ddx4 (Spermatogonia specific genes). MOE administration was shown to ameliorate CP-induced damage by modulating the expression of genes specific to Sertoli and spermatogenic cells. Furthermore, MOE treatment reduced CP-induced DNA damage as evident from lower percentage of γ-H2AX positive spermatogonial cells. ConclusionAdministration of MOE mitigated CP-induced testicular damage by improving blood and, intra-testicular hormonal milieu as well as modulating the expression of genes pertaining to Sertoli and spermatogonial cells.

The Impact of Zinc Oxide Nanoparticle on LH, FSH, and Testosterone Hormones in Mature Male NMRI Rats

Nanoparticles are widely applied in all aspects of modern life because of their unique features such as small size and high surface area. Several types of research have been carried out to discover the feasible detrimental impacts of Nano-particles on human reproduction. The purpose of this study was to examine the impact of zinc oxide nanoparticles in mature male rats through examining LH, FSH, and testosterone sex hormones. Therefore, 30 Naked Mole-Rat Initiative (NMRI) rats were divided into 5 groups. Different doses of zinc oxide nanoparticles (250, 500 and 700 mg.kg-1) were intra peritoneally injected to animals only once. Then, the serum level of luteinizing hormone (LH), Follicle Stimulating Hormone (FSH), and testosterone hormones were measured using Enzyme-Linked Immunosorbent Assay (ELISA) method after 21 days. The results were analyzed by ANOVA and Tukey tests. The results indicated that zinc oxide nanoparticles doses caused a significant increase in FSH and testosterone level of blood (Respectively) in 250 and 700mg.kg-1 in comparison with the control group. Moreover, this research illustrated that zinc oxide nanoparticle can cause a dose-related increase in Testosterone and FSH hormones levels while causing no significant change in LH hormone level.

Melatonin ameliorates some biochemical alterations following ketoconazole administration in rats.

Background Ketoconazole (Keto), an antifungal drug and a common therapeutic option in the treatment of advanced prostate cancer, is known to cause reproductive dysfunctions. Like Keto, melatonin has antifungal and anticarcinogenic actions. Moreover, the hormone has been used to reverse the damaging effects of different toxicants on the reproductive system. Therefore, this study investigated the effects of Keto with/without melatonin on selected biomarkers in rats. Methods Forty rats of 10 animals per group were used in this study, which lasted for 6 weeks. The control group was administered with saline (0.1 mL/day), while group 2 was administered with Keto during the last 3 weeks of experiment; however, in groups 3 and 4, Keto was administered during the first 3 weeks; thereafter, they were administered with saline and melatonin, respectively, during the subsequent 3 weeks. Keto and melatonin were administered at 100 and 10 mg/kg b.w./day (p.o.), respectively. Results The central effects of Keto are independent of the follicle stimulating hormone (FSH) and prolactin; however, relative to the control group, the drug significantly decreased the gonadotrophin releasing hormone (GNRH) and the luteinizing hormone (LH), substantiated by the corresponding significant decreases in sperm count and sperm morphology. Keto caused significant elevations in malondialdehyde (MDA) and lactate dehydrogenase (LDH) and a significant decrease in catalase (CAT) compared with the control group. Moreover, the drug triggered pro-inflammatory events. In group 3 (Keto recovery), MDA and uric acid levels were returned to the baseline (i.e. control), but not GNRH, LH, C-reactive protein (CRP), LDH, and CAT. Treatment with melatonin after Keto administration caused significant increases in FSH, LH, superoxide dismutase, total antioxidant capacity (TAC), sperm count, and sperm morphology but significant decreases in MDA and CRP, relative to groups 2 and 3. Conclusions Melatonin ameliorates some biochemical alterations following ketoconazole administration.

A Retrospective Study of the Relationship Between Testicular Damage and Urinary Creatine Excretion: Possible Markers of Testicular Toxicity Induced by Drugs

ObjectivesCreatine and creatine phosphate act as a buffer system for the regeneration of ATP in tissues with high and fluctuating energy demands. Total creatine content of the rat testis is high compared to all other tissues except skeletal muscle and creatine excretion in rat urine has been shown to increase following testicular damage caused by toxicants. Because the use of biomarkers in toxicology is becoming increasingly important, we investigated whether urinary creatine might be a useful marker for testicular damage in human.MethodsIn a retrospective study, the records of 22 male patients with urological malignancies treated with cisplatin, leuprorelin or goserelin at 4‐week intervals between October 2005 and October 2015 were evaluated. Urinary creatine and serum follicle‐stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels were assessed in all patients. Single‐voided urine samples were collected to determine urinary creatine‐to‐creatinine ratios. Blood sample collection was done in the morning when serum testosterone levels are around their peak: such morning time sampling for testosterone measurements is recommended in the clinical setting and routinely used in epidemiological studies.ResultsSeven patients with urothelial carcinoma treated with cisplatin based chemotherapy (mean age, 64.1 years) showed no significant changes in urine creatine/creatinine ratio during treatment and had a significant increase in FSH and LH levels and a significant decrease in testosterone levels compared to those at baseline. Similarly, no significant changes in urine creatine/creatinine ratio occurred in patients with prostatic carcinoma treated with leuprorelin (n=8; mean age, 70.0 years) or goserelin (n=7; mean age, 70.4 years), both of whom had castrate levels of testosterone (≤0.5 ng/mL) and suppressed levels of FSH and LH during treatment.ConclusionsOur data demonstrate that testicular damage could not be detected by urinary creatine in patients treated with drugs showing testicular toxicity. Two major testicular functions, i.e., the production of testosterone and formation of haploid germ cells, are generally considered to be regulated by pituitary gonadotrophins, with LH acting on the testosterone‐producing Leydig cells located in the interstitium and FSH affecting Sertoli cells in the seminiferous tubules. Thus, our hormonal data may indicate the presence of cisplatin‐induced Sertoli cell dysfunction and inhibition of Leydig cell function by LH‐RH analogues.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of hormonal suppression with two contraceptive regimens using ethinyl estradiol and desogestrel

Because of the lack of data on hormone levels in the hormone-free interval of the contraceptive regimens with desogestrel and ethynil estradiol, the objective of this study was to compare hormonal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin B using two contraceptive regimens with those steroids. Prospective and randomized study with 21 patients. Eleven patients received a 21/7 regimen (group 1) and ten patients received a 21/2 placebo/5 ethinyl estradiol 10 μg regimen (group 2). We found a significant increase in FSH and LH levels in both groups. There was a significant reduction of inhibin B in the 21/2/5 regimen. No difference in estradiol levels was found. Steroids withdrawal in the hormone-free interval causes reduced inhibition of the HPO axis. The significant decrease in inhibin B levels of group 2 suggests better suppression of the HPO axis in the 21/2/5 regimen.

Evaluation of Endocrine Profile, Hypothalamic–Pituitary–Testis Axis and Semen Quality in Multiple Sclerosis

Several endocrine and sexual disturbances have been demonstrated in multiple sclerosis (MS) patients of both sexes. The endocrine profile, hypothalamic-pituitary-testis (HPT) axis and semen quality were evaluated in male patients with MS. A total of 68 male MS patients aged 18 years or older were recruited. Forty-eight age-matched healthy male volunteers served as controls. All subjects underwent complete physical examination and routine semen analysis. Two blood samples were drawn from each participant at 15-min intervals for the determination of the resting levels of: luteinising-hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, oestradiol and sex hormone binding globulin. The HPT axis was assessed using gonadotrophin-releasing hormone (GnRH) and human chorionic gonadotrophin tests. The mean basal serum levels for LH, FSH and testosterone in MS patients were significantly lower than the mean for normal controls (P = 0.01). The injection of GnRH analogue did not yield a significant increase in FSH and LH levels in the MS patients compared to normal controls (P = 0.001). Total sperm count, sperm motility and percent normal sperm morphology were lower in MS patients compared to controls. MS subjects with progressive disease had higher and more severe HPT axis abnormalities than that for patients with relapsing remitting MS. Most subjects with MS have hypogonadotrophic hypogonadism state and fertility impairment. It appears that the damage to HPT axis is both in pituitary and testicular levels. Further studies are needed to better elucidate the underlying pathophysiology of HPT axis dysregulation.

The beneficial effects of toremifene administration on the hypothalamic-pituitary-testicular axis and sperm parameters in men with idiopathic oligozoospermia

To evaluate whether toremifene, a selective estrogen receptor modulator (SERM), has a beneficiary effect on all three main sperm parameters. Prospective interventional clinical study. University hospital. One-hundred subfertile men with idiopathic oligozospermia. Toremifene (60 mg daily) was administered to all men for 3 months. At baseline and at the end of each month, serum concentrations of follicle-stimulating hormone (FSH), testosterone, inhibin B, and sex hormone-binding globulin (SHBG) were measured. At baseline and at the end, semen analysis was performed and sperm concentration, spermatozoal motility and normal sperm forms were determined. Gonadotropin, testosterone, inhibin-B levels, total sperm count, sperm morphology and motility. Toremifene administration resulted in a significant increase in FSH, testosterone, SHBG, and inhibin B levels, as well as in sperm concentration, percentage motility and normal sperm forms. Twenty-two men's partners achieved pregnancy within 2 months of the end of treatment. At the end of the third month, serum FSH levels were significantly higher in the men whose partners did not achieve pregnancy, and total sperm count and normal sperm forms were significantly lower compared with the group of men whose partners achieved pregnancy. Toremifene administration for a period of 3 months in men with idiopathic oligozoospermia is associated with significant improvements of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. The above findings are also indicative of a better testicular exocrine (improved sperm parameters) response to treatment in men whose partners achieved pregnancy compared with those who did not. Further randomized, placebo-controlled trials should be conducted to determine whether this particular selective estrogen receptor modulator can be useful as an initial approach in men with oligozoospermia.

Metformin in normal-weight hirsute women with polycystic ovary syndrome with normal insulin sensitivity

Fifteen normal-weight (body mass index (BMI) 21.50 ± 1.65 kg/m2) hirsute women with polycystic ovary syndrome and normal insulin sensitivity were treated with 850 mg metformin orally, three times daily, for 4 months. Before and at the end of the treatment, clinical data as well as serum concentrations of sex steroid hormones, gonadotropins, fasting plasma glucose and insulin, insulin resistance – homeostasis model assessment (HOMA-IR), carbohydrate tolerance and the area under the curve for insulin (AUCinsulin) were analyzed. Three patients withdrew from the study. Seven of the remaining 12 patients presented menstrual pattern improvement, followed by ovulatory cycles at the end of the treatment period. There were no changes in BMI and hirsutism score. A significant (p < 0.05) decrease in luteinizing hormone (LH) (from 8.18 ± 4.34 to 5.05 ± 1.53 IU/ml), testosterone (from 104.66 ± 27.54 to 82.00 ± 23.05 ng/dl), fasting insulin (from 9.66 ± 4.79 to 7.83 ± 3.06 µIU/ml), AUCinsulin (from 9239 ± 3285 to 7660 ± 2565 µUI/ml × min) and HOMA-IR (from 2.15 ± 1.2 to 1.67 ± 0.74), and a significant increase in follicle-stimulating hormone (FSH) (from 4.05 ± 1.53 to 5.96 ± 2.13 IU/ml), were observed at the end of the treatment period. A higher LH and a lower FSH predicted clinical improvement, while basal insulin and AUCinsulin showed lower predictive value.

Effects of metformin treatment in women with polycystic ovary syndrome depends on insulin resistance

Polycystic ovary syndrome (PCOS) affects 5–10% of women at reproductive age, and is the most common reason for hyperandrogenism and chronic anovulation. Some patients with PCOS are insulin-resistant. Also, lowered sex hormone-binding globulin (SHBG) concentration is usually observed. As a consequence, the amount of free and biologically active androgens increases. This implies that, by improving insulin and carbohydrate metabolism, metformin administration in PCOS patients could indirectly contribute to increase SHBG concentration. The aim of the present study was to assess the effects of metformin treatment in PCOS patients both with and without insulin resistance. Thirty-six patients completed treatment. Body mass index (BMI) was considerably reduced after therapy. Statistically significant decreases were noted in luteinizing hormone (LH) and fasting insulin concentrations and the free androgen index (FAI), and significant increases in follicle-stimulating hormone (FSH)/LH ratio and SHBG concentration. In the insulin-resistant group, BMI and fasting insulin concentrations were reduced considerably after treatment, and SHBG increased slightly. In the group of patients without insulin resistance, BMI, LH and FAI showed significant reductions, and FSH/LH and SHBG considerable increases. Considering the favorable effects of metformin treatment in PCOS patients both with insulin resistance and without it, it is purposeful to use this drug in both groups of women.

Age-related differences in serum gonadotropin (FSH and LH), salivary testosterone, and 17-? estradiol levels among Ache Amerindian males of Paraguay

Age-related differences in serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), salivary testosterone, and 17-beta estradiol levels are reported for Ache Amerindian males (n = 17; mean age, 37.1 +/- 14.2 SD) of Paraguay in order to explore population variation in patterns of male reproductive senescence in a foraging/agricultural community. Hormone associations were examined to test various hypotheses for age-related differences in hypothalamic-pituitary function. Significant increases in FSH (r = 0.75, P < 0.0005) and LH (r = 0.65, P < 0.01) were noted in association with aging. No significant correlation was observed between morning or evening testosterone and age. Morning and evening estradiol levels were associated with morning and evening testosterone, respectively (morning, r = 0.53, P = 0.05; evening, r = 0.63, P = 0.02). Evening estradiol was also positively associated with LH (r = 0.66, P = 0.02), suggesting testicular production to be an important source of circulating estradiol. Morning estradiol tended to rise with age, but was not significant (r = 0.39, P = 0.15). Anthropometric measurements of height, weight, body mass index, and fat percent did not change significantly with age. In contrast to testosterone, age-related differences in gonadotropin levels may be independent of energetic status, less variant, and more universal among male populations. Implications for gonadotropin function and aging on human male reproductive senescence and life histories are discussed.

Sirolimus Impairs Gonadal Function in Heart Transplant Recipients

The impact of sirolimus on hormone levels involved in the hypothalamus-pituitary-gonad axis in male heart transplant recipients was investigated.A pair-matched analysis with 132 male heart transplant recipients on either sirolimus based- or calcineurin inhibitor-based immunosuppression was performed. Matching criteria were age, years after transplantation and creatinine levels. Measured parameters were testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sexual hormone-binding globulin (SHBG) and free androgen index (FAI).Mean testosterone was 3.86 ± 1.41 ng/mL in the sirolimus group and 4.55 ± 1.94 ng/mL in the controls (p = 0.025). Serum LH was 12.82 ± 11.19 mlU/mL in the sirolimus patients and 6.2 ± 5.25 mlU/mL in the controls (p = 0.015). Follicle stimulating hormone levels were 13.31 ± 18.4 mlU/mL vs. 7.32 ± 5.53 mlU/mL, respectively (p = 0.015). The analysis revealed a significant decrease in testosterone and a significant increase in FSH and LH in the sirolimus group. The duration of sirolimus treatment correlated positively with SHBG (p < 0.01), LH (p < 0.05) and FSH (p < 0.05) and negative with the FAI (p < 0.05). Sirolimus trough levels correlated with LH and FSH levels (p < 0.01).Heart transplant recipients treated with sirolimus revealed significantly lower testosterone levels and a significant increase in gonadotropic hormones. These effects were trough-level dependent. All candidates awaiting organ transplantation should be informed about these adverse effects.

Effects of chronic valproate treatment on reproductive endocrine hormones in female and male Wistar rats

Valproate (VPA) has been claimed to induce endocrine disorders in both sexes in humans. There is sparse information regarding the mechanisms behind these disturbances. By using an animal model, we wanted to study the effect of valproate on hormonal function in non-epileptic rats. Female rats were given 0 (vehicle control, n=15), 200 mg/kg ( n=15), or 300 mg/kg ( n=20) valproate twice daily by gavage for 90 days, resulting in mean valproate concentrations within the therapeutic range 4–6 h after the last dose given. Serum testosterone concentrations remained unchanged, while estradiol levels were significantly reduced in both treatment groups, leading to significantly increased testosterone/estradiol ratios. Follicle stimulating hormone (FSH) levels remained unaltered in valproate treated rats, whereas the luteinizing hormone (LH) concentrations were reduced at the lowest valproate dose. Male rats received 0 (vehicle control, n=15), 200 mg/kg ( n=15), or 400 mg/kg ( n=20) valproate twice daily by gavage for 90 days, resulting in mean valproate concentrations within the therapeutic range 4–6 h after the last dose. Serum testosterone levels were not significantly changed, but there was a highly significant increase in FSH and LH concentrations at the high dose. In conclusion, the study demonstrates a drug-induced effect of valproate on endocrine function in both male and female rats. The results indicate that the drug exerts its effect primarily at the gonadal level, although a centrally mediated effect cannot be ruled out.

Effects of Polyamines on the Release of Gonadotropin-Releasing Hormone and Gonadotropins in Developing Female Rats

Polyamines, putrescine (PUT), spermidine (SPD), spermine (SPM), and agmatine (AGM), are polycationic amines related to multiple cell functions found in high concentrations during the development of hypothalamus and pituitary. In previous works, we demonstrated that alpha-difluoromethylornithine (DFMO), an inhibitor of polyamines biosynthesis, induced a delay in puberty of female rats, accompanied by high, sustained follicle-stimulating hormone (FSH) levels during the infantile period. Also, DFMO treatment induced changes in polyamine concentration both in hypothalamus and pituitary of rats, mainly a decrease of PUT and SPD, an increase in SPM, and no change in AGM. In the present work, we investigated the direct effects of polyamines on the secretion of hypothalamic GnRH and pituitary gonadotropins in 6- and 15-day-old female rats. In 6-day-old animals, in vitro incubations with PUT, SPD, and AGM of hypothalami or anterior pituitaries were able to inhibit GnRH, FSH, and leutinizing hormone (LH) secretion, respectively. SPM showed a nonspecific transient inhibitory effect on FSH. When challenged with either high K(+) (hypothami) or GnRH (pituitaries), the tissues incubated in the presence of polyamines showed no differences when compared with their controls. No effects of polyamines in 15-day-old rats in either tissue were observed. Pituitary cell cultures of 6-day-old animals incubated with DFMO for 4 days showed a significant increase in FSH, but not in LH. We conclude that high PUT, SPD, and AGM levels during the first 10 days of life are important for the development of the hypothalamic-hypophyseal unit, probably related to an inhibitory effect on GnRH and gonadotropins. Therefore, polyamine participation, especially PUT and SPD, is of importance in the regulation of GnRH and gonadotropin secretion in the neonatal and infantile periods, critical stages in the establishment of sexual differentiation.