Reduced Androgen Levels Research Articles

Sertoli Cell-Specific Modification of The Androgen Receptor DNA-Binding Domain Disrupts Sertoli Cell Function and Completion of Spermatogenesis.

Androgen receptor (AR) actions are vital for spermatogenesis, but male germ cells do not express AR, highlighting its key role in testicular somatic cells. Recent genetic models with targeted Sertoli cell (SC) AR disruption confirmed the vital role for Sertoli AR-activated pathways in spermatogenesis. However, complete loss of functional AR in these SC AR knockout (SCARKO) models excludes selective analysis of classical (via direct AR DNA binding) versus potential indirect non-classical or non-genomic AR actions. We have used a Cre-loxP strategy to selectively study the in vivo requirement of AR DNA-binding in SC function. Transgenic (Tg) mice with SC-specific Cre were crossed with mice carrying a floxed-AR gene (Arflox) to target exon 3. Cre-mediated inframe excision of exon 3, encoding a zinc finger essential for DNA-binding, was predicted to generate mutant ARΔex3 to selectively disrupt AR-regulated gene transcription via direct DNA interaction. We established two unique SC-specific ARΔex3 (SCARΔex3) models: i) AMH.SCARΔex3 derived from [Tg antimullerian hormone (AMH) promoter-driven Cre mice] X [Arflox mice], and ii) Abp.SCARΔex3 derived from [Tg androgen-binding protein (Abp) promoter-driven Cre mice] X [Arflox mice]. ROSA-LacZ reporter mice showed that the Abp promoter directs SC-specific Tg expression consistent with our past work, with testis Abp.Cre expressed as early as day 17 postcoitum. RT-PCR detected testis ArΔex3 RNA in both SCARΔex3 models. Using hemizygous TgCre mice, Abp.SCARΔex3 (49.3 ± 1.8 mg) testes were significantly larger (p < 0.001) than AMH.SCARΔex3 testes (29.9 ± 0.9 mg), and both were smaller (p < 0.001) than age-matched 9 week old controls (105.4 ± 4.4 mg). Homozygous TgCre mice were used to increase Cre expression levels. Testis size was further reduced in homozygous Abp.SCARΔex3 (31.6 ± 1.9 mg, p < 0.001) but not homozygous AMH.SCARΔex3 (32.1 ± 1.5 mg) mice relative to corresponding hemizygous TgCre SCARΔex3 testes, suggesting a maximal effect for SC Ar exon 3 disruption was achieved using Tg homozygous Abp.Cre or hemizygous AMH.Cre mice. Immunohistochemistry revealed SC nuclear AR expression was retained in SCARΔex3 testes. Despite histological detection of Leydig cell hypertrophy in SCARΔex3 testes, serum testosterone levels were equivalent to normal (22.8 ± 5.0 nM) in Abp.SCARΔex3 (15.7 ± 8.0 nM) and AMH.SCARΔex3 (16.6 ± 7.0 nM) 9 week old males, unlike the elevated or reduced androgen levels reported in SCARKO models with complete SC AR loss. Stereology revealed total SC numbers were normal in SCARΔex3 testes, whereas spermatogenesis in both SCARΔex3 models showed predominant meiotic arrest, noting larger Abp.SCARΔex3 testes using hemizygous Tg Abp.Cre mice exhibited more post-meiotic development. The testicular phenotype of these unique SCARΔex3 models demonstrates that despite nuclear ARΔex3 localisation, a functional AR DNA-binding domain is vital for Sertoli cell function and full spermatogenic development. The SCARΔex3 testes resemble SCARKO testes with complete SC AR loss, suggesting that non-genomic or pathways independent of direct AR-DNA binding play no major role in SC function. In combination, our novel SCARΔex3 models provide unique opportunity to further determine dose-dependent effects of AR activity in Sertoli cells. This research was supported by NHMRC funding.

Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

BackgroundWomen with polycystic ovary syndrome (PCOS) are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD), which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR) gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a) mice, possessing a mutation (Ay) in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction.MethodsFemale LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4) or an equal volume of vehicle (DMSO; n = 4) for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression.ResultsTwenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM), and actin-related protein 6 homolog (ARP6). For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a) non-mutant lean mice.ConclusionTZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

Effects of Weight, Body Composition, and Testosterone on Bone Mineral Density in HIV-Infected Women

Recent studies suggest that bone loss occurs among HIV-infected women. This study examined the effects of reduced androgen levels, changes in weight, body composition, and menstrual dysfunction on bone mineral density (BMD) among 152 HIV-infected women characterized by normal weight (>90% ideal body weight [IBW], n = 124) and low weight (<or=90% IBW, n = 28) compared with 100 non-HIV-infected control subjects. BMD was assessed by dual x-ray absorptiometry, and free testosterone was assessed by equilibrium dialysis. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were determined by computed tomography scan. A significant difference was seen in BMD between groups at the lumbar spine (0.92 +/- 0.02 g/cm vs. 1.01 +/- 0.01 g/cm vs. 1.07 +/- 0.01 g/cm; P < 0.0001), total hip (0.84 +/- 0.03 g/cm vs. 0.94 +/- 0.01 g/cm vs. 0.98 +/- 0.01 g/cm; P < 0.0001), and femoral neck (0.73 +/- 0.03 g/cm vs. 0.83 +/- 0.01 g/cm vs. 0.87 +/- 0.01 g/cm; P < 0.0001) (HIV-infected low-weight group, HIV-infected normal-weight group, and non-HIV-infected control subjects, respectively, for each comparison; mean +/- SEM). Among the HIV-infected subjects, lumbar BMD correlated with percent IBW (r = 0.37, P < 0.0001), total body lean mass (r = 0.43, P < 0.0001), total body fat mass (r = 0.35, P < 0.0001), and SAT (r = 0.41, P < 0.0001), but not VAT (r = 0.07, P = 0.417). Clinical risk factors for osteopenia and osteoporosis in the HIV population identified in univariate analysis included low free testosterone (<1.1 pg/mL [lower limit of the normal range of free testosterone for women] or 3.8 pmol/L; P = 0.0007), low weight (P = 0.014), and oligomenorrhea (P = 0.0006). In multivariate regression analysis, lean body mass was most significantly associated with BMD among those with HIV. These data demonstrate that BMD is reduced among HIV-infected women in association with low weight, reduced lean mass, reduced androgen levels, and abnormal menstrual function.

Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder

Background Depressive symptomatology has been connected with an activation of the hypothalamus–pituitary–adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. Methods We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. Results Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. Conclusions Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.

Essential Role for Estrogen Receptor β in Stromal-Epithelial Regulation of Prostatic Hyperplasia

Estrogens, acting via estrogen receptors (ER) alpha and beta, exert direct and indirect actions on prostate growth and differentiation. Previous studies using animal models to determine the role of ERbeta in the prostate have been problematic because the centrally mediated response to estrogen results in reduced androgen levels and prostatic epithelial regression, potentially masking any direct effects via ERbeta. This study overcomes this problem by using the estrogen-deficient aromatase knockout mouse and tissue recombination to provide new insight into estrogen action on prostate growth and pathology. Homo- and heterotypic aromatase knockout tissue recombinants revealed stromal aromatase deficiency induced hyperplasia in normal prostatic epithelium due to disruption of paracrine interaction between stroma and epithelia. Treatment of tissue recombinants with an ERbeta-specific agonist demonstrated that stimulation of ERbeta elicits antiproliferative responses in epithelium that are not influenced by alterations to systemic androgen levels or the activation of ERalpha. Additionally, work performed with intact aromatase knockout mice demonstrated that the administration of an ERbeta-specific agonist ablated preexisting prostatic epithelial hyperplasia, whereas an ERalpha-specific agonist did not. Therefore, failed activation of ERbeta, resulting from local stromal aromatase deficiency, in conjunction with increased androgen levels, results in increased epithelial cell proliferation and prostatic hyperplasia. These data demonstrate essential and beneficial effects of estrogens that are necessary for normal growth of the prostate and distinguishes them from those that adversely alter prostate growth and differentiation. This highlights the potential of selective estrogen-receptor modulators, rather than aromatase inhibitors, for the management of dysregulated prostate growth.

Seasonal testosterone UDP-glucuronosyltransferase activity and biliary steroids in Eurasian perch: Response to leachate exposure

In previous studies there was evidence of endocrine disruption in fish in waterways contaminated with leachate from a Swedish landfill. Symptoms included fewer sexually mature (SM) female perch ( Perca fluviatilis), distinct sores, reduced gonadosomatic index, and decreased plasma androgen levels. Based on previous findings it was hypothesized that the decrease in plasma androgen concentrations could have been caused by increased steroid excretion. Therefore, testosterone UDP-glucuronosyl transferase (UDPGT) activity and biliary steroids were measured in SM and sexually immature (SIM) female perch during one reproductive cycle. UDPGT activity in exposed fish did not differ from reference fish and was similar in both SM and SIM female perch. Since androgen levels in SIM fish usually are much lower than in SM fish, this indicates expression of testosterone UDPGT irrespective of substrate availability. There was no general increase in biliary steroids in exposed female perch. Biliary steroid levels correlated with corresponding plasma steroid levels. In conclusion, the reduced androgen levels in exposed female perch are most likely not caused by increased steroid excretion.

Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling THIS ARTICLE HAS BEEN RETRACTED

To evaluate the effects of metformin on insulin resistance, androgen concentration, ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS).Forty-two infertile women with PCOS were selected in this randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were randomly divided into group 1 (n = 21) and group 2 (n = 21). Group 1 patients were treated with laparoscopic ovarian drilling (LOD). Group 2 patients underwent laparoscopic ovarian drilling (LOD) and received 1700 mg per day of metformin for 6 months. LOD was performed in women with PCOS using a unipolar electrode. Serum progesterone (P) level > 5 ng/mL was considered as a confirmation of ovulation. Ovulation and pregnancy rates were determined after six cycles.Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD (34.6 +/- 25.4 ng/mL, 8.4 +/- 1.1 mm) than in those treated with LOD alone (26.2 +/- 24.7 ng/mL, 7.9 +/- 2.8 mm) (P < 0.05). The ovulation (56 of 65 cycles, 86.1% vs 29 of 65 cycles, 44.6%) and pregnancy rates (nine of 21 women, 47.6% vs four of 21 women, 19.1%) were significantly higher in group 2 than in group I.Metformin improves insulin resistance, reduces androgen levels and significantly increases the ovulation and pregnancy rates in infertile women, following LOD.

The effects of maternal exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on testicular steroidogenesis in infantile male rats

Exposure of adult male animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases serum androgen concentrations. Reduction in androgen levels after maternal exposure has also been reported, but these results have not been reproduced. We have earlier shown that TCDD stimulates rather than inhibits testosterone synthesis in the prenatal rat testis. The aim of the present study was to elucidate in utero-induced effects of TCDD on testicular steroidogenesis in the 14-day-old infant rats. At that time the foetal Leydig cell population is still the prevailing source of androgens. Pregnant Sprague-Dawley dams were given a single oral dose of TCDD (0, 0.04, 0.2, or 1.0 microg/kg) on day 13 of pregnancy. On postnatal day 14, the body weight of male offspring was reduced after exposure to 1.0 microg/kg TCDD (from 33.9 +/- 1.66 g to 31.6 +/- 2.67 g). Relative testis weight, plasma testosterone, luteinizing hormone and follicle-stimulating hormone levels remained unaltered in all exposure groups. Moreover, in ex vivo incubations, testosterone and cAMP production was not affected. StAR protein level in the freshly isolated testes was increased in the 0.2 microg/kg group, and seminiferous cord diameter in the 0.04 microg/kg group. The present study confirms our earlier findings in in utero TCDD-exposed foetal testis indicating that maternal TCDD exposure does not negatively influence the developmental testosterone production of foetal type Leydig cells in rats.

Increased adrenal androgen secretion with inhibition of 11β-hydroxylase in HIV-infected women

Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11beta-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg p.o. qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 +/- 0.9 yr), weight (91.7 +/- 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 +/- 54 vs. -0.4 +/- 2 ng/dl, P = 0.024), free testosterone (6.5 +/- 2.8 vs. 0.1 +/- 0.1 pg/ml, P = 0.024), DHEA (5.0 +/- 3.2 vs. -0.6 +/- 0.5 microg/l, P = 0.024), and 11-deoxycortisol (2,145 +/- 820 vs. -14 +/- 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 +/- 48 vs. 3 +/- 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11beta-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency.

Practical Aspects in the Management of Vaginal Atrophy and Sexual Dysfunction in Perimenopausal and Postmenopausal Women

The decline in circulating estrogen levels in peri- and postmenopause has a wide range of physiological effects, including atrophy of tissues in the urogenital tract. Vaginal atrophy is an important contributor to postmenopausal sexual dysfunction. To provide a framework for clinical evaluation and clinical management of sexual dysfunction secondary to vaginal atrophy. Conduct a brief overview of literature on evaluation and treatment of vaginal atrophy, augmented with the authors' clinical observations and experience. Estrogen decline disrupts many physiological responses characteristic of sexual arousal, including smooth muscle relaxation, vasocongestion, and vaginal lubrication; genital tissues depend on continued estrogen and androgen stimulation for normal function. An upward shift in vaginal pH as the result of vaginal atrophy alters the normal vaginal flora. Reduced lubrication capability and reduced tissue elasticity, in addition to shortening and narrowing of the vaginal vault, can lead to painful and/or unpleasant intercourse. At the same time, diminished sensory response may reduce orgasmic intensity. Other contributors to peri- and postmenopausal sexual dysfunction include reduced androgen levels, aging of multiple body systems, and side-effects of medications. Workup of sexual health problems starts by taking a comprehensive sexual, medical, and psychosocial history, followed by complete physical examination and laboratory evaluation. Clinical management includes measures to preserve and enhance overall health, adjustment of medication regimes to reduce or avoid side-effects, and topical or systemic hormone supplementation with estrogens and/or androgens. No single therapeutic approach is appropriate for every woman with peri- or postmenopausal sexual dysfunction; instead, treatment should be based on a comprehensive evaluation and consideration of medical and psychosocial contributors to the individual's dysfunction. Further research is required to establish optimal regimens of hormonal and nonhormonal agents, including dosages/dosage forms and duration of treatment, for specific subtypes of sexual dysfunction.

Guest Editorial: Phthalate Exposure during Pregnancy and Lower Anogenital Index in Boys: Wider Implications for the General Population?

Guest Editorial: Phthalate Exposure during Pregnancy and Lower Anogenital Index in Boys: Wider Implications for the General Population?

Gonadotropin-releasing hormone in apoptosis of prostate cancer cells

GnRH and its analogs (GnRH-a) are used extensively for the treatment of prostate cancer and other hormone-dependent diseases via the desensitization of pituitary gonadotropes, which consequently leads to the inhibition of gonadotropins, gonadal steroids and tumor growth. The actions of GnRH-a are mediated by the GnRH receptor (GnRHR) that is expressed in both the pituitary and extrapituitary sites, including normal tissues and tumors. Several studies have provided evidence that besides its pituitary effects, GnRH-a may exert direct anti-proliferative and apoptotic effects in tumor cells. These effects are mediated by the GnRHRs via signal transduction mechanisms that are distinct from the classical pituitary mechanisms. Here we describe the direct effects of GnRH-a on prostate cancer and other types of cancer. Interestingly, androgen ablation by GnRH-a is the main treatment for hormone-dependent prostate cancer. However, most of these tumors become eventually hormone-refractory, and are no longer sensitive to the GnRH-a-mediated reduction in androgen levels. Hence, the ability of GnRH-a to induce direct effects such as apoptosis may have large implications regarding the clinical use of GnRH-a. Therefore, an understanding of the cellular mechanisms involved in GnRH-a action may lead to better therapeutic modalities for the treatment of advanced prostate cancer and other malignancies.

Androgen Receptor Activation by Gs Signaling in Prostate Cancer Cells

The androgen receptor (AR) is activated in prostate cancer patients undergoing androgen ablative therapy and mediates growth of androgen-insensitive prostate cancer cells, suggesting it is activated by nonandrogenic factors. We demonstrate that activated alpha subunit of heterotrimeric guanine nucleotide-binding G(s) protein activates the AR in prostate cancer cells and also synergizes with low concentration of androgen to more fully activate the AR. The G alpha(s) activates protein kinase A, which is required for the nuclear partition and activation of AR. These data suggest a role for G alpha(s) and PKA in the transactivation of AR in prostate cancer cells under the environment of reduced androgen levels.

Randomized Controlled Trial Evaluating Response to Metformin Versus Standard Therapy in the Treatment of Adolescents with Polycystic Ovary Syndrome

We evaluated the hypothesis that metformin would improve signs and symptoms of polycystic ovary syndrome (PCOS) in adolescents as compared to oral contraceptive pills (OCP) and have a favorable effect on obesity. Thirty-five obese, post-menarchal, non-sexually active adolescents aged 12-21 years with PCOS and hyperinsulinism were randomly assigned to receive either OCP or metformin for 6 months. There was a significant decrease in BMI in the two groups over time, from 40.1 to 38.6 in the OCP group, and 37.3 to 36.3 in the metformin group, p = 0.0026, but no significant difference in the degree of change between the two groups. Both groups had decreased free testosterone (OCP: 1.8 pg/ml to 0.96 pg/ml; metformin: 2.1 pg/ml to 1.6 pg/ml), p < 0.0001, and improvements in insulin resistance as evidenced by increased glucose/insulin (G/I) ratio (p < 0.005) and increased QUICK1 scores (p < 0.0005). No significant differences in response to treatment were found between the metformin and OCP groups in outcome variables. Adolescents with PCOS treated with metformin or OCP experienced similar beneficial outcomes including reduction in androgen levels, weight loss, and increased insulin sensitivity. The choice of a treatment agent for long-term use will depend on safety profiles, therapeutic goals and patient adherence.

Regulation of androgen receptor signaling in prostate cancer

Prostate cancer is a significant cause of morbidity and mortality worldwide. Normal prostate tissue is regulated by androgens, which activate the androgen receptor, a nuclear receptor transcription factor. Most prostate tumors retain androgen dependence, therefore, current therapies for advanced prostate cancer either reduce androgen levels or prevent binding to the androgen receptor. Despite this regimen, prostate cancer invariably progresses to a fatal, androgen-refractory state. Although these relapsed tumors are androgen independent, they are still dependent on the androgen receptor for their growth and survival. The focus of this review will be to highlight our current understanding of the mechanisms of androgen receptor activation in androgen-refractory prostate cancer. How these mechanisms of androgen receptor activation could be targeted in this advanced stage of the disease is also discussed.

Effect of Exercise on Serum Androgens in Postmenopausal Women: A 12-Month Randomized Clinical Trial

Abstract Postmenopausal women with elevated circulating androgen concentrations have an increased risk of developing breast cancer, yet interventions to reduce androgen levels have not been identified. We examined the effects of a 12-month moderate intensity exercise intervention on serum androgens. The study was a randomized clinical trial in 173 sedentary, overweight (body mass index ≥ 24.0 kg/m2, body fat &amp;gt; 33%), postmenopausal women, ages 50 to 75 years, not using hormone therapy and living in the Seattle, WA area. The exercise intervention included facility-based and home-based exercise (45 minutes, 5 days per week of moderate intensity sports/recreational exercise). A total of 170 (98.3%) women completed the study, with exercisers averaging 171 minutes per week of exercise. Women in the exercise and control groups experienced similar, nonsignificant declines in most androgens. Among women who lost &amp;gt;2% body fat, testosterone and free testosterone concentrations fell by 10.1% and 12.2% between baseline and 12 months in exercisers compared with a decrease of 1.6% and 8.0% in controls (P = 0.02 and 0.03 compared with exercisers, respectively). Concentrations of testosterone and free testosterone among exercisers who lost between 0.5% and 2% body fat declined by 4.7% and 10.4%. In controls who lost this amount of body fat, concentrations of testosterone and free testosterone declined by only 2.8% and 4.3% (P = 0.03 and 0.01 compared with exercisers, respectively). In summary, given similar levels of body fat loss, women randomized to a 12-month exercise intervention had greater declines in testosterone and free testosterone compared with controls. The association between exercise and breast cancer risk may be partly explained by the effects of exercise on these hormones.

Metformin treatment before IVF/ICSI in PCOS women: a prospective, randomized, double-blind study

Metformin treatment before IVF/ICSI in PCOS women: a prospective, randomized, double-blind study

The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome

Objective(s): To evaluate the effects of metformin on insulin resistance, ovarian androgen production, and clomiphene-induced ovulation and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS). Study design: Twenty-one infertile women with PCOS were selected in this prospective randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were divided randomly into group 1 ( n11) and group 2 ( n10). Group 1 patients were treated with 1700 mg per day of metformin for 3 months. The basal tests and OGTT were repeated after metformin therapy. Group 2 patients did not receive metformin. The patients in both groups received 100 mg of clomiphene citrate (CC) daily for 5 days until either a pregnancy occurred, or six CC cycles were reached. Metformin administration continued during CC therapy until the day of hCG in group 1. Serum progesterone (P) level ≥5 ng/ml was considered as confirmatory of ovulation. Ovulation and pregnancy rates after six cycles were determined. Results: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Midluteal serum P level was significantly higher in cycles treated with metformin plus CC ( P<0.05). The ovulation (38 of 51 cycles, 74.4% versus 34 of 55 cycles, 61.8%) and pregnancy rates (5 of 11 women, 45.5% versus 3 of 10 women, 30%) were higher, but not significantly, in the metformin plus CC group than in the CC alone group. All the patients who conceived had insulin resistance in group 1 whereas non-insulin resistance in group 2. Conclusion(s): Metformin improves insulin resistance and reduces androgen levels. Metformin did not increase significantly the ovulation and pregnancy rates.

Short-term dexamethasone can further reduce androgen levels in women with polycystic ovary syndrome treated with metformin

Short-term dexamethasone can further reduce androgen levels in women with polycystic ovary syndrome treated with metformin

Dexamethasone reduces androgen levels in metformin-treated patients with polycystic ovary syndrome

Women with polycystic ovary syndrome treated with metformin and lifestyle advice were studied. Additional treatment with dexamethasone, but not with bromocriptine, further reduced circulating androgen levels.