Ovarian Androgen Research Articles

Effect of Electroacupuncture at Different Acupoints on Steroid Hormones and Ovarian Androgen Receptor Expression in Polycystic Ovary Syndrome Rats

To observe the effect of electroacupuncture (EA) at different acupoints on hyperandrogenism and ovarian androgen receptor (AR) expression in rats with polycystic ovary syndrome (PCOS), so as to explore its mechanisms underlying improvement of PCOS. Sixty female SD rats were randomly divided into control, model, Zusanli (ST 36), Sanyinjiao (SP 6), Guanyuan (CV 4) and comprehensive groups (10 rats/group). The PCOS model was established by giving (gavage) the animals with Letrozole solution (1.0 mg/kg), once daily for 21 consecutive days. EA stimulation was applied to ST 36, SP 6, or CV 4 respectively, once daily for 14 days. The comprehensive group was treated by EA treatment of the abovementioned three acupoints in the meantime. Before and after the treatment, the body mass and the ovary weight were measured. The morphological structure of the ovary was observed under microscope after H．E. staining. The levels of serum hormone and sex hormone binding globulin (SHBG) were assayed by ELISA. Free androgen index (FAI) was calculated and the expression of AR in the ovary was detected by immunohistochemistry. After modeling, the body mass, ovary weight, serum testosterone (T) and FAI levels and the expression of AR protein in late ovarian follicles were significantly increased (P<0.01, P<0.05), and serum estradiol (E2) and SHBG contents were significantly decreased relevant to the control group (P<0.01). Following EA intervention and compared with the model group, the body weight of each EA group was significantly reduced (P<0.05), the ovarian pathological changes were improved, and serum T and FAI levels were significantly decreased (P<0.01), and serum E2 and SHBG contents significantly increased in the ST 36, CV 4 and comprehensive groups (P<0.01, P<0.05). The ovary weight of only CV 4 group was significantly lower than that of the model group (P<0.01). The expression of AR protein in late follicles of both CV 4 and SP 6 groups was markedly decreased (P<0.05, P<0.01). EA at ST 36, SP 6, and CV 4 all can improve the hyperandrogenism and ovarian polycystic morphological changes of PCOS rats, while different acupoints have different functional characteristics.

POLYCYSTIC OVARY SYNDROME: PATHOGENESIS, TREATMENT AND SECONDARY ASSOCIATED DISEASES

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension, and dyslipidemia as frequent metabolic traits (metabolic syndrome) that culminate in serious long-term consequences such as type 2 diabetes mellitus, endometrial hyperplasia, and coronary artery disease. It is one of the most common causes of anovulatory infertility. A complete understanding of the underlying Pathophysiology of PCOS is still lacking. Because of the heterogeneity of this disorder, there are most likely multiple underlying pathophysiologic mechanisms. Pathogenesis of PCOS is explaining as alteration in gonadotropin-releasing hormone secretion results in increased luteinizing hormone (LH) secretion. An alteration in insulin secretion and insulin action results in hyperinsulinemia and insulin resistance. A defect in androgen synthesis that results in increased ovarian androgen production.Treatment of PCOS include maintaining a normal endometrium, antagonizing the actions of androgens on target tissues, reducing insulin resistance (when present), and correcting anovulation. Women with polycystic ovary syndrome (PCOS) are at higher risk for several other health conditions as Insulin Resistance, Metabolic Syndrome, Type 2 Diabetes, Obesity, Heart Disease and High Blood Pressure (Cardiovascular Disease)&#x0D;

Women undergoing assisted fertilisation and high-intensity interval training: a pilot randomised controlled trial

ObjectivesOverweight and obese women often seek assisted fertilisation. In the obese population, pregnancy rates are 30%–75% below that of normal weight women who undergo assisted fertilisation. We hypothesised that high-intensity...

An update of genetic basis of PCOS pathogenesis.

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder that affects 5-20% of reproductive age women. PCOS clinical symptoms include hirsutism, menstrual dysfunction, infertility, obesity and metabolic syndrome. There is a wide heterogeneity in clinical manifestations and metabolic complications. The pathogenesis of PCOS is not fully elucidated, but four aspects seem to contribute to the syndrome to different degrees: increased ovarian and/or adrenal androgen secretion, partial folliculogenesis arrest, insulin resistance and neuroendocrine axis dysfunction. A definitive etiology remains to be elucidated, but PCOS has a strong heritable component indicated by familial clustering and twin studies. Genome Wide Association Studies (GWAS) have identified several new risk loci and candidate genes for PCOS. Despite these findings, the association studies have explained less than 10% of heritability. Therefore, we could speculate that different phenotypes and subphenotypes are caused by rare private genetic variants. Modern genetic studies, such as whole exome and genome sequencing, will help to clarify the contribution of these rare genetic variants on different PCOS phenotypes. Arch Endocrinol Metab. 2018;62(3):352-61.

Genetic association study from North India to analyze association of CYP19A1 and CYP17A1 with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex multifactorial endocrine disorder affecting approximately 5-10% of women of reproductive age. Affected women have menstrual disturbances due to anovulation, infertility, and hyperandrogenism. Ovarian androgen overproduction is the key physiopathologic feature of PCOS. A number of genes encoding major enzymes of the androgen metabolic pathways, such as HSD17B6, CYP19A1, CYP11A1, CYP17A1, and INSR, have been examined. Very few studies have been done in North India. There is an increasing prevalence of PCOS in women in Punjab and it is the leading cause of female infertility. In view of the strong evidence implicating the importance of CYP19A1 and CYP17A1 in androgen metabolic pathways, we investigated the association of rs700519, rs2414096, and rs743572 (- 34T>C) polymorphisms on susceptibility of developing PCOS, in North India. A total of 500 subjects (women of reproductive age) including 250 PCOS cases and 250 healthy age-matched controls were included in the present study. DNA was extracted from venous blood for all samples, and association analysis for rs2414096, rs700519, and rs743572 was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Lipid profile was done using a biochemical analyzer and body mass index (BMI) was measured for all cases. Statistical analysis was performed. Significant association of - 34T>C polymorphism of CYP17A1 was found with PCOS (p = 0.0005). BMI was statistically different between PCOS cases and controls (p = 0.000). Triglycerides were high in PCOS women. Variations of CYP19A1 were not statistically significant with PCOS. These data suggest that - 34T>C polymorphism in CYP17A1 is associated with PCOS in North India. No polymorphism of CYP19A1 was found to be associated.

New possibilities of correction of metabolic disorders in women with PCOS

The aim of the study, the results of which are described in the article, was to study the possibilities of using a polycomponent drug containing D-kiro-inositol in the polycystic ovarian syndrome.A comparative prospective study was conducted with the participation of 60 patients of reproductive age suffering from polycystic ovarian syndrome (phenotype A). The criteria for participation in the study were: a confirmed diagnosis of polycystic ovarian syndrome with ovarian enlargement and oligo/anovulation and a raised level of ovarian androgens; body mass index from 26 to 30 kg/m2. Patients with severe endocrine and somatic pathology were excluded from the study.Women aged 18–35 years were on out-patient treatment in the Endocrine gynecology department of the SI “Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”. By random sampling, the patients were divided into 2 groups of 30 people each. For 6 months, the patients of the main group received twice a day 1 Protalis complex drug containing D-kiroinositol, which is recommended for normalization of ovarian function and stimulation of spontaneous ovulation in polycystic ovarian syndrome, improvement of oocyte state, and also to promote reduction of oxidative and inflammatory stress, reducing the level of total testosterone and increasing fertility. Patients of the control group received recommendations on dietary nutrition and exercise.Analysis of the results of therapy showed a recovery in the main group of regular ovulatory menstrual cycles in 53.33% of cases, a decrease in the frequency of androgen-dependent dermatopathy by 50%, normalization of body weight and a reliable decrease in androgen levels. In addition, a positive effect on metabolic parameters such as HOMA index and homocysteine level was noted.The results of the study allow us to recommend the use of Protalis course therapy (D-kiro-inositol and synergists) to restore ovulatory menstrual cycles, and as a means of preventing metabolic disorders in women with polycystic ovarian syndrome and overweight.

New Biomarkers to Evaluate Hyperandrogenemic Women and Hypogonadal Men.

Androgens can have variable effects on men and women. Women may be evaluated for androgen excess for several reasons. Typically, young premenopausal women present with clinical symptoms of hirsutism, alopecia, irregular menses, and/or infertility. The most common cause of these symptoms is polycystic ovary syndrome. After menopause, even though ovaries stop producing estrogen, they continue to produce androgen, and women can have new onset of hirsutism and alopecia. Laboratory evaluation involves measurement of the major ovarian and adrenal androgens. In women, age, phase of the menstrual cycle, menopausal status, obesity, metabolic health, and sex hormone-binding proteins significantly affect total-androgen levels and complicate interpretation. This review will summarize the clinically relevant evaluation of hyperandrogenemia at different life stages in women and highlight pitfalls associated with interpretation of commonly used hormone measurements. Hypogonadism in men is a clinical syndrome characterized by low testosterone and/or low sperm count. Symptoms of hypogonadism include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men. Hypogonadism is observed rarely in young boys and adolescent men. Based on the defects in testes, hypothalamus, and/or pituitary glands, hypogonadism can be broadly classified as primary, secondary, and mixed hypogonadism. Diagnosis of hypogonadism in men is based on symptoms and laboratory measurement. Biomarkers in use/development for hypogonadism are classified ashormonal, Leydig and Sertoli cell function, semen, genetic/RNA, metabolic, microbiome, and muscle mass-related. These biomarkers are useful for diagnosis of hypogonadism, determination of the type of hypogonadism, identification of the underlying causes, and therapeutic assessment. Measurement of serum testosterone is usually the most important single diagnostic test for male hypogonadism. Patients with primary hypogonadism have low testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Patients with secondary hypogonadism have low testosterone and low or inappropriately normal LH andFSH. This review provides an overview of hypogonadism in men and a detailed discussion of biomarkers currently in use and in development for diagnosis thereof.

Metformin-A drug of plant origin

Galega officinalis is a summer-flowering perennial herb found in most temperate regions. One of the first use of this herb was to cure the frequent urination associated with the disease, now called as diabetes mellitus. In 1926, polymethethylene diguanides had been introduced for the treatment of diabetes and due to its debilitating effect on the liver, it had been withdrawn in the 1940s. On working with dicyanodiamide and dimethylammonium, Dublin chemists, Emil Werner and James Bell had discovered a compound in 1922. They found out that dicyanodiamide on reaction with dimethyl ammonium chloride yielded dimethyldiguanide, i.e., metformin. The Food and Drugs Administration approves metformin to be used for the treatment of Type 2 Diabetes Mellitus. Metformin was approved for the treatment of Type 2 Diabetes Mellitus in 1958 for UK, in 1972 for Canada and in 1995 by FDA in USA. Although metformin was initially proven to treat high sugar levels, there are many uses of metformin proven to be effective. Metformin not only for diabetes, but also for gestational diabetes mellitus, obesity, hypersecretion of ovarian androgens, polycystic ovary syndrome (PCOS), antipsychotic therapy induced weight gain, cancer treatment and anti-aging. Metformin is the drug of choice for patients who are obese and have type 2 diabetes mellitus. It works by decreasing hepatic glucose production and decreasing peripheral insulin resistance. Metformin acts on obesity by causing a decrease in the appetite. The other action of metformin is reduction of circulating levels of insulin and insulin like growth factor 1 (IGF-1) which is associated with anticancer action. There are ongoing research about the effect of metformin on anti-aging properties and proved that metformin is linked with anti-aging factors. Three main factors that are related with aging are oxidation, glycation and methylation.

Evaluation of the correlation between insulin like factor 3, polycystic ovary syndrome, and ovarian maldescent

The aim of this study was to investigate a proposed correlation between the incidentally discovered undescended ovaries and their confirmed diagnosis as a polycystic ovary disease (PCOD) for all cases included, and to evaluate the role of estimated insulin like factor 3 (INSL3) circulating level in the pathogenesis of both abnormal findings. The study group (A) comprised 35 women whose ovaries had been incidentally found to be undescended during the routine laparoscopy for infertility causes, and all had been diagnosed as PCOD. The control category included two subgroups; subgroup (B) included 35 women group, diagnosed as PCOD but with normally allocated ovaries in the true pelvis, and subgroup (C) included 35 healthy women with regular menses and no signs of hyperandrogenism. Correlations between the level of INSL3 and other PCOD relevant biochemical tests: [e.g. BMI, waist-to-hip ratio (WHR), LH, FSH, androstendione (A), total and free testosterone (T & Ft), DHEA-S, and SHBG] had been also investigated. INSL3 levels were significantly higher in PCOD groups (A) and (B) compared to the healthy fertile control subgroup (C) (80.5 ± 29.4, 65.11 ± 15.6, and 41.11 ± 10.2 pg/mL, respectively), and was highest in group (A). Moreover, we identified a strong correlation between INSL3 and androstenedione (r = 0.42, p = 0.0012), and free (r = 0.42, p = .0123) and total testosterone (r = 0.41, p = .004) in the PCOD (A) and (B) subgroup compared to the levels in subgroup (C). LH was significantly higher in all PCOD women in groups (A&B) (12. 3 ± 3.4, and 11.2 ± 1.4 mIU/L, respectively) compared to those in group (A) (5.7 ± 2.5 mIU/L), with a fair correlation with INSL3. However, there was no statistically significant correlation between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR in all PCOD women. The strong positive correlation between INSL3, and high ovarian androgens levels in all PCOD women, which appeared clearly in undescended polycystic ovaries could support the proposed syndrome hypothesis between those abnormal findings.

Roles of Hypothalamic-Pituitary-Adrenal Axis and Hypothalamus-Pituitary-Ovary Axis in the Abnormal Endocrine Functions in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome(PCOS) is a common reproductive endocrine disease in women of childbearing age. While it can be affected by a variety of factors,its pathophysiology remains unclear. Its clinical features mainly include anovulation,hyperandrogenism,and hyperinsulinemia,which are closely related with abnormal neuroendocrine system. Hypothalamic-pituitary-gonadal axis(HPG) plays a crucial regulatory role in various life activities in mammals. In particular,hypothalamic-pituitary-adrenal(HPA) axis and hypothalamus-pituitary-ovary(HPO) axis can be abnormal in PCOS patients. The corresponding abnormalities include abnormal gonadotropin releasing hormone pulse frequency,increased luteinizing hormone/follicle-stimulating hormone ratio,and excessive excretion of adrenal and ovarian androgens. Meanwhile,insulin and leptin also play key roles in endocrine dysfunction in PCOS patients. This article systematically reviews the role of HPA axis and HPO axis in the neuroendocrine dysfunction in PCOS patients.

No. 350-Hirsutism: Evaluation and Treatment.

To review the etiology, evaluation, and treatment of hirsutism. A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment. Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response. At least 6 to 9 months of therapy are required to produce improvement in hirsutism. The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. Hirsutism can be slowly but dramatically improved with a 3-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes, including weight loss and exercise, will lower serum androgen levels and improve self-esteem in patients with polycystic ovary syndrome. The patient should be educated regarding the associated health problems or long-term medical consequences of hyperandrogenism, particularly in the context of polycystic ovary syndrome, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease. RECOMMENDATIONS.

Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS)

Chronic low-grade inflammation has been suggested as a key contributor of the pathogenesis and development of polycystic ovary syndrome (PCOS). To investigate the association between oxidative stress status and inflammatory cytokines in follicular fluid of 21 PCOS women compared to 21 women with normal ovarian function who underwent intra-cytoplasmic sperm injection. Concentration of IL-6, IL-8, IL-10, and TNF-α was measured using sandwich ELISA. Oxidative stress was examined by measuring total oxidant status (TOS), malondialdehyde (MDA), total antioxidant capacity (TAC), and thiol groups. PCOS women had an elevated concentration of MDA and TOS compared to controls. Levels of TAC and thiol groups were lower in PCOS compared to controls. PCOS patients had a higher concentration of IL-6, IL-8, and TNF-α compared to controls. Concentration of IL-10 was lower in PCOS compared to controls. Significant correlations were found between MDA and TOS concentration with TNF-α and between IL-6 and MDA, IL-8 and TAC, IL-10 and TOS levels and also between IL-10 and TAC levels. TAC and thiol groups were negatively correlated with TNF-α. Increased oxidative stress in PCOS is associated with inflammation which is closely linked. Inflammation can induce production of inflammatory cytokines in this syndrome and directly stimulates excess ovarian androgen production.

A 16-Year-Old Girl with Torsion of a Hyperstimulated Ovary Caused by an Aromatase Deficiency

Abstract Background: Aromatase and P450 oxidoreductase deficiencies are disorders of steroidogenesis, with a phenotypic spectrum ranging from ambiguous genitalia to Antley–Bixler syndrome. The aromatase complex affects estrogen synthesis and androgen metabolism and maintains the balance of the androgen–estrogen ratio in different tissues. Due to a lack of aromatase, high levels of ovarian androgens and gonadotropins facilitate ovarian cyst formation. Case: A 16-year-old patient was admitted to a clinic with acute lower abdominal and pelvic pain. Her menarche had occurred at 12 years of age and continued with irregular menses. She had partial labial fusion and clitoromegaly (Prader classification 2), with Tanner stage 3 pubertal development. A pelvic ultrasound showed enlarged and multicystic ovaries on both sides, with torsion of the right ovary. Laboratory investigations of marker levels revealed high follicle-stimulating hormone (31.28 mIU/mL; normal range: 1.7–7.7 mIU/mL), high luteinizing hormone (32....

Can the source of hyperandrogenism in adolescents with polycystic ovary syndrome predict metabolic phenotype?

In this study, we demonstrated an association between adrenal hyperandrogenism, as determined by dehydroepiandrostenedione-to-free testosterone (DHEA-S/FT) ratio, and metabolic phenotype in obese and lean adolescents with polycystic ovary syndrome (PCOS). We compared 64 overweight/obese adolescents with PCOS (PCOS-O) with 18 lean (PCOS-L) adolescents. We analyzed the association between DHEA-S/FT ratios and metabolic parameters. Patients in the PCOS-O group were younger (median [interquartile range]) than those in the PCOS-L group (15 [15-17] vs. 16 [16–17] years; p = .04). The median DHEA-S/FT ratio and total testosterone concentrations did not differ. However, androstenedione concentrations were higher in the PCOS-L group (p = .02) and free testosterone levels lower in the PCOS-L group compared with the PCOS-O group (p = .02). Insulin resistance was present in 30 of 64 (46.9%) adolescents with PCOS-O compared with 1 of 18 (5.6%) with PCOS-L (p = .001). A significant negative correlation between DHEA-S/FT ratios and insulin concentrations in PCOS-O (p = .03) and PCOS-L (p = .04) groups was noted. In the PCOS-O group, the DHEA-S/FT ratio was negatively associated with serum triglyceride (p = .03) and total cholesterol concentrations (p = .02). We conclude that in adolescents with PCOS, a higher ratio of adrenal to ovarian androgens, signified by DHEA-S/FT, may be associated with a more favorable metabolic phenotype.

Fasting as possible complementary approach for polycystic ovary syndrome: Hope or hype?

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation.Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis.Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.

Polycystic ovary syndrome, adipose tissue and metabolic syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD). A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulin resistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included. PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle. The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

Hyperandrogenism in adolescent girls: relationship with the somatotrophic axis.

During puberty there is a physiologic increase in adrenal and ovarian androgens. It has been suggested that the somatotrophic axis may be related to the development of hyperandrogenism and anovulation in non-obese adult women with polycystic ovarian syndrome (PCOS). The objective of the study was to investigate whether ovarian androgen secretion in young postmenarchal girls is related to the function of their somatotropic axis. This was a cross-sectional study of adolescent girls. We studied non-obese adolescent girls with hyperandrogenism (HA; n = 21) matched with control girls (C; n = 25) for chronological age, age at menarche and body mass index. We obtained a fasting blood sample for measurement of serum glucose, insulin, 17-hydroxyprogesterone (17OH-Prog), dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, sex hormone-binding globulin (SHBG), total testosterone, IGF-I, IGF-II, IGFBP-1, IGFBP-3, ghrelin, leptin, AMH (antiMüllerian hormone), luteinizing hormone (LH) and follicle stimulating hormone (FSH) during the follicular phase of the menstrual period. We performed an oral glucose tolerance test to determine blood glucose, insulin and ghrelin levels and urine samples to measure urinary GH (growth hormone) levels. As expected, the hyperandrogenic girls had significantly higher Ferriman scores, basal total testosterone, free androgen index (FAI), androstenedione, AMH, and basal LH levels compared with the girls in controls. Serum IGF-I, IGF-II, IGFBP-3 and urinary GH did not differ between HA and C. There was a correlation between urinary GH and FAI in all girls (r 0.29, p < 0.05). In addition, in HA girls FAI correlated with insulin, homeostasis model assessment (HOMA) and ghrelin. We observed a correlation between urinary GH and FAI in the hyperandrogenic and control girls, suggesting that the function of the somatotrophic axis may influence the secretion of androgens in adolescent girls.

A model of ovulatory regulation examining the effects of insulin-mediated testosterone production on ovulatory function

Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is often accompanied by abnormal reproductive and metabolic hormone levels. Specifically, androgens such as testosterone are elevated in many PCOS women, and the syndrome itself is frequently associated with insulin resistance, which leads to hyperinsulinemia, i.e., elevated insulin. Although the precise role of insulin in ovulatory function is unclear, its role in ovulatory dysfunction is often linked to the effects of increased ovarian androgen production. We present a mathematical model of the menstrual cycle that incorporates regulation by the pituitary-ovarian axis and mechanisms of ovarian testosterone production. We determine a physiological role for testosterone in the normal ovulatory cycle and study the role of hyperinsulinemia in pathological regulation of the cycle. Model results indicate increased ovulatory disruption with elevated insulin-mediated testosterone production and suggest that variations in the response of ovarian follicles to essential signals can alter the degree to which hyperinsulinemia disrupts the ovulatory cycle. The model also provides insight into the various PCOS phenotypes and the severity of ovulatory dysfunction.

Hormonal therapies for acne

Acne is a common, worldwide problem that is usually multifactorial in etiology, but androgens may play a pivotal role in the development and severity of acne. Endocrinopathies, such as polycystic ovarian syndrome, ovarian tumors, or adrenal hyperplasia or tumors, may be detected in some patients with acne, especially if acne is sudden in onset, associated with hirsutism or menstrual irregularities, or associated with cushingoid facies, acanthosis nigricans, patterned hair loss, or deepened voice. In these instances, serum-free and total testosterone, dehydroepiandrosterone, luteinizing hormone, and follicle stimulating hormone should be tested. Appropriate referral and long-term follow-up is warranted in patients diagnosed with an endocrinopathy. Hormonal therapies for acne include systemic medications with various mechanisms: androgen receptor blockers, adrenal androgen production blockers, or ovarian androgen production blockers. Androgen receptor blockers include spironolactone, cyproterone acetate, chlormadinone, and flutamide; adrenal androgen production blockers include glucocorticoids; and ovarian production blockers include gonadotropin-releasing agonists and oral contraceptives. Practical guidelines are shared for the practicing physician treating hormonally related acne.

Effects of Resveratrol on Polycystic Ovary Syndrome: A Double-blind, Randomized, Placebo-controlled Trial.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism is the central feature of PCOS. Studies on isolated ovarian theca-interstitial cells suggest that resveratrol, a natural polyphenol, reduces androgen production. This study was designed to evaluate endocrine and metabolic effects of resveratrol on PCOS. This was a randomized (1:1) double-blind, placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital. Subjects with PCOS were identified according to the Rotterdam criteria. Thirty-four subjects were enrolled and 30 subjects completed the trial. Evaluations were performed at baseline and repeated after 3 months of treatment. Resveratrol (1,500 mg p.o.) or placebo were administered daily. Primary outcome was the change in the serum total T. Resveratrol treatment led to a significant decrease of total T by 23.1% (P = .01). In parallel, resveratrol induced a 22.2% decrease of dehydroepiandrosterone sulfate (P = .01), a decrease of fasting insulin level by 31.8% (P = .007) and an increase of the Insulin Sensitivity Index (Matsuda and DeFronzo) by 66.3% (P = .04). Levels of gonadotropins, the lipid profile as well as markers of inflammation and endothelial function were not significantly altered. Resveratrol significantly reduced ovarian and adrenal androgens. This effect may be, at least in part, related to an improvement of insulin sensitivity and a decline of insulin level.