Genetic aspects of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM - non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. Most women with PCOS, both obese and lean, have a degree of insulin resistance. The minisatellite of insulin gene (INS VNTR), especially class III alleles and III/III genotypes might not only determine the predisposition to anovulatory PCOS but also the concomitant risk for development of type 2 diabetes. The function of the insulin receptor (IR) is probably normal in woman with PCOS. However abnormal serine phosphorylation in the receptor may impair signal transduction accounting for a post-binding defect in insulin action. Serine phosphorylation is also involved in the postranslational regulation of 17,20-lyase activity (CYP17). There may be a common aetiology for both insulin resistance and hyperandrogenism. Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. PCOS appears to be associated with the absence of the four-repeat-units allele in a polymorphic region of pentanucleotide (TTTTA)n repeats within CYP11A gene, which encodes cytochrome P450scc. It has been hypothesized that up-regulation of this enzyme could lead to increased androgen production. There is no evidence of any association of alleles of CYP19 gene (encoding cytochrome P450arom) with PCOS. Association exists between androgen receptor gene (AR) polymorphisms an androgens action in PCOS. Increased hirustism and decreased CAG repeat length within AR gene has been also demonstrated in women with normal testosterone levels. Expression of estrogen receptor (ERs) as well as 5-alpha-reeducates (SRD5A1-2 genes) activity was analysed in granulosa (GC) and theca cells (TC). The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. On the other hand elevated SRD5A activity in polycystic ovaries supported the hypothesis that 5-alpha-reduced androgens may play a role in the pathogenesis of the syndrome. The genetic aetiology of PCOS remains unknown. There are a number of interlinking factors that affects expression of PCOS. Single cause of PCOS is unlikely. Other possible mechanisms in pathogenesis of PCOS are discussed.     

Polycystic ovary syndrome: evidence for a primary disorder of ovarian steroidogenesis

Polycystic ovary syndrome (PCOS) is a very common endocrinopathy of uncertain aetiology in which the most consistent biochemical abnormality is hypersecretion of androgens. In this review, evidence is presented to support the view that a primary abnormality of ovarian androgen biosynthesis provides the basis for the syndrome. PCOS is a familiar disorder and we demonstrate, in molecular genetic studies, that CYP11a, the gene coding for P450 side chain cleavage, is a key susceptibility locus for development of hyperandrogenism.     

Mouse models to study polycystic ovary syndrome: A possible link between metabolism and ovarian function?

Polycystic ovary syndrome (PCOS) is the most common cause of female infertility affecting 6–8% of women worldwide. PCOS is characterized by two of the following three criteria: clinical or biochemical hyperandrogenism, oligo- or amenorrhea, and polycystic ovaries (PCO). In addition, women with PCOS are often obese and insulin resistant, and are at risk for type 2 diabetes and cardiovascular disease. The etiology of PCOS remains unknown. Therefore, several animal models for PCOS have been generated to gain insight into the etiology and development of the PCOS-associated phenotypes. Androgens are considered the main culprit of PCOS, and therefore, androgenization of animals is the most frequently used approach to induce symptoms that resemble PCOS. Prenatal or prepubertal androgen treatment results in many characteristics of human PCOS, including anovulation, cyst-like follicles, elevated luteinizing hormone (LH) levels, increased adiposity, and insulin insensitivity. However, PCOS has a heterogeneous presentation, and therefore it is difficult to generate a model that exactly reproduces the reproductive and metabolic phenotypes observed in women with PCOS. In this review, we discuss several mouse models for PCOS, and compare the reproductive and/or metabolic phenotypes observed in several androgen-induced models as well as in several genetic models.     

Association between the prevalence of hyperuricemia and reproductive hormones in polycystic ovary syndrome

Background

The prevalecne of hyperuricemia in polycystic ovary syndrome (PCOS) is still uncertain. We aimed to investigate the prevalence of hyperuricemia in PCOS and to determine the influence of reproductive hormones on uric acid concentration.

Methods

This retrospective cross-sectional study was performed at a large reproductive medicine center. Between March 2007 and October 2016, a total of 1,183 women with PCOS and 10,772 women without PCOS were included. PCOS was diagnosed according to the Rotterdam criteria. Anthropometric parameters, blood pressure, uric acid, reproductive hormones, glucose and lipids were measured in all subjects.

Results

The serum uric acid (SUA) level was higher in women with PCOS than in women without PCOS. The prevalence of hyperuricemia in women with PCOS (25.48%) was significantly higher than that in women without PCOS (8.74%). Analysis stratified for age and body mass index (BMI) showed that both the SUA level and the prevalence of hyperuricemia were higher in women with PCOS of different age and BMI groups than in women without PCOS. After adjusting for age, BMI and estimated glomerular filtration rate (eGFR), logistic regression analysis revealed that the luteinizing/follicle-stimulating hormone (LH/FSH) ratio (odds ratio (OR)?=?1.20, 95% CI?=?1.01–1.43) and testosterone level (OR?=?1.56, 95% CI?=?1.27–1.90) were positively associated with the prevalence of hyperuricemia in females with PCOS.

Conclusions

The serum uric acid (SUA) level and the prevalence of hyperuricemia markedly increased in women with PCOS. The testosterone level was positively associated with the SUA level and the prevalence of hyperuricemia in females with PCOS.

     

Dyslipidemia in relation to body mass index and insulin resistance in Chinese women with polycystic ovary syndrome

Dyslipidemia is a common metabolic disorder in women with polycystic ovary syndrome (PCOS) and has been reported to be different in PCOS sufferers from various ethnic and geographic backgrounds. This study aims to investigate the prevalence of dyslipidemia in Chinese women with PCOS and its relationship to body mass index (BMI) and insulin resistance (IR). In this paper, a retrospective study was performed on 507 PCOS patients and 1246 age- and BMI-matched controls. Anthropometric indices of hormonal, adiposity, and metabolic variables were measured. All patients were divided into subgroups according to BMI and the homeostasis model assessment (HOMA) values. Accordingly, the prevalence of IR was 38.1 percent in our subjects. We found that mean fasting total triglyceride, low density lipoprotein (LDL) cholesterol and total cholesterol levels were significantly higher and the mean high density lipoprotein (HDL) cholesterol level was significantly lower in the IR group than in the non-IR (NIR) group. The prevalence of dyslipidemia was 24.7 percent in PCOS patients and the prevalence of dyslipidemia was significantly higher in the IR group than in the NIR group (39.9 percent vs 15.3 percent, P<0.05). The HOMA index was found to be positively correlated with TG, TC and LDL, and negatively correlated with HDL. TG and HDL levels remained significantly correlated with HOMA even after adjustment for BMI. Generally, the prevalence of various patterns of dyslipidemia in PCOS patients increased with HOMA value. In conclusion, the prevalence of IR and dyslipidemia were both found to be high in PCOS women in our study, although no higher than other ethnicities. Lipid abnormality was demonstrated to be associated with IR and BMI in Chinese PCOS women. We speculate that insulin sensitizer might ameliorate dyslipidemia through improving IR in PCOS women.     

Genetic construction between polycystic ovarian syndrome and type 2 diabetes

Polycystic ovarian syndrome (PCOS) in reproductive-aged women is identified to be one of the endocrine disorders. This heterogeneous disorder is categorized through oligo-anovulation and hyperandrogenemia. National institutes of health and Rotterdam criterions were used to diagnose PCOS women. Type 2 Diabetes (T2D) is one of the complications in PCOS which is connected through insulin resistance (IR), which is a condition in which liver, muscles and fat infrequently respond to the hormones, and this leads to extreme IR and consequently leads to T2D disease. PCOS is inherited by the autosomal dominant mode of inheritance and may also with the different intricate patterns. Till now, many studies have been performed in PCOS with the genes identified by T2D and till now no studies have shown the similar genetic association and pathophysiology between both the diseases. So, the current review aims to investigate the genetic relation between PCOS and T2D and why both the diseases cannot be reverted. In this review, published data were screened with the T2D related genes and single nucleotide polymorphisms in PCOS women. The case-control, hospital-based and meta-analysis molecular studies disclosed both positive and negative connotations. Genetically, no relationship has been established between PCOS and T2D. Maximum studies have shown as PCOS women had developed T2D later in life because as a risk-factor, but none of the studies documented T2D women having developed PCOS as a risk factor. Apart from this, the disease PCOS is developed in women with reproductive age and T2D develops in both the men and women during adulthood. This review concludes as there is a genetic relation only in between PCOS and T2D, but not with T2D to PCOS and further it cannot be explicitly reverted from T2D to PCOS.     

多囊卵巢综合征并发抑郁症的研究现状

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄女性最常见的内分泌疾病之一,表现为生殖和代谢异常。近些年来,越来越多的人群学研究发现,PCOS病人患精神心理疾病,尤其是抑郁症的发生率高于正常人群。本文概述了PCOS并发抑郁症的相关危险因素和可能机制,并简要论述了PCOS的治疗药物对抑郁症作用的最新研究进展。     

Molecular mechanisms of insulin resistance in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy of unknown aetiology that affects women of reproductive age. During the past ten years, defective insulin activity in PCOS has been demonstrated in target tissues and causes insulin resistance and hyperinsulinaemia. Furthermore, presence of insulin receptors in the ovarian tissue and overproduction of androgens by theca cells leads to characteristic hyperandrogenaemia. Recent data suggest a divergence in post-receptor signalling pathways for insulin in its target tissues (muscle, adipocytes and ovarian tissue), where the metabolic pathway of insulin activity is defective, whereas the activation of steroidogenesis is maintained. Investigators are still searching for clues to understand the cause of this enigmatic syndrome, despite great advances in molecular medicine and genetics.     

Age-related differences in the reproductive and metabolic implications of polycystic ovarian syndrome: findings in an obese, United States population

The objective of this study was to explore age-related differences in the reproductive and metabolic manifestations of polycystic ovarian syndrome (PCOS). Using a prospective cross-sectional design, we compared metabolic and reproductive findings in women attending a multidisciplinary clinic for PCOS, stratified across the following age groups: 18-25 (n = 71), 26-35 (n = 129), and 36-45 (n = 29). The study included primarily overweight and obese women, with a mean BMI of 31.1 in the entire study group. Older women had a decreased prevalence of biochemical hyperandrogenemia (p-trend: 0.0005). Of women meeting diagnostic criteria for PCOS, older women (n = 15) had larger median waist circumference and higher median diastolic blood pressure, total cholesterol, LDL cholesterol and fasting glucose compared to younger women (p-trend: 0.03, 0.01, 0.01, 0.01 and 0.06, respectively). The odds of metabolic syndrome for women ages 36-45 are increased four-fold relative to the younger groups (OR: 4.01; 95% CI: 1.04-15.4; p = 0.04). We conclude that there are significant age-related differences in both the clinical presentation and metabolic manifestations of PCOS.     

Defects in insulin signaling pathways in ovarian steroidogenesis and other tissues in polycystic ovary syndrome (PCOS)

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age today. Women with PCOS often demonstrate defective ovarian steroid biosynthesis and present with hyperandrogenemia. Moreover, 50-70% of PCOS women are insulin resistant and hyperinsulinemic. Insulin acts on the ovary via its own receptor and interacts with gonadotrophins, modulating steroidogenesis. The precise role of insulin and the molecular mechanisms that take place are not yet completely explicated. This review will be focused on insulin's action on the ovary and other target tissues, describing the intracellular signaling pathways implicated in steroidogenesis and their defects in women with PCOS.     

Serum metabolomics analysis of patients with polycystic ovary syndrome by mass spectrometry

Polycystic ovary syndrome (PCOS) is a set of symptoms caused by elevated androgens (male hormones) in females. PCOS is the most common endocrine disorder among women between 18 and 44 years. Currently, the pathogenesis of PCOS remains unclear. Liquid chromatography–mass spectrometry (LC/MS)‐based metabolomics is becoming more and more useful for medical research, especially in revealing the mechanism of the disease. The aim of this study was to investigate the difference of serum metabolic profiles in patients with PCOS and healthy control to better understand the mechanism of this disease. Ten patients with PCOS and 10 healthy people were recruited for this study. The serum samples were collected for LC/MS analysis. Multivariate statistical analysis was performed to discover and identify the potential biomarkers. Six biomarkers were found and identified. The biomarkers belonged to different metabolic pathway including lipid metabolism, carnitine metabolism, androgen metabolism, and bile acid metabolism. Those biomarkers also played different roles in disease progression. Metabolomics is a powerful tool used in research of the mechanism involved in this disease to provide useful information for better understanding of PCOS.     

Intergenerational associations of chronic disease and polycystic ovary syndrome

Background

Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility.

Objective

To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life.

Design, Setting and Participants

Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant.

Results and Conclusions

Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.     

Polycystic ovary syndrome in Indian women: a mass spectrometry based serum metabolomics approach

Introduction

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous endocrinological disorder with uncertain pathogenesis and is very common in women of reproductive age. There are few reports of utilizing metabolomics approach to understand the complex pathophysiology of PCOS. However, excluding one previous NMR-based metabolomics study, none of the study was conducted in Indian population.

Objective

The study aims to compare the serum metabolomic profile of PCOS women with controls from the Eastern region of India.

Methods

PCOS women (n?=?35) and healthy control women (n?=?30) undergoing tubal ligation were recruited for this study. Serum metabolic profiles were generated using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–mass spectrometry (GC-MS). Multivariate statistical analysis was applied to spectral data obtained from both the LC-MS/MS and GC/MS.

Results

Nine metabolites were identified to be most significantly dysregulated in sera of PCOS women; however, few other identified metabolites were also altered but with lesser significance. Amongst these metabolites, riboflavin, sucrose, adenine and N-acetyl glycine, phosphoric acid and cortisol were down-regulated, whereas, thymine, cystathionine, and phenylalanine were up-regulated in PCOS when compared with controls. The observed changes in metabolite expression suggested alterations in aminoacyl-tRNA biosynthesis, metabolism of nitrogen, alanine-aspartate-glutamate, galactose, glycine-serine-threonine, and pyrimidine-purine among several metabolic pathways possibly implicated in these PCOS women.

Conclusion

The altered metabolites identified in PCOS women of Eastern Indian population, provide insight into current perceptive of the disease pathology, metabolic involvements, and may be considered as putative markers of PCOS.

     

Current and future aspects of several adjunctive treatment strategies in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. PCOS is characterized by hyperandrogenism, menstrual disorders, and polycystic ovarian morphology. PCOS patients have an increased risk of type 2 diabetes, cardiovascular disease, and infertility. The mechanism of PCOS is not yet fully understood, but insulin resistance and genetic factors may play distinct roles in the pathomechanism.There is ongoing research on new therapeutic modalities for women with PCOS. In this minireview, we assessed the evidence for the effectiveness and safety of selected adjunctive agents (metformin, statins, resveratrol, melatonin, and inositols) for the treatment of women with PCOS. Metformin is a safe medication used in PCOS for 25 years that is currently recommended in select PCOS subpopulations, such as adolescents, women with metabolic disorders, and infertility infertile women undergoing ovarian hyperstimulation. Statins are also suggested in PCOS therapy, as these compounds decrease testosterone concentrations, improve lipid profiles, and ameliorate inflammatory reactions. Despite promising results, the role of statins in PCOS management needs to be further validated. Dietary supplements have also been tested in PCOS patients. Resveratrol was shown to decrease total testosterone production and improve fasting insulin but, until recently, only in one randomized study. Data on the therapeutic efficacy of melatonin and inositols on endocrine and metabolic abnormalities are limited and inconclusive. The multifactorial etiology of PCOS makes tailoring of its treatment more demanding, and there is a constant need for causative and effective modes of PCOS therapy.     

A study on the immunological vitality of an inflammatory biomarker explored with rs5743708 polymorphism in TLR2 gene among Saudi women confirmed with polycystic ovarian syndrome

IntroductionPolycystic ovary syndrome (PCOS) is an ovarian health condition as well as a long-term endocrine dysfunction that affects reproductive-aged women. Toll-like receptor 2 (TLR2) gene was linked to PCOS and chronic inflammation, and the prevalence of obesity was rising in Saudi women. Previous studies on rs5743708 polymorphism were documented in the obesity as well as in PCOS women.AimIn this study, we investigated the molecular role of rs5743708 polymorphism in TLR2 gene among Saudi women diagnosed with PCOS using the Rotterdam criteria.MethodsBlood samples were collected from 220 Saudi women in this hospital-based case-control study; 110 were PCOS women and remaining 110 were non-PCOS (control women). Biochemical analysis was performed on serum samples, and molecular analysis was performed on EDTA blood. Genotyping for rs5743708 polymorphism was performed with polymerase chain reaction-restriction fragment length polymorphism analysis.ResultsIn both groups, clinical data was calculated using t-test, which revealed both positive (p < 0.05) and negative (p > 0.05) associations. HWE analysis supported the rs5743708 polymorphism (p < 0.05). In the rs5743708 polymorphism, none of the genotypes, genetic models, or allele frequencies were found to be associated with PCOS and non-PCOS women. However, both ANOVA and regression analyses revealed a positive relationship in PCOS with weight and BMI (p < 0.0001).ConclusionThe rs5743708 polymorphism was not associated to PCOS in Saudi women. One of the predictions could be that 42.7% of PCOS and 73.6% of non-PCOS women were obese, and the rs5743708 polymorphism has been linked to both obesity and PCOS in the previous studies. This study suggests screening for additional polymorphisms with a large sample size.     

Identifying genes associated with the development of human polycystic ovary syndrome

The pathophysiology of polycystic ovary syndrome (PCOS) is confusing until today as it is a multifactorial endocrine disorder. It is presented with altered gonadotropin levels, bulky multi-follicular ovaries, infertility, and obesity. This complex pathophysiology is linked with insulin resistance and hyperandrogenism. Hyperandrogenemia significantly contributes towards cosmetic anomalies including hirsutism, acne, and alopecia in the PCOS women. The preexisting insulin resistance in women with PCOS is likely to aggravate the increased levels of androgen. The review findings have shown that in the steroidogenic pathway, ovarian steroidogenesis patterns classify mainly towards the hypertrophy of theca cells along with alteration in the expression of key enzymes. The association of polymorphisms in genes encoding the process of an intricate cascade of steroidogenesis is delineated. The emergence of an unanimously accepted genetic marker for susceptible PCOS was affected based on inconsistent findings. The present study has provided a comprehensive summary of the impact of polymorphisms among the common androgen-related genes to govern the genetic predisposition.     

Elevated ghrelin plasma levels in patients with polycystic ovary syndrome.

Polycystic ovary syndrome is a common endocrine disorder in women. It is associated with hirsuitism, obesity, insulin resistance, abnormality in the growth hormone/insulin-like growth factor I (IGF-1) axis and polycystic ovaries. The etiology of PCOS has not been clarified. Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor. It is mainly secreted by stomach cells but has also been shown to be present in hypothalamus, pituitary, pancreas and gonads. Ghrelin is a regulator of energy homeostasis and GH secretion. The influence of ghrelin on insulin secretion and gonadal function is known. Since ghrelin may play an important role in pathophysiology of PCOS, we studied ghrelin levels in a group of 52 women with PCOS and in 16 women in a control group. Plasma levels of insulin, total testosterone, SHBG, LH, and FSH were also measured. In conclusion, PCOS women have higher ghrelin levels than controls. Ghrelin negatively correlates with BMI and insulin levels in PCOS group. A relation between ghrelin and SHBG was observed. Our data suggest that ghrelin could be the possible link in PCOS etiology.     

microRNAs and long non‐coding RNAs as biomarkers for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and diagnostic emphasized the role of non‐coding regulatory RNAs as molecular biomarkers in studying, diagnosing and even as therapeutics of PCOS. This review discusses a comparative summary of research into microRNAs (miRNAs) and long non‐coding RNAs (lncRNAs) that are molecularly or statistically related to PCOS. We categorize the literature in terms of centering on either miRNAs or lncRNAs and discuss the combinatory studies and promising ideas as well. Additionally, we compare the pros and cons of the prominent research methodologies used for each of the abovementioned research themes and discuss how errors can be stopped from propagation by selecting correct methodologies for future research. Finally, it can be concluded that research into miRNAs and lncRNAs has the potential for identifying functional networks of regulation with multiple mRNAs (and hence, functional proteins). This new understanding may eventually afford clinicians to control the molecular course of the pathogenesis better. With further research, RNA (with statistical significance and present in the blood) may be used as biomarkers for the disease, and more possibilities for RNA therapy agents can be identified.     

Sex hormone-binding globulin and female reproductive function

Although sex steroids have long been known to influence serum concentrations of SHBG, it is now recognized that nutritional factors may be more important in the regulation of SHBG in women. Thus, SHBG concentrations are negatively correlated with body mass index (BMI) and, more particularly, to indices of central adiposity. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is associated with truncal obesity, hyperandrogenism and hyperinsulinaemia. There is evidence that insulin may be the humoral mediator of the weight-dependent changes in SHBG. Serum SHBG concentrations are inversely correlated with both fasting and glucose-stimulated insulin levels, and insulin has been shown to have a direct inhibitory effect on SHBG synthesis and secretion by hepatocytes in culture. However, the interrelationship of BMI, insulin and SHBG appears to be different in women with PCOS from that in normal subjects. The clinical importance of the weight-related suppression of SHBG is illustrated by the finding of a greater prevalence of hirsutism in obese women with PCOS compared with their lean counterparts. Obese subjects with PCOS have similar total testosterone concentrations to lean PCO women but have lower SHBG and reciprocally higher free testosterone levels. Calorie restriction results in reduction of serum insulin followed by an increase in SHBG and a fall in free testosterone but an isocaloric, low-fat diet has no significant effect on SHBG concentrations. Weight reduction in obese, hyperandrogenaemic women with PCO is an important approach to the management of both anovulation and hirsutism.     

Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients

Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention.