Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relatively small studies published to date do not permit reaching a definitive conclusion. We aimed at conducting a systematic review and meta-analysis of studies evaluating circulating markers of oxidative stress in patients with PCOS. We conducted a systematic review of studies reporting circulating markers of oxidative stress in women with PCOS and controls published up to June 2012, using Entrez PubMed and EMBASE online facilities. Meta-analysis calculated standardized mean differences (SMDs) and 95% confidence intervals (95CI). From 1633 potential studies identified electronically, 68 studies, including 4933 PCOS patients and 3671 controls, were selected. For each of nine circulating markers of oxidative stress, an individual meta-analysis was conducted. Compared with control women, patients with PCOS presented higher circulating concentrations of homocysteine (23% increase, SMD 0.6, 95CI, 0.4–0.8), malondialdehyde (47% increase, SMD 1.9, 95CI 1.2–2.6) and asymmetric dimethylarginine (36% increase, SMD 1.1, 95CI 0.6–1.6), and increased superoxide dismutase activity (34% increase, SMD 1.0, 95CI 0.5–1.4) and decreased glutathione levels (50% decrease, SMD −3.7, 95CI −6.2 to −1.2) and paraoxonase-1 activity (32% decrease, SMD −0.9, 95CI −1.3 to −0.4). Similar results were found when restricting the analyses to studies in which patients and controls were matched for age and body mass index. Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess. This finding suggests that oxidative stress may participate in the pathophysiology of this common disorder.

Context Gut microbiota plays a major role in health and disease in by influencing physiology and metabolism, nutrition and immune function. Objective We aimed to evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found. Design Cross-sectional study Setting Academic hospital. Participants We recruited 16 non-hyperandrogenic control women, 15 women with PCOS, and 15 control men. Subjects were classified as non-obese (< 30 kg/m²) or obese (≥ 30 kg/m²) according to their body mass index (BMI). Interventions Standardization of diet for 3 consecutive days (at least 300g of carbohydrates per day) followed by fecal sampling and a standard 75-g oral glucose tolerance test. Main Outcome Measures Analysis of bacterial abundance and composition of gut microbiota by massive sequencing of 16S rDNA amplicons in a MiSeq Illumina platform. Results Alpha bacterial diversity was reduced in women compared with men, and beta diversity was reduced particularly in obese patients with PCOS. Women with PCOS presented with specific abnormalities in gut microbiota consisting of an increased abundance of the Catinebacterium and Kandleria genera. When considering all subjects as a whole, indexes of bacterial diversity and the abundance of several bacterial genera correlated positively with serum androgen concentrations and negatively with estradiol levels. Conclusions The diversity and composition of the gut microbiota of young adults are influenced by the combined effects of sex, sex hormone concentrations and obesity, presenting with specific abnormalities in women with PCOS.

MicroRNAs (miRNAs) are small, noncoding RNA sequences that negatively regulate gene expression at the post-transcriptional level. miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 have been associated with metabolic disorders such as obesity and diabetes, which are also associated with polycystic ovary syndrome (PCOS). We aimed to evaluate the effects of sex, sex hormones, and PCOS and their interactions with obesity on the expression in the circulation of these miRNAs. This was a case-control study. The setting was an academic hospital. We included 12 control women, 12 patients with PCOS, and 12 men selected as to have similar body mass index (BMI) and age. Six subjects per group had normal weight (BMI < 25 kg/m(2)), and six subjects per group were obese (BMI ≥ 30 kg/m(2)). Blood samples were collected early in the morning after a 12-hour fast. We measured whole blood expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-155. Obesity significantly reduced the expression of miRNA-21, miRNA-27b, and miRNA-103. However, there was a significant interaction between obesity and the group of subjects in the expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 consisting of obesity reducing the expression of these miRNAs in control woman and men, but tending to increase their expression in women with PCOS. These differences paralleled those observed in serum T concentrations. The present results suggest that miRNAs that play an important role in metabolic and immune system processes are influenced by obesity and circulating androgen concentrations.

BACKGROUND: Abdominal adiposity and obesity influence the association of polycystic ovary syndrome (PCOS) with insulin resistance and diabetes. We aimed to characterize the intermediate metabolism phenotypes associated with PCOS and obesity. METHODS: We applied a nontargeted GC-MS metabolomic approach to plasma samples from 36 patients with PCOS and 39 control women without androgen excess, matched for age, body mass index, and frequency of obesity. RESULTS: Patients with PCOS were hyperinsulinemic and insulin resistant compared with the controls. The increase in plasma long-chain fatty acids, such as linoleic and oleic acid, and glycerol in the obese patients with PCOS suggests increased lipolysis, possibly secondary to impaired insulin action at adipose tissue. Conversely, nonobese patients with PCOS showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization (increased lactic acid concentrations) in peripheral tissues, and PCOS patients as a whole showed decreased 2-ketoisocaproic and alanine concentrations, suggesting utilization of branched-chain amino acids for protein synthesis and not for gluconeogenesis. These metabolic processes required effective insulin signaling; therefore, insulin resistance was not universal in all tissues of these women, and different mechanisms possibly contributed to their hyperinsulinemia. PCOS was also associated with decreased α-tocopherol and cholesterol concentrations irrespective of obesity. CONCLUSIONS: Substantial metabolic heterogeneity, strongly influenced by obesity, underlies PCOS. The possibility that hyperinsulinemia may occur in the absence of universal insulin resistance in nonobese women with PCOS should be considered when designing diagnostic and therapeutic strategies for the management of this prevalent disorder.

Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.