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.

The genetic mechanisms underlying functional hyperandrogenism and the polycystic ovary syndrome (PCOS) remain largely unknown. Given the large number of genetic variants found in association with these disorders, the emerging picture is that of a complex multigenic trait in which environmental influences play an important role in the expression of the hyperandrogenic phenotype.Among others, genomic variants in genes related to the regulation of androgen biosynthesis and function, insulin resistance, and the metabolic syndrome, and proinflammatory genotypes may be involved in the genetic predisposition to functional hyperandrogenism and PCOS.The elucidation of the molecular genetic basis of these disorders has been burdened by the heterogeneity in the diagnostic criteria used to define PCOS, the limited sample size of the studies conducted to date, and the lack of precision in the identification of ethnic and environmental factors that trigger the development of hyperandrogenic disorders. Progress in this area requires adequately sized multicenter collaborative studies after standardization of the diagnostic criteria used to classify hyperandrogenic patients, in whom modifying environmental factors such as ethnicity, diet, and lifestyle are identified with precision.In addition to classic molecular genetic techniques such as linkage analysis in the form of a whole-genome scan and large case-control studies, promising genomic and proteomic approaches will be paramount to our understanding of the pathogenesis of functional hyperandrogenism and PCOS, allowing a more precise prevention, diagnosis, and treatment of these prevalent disorders.

Sexual dimorphism manifests noticeably in obesity-associated gonadal dysfunction. In women, obesity is associated with androgen excess disorders, mostly the polycystic ovary syndrome (PCOS), whereas androgen deficiency is frequently present in obese men in what has been termed as male obesity-associated secondary hypogonadism (MOSH). Obesity-associated gonadal dysfunction, consisting of PCOS in women and MOSH in men, is a frequent finding in patients with severe obesity and it may be ameliorated or even resolve with marked weight loss, especially after bariatric surgery. We aimed to obtain an estimation of the prevalence of obesity-associated gonadal dysfunction among women and men presenting with severe obesity and to evaluate the response to bariatric surgery in terms of resolution and/or improvement of this condition and changes in circulating sex hormone concentrations. We searched PubMed and EMBASE for articles published up to June 2016. After deleting duplicates, the abstract of 757 articles were analyzed. We subsequently excluded 712 articles leaving 45 studies for full-text assessment of eligibility. Of these, 16 articles were excluded. Hence, 29 studies were included in the quantitative synthesis and in the different meta-analyses. Quality of the studies was assessed using the Quality index for prevalence studies and the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group available from the National Heart, Lung and Blood Institute. For meta-analyses including more than 10 studies, we used funnel and Doi plots to estimate publication bias. In severely obese patients submitted to bariatric surgery, obesity-associated gonadal dysfunction was very prevalent: PCOS was present in 36% (95CI 22–50) of women and MOSH was present in 64% (95CI 50–77) of men. After bariatric surgery, resolution of PCOS was found in 96% (95CI 89–100) of affected women and resolution of MOSH occurred in 87% (95CI 76–95) of affected men. Sex hormone-binding globulin concentrations increased after bariatric surgery in women (22 pmol/l, 95CI 2–47) and in men (22 pmol/l, 95CI 19–26) and serum estradiol concentrations decreased in women (−104 pmol/l, 95CI −171 to −39) and to a lesser extent in men (−22 pmol/l, 95CI −38 to −7). On the contrary, sex-specific changes were observed in serum androgen concentrations: for example, total testosterone concentration increased in men (8.1 nmol/l, 95CI 6–11) but decreased in women (−0.7 nmol/l, 95CI −0.9 to −0.5). The latter was accompanied by resolution of hirsutism in 53% (95CI 29–76), and of menstrual dysfunction in 96% (95CI 88–100), of women showing these symptoms before surgery. Obesity-associated gonadal dysfunction is among the most prevalent comorbidities in patients with severe obesity and should be ruled out routinely during their initial diagnostic workup. Considering the excellent response regarding both PCOS and MOSH, bariatric surgery should be offered to severely obese patients presenting with obesity-associated gonadal dysfunction.

BACKGROUND: We conducted a cross-sectional case–control study to evaluate the possible involvement of adiponectin and resistin in the pathogenesis of polycystic ovary syndrome (PCOS). METHODS: Seventy-six PCOS patients and 40 non-hyperandrogenic women matched for BMI and degree of obesity were included. Serum adiponectin and resistin levels, anthropometrical and hormonal variables, the 45 T→G and 276 G→T polymorphisms in the adiponectin gene, and the −420 C→G variant in the resistin gene, were analysed. RESULTS: Serum adiponectin concentrations were reduced in PCOS patients compared with controls (P = 0.038) irrespective of the degree of obesity, whereas serum resistin levels were increased in overweight and obese women compared with lean subjects (P = 0.016), irrespective of their PCOS or controls status. The adiponectin and resistin polymorphisms were not associated with PCOS and did not influence serum levels of adiponectin, resistin and other clinical and hormonal variables. In a multiple regression model, the waist-to-hip ratio, free testosterone levels and age, but not insulin resistance, were the major determinants of hypoadiponectinaemia. CONCLUSIONS: PCOS patients present with hypoadiponectinaemia, in relation with abdominal adiposity and hyperandrogenism. Our present results suggest that hyperandrogenism and abdominal obesity, by reducing the serum levels of the insulin sensitizer adipokine adiponectin, might contribute to the insulin resistance of PCOS.

BACKGROUND We evaluated carotid intima-media thickness (CIMT) as an early marker of atherosclerosis, as well as its main determinants among androgen excess, obesity and insulin resistance, in patients with polycystic ovary syndrome (PCOS).