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.

The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. On the contrary, the prevalences of other disorders of androgen excess such as idiopathic hyperandrogenism and idiopathic hirsutism remain unknown. We aimed to obtain an unbiased estimate of the prevalence in premenopausal women of (i) signs of androgen excess and (ii) PCOS, idiopathic hyperandrogenism and idiopathic hirsutism. A multicenter prevalence survey included 592 consecutive premenopausal women (393 from Madrid, Spain and 199 from Bologna, Italy) reporting spontaneously for blood donation. Immediately before donation, we conducted clinical and biochemical phenotyping for androgen excess disorders. We determined the prevalence of (i) hirsutism, acne and alopecia as clinical signs of androgen excess and (ii) functional disorders of androgen excess, including PCOS, defined by the National Institute of Child Health and Human Development/National Institute of Health criteria, idiopathic hyperandrogenism and idiopathic hirsutism. Regarding clinical signs of hyperandrogenism, hirsutism and acne were equally frequent [12.2% prevalence; 95% confidence interval (CI): 9.5–14.8%], whereas alopecia was uncommon (1.7% prevalence, 95% CI: 0.7–2.7%). Regarding functional disorders of androgen excess, PCOS and idiopathic hirsutism were equally frequent (5.4% prevalence, 95% CI: 3.6–7.2) followed by idiopathic hyperandrogenism (3.9% prevalence, 95% CI: 2.3–5.4). Clinical signs of hyperandrogenism and functional disorders of androgen excess show a high prevalence in premenopausal women. The prevalences of idiopathic hyperandrogenism and idiopathic hirsutism are similar to that of PCOS, highlighting the need for further research on the pathophysiology, consequences for health and clinical implications of these functional forms of androgen excess.

Sex hormones, particularly androgens, may influence not only adipose tissue distribution but also its functions. We explored the possibility of sexual dimorphism in adipose tissue and skeletal muscle function. This was a case-control study. The setting was an academic hospital. Participants were severely obese men (n = 7), control women (n = 7), and hyperandrogenic women presenting with polycystic ovary syndrome (PCOS) (n = 7) submitting to bariatric surgery and an independent series of 40 patients with PCOS and 40 control women matched for age and body mass index. Samples of subcutaneous (SAT) and visceral adipose tissue (VAT) and skeletal muscle were obtained during bariatric surgery in severely obese subjects. Gene expression of chemerin, lipocalin-2, and omentin-1 in tissue samples was measured. We analyzed the effects of PCOS and obesity on serum concentrations of these adipokines in the larger series of women with PCOS and in control women. Expression of chemerin and lipocalin-2 was higher in VAT than in SAT in men and women with PCOS; the opposite was observed in control women. Omentin-1 expression was higher in VAT than in SAT in the three groups. No differences were observed in the skeletal muscle expression of these adipokines. Obesity increased serum chemerin and lipocalin-2 levels and tended to decrease omentin-1, irrespective of PCOS. The present results suggest that there is sexual dimorphism in some adipose tissue functions and that this dimorphism may be related to differences in androgen concentrations because women with PCOS show a masculinized pattern of expression of some adipokines.

OBJECTIVE: Increased serum ferritin levels and iron stores may be involved in the development of abnormal glucose tolerance in women presenting with obesity and/or polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum ferritin levels in premenopausal women among indexes of insulin resistance, adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative stress, and iron metabolism. RESEARCH DESIGN AND METHODS: A total of 257 premenopausal women, classified depending on the presence or absence of PCOS, obesity, and/or abnormal glucose tolerance, underwent a complete metabolic evaluation, serum ferritin, haptoglobin, and C-reactive protein (CRP) measurements, and genotyping for proinflammatory and prooxidant variants and mutations in the HFE gene. RESULTS: Serum ferritin concentrations were increased in women presenting with PCOS and/or abnormal glucose tolerance, independent of obesity. A stepwise multivariate linear regression analysis (R2 = 0.18, P < 0.0001) retained menstrual dysfunction (β = 0.14, P = 0.035), free testosterone (β = 0.14, P = 0.052), insulin sensitivity index (β = −0.12, P = 0.012), the His63Asp variant in HFE (β = 0.16, P = 0.008), and abnormal glucose tolerance (β = 0.15, P = 0.015) as significant predictors of the logarithm of ferritin levels, whereas CRP, haptoglobin, waist-to-hip ratio, or variants in the TNFα, TNFRSF1B, IL6, IL6ST, IL6Rα, PON1, and HFE Cys282Tyr mutation exerted no influence. CONCLUSIONS: Androgen excess (partly because of hyperandrogenemia and partly because of menstrual dysfunction), insulin resistance, abnormal glucose tolerance, and the HFE His63Asp variant correlate with ferritin levels in premenopausal women.

Do the circulating levels of a panel of adipokines involved in glucose metabolism exhibit sexual dimorphism in the fasting state and after an oral glucose load? Our results indicate sexual dimorphism in the circulating concentrations of adipokines involved in intermediate metabolism in the fasting state and during an oral glucose load. This finding suggests an influence of sex steroids on adipose tissue function. Sexual dimorphism in adipose tissue distribution fully develops after puberty and modulates the risk for cardiometabolic disorders. However, the possibility that adipose tissue function exhibits sexual dimorphism as well as its distribution is unproved. Cross-sectional case–control study including 32 subjects. Sixteen subjects with weight excess (8 men and 8 women, including 4 overweight and 4 obese subjects in each group) and 16 normal weight healthy volunteers (8 men and 8 women) presenting with similar age were submitted to a 75-g oral glucose tolerance test (oGTT). We measured circulating concentrations of insulin, glucose, chemerin, lipocalin-2, omentin-1, leptin and adiponectin and calculated their areas under the oGTT curve (AUC). Leptin and adiponectin concentrations were higher throughout the oGTT in women compared with men. Lipocalin-2 concentrations decreased during the oGTT in the whole group of study subjects. However, these levels remained higher in men with weight excess compared with normal weight men, whereas in women with weight excess lipocalin-2 levels at the end of the oGTT were lower compared with normal weight women. Sex was among the main determinants of the AUC of omentin-1 and leptin in linear regression models, and lower estradiol and testosterone concentrations were related to higher AUC of chemerin and omentin-1, respectively. Subjects with weight excess had higher AUC of chemerin and leptin and lower AUC of omentin-1 and adiponectin levels, independently of sex. We included a relatively small sample size and, because this was a cross-sectional study, we cannot infer causality to the associations between the changes in circulating adipokine concentrations and the variables studied here. Sexual dimorphism in adipose tissue function should be considered when studying adiposity and obesity, and also when designing strategies for their diagnosis and management. Supported by grants FIS PI080944 and PI1100357 from Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness and grant EC10-096 from Dirección General de Farmacia, Spanish Ministry of Health, Social Services and Equality. The authors have no competing interests to declare.