Developmental Programming: Impact of Prenatal Testosterone Excess and Postnatal Weight Gain on Insulin Sensitivity Index and Transfer of Traits to Offspring of Overweight Females

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women and is exacerbated by obesity. Exposure of ewes to excess testosterone (T) from d 30–90 of gestation culminates in anovulation, functional hyperandrogenism, LH excess, and polyfollicular ovaries, features similar to those of women with PCOS, with some reproductive defects programmed by androgenic actions of T and others not. Excess weight gain during postnatal life increases the severity of these reproductive defects. Prenatal T-treated ewes also manifest reduced insulin sensitivity, a feature found in more than 70% of PCOS women. We tested the hypotheses that reduced insulin sensitivity of prenatal T-treated ewes is programmed by androgenic actions of T, and excess postnatal weight gain exaggerates this defect. In addition, we tested whether disruptive effects of excess weight gain on insulin sensitivity index are transferred to female offspring. Insulin sensitivity was assessed using iv glucose tolerance tests. Results revealed that disruptive effects of prenatal T excess on insulin sensitivity were programmed by androgenic action of T and postnatal overfeeding-impaired insulin sensitivity in both T-treated and controls and that prenatal T-treated sheep tend to manifest such overfeeding impairments earlier than controls. Importantly, offspring of overweight controls also manifest defects in insulin dynamics supportive of intergenerational transfer of obesity-related traits. The findings are of relevance in the context of developmental programming of insulin resistance by prenatal steroids and excess weight gain

The Polycystic Ovary Syndrome: A Position Statement From The European Society Of Endocrinology

Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.Wo

Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: A consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society

Objective: Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. Participants: An expert panel in PCOS and CVD reviewed literature and presented recommendations. Evidence: Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. Consensus Process: Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board. Conclusions: Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.Robert A. Wild, Enrico Carmina, Evanthia Diamanti-Kandarakis, Anuja Dokras, Hector F. Escobar-Morreale, Walter Futterweit, Rogerio Lobo, Robert J. Norman, Evelyn Talbott and Daniel A. Dumesi