Endocrine Abstracts

The polycystic ovary syndrome (PCOS), affecting 4–7% of women worldwide, is one of the most common causes of infertility. Hyperandrogenism and chronic oligo-anovulation are the prominent clinical features. However, PCOS is no longer considered as a constellation of disorders only related to the reproductive sphere, but represents an aggregation of metabolic disorders having an early onset and with advancing age predominating over reproductive disorders. Obesity, particularly the abdominal phenotype, represents the common metabolic abnormality at earlier onset in PCOS and, sometimes, it precedes the development of PCOS. The increasing prevalence of PCOS among young patients may partly depend on the exponential and epidemic increase of obesity, although long-term prospective epidemiological trials need to corroborate this hypothesis. The dominant distribution of fat in abdominal depots is known to induce profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. However, the visceral distribution of fat is unlikely to be the entire explanation for the metabolic abnormalities observed in PCOS women. It has been shown that adipose tissue of PCOS has an aberrant morphology and function. In particular, adipocytes from PCOS women are usually hypertrophic. Moreover, a local low-grade inflammation with an increased production of cytokines, chemokines, adipokines, and a decreased production of adiponectin has been described in PCOS patients. Interestingly, this chronic low-grade inflammatory state has been associated with local and systemic insulin resistance and, probably through this mechanism, to type 2 diabetes and to others cardiovascular risk factors. The crucial role of obesity in the pathogenesis and in the maintenance of PCOS is further emphasized by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism and fertility.