Hyperandrogenic anovulation (PCOS): A unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. Recent prevalence estimates suggest that 5-10% of premenopausal women have the full-blown syndrome of hyperandrogenism, chronic anovulation, and polycystic ovaries. Evidence suggests that women with polycystic ovary syndrome have a unique disorder of insulin action and are at increased risk to develop non-insulin-dependent diabetes mellitus. Further, non-insulin-dependent diabetes mellitus in women with polycystic ovary syndrome has a substantially earlier age of onset (third to fourth decades) than it does in the general population (sixth to seventh decades). Studies assessing whether abnormalities in insulin action are intrinsic or secondary to the hormonal milieu have found that insulin-induced receptor autophosphorylation is markedly diminished in approximately 50% of polycystic ovary syndrome women. This defect is unique to women with polycystic ovary syndrome and is not seen in other common insulin-resistant states of obesity and non-insulin-dependent diabetes mellitus. In polycystic ovary syndrome women who have normal receptor autophosphorylation, it remains likely that signaling mechanisms downstream of the receptor are abnormal, since these women are also insulin resistant. This distinctive post-insulin-binding defect appears to be genetic, since it is present in cells removed from the in vivo environment for generations.