The multifarious role of insulin in PCOS: From pathophysiology to therapeutic management

Insulin plays a multifarious role in the pathophysiology of PCOS. A number of data strongly support a key role of insulin resistance and the associated hyperinsulinemia in the pathogenesis of PCOS, although the underlying molecular mechanisms still remain undefined. Findings in animal models and results of experimental short-term in vivo exposure to increased plasma insulin levels in hyperandrogenic women consistently indicate a direct role of insulin in the endocrine alterations typical of PCOS. Moreover, insulin resistance plays a key role in the metabolic alterations of these subjects. There is also evidence that androgen excess can participate in determining the increase in insulin levels, by impairing insulin action and reducing metabolic clearance of insulin, with several vicious circles linking hyperandrogenism and insulin resistance. In accordance with these findings, treatment with insulin sensitizers proved to be a valuable option in the treatment of both the metabolic and reproductive alterations of these women.