Hyperandrogenism, insulin resistance and acanthosis nigricans. 10 years of progress.

Polycystic ovary disease is a heterogeneous endocrinopathy with many interacting causal factors. One potential such factor is chronic hyperinsulinemia. Multiple, independent lines of evidence support the contention that chronic hyperinsulinemia causes ovarian hyperandrogenism. This evidence includes: (1) mutations in the insulin receptor gene that cause severe hyperinsulinemia appear to be associated with ovarian hyperandrogenism, (2) insulin stimulates ovarian thecal and stromal androgen secretion in vitro, and (3) in some experimental models, manipulation of circulating insulin concentrations results in changes in circulating androgens. Although the association between hyperinsulinemia and hyperandrogenism remains to be fully explained at the molecular level, chronic hyperinsulinemia appears to be an important cause of hyperandrogenism.