Hyperinsulinemia and ovarian hyperandrogenism. Cause and effect.

The evidence that supports the hypothesis that hyperinsulinemia causes ovarian hyperandrogenism was reviewed. The most dramatic clinical expression of the association between hyperinsulinemia and hyperandrogenism is the HAIR-AN syndrome. In the HAIR-AN syndrome, severe insulin resistance results in a compensatory hyperinsulinemia that stimulates ovarian androgen production. Acanthosis nigricans, a dermatologic manifestation of severe insulin resistance, is an epiphenomenon of the disease. Hyperandrogenic (HA) women can be divided into two major groups: insulin-resistant (HA-IR) and non-insulin-resistant (HA-nIR). HA-nIR women have markedly elevated LH, often have minimally elevated serum prolactin, and have polycystic ovaries. HA-IR women have minimally elevated LH, markedly elevated plasma insulin, and stromal hyperthecosis. Women with HA-nIR probably have a primary hypothalamic-pituitary abnormality as the cause of their hyperandrogenism. Women with HA-IR probably have a primary metabolic abnormality as the cause of their hyperandrogenism. The relationship between hyperinsulinemia and hyperandrogenism is one example of the complex interrelationships that exist between central metabolism and reproduction.