Insulin as an effector of human ovarian and adrenal steroid metabolism

Evidence is accumulating that insulin is a potent effector of human steroid hormone metabolism. In this article, we have reviewed primarily in vivo studies showing that physiologic elevations in serum insulin levels can increase circulating ovarian androgens, decrease serum levels of adrenal androgens, and decrease serum SHBG levels. In addition, insulin resistance at the level of the adrenals appears to be associated with loss of responsiveness to the suppressive effect on adrenal androgens. We have proposed an integrated hypothesis as to how these complex actions of insulin might all come into play in the genesis of a common endocrinopathy--PCO. At least one clinically relevant aspect of these findings is that therapies aimed at reducing the magnitude of hyperinsulinemic insulin resistance in women with PCO may ameliorate the hyperandrogenism. One example of this possibility is the well recognized observation that substantial weight loss is associated with a reduction in serum androgen levels and clinical manifestations of hyperandrogenism in this disorder.