On the Paradox of Insulin-Induced Hyperandrogenism in Insulin-Resistant States

Abstract

FREQUENT coexistence of insulin resistance and ovarian hyperandrogenism is a well known phenomenon. Although the precise mechanisms underlying this phenomenon have not been clearly defined, the hypothesis that hyperandrogenism of insulin-resistant states is due to ovarian stimulation by high levels of circulating insulin has gained popularity. Clinical observations and experimental data obtained in humans and in animals, both in vitro and in vivo, support this hypothesis. However, the following question is often raised: how can the ovary remain sensitive to insulin, when “classical” target organs for insulin (such as liver, fat or muscle) are insulin resistant, and thus do not respond to insulin normally? Although the answer to this question has not yet been found, a substantial body of data that shed light on this issue has accumulated in the literature. One can now envision a variety of circumstances in which the ovary may overproduce androgens in response to stimulation by insulin, even though other organs are insulin resistant. In this article I will discuss possible mechanisms of preserved ovarian sensitivity to insulin in insulin-resistant states. I will also outline directions of future studies in this exciting new area of endocrine knowledge.