Insulin Resistance and Hyperinsulinemia Induce Hyperandrogenism in a Young Type B Insulin-Resistant Female*

An adolescent female with type B insulin resistance and hyperandrogenemia is described. Evidence presented suggests that hyperinsulinemia leads to an increase in serum total and free testosterone. Support for this hypothesis is noted during an in vivo experiment in which large doses of regular insulin (305 U/kg-day) were infused iv, and multiple serum total testosterone measurements obtained. After 35 days of iv insulin therapy, the serum total testosterone values rose from 4.9 nmol/L (142 ng/dL) to 22.8 nmol/L (660 ng/dL), and the ovarian volume increased 2-fold. Basal (9.8 nmol/L; 282 ng/dL) and stimulated (16.8 nmol/L; 481 ng/dL) androstenedione measurements were elevated, and the dehydroepiandrosterone/androstenedione ratio was low, suggesting increased 3 beta-hydroxysteroid dehydrogenase activity. After resolution of the insulin-resistant state and the concomitant hyperinsulinemia, the serum total testosterone values returned to normal. This case illustrates that long term hyperinsulinemia leads to elevation of serum total testosterone.