Suppression of Serum Insulin by Diazoxide Reduces Serum Testosterone Levels in Obese Women with Polycystic Ovary Syndrome*

Abstract

To test the hypothesis that insulin plays a role in the hyperandrogenism of obese women with polycystic ovary syndrome, we conducted a prospective study in which the androgen status of five obese women with polycystic ovary syndrome was assessed on two occasions: before and after 10 days of oral diazoxide (100 mg, three times daily) administration. Fasting serum insulin levels decreased from 177 ± 45 (±SE) to 123 ± 43 pmol±L (P < 0.01) and insulin release in response to 100 g oral glucose administration decreased from 223.0 ± 29.2 to 55.6 ± 7.9 nmol·min±L (P < 0.002) after diazoxide administration. At the same time, serum total testosterone fell from 2.5 ± 0.4 to 2.1 ± 0.3 nmol±L (P < 0.007), serum testosterone not bound to sex hormone-binding globulin fell from 1.9 ± 0.3 to 1.4 ± 0.2 nmol± L (P < 0.01), and the molar ratio of serum androstenedione to serum estrone fell from 25.7 ± 7.7 to 16.6 ± 5.5 (P < 0.04). Serum sex hormone-binding globulin levels increased slightly but not significantly from 13.2 ± 1.0 to 21.7 ± 4.1 nmol±L. Serum androstenedione, dehydroepiandrosterone sulfate, estradiol, estrone, and progesterone concentrations did not change, nor did basal or GnRH-stimulated serum LH and FSH concentrations. These results suggest that hyperinsulinemia in obese women with polycystic ovary syndrome may directly increase serum testosterone levels.