Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome.

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 less than 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 less than 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 less than 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 less than 0.01), and the molar ratio of serum androstenedione to serum estrone fell from 25.7 +/- 7.7 to 16.6 +/- 5.5 (P less than 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.