17 alpha-hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome after dietary weight loss

Insulin resistance and increased ovarian cytochrome P450c17 alpha activity (i.e. increased 17-alpha-hydroxylase and, to a lesser extent, increased 17,20-lyase) are both features of the polycystic ovary syndrome (PCOS). Evidence suggests that hyperinsulinemia may stimulate ovarian P450c17 alpha activity in obese women with PCOS. We hypothesized that weight loss would decrease serum insulin and P450c17 alpha activity in PCOS. Therefore, we measured serum steroid concentrations and 17 alpha-hydroxyprogesterone responses to leuprolide administration and performed oral glucose tolerance tests before and after 8 weeks of a hypocaloric diet in 12 obese women with PCOS (PCOS group) and 11 obese women with normal menses (control group). Serum insulin decreased in both groups. In the PCOS group, basal serum 17 alpha-hydroxyprogesterone decreased from 4.2+/-0.6 to 3.0+/-0.5 nmol/L (P <0.05), and leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone decreased from 14.9+/-2.6 to 8.9+/-0.8 nmol/L (P <0.025). Serum testosterone decreased from 2.47+/-0.52 to 1.56+/-0.33 nmol/L (P <0.05), and free testosterone decreased from 9.03+/-1.39 to 5.95+/-0.50 pmol/L (P <0.02). None of these values changed in the control group. Serum sex hormone-binding globulin increased by 4.5- and 3-fold in the PCOS (P <0.003) and control (P < 0.007) groups, respectively. We conclude that dietary weight loss decreases ovarian P450c17 alpha activity and reduces serum free testosterone concentrations in obese women with PCOS, but not in obese ovulatory women. The changes in women with PCOS may be related to a reduction in serum insulin.