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 acti vity (i.e. increased 17-alpha-hydroxylase and, to a lesser extent, inc reased 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 i n PCOS. Therefore, we measured serum steroid concentrations and 17 alp ha-hydroxyprogesterone responses to leuprolide administration and perf ormed oral glucose tolerance tests before and after 8 weeks of a hypoc aloric diet in 12 obese women with PCOS (PCOS group) and 11 obese wome n with normal menses (control group). Serum insulin decreased in both groups. In the PCOS group, basal serum 17 alpha-hydroxyprogesterone de creased from 4.2+/-0.6 to 3.0+/-0.5 nmol/L (P <0.05), and leuprolide-s timulated peak serum 17 alpha-hydroxyprogesterone decreased from 14.9/-2.6 to 8.9+/-0.8 nmol/L (P <0.025). Serum testosterone decreased fro m 2.47+/-0.52 to 1.56+/-0.33 nmol/L (P <0.05), and free testosterone d ecreased from 9.03+/-1.39 to 5.95+/-0.50 pmol/L (P <0.02). None of the se values changed in the control group. Serum sex hormone-binding glob ulin 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 testos terone concentrations in obese women with PCOS, but not in obese ovula tory women. The changes in women with PCOS may be related to a reducti on in serum insulin.