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17α-Hydroxyprogesterone Responses to Leuprolide and Serum Androgens in Obese Women with and without Polycystic Ovary Syndrome after Dietary Weight Loss 1

1997; Oxford University Press; Volume: 82; Issue: 2 Linguagem: Inglês

10.1210/jcem.82.2.3753

1945-7197

Daniela Jakubowicz, John E. Nestler,

Reproductive Biology and Fertility

Insulin resistance and increased ovarian cytochrome P450c17␣ activity (i.e.increased 17␣-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␣ activity in obese women with PCOS.We hypothesized that weight loss would decrease serum insulin and P450c17␣ activity in PCOS.Therefore, we measured serum steroid concentrations and 17␣-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␣-hydroxyprogesterone decreased from 4.2 Ϯ 0.6 to 3.0 Ϯ 0.5 nmol/L (P Ͻ 0.05), and leuprolide-stimulated peak serum 17␣-hydroxyprogesterone decreased from 14.9 Ϯ 2.6 to 8.9 Ϯ 0.8 nmol/L (P Ͻ 0.025).Serum testosterone decreased from 2.47 Ϯ 0.52 to 1.56 Ϯ 0.33 nmol/L (P Ͻ 0.05), and free testosterone decreased from 9.03 Ϯ 1.39 to 5.95 Ϯ 0.50 pmol/L (P Ͻ 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 Ͻ 0.003) and control (P Ͻ 0.007) groups, respectively.We conclude that dietary weight loss decreases ovarian P450c17␣ 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.