OVARIAN 17-HYDROXYPROGESTERONE HYPERRESPONSIVENESS TO GONADOTROPIN-RELEASING-HORMONE (GNRH) AGONIST CHALLENGE IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME IS NOT MEDIATED BY LUTEINIZING-HORMONE HYPERSECRETION - EVIDENCE FROM GNRH AGONIST AND HUMAN CHORIONIC-GONADOTROPIN STIMULATION TESTING

Women with polycystic ovary syndrome (PCOS: hyperandrogenism and oligo menorrhea) have been shown to have exaggerated ovarian 17-hydroxyproge sterone (17-OHP) responses after GnRH agonist stimulation, suggestive of disordered ovarian cytochrome P450c17 alpha activity. However, most hyperandrogenic women also have an exaggerated LH response to both na tive GnRH and GnRH agonists. To assess whether the known LH hyperrespo nsiveness in PCOS patients mediates their exaggerated 17-OHP response to GnRH agonist challenge or whether the 17-OHP response can be duplic ated by direct stimulation of the ovary with a fixed amount of hCG, 25 PCOS women [age, 20.6 +/- 1.1 yr; body mass index (BMI), 24.9 +/- 1.3 kg/m(2)] and 5 controls (age, 29.4 +/- 2.3 yr; BMI, 29.2 +/- 3.0) und erwent both GnRH agonist (leuprolide acetate) and hCG testing. In addi tion, 23 normal women (age, 26.5 +/- 1.5 yr; BMI, 27.2 +/- 1.7 kg/m(2) ) underwent hCG testing, and 21 other normal women (age, 19.3 +/- 0.5 yr; BMI, 23.0 +/- 0.8 kg/m(2)) underwent leuprolide acetate challenge. Blood was sampled before and 24 h after (the previously determined ti me of the peak response) leuprolide acetate (500 mu g, sc) and hCG (50 00 IU, im) stimulation tests. The tests were administered during the e arly follicular phase in women who were ovulatory and in randomized or der in the subjects receiving both stimuli. Peak serum 17-OHP levels d id not differ between leuprolide acetate or hCG stimulation in PCOS pa tients or controls when measured at 24 h (324.9 +/- 41.9 vs. 360.4 +/- 54.0 in PCOS; 183.2 +/- 19.6 us. 141.2 +/- 11 ng/dL in controls). Pea k 17-OHP levels after hCG challenge and GnRH agonist stimulation were highly correlated (r = 0.82; P < 0.001) in the subjects receiving both stimuli. Although leuprolide acetate elicited a higher estradiol (E(2 )) response than hCG in all subjects, serum E(2) levels increased sign ificantly after hCG treatment in both patients and controls (P < 0.001 and P < 0.0001). The small, but significant, increase in serum E(2) a fter hCG stimulation suggests that a rigid two-cell model of ovarian s teroidogenesis may be an oversimplification of in vivo physiology. Our results suggest that exaggerated 17-OHP responses to GnRH agonist sti mulation in hyperandrogenic women are not mediated by the known hyperr esponsiveness of LH in these patients, but are due to increased ovaria n androgen sensitivity to LR stimulation.