Clinical Evidence for Predominance of Delta-5 Steroid Production in Women with Polycystic Ovary Syndrome

Abstract

AbstractContext:In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway.Objective:This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women.Design:We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women.Setting:The study was conducted in a General Clinical Research Center in an academic medical center.Participants:Women with PCOS (age, 18–37 yr; n = 10) and normal ovulatory controls (age, 18–37 yr; n = 11) were recruited.Interventions:For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 μg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 μg of recombinant hCG.Main Outcome Measure(s):We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration.Results:In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women.Conclusion:In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.