The Effect of Androgen Blockade on Granulosa Cell Estradiol Production after Follicle-Stimulating Hormone Stimulation in Women with Polycystic Ovary Syndrome

Abstract Context: Previously, we have shown that women with polycystic ovary syndrome (PCOS) exhibit an exaggerated serum estradiol (E2) response to recombinant human FSH (rhFSH) (150 IU) compared with similarly treated normal women. This enhanced granulosa cell responsiveness is consistent with excessive follicular development after gonadotropin therapy and the corresponding risk of ovarian hyperstimulation syndrome. In vitro studies have shown that granulosa cells treated with androgens display greater FSH-induced E2 production than untreated cells, suggesting a role for androgens in granulosa cell responsiveness. Main Objective: This study was conducted to determine whether blockade of androgen action in PCOS women by administration of the antiandrogen flutamide would alter E2 responses to rhFSH. Design: We conducted a prospective cohort study. Subjects and Setting: We studied 11 women with PCOS at an institutional general clinical research center. Intervention: On study d 1, each subject received 150 IU rhFSH iv. Frequent blood samples were obtained over 24 h. After completion of rhFSH stimulation, each subject was treated with flutamide, 125 mg, twice daily, for 6 wk. Thereafter, the rhFSH stimulation test was repeated. Main Outcome Measures: Baseline and stimulated E2 levels before and after treatment were assayed. Results: Mean baseline and maximally stimulated E2, integrated E2 response, and fold change in E2 were not different before and after treatment. Levels of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, estrone, and SHBG before and after treatment were unchanged. Baseline dehydroepiandrosterone sulfate levels declined significantly after flutamide therapy. Conclusion: These findings indicate that in women with PCOS, the E2 hyperresponsiveness to FSH may not be attributable to increased circulating androgens.