Context: Previously, we have shown that women with PCOS exhibit an exaggerated serum estradiol (E₂) response to recombinant human FSH (r-hFSH, 150 IU) compared with similarly treated normal women. This enhanced granulosa cell responsiveness is consistent with excessive follicular development following 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 anti-androgen flutamide, would alter E₂ responses to r-hFSH.

Design: Prospective cohort study.

Setting: Institutional general clinical research center.

Subjects: 11 women with PCOS.

Intervention: On study day 1, each subject received 150 IU r-hFSH intravenously. Frequent blood samples were obtained over 24 h. After completion of r-hFSH stimulation, each subject was treated with flutamide, 125 mg, twice daily, for 6 weeks. Thereafter, the r-hFSH stimulation test was repeated.

Main outcome measures: Baseline and stimulated E₂ levels before and after treatment.

Results: Mean baseline and maximally stimulated E₂, integrated E₂ response, and fold change in E₂ were not different before and after treatment. Levels of T, A, P, 17-OHP, E₁ and SHBG before and after treatment were unchanged. Baseline DHEAS levels declined significantly after flutamide therapy.

Conclusions: These findings indicate that in women with PCOS, the E₂ hyperresponsiveness to FSH may not be attributable to increased circulating androgens.