The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome

Background: The influence of estradiol (E-2) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E-2 influences GC responses to FSH in women with PCOS. Methods: This is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E-2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks. Results: In Phase 1, recovery of FSH, E-2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E-2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E-2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E-2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively. Conclusion: In anovulatory women with PCOS, chronic, unopposed E-2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH.