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. TRIAL REGISTRATION: NCT02389088