UC San Diego

Background

The influence of estradiol (E₂) 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 E₂ 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 E₂ 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, E₂ 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 E₂ levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E₂ and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E₂ 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 E₂ secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH.

Trial registration

NCT02389088.