A bovine model for examining the effects of an aromatase inhibitor on ovarian function in women

Objective: To test the hypothesis that treatment with an aromatase inhibitor (letrozole) will terminate dominant ovarian follicle growth and result in the emergence of a new follicular wave, regardless of the stage of follicular development at the time of treatment. Design: Prospective study. Setting: Academic research center. Animal(s): Postpubertal beef heifers. Intervention(s): Randomized trial involving treatment with letrozole on days 1-3, 3-5, 5-7 (day 0 = pretreatment ovulation) or no treatment. Main Outcome Measure(s): Follicular development, corpus luteum (CL) development, hormone profiles, and plasma aromatase inhibitor concentration. Result(s): Multiple doses of letrozole lengthened the period of follicular dominance, delayed emergence of the next follicular wave, and resulted in a larger CL regardless of the stage of the follicular wave in which treatments were initiated. No effects on circulating FSH concentrations were detected, but the stimulatory effects on the dominant follicle and CL were associated with increased plasma concentrations of LH in letrozole-treated animals. Plasma P concentrations were numerically higher throughout the luteal phase in letrozole-treated versus control heifers, but differences were not significant. Conclusion(s): The results provide rationale for the hypothesis that the mechanism of action responsible for the stimulatory effect of aromatase inhibitors on ovarian function involves an elevation in circulating concentrations of LH rather than FSH. (Fertil Steril (R) 2011;96:434-8. (C) 2011 by American Society for Reproductive Medicine.)