Effects of a Non-Steroidal Aromatase Inhibitor on Human Ovarian Function
Introduction: Ovarian folliculogenesis occurs in a wave-like pattern of growth during the menstrual cycle. A better understanding of the role of estrogen in folliculogenesis may lead to the development of better contraceptive and fertility protocols. Aromatase inhibitors cause a transient decline in natural estrogen production. Multiple small doses of an aromatase inhibitor have been used during fertility therapy to induce dominant follicle growth and ovulation. Objectives: Our objectives were to elucidate the effects of a single 20 mg dose of an aromatase inhibitor (Letrozole/FemaraTM) on folliculogenesis and test the hypothesis that an AI administered during defined times of the follicular phase or immediately after ovulation would result in atresia of the extant dominant follicle and initiate new wave emergence. Methods: Healthy, reproductive age, female volunteers not taking hormonal contraceptives were recruited (n=41). Ultrasound examinations began on day 4 of the menstrual cycle (day 1=first day of menses). Volunteers were randomized into 1 of 4 groups: treatment at a follicle diameter of 1) 12 mm, 2) 18 mm, 3) the first day following ovulation, or 4) control. Serial ultrasonography and phlebotomy were performed until ovulation in the subsequent cycle. Differences were analyzed using t-test, ANOVA, repeated measures ANOVA, or Kruskal-Wallis ANOVA where appropriate. Results: The dominant follicle in all treatment groups ovulated. There were no differences among experimental groups for peak follicle diameter, follicular growth rate, endometrial thickness at ovulation, or inter-ovulatory interval. Maximum FSH concentrations in the 12 mm, 18 mm and post-OV groups were 12.58 ± 1.41 mIU/mL, 18.62 ± 2.27 mIU/mL, 12.38 ± 1.10 mIU/mL, respectively. Maximum LH concentrations in the 12 mm, 18 mm and post-OV groups were 16.20 ±2.06 mIU/mL, 40.43 ± 4.32 mIU/mL, 16.34 ± 2.59 mIU/mL, respectively. The 18 mm group had higher FSH and LH concentrations (P < 0.02) compared to the 12 mm and post-OV groups. Conclusions: Administration of a single 20 mg dose of an aromatase inhibitor at defined times of the menstrual cycle did not induce dominant follicle regression or new wave emergence. Treatment resulted in continued follicle development, a transient decrease in E2 levels and elevated circulating FSH and LH concentrations. The failure of an aromatase inhibitor to interrupt dominant follicle development suggests a compensatory mechanism for the acute drop in E2 that may involve increased LH and FSH levels.
DegreeMaster of Science (M.Sc.)
SupervisorPierson, Roger A.
CommitteeChizen, Donna R.; Baerwald, Angela R.; Adams, Gregg P.
Copyright DateMay 2012