A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women

Fertil Steril. 2002 Aug;78(2):280-5. doi: 10.1016/s0015-0282(02)03241-7.


Objective: To evaluate the ovarian follicular dynamics of cycle modification with the aromatase inhibitor letrozole compared with clomiphene citrate in normal ovulatory women.

Design: Randomized double-blind controlled trial.

Setting: Tertiary care hospital.

Patient(s): Nineteen ovulatory female volunteers, ages 18-35 years.

Intervention(s): Subjects were monitored in one control cycle. Subjects then received either letrozole 2.5 mg daily or clomiphene citrate 50 mg daily on days 5-9 after menses.

Main outcome measure(s): Number of mature follicles, endometrial thickness and endometrial pattern at ovulation, and follicular profiles of LH, FSH, and E(2).

Result(s): The number of mature follicles at the LH surge in natural cycles was 1.0 with an exaggerated response seen for treatment both with clomiphene and letrozole. There was no difference in the endometrial thickness at midcycle during either the natural cycles or the medicated cycles. LH surges and spontaneous ovulation were documented in all natural and medicated cycles. When measured daily, follicular profiles of LH and FSH are similar between the groups in both the natural and medicated cycles. In the medicated cycles, clomiphene results in a significant increase in E(2) levels, while E(2) levels in letrozole-stimulated cycles appeared lower than in natural cycles.

Conclusion(s): Transient inhibition of aromatase activity in the early follicular phase with the aromatase inhibitor letrozole results in stimulation of ovarian folliculogenesis similar to that seen with clomiphene citrate with no apparent adverse effect on endometrial thickness or pattern at midcycle.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aromatase Inhibitors*
  • Clomiphene / pharmacology*
  • Double-Blind Method
  • Estrogen Antagonists / pharmacology*
  • Fertility Agents, Female / pharmacology*
  • Follicle Stimulating Hormone / blood
  • Humans
  • Letrozole
  • Middle Aged
  • Nitriles / pharmacology*
  • Ovulation / drug effects*
  • Pilot Projects
  • Triazoles / pharmacology*


  • Aromatase Inhibitors
  • Estrogen Antagonists
  • Fertility Agents, Female
  • Nitriles
  • Triazoles
  • Clomiphene
  • Letrozole
  • Follicle Stimulating Hormone