Reproductive Endocrinology · Ovarian Hormones

Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat

Kilic-Okman T, Kucuk M, Altaner S

Published December 12, 2003 Fertility and Sterility, 80(6), 1330-1332
DOI 10.1016/j.fertnstert.2003.05.002 PMID 14667861

RRM Academy Synopsis

Letrozole and clomiphene stimulate similar follicle growth in rats

Letrozole raised mature follicle counts in rats to a level similar to clomiphene citrate, in a controlled prospective study of 30 female rats in three groups of 10. Both drug groups had more mature follicles than the saline group. Endometrial thickness was similar in all three groups.

Key Findings

  • Mature follicle counts averaged 29.10 with letrozole, 27.60 with clomiphene citrate and 25.00 with saline. Follicle counts did not differ significantly between the letrozole and clomiphene citrate groups.
  • Ovary size was larger in both drug groups than in the saline group and did not differ significantly between letrozole and clomiphene citrate.
  • Estradiol was lower with letrozole than with clomiphene citrate or saline, and testosterone was higher with letrozole than with either. Clomiphene citrate and saline did not differ on estradiol or testosterone.
  • Endometrial thickness averaged 0.80 mm with letrozole, 0.80 mm with clomiphene citrate and 1.0 mm with saline, with no significant difference among the groups.

Interpretation

The authors report the first controlled prospective comparison of the two drugs in rats. Dosing lasted 2 days in 30 cycling rats, 10 per group. A pathologist unaware of group assignment read the tissue sections. Outcomes measured were mature follicle number, ovary size, endometrial thickness and serum hormone levels. The authors note that clomiphene citrate at the dose used may have blocked estrogen action or production. The findings support further study of letrozole for ovulation induction.

RRM Context

The paper calls clomiphene citrate the most commonly prescribed drug for inducing ovulation and tests letrozole as a candidate. Restorative reproductive medicine starts by finding why a woman is not ovulating. That evaluation comes before any drug choice. Animal studies of how a drug acts on the ovary add to that picture.

Abstract

Objective

To compare the effects of letrozole and clomiphene citrate in the rat in terms of number of ovarian follicles; endometrial thickness; and serum levels of E2, FSH, LH, and T.

Design

Controlled prospective study.

Setting

University research laboratory.

Animals

Thirty sexually mature female Wistar-Albino rats that were 20 weeks of age.

Interventions

Letrozole, 5 mg/kg of body weight daily (10 rats); clomiphene citrate, 100 microg/kg daily (10 rats); or saline solution, 2 mL/d (10 rats). After 2 days, rats were euthanized and ovariectomized.

Main Outcome Measures

Number of mature follicles, endometrial thickness, and serum levels of hormones.

Results

Mean levels of FSH, LH, E2, and T; number of mature follicles; and ovary size differed among the groups, whereas the mean endometrial thickness did not differ.

Conclusions

In rats, the effect of letrozole on follicular maturation is similar to that of clomiphene citrate.

Topics

Related research

Reproductive Endocrinology › Ovarian Hormones › Estrogen · Therapeutics › Ovulation Agents › Aromatase Inhibitors
Tulay Kilic-Okman, Mustafa Kucuk, Semsi Altaner
T Kilic-Okman, M Kucuk, S Altaner
PMID 14667861 14667861 DOI 10.1016/j.fertnstert.2003.05.002 10.1016/j.fertnstert.2003.05.002 Kilic-Okman et al. 2003, Kilic-Okman 2003