Comparison of antiproliferative effects of metformine and progesterone on estrogen-induced endometrial hyperplasia in rats

Abstract

Metformin has been shown to inhibit the growth of endometriotic implants, and reverse endometrial hyperplasia when combined with oral contraceptive in a case report. The aim of this study is to compare the antiproliferative effects of medroxyprogesterone acetate (MPA), and metformin in oopherectomized rat endometrium. Forty oopherectomized Wistar-Albino rats were used, and assigned to receive saline, 17 β Estradiol hemihydrate (4 mg/kg), 17 β Estradiol hemihydrate (4 mg/kg) and metformin (50 mg/kg), 17 β Estradiol hemihydrate (4 mg/kg) and MPA (1 mg/day) for 14 days. Histological markers of uterotrophy, including endometrial height, luminal ephitelial cell height and density of endometrial glands on hysterectomy speciments were quantified for each specimen. Rats treated with estradiol had significantly increased in endometrial height, endomerial luminal epithelial height and endometrial gland densitiy than the other groups. Metformin and MPA acetate significantly reduced all parameters indicating endometrial hyperplasia, and uterotrophy with respect to the control group. Antiproliferative effects of metformin, and MPA was found to be comparable for all three parameters. In conclusion, metformin attenuates estrogen-induced endometrial hyperplasia in ooferectomized rats to the same degree as progesterone.