Metformin has direct effects on human ovarian steroidogenesis

Abstract

Objective: To investigate the possibility of direct effects of metformin on ovarian steroidogenesis.

Design: Cultured ovarian cells.

Setting: Academic research environment.

Patient(s): Women undergoing bilateral salpingoophorectomy for benign gynecological disease.

Main outcome measure(s): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium.

Result(s): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude.

Conclusion(s): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).