Metformin has direct effects on human ovarian steroidogenesis

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 E-2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E-2 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). (C) 2003 by American Society for Reproductive Medicine.