Metformin has direct effects on human ovarian steroidogenesis

• Published in: Fertility and sterility Vol. 79; no. 4; pp. 956 - 962
• Main Authors: Mansfield, Rebecca, Galea, Ray, Brincat, Mark, Hole, David, Mason, Helen
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2003; Elsevier Science
• Subjects: Adult; Androstenedione - biosynthesis; Biological and medical sciences; Estradiol - biosynthesis; Female; Fundamental and applied biological sciences. Psychology; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Hormone metabolism and regulation; Humans; Hypoglycemic Agents - pharmacology; Mammalian female genital system; Metformin; Metformin - pharmacology; Middle Aged; Ovarian Follicle - cytology; Ovarian Follicle - drug effects; Ovarian Follicle - metabolism; polycystic ovary syndrome; Progesterone - biosynthesis; steroidogenesis; Theca Cells - drug effects; Theca Cells - metabolism; Vertebrates: reproduction; steroidogenesis; Metformin; polycystic ovary syndrome; Human; Theca folliculi; Estrogen; Female sterility; Polycystic ovary; Estradiol; Ovarian hormone; Female genital diseases; Ovarian diseases; Ovary; Hypoglycemic agent; Regulation(control); Biguanides; Female genital system; Cyst; Female; Steroidogenesis; Benign neoplasm; Granulosa; Progesterone; Sex steroid hormone; Ovarian follicle
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/S0015-0282(02)04925-7

To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. Cultured ovarian cells. Academic research environment. Women undergoing bilateral salpingoophorectomy for benign gynecological disease. Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. 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. 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).