Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome

Objective: To determine whether the administration of metformin, an insulin-sensitizing agent, is followed by changes in adrenal steroidogenesis in women with polycystic ovary syndrome (PCOS). Design: Prospective trial. Setting: Department of Obstetrics and Gynecology, University of Siena, Siena, Italy. Patient(s): Fourteen women with PGOS. Intervention(s): Blood samples were obtained before (-15 and 0 minutes) and after (15, 30, 45, and 60 minutes) the administration of ACTH (250 mu g) Metformin then was given at a dosage of 500 mg three times a day for 30-32 days, at which time the pretreatment study was repeated. Main Outcome Measure(s): The adrenal androgen responses to ACTH before and after treatment with metformin. Result(s): Ovulation occurred in two women (14%) in response to metformin treatment. A significant reduction in basal concentrations of free testosterone and a significant increase in concentrations of sex hormone-binding globulin were observed. The administration of metformin was associated with a significant reduction in the response of 17 alpha-hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH. The ratio of 17 alpha-hydroxyprogesterone to progesterone, which indicates 17 alpha-hydroxylase activity, and the ratio of androstenedione to 17 alpha-hydroxyprogesterone, which indicates 17,20-lyase activity, were signif icantly lower after a month of metformin treatment, indicating a reduction in the activities of these enzymes. Conclusion(s): The administration of metformin to unselected women with PCOS led to a reduction in the adrenal steroidogenesis response to ACTH. This finding supports the hypothesis that high insulin levels associated with PCOS may cause an increase in plasma levels of adrenal androgens. ((C)1999 by American Society for Reproductive Medicine.).