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 PCOS. Intervention(s): Blood samples were obtained before (-15 and 0 minutes) and after (15, 30, 45, and 60 minutes) the administration of ACTH (250 μg). 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 17α- hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH. The ratio of 17α-hydroxyprogesterone to progesterone, which indicates 17α-hydroxylase activity, and the ratio of androstenedione to 17α- hydroxyprogesterone, which indicates 17,20-lyase activity, were significantly 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.