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 microg). 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 17alpha-hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH. The ratio of 17alpha-hydroxyprogesterone to progesterone, which indicates 17alpha-hydroxylase activity, and the ratio of androstenedione to 17alpha-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.