Metformin reduces serum müllerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment

Assessment of ovarian responses to metformin treatment in obese women with polycystic ovary syndrome (PCOS). Prospective treatment with randomization to two doses of metformin. University teaching hospital. Obese women (n = 82) with PCOS. Markers of ovarian function were assessed after 4 and 8 months. Hormone (androgens and müllerian-inhibiting substance [MIS]) changes over time. There was no difference in the reproductive hormone changes between the doses of metformin, and data were combined for further analyses. Significant responses to treatment were recorded for menstrual frequency and androstenedione (A) (reduction) within the first 4 months of treatment. However, suppression of the elevated circulating MIS concentrations required protracted treatment, because no change was observed in the first 4 months--only in the second 4-month assessment period. Metformin treatment of PCOS leads to rapid suppression of A and improved menstrual frequency. Suppression of MIS is a delayed response that may be secondary to the development of a cohort of follicles that underwent initial recruitment in an environment of reduced insulin stimulation.