Early effects of metformin in women with polycystic ovary syndrome: A prospective randomized, double-blind, placebo-controlled trial

Context: Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome (PCOS). No data of the exact point and the impact of insulin resistance (IR) on metformin's efficacy exist. Objective: The objective of the study was to evaluate the early potential effects of metformin treatment, their time of onset, and the role of IR on metformin's efficacy. Design: This was a prospective randomized, double-blind, placebo-controlled trial. Setting: The study was conducted at the University of Heidelberg, Heidelberg, Germany. Patients: The patient population was 45 oligo-/anovulatory PCOS women with typical ovaries. Interventions: Women were stratified for IR (32 of 13) and then randomly allocated to receive either metformin (n = 22) or placebo (n = 23) and were assessed before and every 4 wk within a treatment period of 12 wk. Main Outcome Measures: Menstrual disturbance and markers of insulin metabolism were measured. Results: The main outcome criterion menstrual disturbance was successfully improved in the metformin-treated group, depending on IR (12 of 15 vs. three of 17), whereas women without IR (four of seven vs. four of six) had no significant amelioration of their menstrual irregularities (P < 0.05). Estradiol levels increased continuously only in the treatment group (P < 0.005), indicating an improvement of ovulatory function. Sixty-seven percent of metformin-treated women had at least one ovulation, compared with only 45% in the placebo group, shown by biphasic body temperature curves. Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005). Conclusions: IR is a baseline predictor of clinical efficacy in metformin treatment in PCOS women measured by improved menstrual cyclicity and ovulatory function.