Combined Lifestyle Modification and Metformin in Obese Patients with Polycystic Ovary Syndrome: A Randomized, Placebo-controlled, Double-blind Multicentre Study

Abstract

Metformin therapy reportedly benefits women with polycystic ovary syndrome (PCOS). Its effect is presumably based on lowering serum insulin levels. Metformin inhibits glucose production in the liver and also enhances insulin sensitivity at the cellular level. This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of lifestyle change and metformin therapy in 143 women with PCOS who were oligomenorrheic or amenorrheic and had a body mass index (BMI) greater than 30 kg/m2. All patients received standard dietary advice and were placed on an individualized high-carbohydrate, low-fat diet. Metformin, given in a dose of 850 mg twice daily, was compared with placebo over 6 months. The 69 patients placed on metformin and the 74 given placebo had similar characteristics at baseline and had been infertile for similar periods. Menstrual cycles became significantly more frequent in both metformin-treated and placebo patients. The median improvement was one cycle per 6 months. Reductions in body weight and BMI were documented in both groups. None of these parameters differed significantly between the actively treated and placebo patients. In neither group did insulin sensitivity or lipid profiles change significantly. Patients given metformin had significant reductions in waist circumference and the free androgen index. On logistic regression analysis, considering metformin therapy, percentage of weight loss, initial BMI, and age, only the percentage weight loss correlated with improved menstrual function. There were 2 pregnancies in each group. In this trial, metformin did not enhance weight loss or menstrual frequency in obese patients with PCOS compared with placebo patients. Only weight loss during dietary management made menstruation more frequent.