Improved Efficacy of Low-Dose Spironolactone and Metformin Combination Than Either Drug Alone in the Management of Women With Polycystic Ovary Syndrome (PCOS): A Six-Month, Open-Label Randomized Study

Context: To improve the treatment outcomes in women with polycystic ovary syndrome (PCOS), various drugs like glitazones, oral contraceptive pills, or antiandrogens have been combined with metformin. Objective: The aim of the study was to compare the efficacy of the combination of low-dose spironolactone and metformin with either drug alone in the management of women with PCOS. Design and Setting: The present study was an open-label, randomized study conducted at a tertiary care referral center. Patients and Intervention: Of 204 women who met the 2006 Androgen Excess-PCOS criteria for PCOS, 198 were randomized into 3 equal groups to receive metformin (1000 mg/d), low-dose spironolactone (50 mg/d), or a combination of both drugs for a period of 6 months. A total of 169 subjects (n = 56 metformin, 51 spironolactone, 62 combination) completed the study. Main Outcome Measures: Menstrual cycle pattern, Ferriman-Gallwey score, body mass index (BMI), waist-hip ratio, blood pressure, LH, FSH, total T, glucose and insulin sensitivity indices were measured at baseline (0 mo) and 3 and 6 months after the intervention. Recording of adverse events and drug compliance was assessed at each of the visits. Results: The 3 groups had comparable mean age and BMI at baseline. By 6 months, menstrual cycles/y increased, whereas Ferriman-Gallwey score, serum total T, and area under the curve-glucose and -insulin decreased significantly (P < .05) in the combination group as compared to either drug alone. There was no significant change in body weight, BMI, waist-hip ratio, and blood pressure in any of the 3 groups. The combination group had better compliance than either drug alone, and the adverse event rate was not higher. Conclusion: The combination of low-dose spironolactone with metformin seems superior to either drug alone in terms of clinical benefits and compliance in women with PCOS. (J Clin Endocrinol Metab 98: 3599-3607, 2013)