The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study

• Published in: Fertility and sterility Vol. 95; no. 3; pp. 1059 - 1066.e7
• Main Authors: Ladson, Gwinnett, M.D, Dodson, William C., M.D, Sweet, Stephanie D., M.D, Archibong, Anthony E., Ph.D, Kunselman, Allen R., M.A, Demers, Laurence M., Ph.D, Williams, Nancy I., Sc.D, Coney, Ponjola, M.D, Legro, Richard S., M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2011; Elsevier
• Subjects: Adult; androgen; animal ovaries; Biological and medical sciences; bladder; body composition; bone density; Caloric Restriction; confidence interval; diarrhea; Diet, Reducing; Double-Blind Method; dual-energy X-ray absorptiometry; Exercise; Female; Female genital diseases; glucose tolerance; glucose tolerance tests; Glycemic Index - drug effects; Gynecology. Andrology. Obstetrics; headache; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; insulin action; insulin resistance; Internal Medicine; Life Style; lifestyle; low calorie diet; Medical sciences; metformin; Metformin - administration & dosage; Metformin - adverse effects; monitoring; Non tumoral diseases; nutrition; Obstetrics and Gynecology; Ovarian function; ovulation; Ovulation - drug effects; Patient Dropouts; patients; phenotype; Placebo Effect; polycystic ovary syndrome; Polycystic Ovary Syndrome - diet therapy; Polycystic Ovary Syndrome - drug therapy; quality of life; secretion; testosterone; Testosterone - analogs & derivatives; Testosterone - blood; therapeutics; Treatment Outcome; urine; weight loss; women; insulin action; exercise; nutrition; androgen; Ovarian function; Physical exercise; Androgen; Nutrition; Gynecology; Female sterility; Polycystic ovary; Insulin; Obstetrics; Female genital diseases; Feeding; Ovarian diseases; Hypoglycemic agent; Randomization; Biguanides; Treatment; Cyst; Double blind study; Clinical trial; Benign neoplasm; Metformin; Life style
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2010.12.002

Objective To determine if the combination of lifestyle (caloric restriction and exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in improving the polycystic ovary syndrome (PCOS) phenotype. Design Double-blind randomized 6-month trial of MET versus PBO. Setting Two academic medical centers. Patient(s) One hundred fourteen subjects with PCOS were randomized to MET (N = 55) or PBO (N = 59). Intervention(s) Subjects collected urine daily for ovulation monitoring, had monthly monitoring of hormones and weight and determination of body composition by dual-energy x-ray absorptiometry, glucose tolerance, and were evaluated for quality of life at baseline and completion. Main Outcome Measure(s) Ovulation rates and testosterone levels. Result(s) Dropout rates were high. There was no significant difference in ovulation rates. Testosterone levels were significantly lower compared with baseline in the MET group at 3 mos but not at 6 mos. There were no differences in weight loss between groups, but MET showed a significant decline at 6 months compared with baseline (−3.4 kg, 95% confidence interval −5.3 to −1.5 kg). We noted divergent effects of MET versus PBO on oral glucose tolerance test indices of insulin sensitivity (increased) and secretion (worsened). Total bone mineral density increased significantly in MET. There were no differences in quality of life measures between the groups. The MET group had increased diarrhea and headache, but fewer bladder infections and musculoskeletal complaints. Conclusion(s) The addition of metformin to lifestyle therapy produced little reproductive or glycemic benefit in women with PCOS, although our study had limited power owing to a high dropout rate. It is not possible at baseline to identify women likely to drop out.