A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: A pilot study☆
Presented in part at the 58th Annual Meeting of the American Society for Reproductive Medicine, Seattle, Washington, October 12–17, 2002.
Received 30 September 2003; received in revised form 4 February 2004; accepted 4 February 2004.
Abstract
Objective
To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS).
Design
Prospective, randomized, placebo-controlled pilot trial.
Setting
Academic medical center.
Patient(s)
Thirty-eight overweight or obese women with PCOS.
Intervention(s)
All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone.
Main outcome measure(s)
Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index.
Result(s)
It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg2. Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2).
Conclusion(s)
Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS.
aDepartment of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
BUniversity of Rochester School of Nursing, Rochester, New York, USA
Reprint requests: Kathleen M. Hoeger, M.D., University of Rochester School of Medicine and Dentistry, Department of Obstetrics and Gynecology, 601 Elmwood Avenue, Box 668, Rochester, New York 14642, USA (FAX: 585-746-4146).
☆ Supported by a Mae Stone Goode foundation grant (KMH); Women's Reproductive Health Research Career Center grant K12 HD01332-03 to the University of Rochester; and General Clinical Research Center grant 5 M01 RR00044, National Center for Research Resources, National Institutes of Health.
ABSTRACT