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.
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).


METHODS
Prospective, randomized, placebo-controlled pilot trial.


METHODS
Academic medical center.


METHODS
Thirty-eight overweight or obese women with PCOS.


METHODS
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.


METHODS
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.


RESULTS
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/kg(2). 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).


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. Kathy_Hoeger@urmc.rochester.edu
Kathleen M
KM
Hoeger
Lynda
L
Kochman
Nellie
N
Wixom
Kimberly
K
Craig
Richard K
RK
Miller
David S
DS
Guzick
D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D004311:Double-Blind Method; D017097:Electric Impedance; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008019:Life Style; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology / Q000534:rehabilitation*; D010352:Patient Dropouts; D018579:Patient Selection; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000503:physiopathology*; D015431:Weight Loss
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin