Improvement in quality-of-life questionnaire measures in obese adolescent females with polycystic ovary syndrome treated with lifestyle changes and oral contraceptives, with or without metformin.

We studied the effect of metformin or placebo in a lifestyle modification program combined with oral contraceptives (OC) on quality-of-life parameters measured by the polycystic ovary syndrome (PCOS) questionnaire in obese adolescent women with validated PCOS. The quality-of-life indicators were measured at baseline and conclusion for five domains on the PCOS questionnaire, with equal improvement in scores in both placebo and metformin groups, suggesting that the addition of metformin does not add improvement to quality-of-life measures above those observed with lifestyle modification and OC treatment.

The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials.

CONTEXT: Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear. OBJECTIVE: We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS. DESIGN: Two small, randomized, placebo-controlled clinical trials were performed. PATIENTS AND PARTICIPANTS: A total of 79 obese adolescent women with PCOS participated. INTERVENTIONS: In the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo. MAIN OUTCOME MEASURES: Serum concentrations of androgens and lipids were measured. RESULTS: Lifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%). CONCLUSIONS: In these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction.

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). 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/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). 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.