Polycystic Overy Syndrome (PCOS) is a broad-spectrum disease characterized by chronic anovulation and androgen excess, affecting 4-8% of women. Onset of the disorder is recognized to occur around the time of puberty but is often not diagnosed until adulthood. More than half of women with PCOS are obese, and insulin resistance appears to be an important part of its underlying pathophysiology. Long-term consequences in PCOS are now recognized to include increased risk of development of type 2 diabetes mellitus and cardiovascular disease. This has led to an interest in reduction of insulin resistance as a long-term treatment strategy. This reduction in insulin resistance can be accomplished by weight reduction or by insulin sensitizers such as metformin. To date, however, there are limited data on the effectiveness of insulin sensitizers and no data on the impact of weight reduction in adolescents with PCOS. Adolescence is a time of tremendous physical and psychosocial change. Obesity in adolescence is often predictive of lifelong obesity. The constellation of hirsutism, irregular bleeding, and obesity, often seen in adolescents with PCOS, could potentially have lifelong social and health consequences. A successful weight reduction strategy with improvement in insulin sensitivity at the onset of the symptoms of PCOS could have substantial long-term health benefits. The applicant hypothesizes that weight loss and metformin in the overweight adolescent with PCOS can reduce insulin resistance and improve the symptoms and metabolic profile associated with PCOS. Accordingly, a randomized, placebo-controlled, parallel-group trial comparing metformin and intensive lifestyle modification is proposed to gather preliminary data on the rate of ovulation, changes in testosterone and insulin and impact on cardiovascular risk of weight reduction and metformin as compared to placebo in a total of 30 subjects. Data obtained from this pilot trial on recruitment rates, drop-out, compliance, and estimated treatment effect sizes will be used to refine power calculations for a large-scale randomized trial focused on a comparison of metformin and weight reduction in obese adolescents.
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| Hoeger, Kathleen; Davidson, Kristen; Kochman, Lynda et al. (2008) The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 93:4299-306 |
| Hoeger, Kathleen M (2006) Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab 20:293-310 |
