Clinical trial NCT00283816
Conditions: Polycystic Ovary Syndrome
Keywords: Polycystic Ovary Syndrome Overweight Adolescent Girls Irregular Menstrual Cycles
Sponsor: University of Rochester
Start date: 2006-01-01; Completion date: 2008-01-01
Enrollment: 36 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Oral contraceptives are known to improve menstrual cycles and symptoms in PCOS, however may increase cholesterol. Metformin, a drug to improve insulin resistance, may benefit metabolic state. This study is to determine whether metformin added to oral contraceptive therapy in adolescent women with PCOS improves metabolic state.The study will also test a lifestyle improvement program to reduce weight.

Detailed description:
Polycystic Ovary Syndrome (PCOS) is a heterogeneous condition characterized by chronic anovulation and androgen excess that occurs in 4-8% of unselected adult women. Although signs and symptoms of the disorder typically appear at the time of puberty, diagnosis is often delayed until adulthood. At least 50% of adult women with PCOS are obese, resulting in a more severe clinical picture. Obesity among adolescents has been increasing in recent years, with overrepresentation of females who show evidence of hyperandrogenism and irregular periods, suggesting an association of obesity and PCOS at an early age. Recent data, however, have drawn attention to the long-term risks of PCOS, including diabetes and cardiovascular disease. Insulin resistance plays a critical role in the pathophysiology of PCOS and is thought to be the metabolic abnormality most closely linked to an increased risk of diabetes and heart disease. Traditional treatments with oral contraceptives are associated with reduction in serum androgens and improvements in menstrual cycles in adolescents with PCOS, however these have not been well-studied in obese adolescents. Oral contraceptives may worsen the dyslipidemia seen in obese women with PCOS and do not address the insulin resistance. Metformin, an insulin sensitizing agent, has been shown to improve metabolic features of PCOS, but combination therapy with oral contraceptives has never been studied in the obese adolescent with PCOS.

The major hypothesis of this proposal is that metformin will improve the metabolic profile of obese adolescent girls with PCOS treated with oral contraceptives. Additionally, a secondary hypothesis will be that compliance with a concurrent lifestyle modification program with be associated with the most significant improvements.

Arms: arm 1: metformin arm 2: placebo
Interventions: intervention 1: Metformin intervention 2: Oral Contraceptive Pill intervention 3: Lifestyle Management Program intervention 4: Quality of Life Questionnaire intervention 5: Oral Glucose Tolerance Test intervention 6: Blood work intervention 7: Abdominal Ultra Sound intervention 8: Dual-energy x-ray absorptiometry (DEXA scan) intervention 9: placebo
Intervention descriptions: intervention 1: Metformin 500 mg. tabs 2 tabs BID for duration of study intervention 2: Yasmin, drospirenone and ethinyl estradiol 28 tablets

1 tab daily for duration of study intervention 3: Subjects and a parent/guardian will participate in a series of classes for training in diet, exercise \& behavior modification skills on a regular weekly basis over the 24 week study intervention 4: Quality of Life questionnaire designed for women with Polycystic Ovary Syndrome. Questions concern health and health related issues Performed twice during study, at baseline and conclusion intervention 5: Insulin response to a glucose challenge in an oral glucose tolerance test (OGTT), as measured by area under the curve (AUC). In this study we will administer an OGTT and calculate the AUC as a measure of insulin resistance.

Performed twice during study, at baseline and conclusion intervention 6: Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids. intervention 7: transabdominal transducer, which contains integrated software for volume calculation will be used to assess ovarian volume.

Performed twice during study, at baseline and conclusion intervention 8: Dual-energy x-ray absorptiometry (DEXA) will be used to assess percent body fat Performed twice during study, at baseline and conclusion intervention 9: placebo capsules, two capsules BID

Protocol documents: