Impact of Metformin in Teens With Polycystic Ovary Syndrome (PCOS) on Oral Contraceptive Therapy

Phase 3

Completed

Conditions: Polycystic Ovary Syndrome

Interventions: Drug: Metformin
Drug: Oral Contraceptive Pill
Behavioral: Quality of Life Questionnaire
Behavioral: Lifestyle Management Program
Procedure: Oral Glucose Tolerance Test
Procedure: Blood work
Procedure: Abdominal Ultra Sound
Procedure: Dual-energy x-ray absorptiometry (DEXA scan)
Drug: placebo

Registration Number: NCT00283816

Lead Sponsor: University of Rochester

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 36

Inclusion Criteria

Age 12-18 years; Menstrual irregularity; Overweight; Must be able to swallow capsules; At lease 6 months since onset of first menstrual cycle.

Exclusion Criteria

Diabetes; Kidney or Liver disease; Tobacco use; Depression or Bipolar Disease; Contraindication to exercise; Weight > 300 lbs.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Oral Glucose Tolerance Test	metformin
1	Oral Contraceptive Pill	metformin
1	Blood work	metformin
1	Abdominal Ultra Sound	metformin
1	Dual-energy x-ray absorptiometry (DEXA scan)	metformin
0	Quality of Life Questionnaire	placebo
0	placebo	placebo
1	Metformin	metformin
1	Lifestyle Management Program	metformin
1	Quality of Life Questionnaire	metformin
0	Oral Contraceptive Pill	placebo
0	Lifestyle Management Program	placebo
0	Oral Glucose Tolerance Test	placebo
0	Blood work	placebo
0	Abdominal Ultra Sound	placebo
0	Dual-energy x-ray absorptiometry (DEXA scan)	placebo

Primary Outcome Measures

Name	Time	Method
Reduction in Abdominal Fat as Measured by Waist Circumference.	baseline and 24 weeks	Change in waist circumference measured in cms used as a measure of abdominal adiposity, pre minus post intervention

Secondary Outcome Measures

Name	Time	Method
Change in Weight Post Minus Pre Intervention.	baseline and 24 weeks	Body mass index change in adolescents enrolled in lifestyle intervention program
Total Testosterone Change	baseline and 24 weeks	Change in total testosterone post minus pre intervention
Change in Sex Hormone Binding Globulin (SHBG)	baseline and 24 weeks	SHBG concentration post minus pre-intervention