Impact of Metformin in Teens With Polycystic Ovary Syndrome (PCOS) on Oral Contraceptive Therapy
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Metformin; Oral Contraceptive Pill; Lifestyle Management Program; Quality of Life Questionnaire; Oral Glucose Tolerance Test; Blood work; Abdominal Ultra Sound; Dual-energy x-ray absorptiometry (DEXA scan); placebo
Intervention type(s): Drug; Drug; Behavioral; Behavioral; Procedure; Procedure; Procedure; Procedure; Drug
Intervention description(s): Metformin 500 mg. tabs 2 tabs BID for duration of study; Yasmin, drospirenone and ethinyl estradiol 28 tablets
1 tab daily for duration of study; 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; 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; 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; Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids.; transabdominal transducer, which contains integrated software for volume calculation will be used to assess ovarian volume.
Performed twice during study, at baseline and conclusion; Dual-energy x-ray absorptiometry (DEXA) will be used to assess percent body fat Performed twice during study, at baseline and conclusion; placebo capsules, two capsules BID
Other intervention name(s): Metformin Hydrochloride Tablets, 500 mg.; manufacturer: Mylan Pharmaceuticals, Morgantown, WV; Yasmin 28 tablets; Manufacturer: Berlex, Montville, NJ 07045; placebo formulation: 240 mg. lactose powder USP; in size 3 capsules from Capsugel
Intervention MeSH terms: Metformin; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Polycystic Ovary Syndrome; Overweight Adolescent Girls; Irregular Menstrual Cycles