Randomized Study of the Effect of Decreased Hyperinsulinemia on the Ovulatory Response to Clomiphene Citrate in Obese Women With Polycystic Ovary Syndrome
Randomized Study of the Effect of Decreased Hyperinsulinemia on the Ovulatory Response to Clomiphene Citrate in Obese Women With Polycystic Ovary Syndrome
OBJECTIVES:

 I. Determine whether reduction of serum insulin levels by metformin increases ovulatory
 response to clomiphene or spontaneous ovulation in obese women with polycystic ovary
 syndrome.
PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study.
 Patients are randomized to one of two treatment arms.

 Patients receive oral metformin (arm I) or oral placebo (arm II) three times daily for 8
 weeks. All patients who do not ovulate by day 28 receive oral clomiphene citrate daily on
 days 36-40.
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 Obese women with chronic anovulation due to polycystic ovary syndrome (PCOS)

 Must have oligoamenorrhea and hyperandrogenemia

 --Prior/Concurrent Therapy--

 At least 2 months since prior standard therapy (including over the counter drugs) At least
 2 months since prior investigational agents

 --Patient Characteristics--

 Hematopoietic: Hematocrit greater than 38%

 Hepatic: Liver function normal No clinically significant hepatic disease

 Renal: No clinically significant renal disease Creatinine less than 1.4 mg/dL No
 proteinuria

 Cardiovascular: No clinically significant cardiac disease

 Pulmonary: No clinically significant pulmonary disease

 Hormonal: Thyroid function normal Prolactin normal Fasting 17 alpha-hydroxy progesterone
 less than 200 mg/dL OR No late onset adrenal hyperplasia 21 alpha-hydroxylase deficiency

 Other: Not pregnant Negative pregnancy test Fertile patients must use effective
 contraception No diabetes mellitus No clinically significant neurologic, psychiatric,
 infectious, neoplastic, or metabolic disease No clinically significant malignant disease
 except nonmelanomatous skin cancer At least 1 year since any prior drug abuse or alcoholism