Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls (JCM025)

Inclusion Criteria:

- Girls ages 10 to 17

- Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the
mean for normal control subjects of the same Tanner Stage)

- Creatinine clearance > 90 ml/min as calculated by the Cockcroft-Gault equation

- Hemoglobin > 12 mg/dL or Hematocrit > 36%

- Normal screening labs (with exception of the expected hormonal abnormalities inherent
in hyperandrogenemia)

- Sexually active subjects must agree to abstain or use double barrier contraception
during the study

- Subjects must agree not to take any other medications during the course of the study
without approval by the study investigators.

Exclusion Criteria:

- Abnormal screening labs (with the exception of the expected hormonal abnormalities
inherent in hyperandrogenemia)

- Creatinine clearance less than 90 ml/min as calculated by Cockcroft-Gault equation

- Hemoglobin <12 mg/dL or hematocrit < 36%

- Abnormal liver function tests (including AST, ALT, Bilirubin, Albumin, and Alkaline
Phosphatase)

- Weight < 34 kg

- History of renal dysfunction, liver dysfunction, congestive heart failure, deep
venous thrombosis, breast cancer, endometrial cancer, or cervical cancer

- Pregnant or breast feeding

- On medications known to affect the reproductive axis within 3 months of the study
(including oral contraceptive pills, metformin, and spironolactone)

- Are currently participating in another study or have been in one in the last 30 days.

- Subjects using restricted medication (see restrictions below) are excluded unless the
subject's primary care provider approves stopping the medication.