Study of Leptin for the Treatment of Hypothalamic Amenorrhea

Inclusion criteria for HA subjects * Hypothalamic amenorrhea of at least 6 months duration with low or normal LH and FSH, e.g. due to strenuous exercise (running \>20 miles per week or equivalent) or low weight * Can be secondary HA OR primary HA with some pubertal development and normal screening labs * Age 18-35 years old * Body weight within +/- 15% of ideal body weight and stable for 6 months (no change \> 5 lbs) * Baseline leptin \<5 ng/mL (except for the Cognitive Sub-Study Baseline visit where baseline leptin will be greater than 5ng/mL) Inclusion criteria for eumenorrheic controls for Reward Sub-study * Normal menstrual cycles (between 25 and 35 days) * Age 18-35 * Body weight within +/- 15% of ideal body weight and stable 6 months (no change \> 5 lbs) * Baseline leptin \>5 ng/mL Exclusion criteria: * We will exclude subjects with: * Significant medical history that may affect the concentrations of the hormones to studied or ability to participate in the study * renal or hepatic disease (creatinine \> 1.4, AST/ALT \> 2x upper limit of normal) * diagnosed diabetes mellitus * myocardial ischemia * malignancy (other than basal cell carcinoma of the skin or in situ carcinoma of the cervix) * malabsorption * alcoholism, drug abuse, or smoking * active eating disorder * depression or other psychiatric disease * anemia (Hb10 gm/dL on 2 occasions) * Conditions that are contraindicated for oral contraceptive use: * Thrombophlebitis or thromboembolic disorders * A past history of deep vein thrombophlebitis or thromboembolic disorders * Cerebral vascular or coronary artery disease * Known or suspected carcinoma of the breast * Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia * Undiagnosed abnormal genital bleeding * Hepatic adenomas or carcinomas * Cholestatic jaundice of pregnancy or jaundice with prior OCP use * Other endocrine causes of amenorrhea, e.g. * hyperprolactinemia * hypothyroidism or hyperthyroidism * Cushing's syndrome * congenital adrenal hyperplasia (elevated 17 OH progesterone) * polycystic ovarian syndrome (elevated androgens or LH/FSH ratio \>1.5) * primary ovarian failure (elevated FSH) * On medications known to affect the hormones to be measured such as * glucocorticoids * anti seizure medications * thyroid hormones * estrogen (must be off at least 3 months prior to participating in the study) * A known history of anaphylaxis or anaphylactoid-like reactions, or a known hypersensitivity to E. Coli derived proteins * Breast feeding, pregnant, or wanting to become pregnant during the next 6 months. * We will screen for these conditions through a detailed history and systems review, physical examination, laboratory evaluation (as described above in Screening Methods), and EKG. * In the Reward Sub-study subjects will be asked to fill out a standard BIDMC MRI safety screening form prior to entering the magnet.