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.