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.