• the difference between the placebo and leptin treated groups in the change in bone mineral density (BMD) at the anteroposterior (AP) spine from baseline to 36 weeks
  

• evidence of ovulation based on menstrual bleeding and progesterone levels
  
• hormone levels and bone markers
  
• immune function
  
• body composition (weight and body fat)
  
• total, radial, hip bone density
  
• resting metabolic rate
  
• overall sense of well-being, appetite and food intake
  

Leptin is a hormone secreted by fat cells under normal conditions and acts in the brain to regulate energy usage and hormone levels. Women with hypothalamic amenorrhea who do not have regular periods have low leptin levels and may also have other hormone abnormalities as well as loss of bone density (osteopenia or osteoporosis). This study will evaluate how leptin (a fat cell hormone that normally circulates in the blood) affects bone density, menstrual periods, hormone levels, bone metabolism (how bone forms and turns over), immune function (how well the body can fight infection), metabolic rate (how many calories are used at rest), and overall sense of well-being and appetite in women with hypothalamic amenorrhea (i.e. no regular menstrual periods due to low levels of pituitary hormones that regulate estrogen production from the ovary).

Comparison: leptin-treated group to placebo-treated group

Inclusion Criteria:

• Hypothalamic amenorrhea of at least 6 months duration with low or normal leutinizing hormone (LH) and follicle stimulating hormone (FSH), e.g. due to strenuous exercise (running >20 miles per week or equivalent) or low weight
• Age 18-35 years old
• Body weight within +/- 15% of ideal body weight and stable ≥ 6 months (no change > 5 lbs)
• Baseline leptin level < 4 ng/mL

Exclusion Criteria:

• Significant medical history that may affect the concentrations of the hormones to be studied or the ability to participate in the study (renal or hepatic disease, 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)
• Other endocrine causes of amenorrhea (hyperprolactinemia, hypothyroidism or hyperthyroidism, Cushing's syndrome, congenital adrenal hyperplasia, polycystic ovarian syndrome, primary ovarian failure)
• On medications known to affect the hormones to be measured (glucocorticoids, anti-seizure medications, thyroid hormones, estrogen)
• Breast feeding, pregnant, or wanting to become pregnant during the next 6 months