Inclusion Criteria:

• Women age 18-55

• Hypopituitarism with central adrenal and/or gonadal deficiencies. To qualify patients will need to have either 1 or 2 and they need to have 3:

  1. To diagnose central adrenal deficiency, patients not on glucocorticoid replacement will have an insulin tolerance test (ITT) (patients with cardiovascular disease will be excluded) in which 0.1U/kg of insulin will be given by iv and a peak cortisol value of less than 20ug/dl, associated with a glucose level of less than 40mg/dL will be considered consistent with central adrenal insufficiency. Patients on glucocorticoid replacement will be evaluated by examining their prior workup and if it is determined that they had evidence of central adrenal deficiency, an ITT will not be required to document central adrenal deficiency (an ITT will still be performed to determine GH deficiency).
  2. To diagnose central gonadal deficiency, patients will be asked if they had amenorrhea or oligomenorrhea prior to estrogen replacement. An FAH of less than 5 MIU/ML will be used to confirm that they have central and not primary gonadal deficiency. In select patients in which the diagnosis of central gonadal deficiency is unclear, we may perform an LHRH stimulation test, in which 100 ug iv of LHRH (Factrel) will be given and a peak LH response of less than 15 MIU/ML will be considered consistent with central gonadotropin insufficiency.
  3. Serum testosterone level on transdermal estrogen replacement of less than 20 ng/dL or free testosterone of less than 1.5 pg/ml.
• No other significant medical condition
• Weight between 80 and 150% of ideal body weight
• Able to provide informed consent
• All races and ethnicities
• All patients regardless of marital status and relationship status.

Exclusion Criteria:

• Physical disabilities that would prevent them from participating in the study.
• Current use of testosterone or other androgenic steroids. Patients who are taking testosterone, DHEA or other androgen precursors will discontinue these medications/supplements three months prior to the study.
• Significant cardiopulmonary disease (prior myocardial infarction causing ventricular dysfunction, angina, arrhythmias, congestive heart failure, valvular problem), venous thrombotic event (pulmonary embolism or deep vein thrombosis), renal disease (creatinine greater than 1.5 mg/dL), diabetes mellitus on insulin, uncontrolled hypertension, malignancy (other than basal cell skin carcinoma) or major psychiatric disease. Patients with depression or anxiety on a stable dose of medication will be allowed to enroll.
• Current abuse of illicit drugs or heavy ethanol use.
• History of breast cancer or abnormal mammogram at entry. If patients with an abnormal mammogram or PAP smear are appropriately evaluated and found not to have cancer, they will be allowed to participate in the study.
• Those with significant liver function abnormalities defined as SGOT, SGPT or alkaline phosphatase value of greater than one and one-half the upper limit of normal in our Clinical Pathology Laboratory or serum bilirubin levels of greater than 2 mg/dL will be excluded.
• Those with history of hyperandrogenic disorders such as hirsutism and polycystic ovary disease will be excluded. These conditions are rare in women with hypopituitarism. Testosterone administration to these patients may exacerbate the underlying disorder.
• Women who are pregnant, seeking to become pregnant in the next 6 months, or breast-feeding.
• Those who have previously experienced intolerance to other transdermal systems or gels
• Drugs known to alter testosterone production such as megace or ketoconazole.
• Patients with untreated hyperprolactinemia or active Cushing's disease. Patients with treated prolactinoma or Cushing's disease will be allowed to participate in the study.
• Hematocrit of greater than 50%
• Male sex
• Not willing to answer all questions on surveys
• EKG showing ischemia or prior myocardial infarction
• Patients with extensive brain surgery, severe head injury, brain tumors or other conditions that profoundly affect CNS function.
• Patients not willing to be placed on a standardized hormonal replacement regimen including transdermal estrogen and growth hormone.