Testosterone Gel Applied to Women With Pituitary Gland Problems

Testosterone is the principal male sex hormone but is also present in smaller amounts in
women and may be important for their health. Among its likely actions in women are the
building of bone and muscle mass, increase in interest in sex (libido) and effects on the
mood. Testosterone is commercially available as a hormone replacement therapy for males with
an absence or lack of testosterone production. Testosterone for males is mainly given in the
form of shots or skin patches which have certain disadvantages such as pain from shots and
skin rashes from patches. It is anticipated that this experimental gel application will
produce levels of the drug in the normal range in women.

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.