Phase II Randomized Study of Physiologic Testosterone Replacement in Premenopausal, HIV-Positive Women

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled study. Patients
are randomized to one of three arms.

Arm I: Patients receive two placebo transdermal patches applied twice a week (every 3-4
days).

Arm II: Patients receive one testosterone transdermal patch and one placebo transdermal
patch applied twice a week (every 3-4 days).

Arm III: Patients receive two testosterone transdermal patches applied twice a week (every
3-4 days).

Patients receive 12 weeks of treatment in the absence of adverse reaction or health
deterioration. Patients are followed on day 1, every 2 weeks during treatment, and at the
end of the recovery period. Quality of life is assessed before treatment begins and at
weeks 6 and 12.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

- Histologically confirmed premenopausal HIV-positive women who have experienced 5-15%
weight loss

--Prior/Concurrent Therapy--

- Endocrine therapy: At least 3 months since megestrol At least 3 months since anabolic
or androgenic steroids At least 3 months since oral contraceptives At least 3 months
since Depo-Provera No concurrent hormone replacement therapy

- Other: Concurrent retroviral or protease inhibitors allowed, dosage must be stable At
least 3 months since ketoconazole At least 6 weeks since the initiation of protease
inhibitors

--Patient Characteristics--

- Hepatic: No significant liver disease SGOT/SGPT no greater than 3 times upper limit
of normal (ULN) Alkaline phosphatase no greater than 3 times ULN Bilirubin no greater
than 2 mg/dL No medical complications due to alcohol abuse

- Renal: Not specified

- Cardiovascular: No significant cardiovascular disease No uncontrolled hypertension

- Other: Testosterone level (early morning) less than 30 ng/dL Normal gastrointestinal
function as indicated by: Absence of diarrhea Normal D-xylose absorption test No
acute opportunistic infections or infectious illness No malignant disease No history
of breast cancer No history of endometrial cancer No fever of known or unknown origin
No unremitting diarrhea defined as: At least 4 watery stools per day OR More than 4
watery stools recently OR Acute change in stool habit with fever No significant
respiratory disease No diabetes No illicit drugs within the past 6 months No history
of hyperandrogenic disorders such as: Hirsutism Polycystic ovary disease Not pregnant
or lactating