PROS-2 Dose Response Effects of Exogenous Testosterone on the Prostate

The investigators overall goals are (i) to determine the relationship between serum and
prostate tissue hormone concentrations in men in response to increasing doses of exogenous
androgens; (ii) to determine the impact that alterations in serum and tissue testosterone
concentrations have on prostate epithelial cell function and phenotype; and (iii) to
determine the relationships between prostatic androgens and alterations in the tissue
microenvironment. The investigators will perform a study in healthy, middle-aged men to
address the following Specific Aims:

Specific Aims: To compare the dose-response relationships between serum testosterone and
intraprostatic androgens and androgen action, and serum testosterone and anabolic activity in
healthy, middle-aged men.

Hypothesis: The investigators hypothesize that very low levels of serum testosterone will
lower concentrations of intraprostatic testosterone and dihydrotestosterone (DHT). However,
when serum testosterone concentrations are within or even above the normal range there will
be no significant increases in intraprostatic testosterone and dihydrotestosterone. In
contrast, the investigators expect that anabolic activity will increase with increasing
concentrations of circulating testosterone.

Secondarily, the investigators hypothesize that increasing levels of serum testosterone
beyond the low normal range will have little impact on androgen action within the prostate.

Approach: The investigators will conduct a randomized, placebo-controlled trial in healthy
men who are medically castrated and administered one of five different doses of testosterone
gel (Androgel) for 12 weeks.

Inclusion Criteria:

In good health, without severe systemic illness (i.e., renal, liver, cardiac or lung
disease, cancer, insulin dependent diabetes)

- Male between the ages of 25 and 55 years old

- Able to understand and comply with protocol instructions and requirements

- International Prostate Symptom Score (IPSS) <11

- Agrees to not donate blood during the study

- Normal serum total T, LH, FSH, urine analysis, COMP, CBC and sperm count

Exclusion Criteria:

- History of, or current breast cancer or prostate cancer

- Clinically significant findings on digital rectal exam such as nodules, areas of
induration or any other malignancy or abnormal prostate ultrasound

- History of invasive therapy for BPH

- Current or past treatment with a 5α-reductase inhibitor

- History of drug or alcohol abuse within the past 12 months

- History of a bleeding disorder or anticoagulation

- Skin disease that might interfere with T-gel absorption

- Participation in another drug study in the past 3 months

- A first-degree relative (i.e. father, brother) with a history of prostate cancer

- History of infertility or desire for fertility within 6 months, or current pregnant
female partner

- Weight >320 pounds or BMI > 40

- PSA Level > 2.1