TRADE-Testosterone Replacement and Dutasteride Effectiveness

The primary aim of this study is to determine whether correction of hypogonadism using a
combination of testosterone and dutasteride spares subjects from increases in prostate size
and symptoms of BPH which may be associated with T alone.

We will also determine the effects of changes in serum T and dihydrotestosterone (DHT) on
both the hormonal milieu and genetic program within the prostate gland itself. The technology
employed will allow us to determine which genes are androgen responsive within each prostate
tissue compartment. Together, these data may determine whether the combination of
testosterone and dutasteride safely corrects the symptoms of BPH and hypogonadism and
minimizes growth stimulus to the prostate at the genetic level. We will also assess the
effects of the combination of T and dutasteride on cognitive function.

This is a six-month, double-blind, randomized, placebo-controlled, single-site study of older
hypogonadal men with mild to moderate BPH.

Within each treatment group, a sub-group of subjects will undergo additional procedures as
part of a Prostate Biopsy sub-study to obtain prostate tissue for hormonal and genetic
analyses. Selection of subjects will be based on clinical indication and/or willingness to
undergo prostate biopsies.

Inclusion Criteria:

- Generally healthy older men 50 years old or older

- Hypogonadism; low testosterone (total T less than 280 ng/dL on one occasion or an
average of equal to or less than 300 ng/dl on two occasions)

- Prostate volume equal to or more than 30 cc by prostate MRI

- Prostate Specific Antigen (PSA) equal to or more than 1.5 ng/mL and equal to or less
than 10 ng/mL

- Subjects with a PSA greater than 4.0 ng/ml must have a negative prostate biopsy

- International Prostate Symptom Score (IPSS) greater than or equal to 8 and less than
or equal to 20 at screening

- Comply with study procedures for the full 10 months

- No contraindications to MRI

Subjects with symptomatic Benign Prostatic Hyperplasia (BPH) will be recruited from the
Urology and General Internal Medicine Clinics at the VA Puget Sound Health Care System and
University of Washington Medical Center in Seattle.

Exclusion Criteria:

- A history of prostate or breast cancer

- Invasive therapy for BPH in the past

- History of acute urinary retention in the 3 months prior to screening

- Previous treatment with a 5 alpha-reductase inhibitor (finasteride or dutasteride)

- Medical therapy for BPH within the past month (alpha-blocker, phytotherapy)

- Use of androgenic or antiandrogenic drugs in the past year

- History or evidence of prostate cancer including suspicious DRE or history of
high-grade PIN on prostate biopsy.

- Severe systemic illness (renal, liver, cardiac, lung disease, cancer, diabetes)

- Known untreated obstructive sleep apnea

- Hematocrit greater than 52

- Severe skin disease which may interfere with testosterone gel absorption

- Hypersensitivity to any of the drugs used in the study

- History of a bleeding disorder or need for chronic anticoagulation

- Participation in a drug study concurrently or in the last 90 days

- History or current evidence of drug or alcohol abuse within 12 mo.

- Weight more than 300 lbs.