The Effect of 5-Alpha Reductase on Testosterone in Men

Testosterone, the predominant circulating androgen in men, serves as the active hormone in
some target tissues; however, testosterone effects in other target organs require its
conversion to two active metabolites, estradiol 17-beta and DHT. The role of 5-alpha
reductase in mediating testosterone's effects on muscle and sexual function remains unclear.
This study will determine whether 5-alpha reduction of testosterone to DHT is necessary for
mediating effects on fat-free mass, muscle size, muscle strength, and leg power in men. The
study will also evaluate the necessity of 5-alpha reductase for maintenance of androgen
effects on sexual function (sexual desire, overall sexual activity, nocturnal penile
tumescence [NPT], response to visual erotic stimulus, and penile rigidity) in men.

Participants in this study will be treated with a drug to suppress endogenous testosterone
production. Participants will then be randomly assigned to receive either testosterone and
placebo or testosterone and the 5-alpha reductase inhibitor dutasteride. Testosterone will
be administered weekly; dutasteride and placebo will both be administered daily. Diet and
exercise will be standardized across both groups. Participants will be assessed at study
entry and Week 20. Assessments will include measurements such as a DEXA scan, MRI scan, and
muscle performance and sexual function tests. Participants will also have blood tests for
safety monitoring; blood tests will include measures of hematocrit, liver enzymes (AST and
ALT), prostate specific antigen (PSA), and cholesterol.

Inclusion Criteria

- General good health and capable of undergoing strength testing

- Normal testosterone (300-1100 ng/dL), LH, and FSH levels

Exclusion Criteria

- Currently participating in competitive sports

- Mental state that would preclude complete understanding of the protocol and
compliance

- Disorder known to cause or be associated with hypogonadism (e.g., pituitary tumors,
hyperprolactinemia, HIV infection, or Klinefelter's Syndrome)

- More than 20% over ideal body weight

- Disabilities that would prevent participation in strength testing (e.g., amputation
of limbs, blindness, severe arthritis, angina, or neurologic disorders such as
Parkinson's disease, stroke, or myopathy)

- Uncontrolled hypertension, diabetes, congestive heart failure, or chronic obstructive
lung disease

- Alcohol or drug dependence in the 6 months prior to study entry

- Disorders that might be exacerbated by androgen treatment (e.g., benign prostatic
hyperplasia or prostate cancer, erythrocytosis [hematocrit > 51% at baseline], or
sleep apnea assessed by Berlin's questionnaire)

- Serum PSA levels > 4 microg/L

- AST, ALT, or alkaline phosphatase elevation greater than three times the upper limit
of normal

- Creatinine greater than 2 mg/dL

- Medications that might affect muscle or bone metabolism (e.g., glucocorticoid, rhGH,
androgenic steroids, oral androgen precursors such as androstenedione or DHEA) or
androgen metabolism, action, or clearance (e.g., dilantin, phenobarbitol, aldactone,
flutamide, finasteride)