5-Alpha Reductase and Anabolic Effects of Testosterone

VA Office of Research and Development

Status and phase: Completed; Phase 2

Conditions: Muscle Atrophy; Benign Prostate Hypertrophy; Sarcopenia; Male Hypogonadism

Treatments: Other: Placebo; Drug: Testosterone Enanthate; Drug: Finasteride

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT00475501

ENDA-014-05F

VA Merit Award (Other Grant/Funding Number)

Details and patient eligibility

About

The purpose of this study is to determine whether a higher-than-replacement dose of testosterone and finasteride can be combined to safely increase muscle strength in older men who have a low blood concentration of testosterone.

Full description

Approximately 40% of older male veterans have a low serum testosterone concentration. The latter is associated with diminished muscle strength and bone mineral density, depressed mood, low pain tolerance, frailty, and increased mortality. Replacement doses of testosterone have been administered to hypogonadal men for the purpose of reversing deficits in muscle and bone. Although testosterone is clearly important for maintaining muscle and bone in men, there are problems associated with T replacement. First, testosterone causes a number of undesired effects, including fluid retention, gynecomastia, worsening of sleep apnea, polycythemia, prostate enlargement and acceleration of early-stage prostate cancer. The anabolic effects obtained to date from testosterone replacement have been relatively modest, especially in older men. Our hypothesis is that combined treatment with a higher-than-replacement dose of testosterone and a 5- reductase inhibitor will produce substantial anabolic effects, while preventing testosterone-induced prostate enlargement and possibly other adverse effects.

We plan to investigate the efficacy and safety of combined treatment with testosterone and finasteride in older hypogonadal male veterans by conducting a 12-month randomized, placebo-controlled trial. We will administer a higher-than-replacement dose of testosterone plus the 5- reductase inhibitor finasteride to a group of hypogonadal, but otherwise healthy older men. We will determine whether this treatment is a safe and effective means to increase muscle mass and strength. Men aged 60 to 80, with circulating total testosterone 300 ng/dL or bioavailable testosterone 70 ng/dL, will be treated with 125 mg testosterone enanthate/week 5 mg finasteride/day for 1 year. We will assess the effects on body composition, 1- repetition maximum (1-RM) strength, grip strength, functional reach, bone mineral density, mood, cognition, hematopoiesis and prostate volume. We have chosen a moderately high dose of testosterone that may cause some adverse effects. We predict that finasteride will not block the anabolic effects of testosterone, but will block any prostate enlargement or symptoms and possibly other adverse effects as well.

Enrollment: 60 patients

Sex: Male

Ages: 60+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age > 60 years males
• Primary care at the Malcolm Randall VA Medical Center in Gainesville, Florida.
• Consenting subjects who have a morning (between 6:00 AM and 10:00 AM) serum total testosterone 300 ng/dL or bioavailable testosterone concentration 70 ng/dL and no exclusion criteria will be randomized to receive either testosterone or placebo.

Exclusion criteria

• Subjects with cognitive impairment will be identified by the Mini-Cog test and excluded. The Mini-Cog has high sensitivity and specificity for cognitive impairment, and is not affected by level of education.
• We will also exclude subjects with receptive aphasia, or a contraindication to testosterone replacement (i.e., history of or active prostate or breast cancer, severe benign prostatic hyperplasia as assessed by elevated American Urologic Association Symptom Index (AUASI) score > 25), congestive heart failure (Class 3 or 4), sleep apnea syndrome, polycythemia (Hct > 55%), or prostate specific antigen (PSA) > 2.6 ng/mL) will be excluded.
• Obese subjects (BMI > 35) will also be excluded.
• Subjects currently receiving testosterone supplementation or subjects who have an allergy to testosterone will also be excluded.
• Subjects previously receiving testosterone replacement therapy must be off such medication for at least four weeks.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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60 participants in 4 patient groups, including a placebo group

Arm 1

Experimental group

Description:

testosterone enanthate

Treatment:

Drug: Testosterone Enanthate

Arm 2

Experimental group

Description:

finasteride

Treatment:

Drug: Finasteride

Arm 3

Experimental group

Description:

testosterone enanthate + finasteride

Treatment:

Drug: Finasteride

Drug: Testosterone Enanthate

Arm 4

Placebo Comparator group

Description:

placebo

Treatment:

Other: Placebo