Exercise and Testosterone Therapy in Elderly Men With Physical Frailty

Decreases in physical abilities, including losses of strength, endurance, balance, and
coordination are major causes of disability and loss of independence in older men. Such
individuals are at high risk for injurious falls, hospitalization, and use of supportive
services. Age-associated testosterone deficiency may contribute to deficits in muscle mass
and strength that are common in this patient population.

The primary aim of this study is to determine, in hypogonadal older men with physical
frailty, whether six months of exercise training combined with testosterone replacement
therapy can improve skeletal muscle mass and skeletal muscle strength, to a greater degree
than six months of exercise training alone.

Secondary study aims are to determine in hypogonadal older men with physical frailty, whether
six months of exercise training combined with testosterone replacement therapy can improve
physical function, bone mineral density, and quality of life, to a greater degree than six
months of exercise training alone.

Comparison: Men age 65 years and older who meet criteria for physical frailty and have a
serum testosterone level below 350 ng/dl are randomly assigned to one of two groups: 1)
transdermal testosterone replacement therapy + supervised exercise training for six months
vs. 2) inactive placebo gel + supervised exercise training for six months.

Inclusion Criteria:

- Male, age 65 years and older

- Total serum testosterone level < 350 ng/dl

- Total Modified Physical Performance Test Score <28

Exclusion Criteria:

- Inability to walk 50 feet independently

- Current use of estrogen, progestin, or androgen containing compound

- Diagnosis of dementia of severity sufficient to interfere with informed consent or
compliance with the protocol, or a score of 11 or greater on the Short Blessed Test of
Orientation, Memory and Concentration

- Visual or hearing impairments that interfere with following directions

- Cardiopulmonary disease (recent MI, unstable angina or CHF, etc.), neuromuscular
impairments, or unstable medical condition that would contraindicate progressive
resistance exercise training

- History of prostate cancer or hormone dependent neoplasia

- PSA level > 4 ng/ml

- Serum liver transaminase levels of greater than 2 standard deviations above normal

- Use of drugs for osteoporosis for less than 1 year

- Current participation in a vigorous exercise or weight-training program more than once
per week

- History of sleep apnea requiring use of CPAP

- Uncontrolled thyroid disease

- Diagnosis of cancer within the past 5 years other than superficial skin cancer
(squamous or basal cell)

- hematocrit > 50%

- AUA symptom score > 16.

- History of alcohol or substance abuse

- Presence of severe facial acne

- Active symptoms of depression with GDS score > 5 and symptoms severe enough to cause
>5% weight loss in previous 3 months or interfere with research assessments