Abstract
BACKGROUND: Low serum testosterone levels are associated with age-related changes in physical and cognitive function. Replacement therapy could, therefore, help alleviate symptoms of aging. OBJECTIVE: To determine whether 6 months’ supplementation with testosterone improved signs of aging in a population of elderly men with low-normal testosterone levels. DESIGN AND INTERVENTION: This was a double-blind, randomized, placebo-controlled trial of testosterone supplementation conducted at a single center in the Netherlands between January 2004 and April 2005. Participants were recruited by direct mailing. Inclusion criteria included age 60–80 years and a serum testosterone level below the 50(th) percentile of the study population-based testosterone distribution (cutoff 13.7 nmol/l). Exclusion criteria included myocardial infarction, heart failure, malignancy, serious liver or renal disease, epilepsy, diabetes mellitus, elevated prostate-specific antigen, use of corticosteroids, and use of testosterone esters within the previous 60 days. Eligible participants were randomly allocated to receive either 80 mg oral testosterone undecenoate or placebo twice daily for 6 months. Functional ability was measured with the timed ‘get up and go’ test, the Stanford Health Assessment Questionnaire, an isometric handgrip strength test, and a maximal voluntary isometric leg strength test. Cognitive parameters assessed included verbal episodic memory, cognitive and perceptual speed, attention and mental flexibility, extrapersonal spatial perception, and visuospatial performance. BMD and total body composition were measured by dual-energy X-ray absorptiometry. Quality of life was assessed with the Short-Form 36 Health Survey (SF-36) and the Questions on Life Satisfaction Modules questionnaires. OUTCOME MEASURES: The main outcome measures were functional mobility, cognitive function, BMD, anthropometry, body composition, biochemical measures, quality of life, and safety parameters. RESULTS: The study enrolled 113 men in the testosterone group (mean age 67.1 years; mean serum testosterone level 11.0 nmol/l) and 110 men in the placebo group (mean age 67.4 years; mean serum testosterone level 10.4 nmol/l). Treatment adherence was >90% for both groups. When compared with the placebo group, treatment with testosterone was associated with increased lean body mass, decreased body fat mass and decreased body fat percentage (P <0.001 for all comparisons); however, no significant changes in parameters of functional ability were observed in either group. Total cholesterol and HDL cholesterol decreased in the testosterone group, whereas insulin and glucose concentrations and measures of insulin resistance increased in the placebo group. Cognitive function improved in both groups but BMD and quality of life were unchanged. The mean number of adverse events per participant was 0.87 in the testosterone group and 0.90 in the placebo group. CONCLUSION: The results of this study suggest that eugonadal or slightly hypogonadal men might not benefit substantially from short-term, low-dose testosterone supplementation.