Are there benefits of testosterone supplementation for older men with low normal testosterone levels?
Of the RCTs that have been conducted in otherwise healthy, older hypogonadal men, most found an increase or maintenance of fat-free mass (bone and muscle) and a decrease in fat mass (including abdominal visceral and intermuscular fat) with testosterone therapy. Whether such physiologic effects translate into strength or functional improvements remains uncertain. Anemia caused by androgen insufficiency improves with testosterone therapy. Improvements in sexual function and sense of well-being have been inconsistent.
The lack of consistent findings among trials of testosterone supplementation is likely related to variability in study cohorts (e.g., baseline testosterone levels, symptoms, body composition, comorbidities, physical function), the type of testosterone supplementation therapy (e.g. oral, transdermal, intramuscular, dose, and average testosterone concentration achieved), and duration of intervention (e.g. months versus years). A placebo-controlled, randomized trial of testosterone gel (1%) applied daily for 3 years in 308 older men (age ≥60 years) that included men with low-normal testosterone levels showed no improvement in insulin sensitivity, atherosclerosis progression, sexual function, or health-related quality of life. These results differ from those of the Testosterone Trials (seven coordinated placebo-controlled trials) in 788 older men with low testosterone levels that showed normalization of testosterone levels in older men with low testosterone led to improved sexual and physical function, mood, and bone mineral density, but also showed evidence of atherosclerosis progression. Longer term studies will be necessary to assess cardiovascular outcome risks.