Effects of Testosterone Replacement Therapy on Muscle Strength in Older Men with Low to Low-Normal Testosterone Levels: A Systematic Review and Meta-Analysis.

TRT resulted in greater muscle strength improvement compared with placebo in older men with low to low-normal testosterone levels.

• Pooled meta-analyses showed Hedges' g = 0.21 (95% CI: 0.15–0.28) favoring TRT over placebo
• Thirteen randomized controlled trials with 2,043 patients were included
• Mean age of subjects across studies ranged from 65.9 years to 76 years
• Random-effects meta-analysis methodology was used
• Studies were published between January 1990 and April 2020

Intramuscular administration of TRT had significantly greater efficacy on muscle strength than transdermal or oral TRT.

• Intramuscular TRT showed Hedges' g = 0.74 (95% CI: 0.34–1.14)
• Difference between intramuscular and other routes was statistically significant (p < 0.001)
• Intramuscular dosages used in included studies were 125 mg/week or 200 mg every 2 weeks
• Transdermal testosterone dosages ranged from 5 to 10 g/day
• Oral testosterone supplementation was given at 160 mg/day in one study

Baseline serum total testosterone level was negatively associated with the magnitude of muscle strength improvement after TRT.

• Metaregression coefficient β = -0.004, p = 0.002
• Lower baseline testosterone levels were associated with greater muscle strength gains
• The metaregression was used to evaluate confounding factors related to muscle strength changes
• This finding supports the conclusion that the effect of TRT was more pronounced in populations with lower baseline testosterone levels

The risk ratios of adverse events associated with TRT were not significantly different from placebo.

• Adverse events evaluated included elevated prostate-specific antigen, acute coronary syndrome, and prostate cancer
• Risk ratios for all assessed adverse events were not statistically significant compared to placebo
• Adverse event analysis was a secondary outcome of the meta-analysis
• Thirteen RCTs with 2,043 patients contributed to the safety analysis

The systematic review included only older men with relatively low testosterone levels in randomized controlled trials, representing a more specific subgroup than previously analyzed.

• Inclusion criteria required participants to be older men (age >60 years) with relatively low testosterone levels
• PubMed, Embase, and Web of Science were searched for articles from January 1990 to April 2020
• Studies were extracted following the PRISMA flowchart
• Included RCTs were evaluated using RoB 2.0 for risk of bias
• Authors noted that no prior meta-analysis had investigated TRT effects specifically in this subgroup of relatively hypogonadal older men