Abstract
The T Trials were a coordinated set of seven double-blind, placebo-controlled trials to assess efficacy and safety of testosterone versus placebo gel treatment for one year in 788 older men 65 years or older with hypogonadism who had self-reported and objective impairment of sexual and physical function and/or vitality and an average of two morning serum testosterone concentrations < 275 ng/dL. Testosterone dose was adjusted to the mid-normal range for young men. Compared to placebo, testosterone treatment moderately improved sexual function, hemoglobin concentration and corrected anemia, and slightly improved walking distance, vitality, mood and depressive symptoms and bone density and strength, but did not improve cognitive function. Testosterone treatment slightly increased non-calcified and total plaque volume; while concerning, the clinical significance of this finding is not clear. Testosterone treatment also increased PSA levels and referral for urological evaluation, and caused erythrocytosis in some men. The T Trials provided definitive evidence for short-term clinically meaningful, albeit modest benefits and risks of testosterone treatment in older men with unequivocal age-related hypogonadism. Larger and longer-term placebo-controlled clinical trials are needed to assess the long-term benefits and risks of testosterone treatment on clinical outcomes such as frailty, depression, fractures, prostate cancer and cardiovascular events.