Testosterone replacement therapy

In older men with low testosterone and symptoms, a year of testosterone gel improved sexual function and slightly improved mood, but not energy or walking distance [1]. The largest safety trial, TRAVERSE, followed more than 5,000 middle-aged and older men with hypogonadism and high heart risk: heart attacks and strokes were no more common than on placebo, but atrial fibrillation, acute kidney injury and blood clots in the lung were [2]. In the same trial, testosterone did not prevent fractures, and fractures were somewhat more common [3].

Other trials point to harm in some groups. A trial in frail older men was stopped early because of more cardiovascular events on testosterone [4], and a year of treatment increased soft coronary plaque in older men with low testosterone [5].

No trial has tested whether TRT extends life or slows aging, and the trials enrolled men with low levels, not men with normal levels who want more. The Endocrine Society recommends diagnosing deficiency only with symptoms and repeated low morning tests, and against treatment in men planning to father children soon [6].

• Testosterone is a prescription drug and a controlled substance in the United States, approved for men with diagnosed hypogonadism. Taking it to slow aging or build muscle in men with normal levels is off-label.
• It suppresses the body's own testosterone and sperm production and can cause infertility, so it is not for men trying to father a child soon.
• It can raise hematocrit, worsen untreated sleep apnea and lower urinary symptoms, and in the TRAVERSE trial it raised rates of atrial fibrillation, acute kidney injury and blood clots in the lung.
• Guidelines advise against it in men with breast or prostate cancer, an unevaluated high PSA, or a high hematocrit, and call for regular blood tests during treatment.
• Stopping after long use can leave levels low for months while the body's own production recovers.