Testosterone therapy cleared of raising heart attack and stroke risk

Testosterone replacement is widely prescribed to middle-aged and older men with low levels and symptoms such as flagging energy and libido, yet its effect on the heart has been an open and contentious question for years. Earlier worries about possible cardiovascular harm left doctors and patients unsure whether restoring testosterone was safe, particularly in men who already had heart disease or were at high risk of developing it. The TRAVERSE trial was designed to answer that safety question directly, and to answer it in exactly the men for whom the stakes are highest.

Researchers enrolled 5246 men aged 45 to 80 who had preexisting cardiovascular disease or a high risk of it, reported symptoms of hypogonadism, and had two fasting testosterone readings below 300 ng per decilitre. The men were assigned at random, with neither participants nor investigators knowing who received what, to a daily transdermal 1.62% testosterone gel adjusted to keep levels between 350 and 750 ng per decilitre, or a matching placebo gel. Treatment lasted a mean of 21.7 months, follow-up averaged 33.0 months, and the primary safety outcome was the first occurrence of cardiovascular death, nonfatal heart attack or nonfatal stroke.

A primary cardiovascular event occurred in 182 men on testosterone (7.0%) and 190 men on placebo (7.3%), meeting the trial's bar for noninferiority: testosterone did not raise the rate of major cardiac events. The secondary outcome, which added coronary revascularisation to the composite, looked similar between groups, as did each individual component of the primary endpoint. Sensitivity analyses that cut off event counting at various points after stopping treatment told the same story. The picture was not entirely clean, though: atrial fibrillation, acute kidney injury and pulmonary embolism were all more frequent in the testosterone group.

This is a landmark test of testosterone therapy's cardiovascular safety, settling a question that smaller studies could not: in men with diagnosed low testosterone and elevated cardiac risk, treatment did not increase heart attacks, strokes or cardiovascular deaths. It does not demonstrate benefit, and it says nothing about men with normal testosterone taking it for muscle or vitality, a group that falls entirely outside the trial. The excess of atrial fibrillation, kidney injury and clots reaching the lungs flags real risks that deserve dedicated follow-up. Whether the reassurance extends beyond roughly three years of follow-up also remains open.

For a man with genuinely low testosterone confirmed by blood tests and accompanied by symptoms, this trial is a reason to be less worried that replacement therapy will trigger a heart attack or stroke, even where heart risk already exists. It is equally a reason for caution on other fronts, since clotting events, heart rhythm disturbance and kidney injury appeared more often with treatment. And it offers nothing to support taking testosterone on top of normal levels, a use this trial did not examine. This is informational only: diagnosis and the treatment decision sit with a clinician.