Testosterone-replacement therapy is safe only for men with hypogonadism, also known as low testosterone, and not for athletes, or bodybuilders, according to a major study on 5,246 men.

Called as the "largest trial of testosterone replacement therapy in men with hypogonadism", the study showed that the therapy did not result in a higher incidence of major adverse cardiac events in middle-aged and older men with hypogonadism.

However, the findings, published in the New England Journal of Medicine, do not justify testosterone treatment of men who do not have hypogonadism.

Urging caution, the researchers said the trial "should not be used to imply that large doses misused by athletes and bodybuilders are safe."

Men with low testosterone should not attempt to treat it without the help of a medical professional. "The market is booming with so-called 'natural' testosterone boosters, and men need to be careful," said Steven Nissen, Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic.

"These products have not been evaluated in rigorous clinical trials and they have not been approved by the FDA to treat low testosterone levels."

Patients were randomly assigned to receive daily transdermal 1.62 per cent testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel.

Results showed that among 5,198 patients who received testosterone or a placebo for a mean duration of 22 months, testosterone-replacement therapy did not cause more major cardiac events than placebo.

But a major cardiac event occurred in 182 patients in the testosterone group and in 190 patients in the placebo group. However, those receiving testosterone did show a higher incidence of atrial fibrillation, acute kidney injury, and issues arising from blood clots in the veins.

Current guidelines recommend that testosterone should be used with caution in men who have had previous blood clots.

"Although the trial showed some evidence that testosterone treatment may be safe for men with low levels of testosterone, these findings should not be used as a justification for widespread prescription of these products to large numbers of men," Nissen said.

"Because testosterone deficiency is not a life-threatening condition, uncertainty about cardiovascular outcomes has weighed on treatment decisions by clinicians and patients," said lead author Michael Lincoff, from Cleveland Clinic. "Our findings may facilitate a more informed consideration of the potential benefits and risks of testosterone therapy among middle-aged and older men with hypogonadism."