Testosterone replacement therapy should only be prescribed to men who have confirmed testosterone deficiency, and any patient eligible for treatment must also be warned about potential cardiovascular risks, the TGA has said.

In a medicines safety update, the TGA says it has received adverse event reports associated with off-label use particularly among ageing men who have been prescribed the therapy to treat normal, age-related decline in testosterone levels and younger men who use testosterone to achieve higher than normal levels to bulk up muscle mass.

While the cardiovascular risk applies to all patients, doctors should weigh up the potential risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) before prescribing the therapy particularly to older men who may be at higher risk of cardiovascular adverse events because of their age and comorbidities, the TGA advised.

The drug regulator said it has been monitoring the therapy in relation to the risk of ATE and VTE since 2014 when the FDA first began issuing safety concerns following reports of increased events linked to testosterone use in the US.

The FDA has since mandated warning labels on the possible increased risk of venous thromboembolism, heart attack and stroke following its evidence review.

But the TGA has said the evidence on cardiovascular risk linked to the therapy is ‘inconclusive’.

While some randomised controlled trials and observational studies have found an increased risk of major adverse cardiovascular events (MACE) linked to testosterone therapy others have found no association and some have hinted at improved outcomes among men with low testosterone who achieve normalisation.

After wrapping up its own lengthy evidence review in September 2016, the TGA concluded that there is a “weak signal” of increased cardiovascular risk with use of testosterone medications in general, but not for specific, events however, it stopped short of asking drug manufacturers to update warning labels.

The TGA has also enacted a number of changes to PBS criteria to curb prescribing including lowering the threshold for treatment from 8nmol/L to 6 nmol/L.

The full list of PBS updated PBS restriction criteria can be found here.