Public health

Testosterone hasn’t lived up to the hype as a panacea for male ageing

Hopes have been ‘dimmed and disappointed if not yet finally dashed’ that testosterone replacement can reverse the ageing process in men, according to an editorial in JAMA.

Responding to a new series of research findings from the short-term NIH-funded Testosterone Trials (TTrials), Professor David Handelsman called out the organisations that have been complicit in overprescribing of the androgen.

Professor Handelsman, director of the ANZAC Research Institute, said professional societies should revise any guidelines that have provided tacit endorsement of widespread, off-label prescribing.

“Overall, the finding from subtrials of the TTrials do not materially change the unfavorable balance of safety and efficacy to initiate testosterone treatment for age-related hypogonadism,” he said.

Professor Handelsman told the limbic low testosterone levels due to obesity and other ageing comorbidities were better addressed by lifestyle measures.

“Smoking cessation and weight loss are difficult but even if lifestyle measures fail, there is no reason to go to unjustified medical treatment with possibly significant hazards,” he said.

TTrials findings published in JAMA included a concerning increase in noncalcified plaque volume in older men with low testosterone given hormone replacement compared to men in a control group.

“The coronary luminal narrowing observed over 12 months in this study is an unprecedented drug effect and appears ominous in signifying accelerated atherosclerosis, and is perhaps a harbinger of increased cardiac ischaemic events,” Professor Handelsman said in the editorial.

Another trial in men with low testosterone and age-associated memory impairment found testosterone treatment provided no improvement in visual memory, executive function, or spatial ability over placebo.

Two other studies published in JAMA Internal Medicine found testosterone increased haemoglobin levels in men with anaemia, and also increased bone mineral density and bone strength.

However Professor Handelsman said the modest beneficial effects were not indications to initiate testosterone treatment.

“These are side benefits of a small magnitude and uncertain value. It would be an awful mistake, for example, to treat an older male with unexplained anaemia on testosterone and risk missing serious conditions such as blood loss due to bowel cancer.”

He added that there were existing treatments for low bone density and men who didn’t qualify for bisphosphonates, were unlikely to gain any significant benefit from testosterone in terms of fracture risk.

Professor Handelsman said testosterone may have important clinical benefits but these should be established by well-designed clinical trials before widescale adoption. For example, the Australian T4DM trial testing whether testosterone can prevent progression to diabetes has just recruited its 1000th patient making it larger and longer than the recently reported US TTrials.

Another editorial in JAMA Internal Medicine concluded that in the absence of large, long-term prospective randomised trials, clinicians and their patients should be aware that the risks and benefits of testosterone replacement in older men have not yet been resolved.

Related stories:

Target symptoms with testosterone therapy in hypogonadal men

New guidelines emphasise clinical diagnosis of pathological hypogonadism

Testosterone scripts plummet following PBS changes

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