Is your virility worth the risk from testosterone replacement therapy?

There is a certain inevitability about the recent finding that testosterone replacement therapy (TRT) poses the same risk to cardiovascular health as hormone replacement therapy (HRT) does in women.

I have been concerned about the trend for medicalising the “andropause” for some time; now we have some evidence that testosterone replacement is associated with an increased risk of stroke and heart attack.

One of the main arguments against the existence of an “andropause” is that unlike women who have gone through the menopause, there is no complete shutting down of the male reproductive system.

Testosterone levels do decline steadily with age but there is no evidence to suggest that men experience a sudden drop in hormone levels in the way women do.


A small number of men do suffer with hypogonadism: TRT for these men is an entirely reasonable intervention.

Rise in prescriptions
Despite this reality, prescriptions for TRT have rocketed. In one region in the UK, prescriptions for TRT have increased by 90 per cent in the past 10 years.

Annual prescriptions for testosterone in the US increased more than five-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion (€1.2billion) in 2011. It seems the monkey gland myth of the 1920s and 1930s lives on, albeit cloaked in pharmaceutical respectability.

The research published last week in the Journal of the American Medical Association (JAMA) looked at some 8,700 men with low levels of testosterone in their blood who underwent a coronary angiogram between 2005 and 2011.

Of these patients, 1,220 subsequently elected to begin testosterone therapy; all participants were followed up to see who developed a subsequent cardiovascular event. Many had co-morbidities such as diabetes or coronary artery disease.

Dr Rebecca Vigen and her colleagues from the University of Texas in Dallas found that the proportion of patients experiencing a stroke or heart attack three years after coronary angiography was 19.9 per cent in the no testosterone therapy group (average age, 64 years) and 25.7 per cent in the testosterone therapy group (average age, 61 years), for an absolute risk difference of 5.8 per cent.

Adverse outcomes
Even accounting for other factors that could explain the differences, use of testosterone therapy was associated with adverse outcomes; significantly the same pattern emerged among patients with and without pre-existing coronary heart disease.

An accompanying JAMA editorial notes: “In light of the high volume of prescriptions and aggressive marketing by testosterone manufacturers, prescribers and patients should be wary. There is mounting evidence of a signal of cardiovascular risk, to which the study by Vigen et al contributes.

This signal warrants both cautious testosterone prescribing and additional investigation.”

It's all reminiscent of the results of the Women's Health Initiative study which sounded the death knell for the long-term use of combined HRT.

Of 16,000 post-menopausal US women, half were given a daily tablet of oestrogen and progestogen for an average 5.2 years. The rest were given a matching placebo, or “dummy” pill. Those on a daily dose of conjugated oestrogen plus medroxyprogesterone acetate were found to be at increased risk of breast cancer, heart attacks, strokes and blood clots. The breast cancer and blood clots outcome were expected; the increased risk of heart attacks and stroke was a major shock, especially as HRT had previously been promoted as being cardioprotective.

It confirmed findings from the Heart and Oestrogen/Progestogen Replacement Study, which also showed an elevated risk of cardiac disease in women during their first year on HRT.

Defining risk
As far as TRT is concerned, large randomised controlled trials are now required to exactly define the risk of testosterone therapy across all age groups, including a growing number of young men who use testosterone for the purpose of physical enhancement.

But already there is a strong case for caveat emptor: enhanced virility may be achievable but at what cost?