Testosterone supplements: why the fuss?

Beginning in middle age, blood levels of testosterone progressively decrease in some men. "El Gabo" - Davide Gabino/Flickr, CC BY-NC-SA

A whole industry has grown around testosterone supplementation for ageing men. But neither the benefits nor risks of the practice are clear yet, and they remain the subject of ongoing research.

Beginning in middle age, blood levels of testosterone progressively decrease in some men. At the same time, muscle mass, strength and bone density decrease, while fat mass and disorders of sexual function increase.

Because studies have found an association between these changes and low levels of testosterone (that is, they happen at the same time), there has been a growing trend in many parts of the world, including Australia, for older men to be prescribed testosterone.

Cause for caution

But two recent studies – the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study and the European Male Ageing Study (EMAS) – have shown that it’s not actually the ageing process as such that decreases testosterone.

Rather, concomitant increases in chronic disease including obesity, cardiovascular disease, and depression may be responsible.

In obese men, low testosterone increases the likelihood of subsequent development of type 2 diabetes. But in these men, testosterone levels increase with weight loss.

Low testosterone levels are also associated with increased risk of all-cause and cardiovascular deaths in community-based studies of men.

But these effects appear to be driven, at least in part, by underlying health status. So while testosterone treatment for preventing the occurrence of diabetes or cardiac disease may appear theoretically appealing, it’s unclear whether it’s beneficial or safe.

Testosterone deficiency

Testosterone deficiency that’s of clinical significance and requiring treatment is known as hypogonadism. True hypogonadism actually affects only 2% to 3% of the male population over the age of 40.

It comes with a set of symptoms that include loss of sexual desire, erectile dysfunction, fatigue, muscle loss and weakness, increased body fat, diminished motivation, sleep disturbance, hot flushes and decreased body hair.

But many of these symptoms may result from other conditions, such as depression or obstructive sleep apnoea, whether or not testosterone is low.

To complicate matters even further, a man may have low levels of testosterone without any symptoms. And the level of testosterone at which different symptoms occur varies within as well as between individuals.

In situations where the testosterone level is low and there are some symptoms, it can be difficult to disentangle cause-and-effect relationships. It is in this group of men that the use of testosterone supplements remains controversial, especially since doubts about its safety remain unresolved.

The cardiovascular controversy

A 2010 clinical study of testosterone treatment in frail men aged over 65 years with low testosterone was stopped prematurely because the group getting the hormone was found to have more cases of heart attacks, heart failure and atrial fibrillation (irregular heart beats).

High doses (and therefore blood levels) of testosterone seemed to be a factor. But there were no such adverse events in a similar study with less frail men and where lower doses of testosterone were used.

But two more recent large studies that analysed patient records from large databases have suggested testosterone treatment may increase cardiovascular events, such as heart failure, heart attacks and strokes.

The first involved 8,000 men with low testosterone undergoing invasive examination of the arteries supplying blood to the heart muscle in a US Veterans Affairs Hospital.

The other study examined the records of 55,593 men maintained in a US health insurance database. Records of the number of heart attacks in the past year were compared with heart attacks in the 90 days following prescription.

But testosterone levels of these men were not reported, either at baseline or subsequently. Indeed, the conclusions to both these studies are flawed because their analyses were flawed. The first has even been the subject of a complaint to the journal involved.

In another study of case records in a Veterans Affairs Hospital, testosterone treatment decreased the risk of death irrespective of age or the presence of diabetes or coronary heart disease.

But observational studies of this sort – and all these studies fall under that banner – do not provide the evidence required to argue a treatment should be used. We need properly controlled trials to make such decisions, especially in light of possible health harms.

This is particularly important because lifestyle measures resulting in weight loss increase blood testosterone and unequivocally benefit the underlying disease state and prevent the development of type 2 diabetes in men at high risk of the disease. Indeed, a more active lifestyle benefits everyone and has a much wider health impact than any medical intervention.

Until the results of clinical trials become available, we have insufficient evidence to support the use of testosterone beyond the 2% to 3% of the population with unequivocal hypogonadism. And caution should clearly be exercised in men with cardiovascular disease.