Optimal, Not High, Testosterone Levels Help Men Live Longer

Older men with optimal testosterone levels-not too high or too low-tend to live longer, according to a new study.

A man’s testosterone level normally declines with age, and lower testosterone has been associated with increased mortality in aging men. This has sparked marketing of testosterone replacement therapy targeting middle-aged and older men, including direct-to-consumer advertising and campaigns aimed at physicians.

"Optimal circulating total testosterone is a robust biomarker for survival in aging men,” notes lead author Professor Bu Yeap, MBBS, FRACP, PhD, of the University of Western Australia. However, older men with midrange levels of testosterone and its metabolite dihydrotestosterone (DHT) had the lowest death rates from any cause, and men with higher DHT levels were at lower risk for dying from ischemic heart disease. Therefore, there was no benefit of having a high-normal testosterone level, he said.

Dr Yeap and colleagues studied 3690 men aged 70 to 89 years living in Perth, Western Australia, as part of the Health In Men Study. Levels of testosterone and DHT were measured in blood samples collected between 2001 and 2004 and compared with survival up to December 2010.

There were 974 deaths, including 325 from ischemic heart disease. Men who died had lower mean baseline testosterone and DHT levels.

After adjustment for other risk factors-including age, overweight, and other confounding factors (eg, education, smoking, body mass index, waist-to-hip ratio, hypertension, dyslipidemia, diabetes mellitus, creatinine levels, and prevalent cardiovascular disease and cancer)-testosterone and DHT levels were associated with all-cause mortality.

Cumulative mortality was highest in those with the lowest levels of testosterone; the second-highest rate was seen among men with the highest levels of testosterone. Those with testosterone in the middle range had the lowest incidence of death from any cause.

These results are particularly important because of conflicting results in studies of testosterone replacement therapy. Some research has suggested lower mortality in men treated with testosterone; other studies have found the opposite.

There is a particular concern about the potential for heart problems after the use of testosterone replacement therapy in older men with comorbidities. Studies have found a higher risk of adverse cardiovascular events, including death, in men with multiple comorbidities undergoing coronary angiography treated with testosterone, compared with those who did not receive it. An NIH study of testosterone supplementation in older men was terminated early in 2010 when there was an excess of cardiovascular events found among men who took testosterone.

Dr Yeap said there needs to be more research of the biological basis for the associations between testosterone levels and the risk of dying, including randomized trials of testosterone supplementation.

“Having the right amount of testosterone and DHT may be important for men's health as they grow older, but we need to conduct clinical trials to determine whether modifying levels of sex hormones would improve health outcomes in older men,” he stated.

The researchers published their results in the January 2014 issue of the Journal of Clinical Endocrinology & Metabolism.