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Testosterone insufficiency linked to increased mortality in older men
Older men with low levels of testosterone had a 40% increased risk for mortality during 20 years.
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Low levels of circulating total testosterone in older men were associated with increased risk for mortality over 20 years compared with older men with normal testosterone levels.
The researchers conducted a prospective, population-based study to examine mortality and serum testosterone levels in 794 men. They followed participants aged 50 to 91 years (average age was 73.6 years).
During an average follow-up of 11.8 years, 538 deaths occurred with a mortality rate of 57.5 per 1,000 person-years.
When adjusted for age, the risk for mortality increased for men in the lowest quartile for total and bioavailable testosterone distributions compared with men with higher levels, according to the researchers.
When adjusted for age, adiposity and lifestyle, the risk for mortality was 40% higher in the lowest quartile (HR=1.40; 95% CI, 1.14-1.71). The hazards ratio was 1.44 (95% CI, 1.19-1.74) for low bioavailable testosterone.
Cause-specific mortality
For low total testosterone, the hazards ratio for cardiovascular death was 1.38 (95% CI, 1.02-1.85), hazards ratio for cancer was 1.34 (95% CI, 0.89-2.00) and for respiratory disease it was 2.29 (95% CI, 1.25-4.20).
For low bioavailable testosterone, hazards ratio for cardiovascular death was 1.36 (95% CI, 1.04-1.79), hazards ratio for cancer was 1.50 (95% CI, 0.99-2.26) and for respiratory disease it was 1.84 (95% CI, 1.03-3.28).
“Testosterone levels above the median for this population did not confer any additional survival benefit, offering no support for widespread testosterone therapy for aging men,” they wrote. “Randomized, placebo-controlled trials are necessary to determine whether physiological testosterone replacement can safely extend the quality and duration of life for older men with well-documented testosterone insufficiency.” – by Christen Haigh
More epidemiological evidence indicates that low endogenous serum testosterone levels predict risk of decreased survival. Only a large, multi-year clinical trial that addresses efficacy and risk issues will be able to determine if testosterone treatment of aging men is truly beneficial. No trial of this magnitude is ongoing, so it will be many years before there is evidence to support or refute widespread testosterone replacement.
Some other studies support the findings of Laughlin et al. However, two prospective studies failed to find low testosterone levels to be associated with decreased survival. The report by Shores and colleagues is a retrospective analysis of veterans at the VA Puget Sound Medical Center in Seattle. Men who had testosterone levels <250 ng/dL were noted to be at increased risk of death when compared with men who had testosterone values >250 ng/dL. Those with some values above and below 250 ng/dL were at intermediate risk. A prospective, population-based, nested case-control study (EPIC-Norfolk) from the United Kingdom found that men with testosterone levels in the lowest quartile had a 25% higher risk of mortality. The average follow-up was 7 years, and there were 825 men who died and 1,489 controls. After adjustment for age, BMI and multiple risk factors, the risk increased to 41%. Two other population-based studies failed to find an association between testosterone levels and survival, but these studies involved younger men (mean age 50s), and the mortality rates were 19% and 31%.
– Glenn R. Cunningham, MD
Endocrine Today Editorial Board member
Deaths by Cause in 794 Men with Low Total Testosterone During 20 Years of Follow-Up |
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For more information:
- Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93:68-75.