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Molly M. Shores, MD; Alvin M. Matsumoto, MD; Kevin L. Sloan, MD; Daniel R. Kivlahan, PhD

Arch Intern Med. 2006;166:1660-1665.

Background  Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans.

Methods  We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. A low testosterone level was a total testosterone level of less than 250 ng/dL (<8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (<0.03 nmol/L). Men were classified as having a low testosterone level (166 [19.3%]), an equivocal testosterone level (equal number of low and normal levels) (240 [28.0%]), or a normal testosterone level (452 [52.7%]). The risk for all-cause mortality was estimated using Cox proportional hazards regression models, adjusting for demographic and clinical covariates over a follow-up of up to 8 years.

Results  Mortality in men with normal testosterone levels was 20.1% (95% confidence interval [CI], 16.2%-24.1%) vs 24.6% (95% CI, 19.2%-30.0%) in men with equivocal testosterone levels and 34.9% (95% CI, 28.5%-41.4%) in men with low testosterone levels. After adjusting for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34-2.63; P<.001) while equivocal testosterone levels were not significantly different from normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a sensitivity analysis, men who died within the first year (50 [5.8%]) were excluded to minimize the effect of acute illness, and low testosterone levels continued to be associated with elevated mortality.

Conclusions  Low testosterone levels were associated with increased mortality in male veterans. Further prospective studies are needed to examine the association between low testosterone levels and mortality.

Author Affiliations: Geriatric Research, Education, and Clinical Center (Drs Shores and Matsumoto) and Center of Excellence in Substance Abuse Treatment and Education (Drs Sloan and Kivlahan), VA Puget Sound Health Care System, Seattle, Wash, and Departments of Psychiatry and Behavioral Sciences (Drs Shores, Sloan, and Kivlahan) and Medicine (Dr Matsumoto), University of Washington, Seattle.

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