Low Serum Testosterone and Mortality in Male Veterans

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.

Testosterone levels decline with aging, with an average decrease in total serum testosterone levels of approximately 1.5% per year. 1 The prevalence of low serum total testosterone levels is approximately 20% by the age of 50 years and 50% by the age of 80 years. Manifestations of low testosterone include decreased muscle mass and bone mineral density, increased fat mass, central obesity, insulin resistance, decreased libido and energy, irritability, and dysphoria. 2 In contrast to menopause, in which all women undergo a nearly complete cessation of gonadal estrogen secretion, in men, gonadal androgen secretion decreases gradually and progressively after the age of 30 years, but does not generally cease, and androgen levels remain highly variable in older men. The prevalence of clinical androgen deficiency (symptoms plus low testosterone levels) was recently reported to be about 6% to 12% in middle-aged and elderly men. 3 Testosterone levels also decrease with acute and chronic illnesses and with medications such as glucocorticoids and opiates. 2 Because of the aging of our society, many older men are affected by age-associated low testosterone levels. 2 In addition, the use of testosterone has increased significantly, with a tripling in prescriptions for testosterone over a 3-year period. 4 However, despite the marked increase in testosterone use, the overall risks and benefits remain unclear. 4 , 5

In a recent small study 6 in a geriatric rehabilitation unit, we found that men with a low testosterone level had an increased 6-month mortality compared with men with a normal testosterone level who were of a comparable age and had comparable medical morbidity. Given these unforeseen preliminary findings, we conducted the present retrospective cohort study to examine if repeatedly low serum testosterone levels were associated with increased mortality in a larger sample of middle-aged and elderly men with a longer follow-up, of up to 8 years.

Article Source: http://archinte.jamanetwork.com/article/?articleid=410768

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