Low serum testosterone and mortality in older men.

Context: Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging; however, studies demonstrating associations of low testosterone with clinical outcomes are few. Objective: The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men. Design, Setting, and Participants: This was a prospective, population-based study of 794 men, aged 50 -91 (median 73.6) yr who had serum testosterone measurements at baseline (1984 -1987) and were followed for mortality through July 2004. Main Outcome Measure: All-cause mortality by serum testosterone level was measured. Results: During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (Ͻ241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14 -1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle. Additional adjustment for health status markers, lipids, lipoproteins, blood pressure, glycemia, adipocytokines, and estradiol levels had minimal effect on results. The low testosterone-mortality association was also independent of the metabolic syndrome, diabetes, and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein. In cause-specific analyses, low testosterone predicted increased risk of cardiovascular (HR 1.38; 95% CI 1.02-1.85) and respiratory disease (HR 2.29; 95% CI 1.25-4.20) mortality but was not significantly related to cancer death (HR 1.34; 95% CI 0.89 -2.00). Results were similar for bioavailable testosterone. Conclusions: Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions. (J Clin Endocrinol Metab 93: 68 -75, 2008) I n contrast to the dramatic fall in estrogen levels at the time of menopause in women, testosterone concentrations in men decline gradually with aging. Many adverse aspects of male aging have been attributed to the decrease in endogenous testosterone, stimulating a surge of interest in testosterone therapy for middleaged and older men. Testosterone sales in the United States increased 20-fold during the 1990s (1). However, solid evidence linking testosterone insufficiency to health-related outcomes in older men is just beginning to emerge, and even less information is available on testosterone and mortality. Approximately 30% of men 60 yr old and older are estimated to have low testosterone (2), which is often accompanied by undesirable signs and symptoms such as low bone and muscle mass; increased fat mass (especially central adiposity); low energy; and impaired physical, sexual, and cognitive function. That these complaints have clinical consequences is supported by prospective cohort studies showing that men with low testosteron