Metabolic syndrome, inflammatory markers may partly explain the link.


TORONTO —Androgen deficiency in men aged 50 years and older may be associated with an increased risk of death, independent of adiposity and lifestyle choices, a study suggests. This association may be explained, in part, by the metabolic syndrome and elevated markers of inflammation.

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“The new study is only the second report linking deficiency of this sex hormone with increased death from all causes, over time, and the first to do so in relatively healthy men who are living in the community,” said investigator Gail Laughlin, PhD, assistant professor in the department of family and preventive medicine at the University of California in San Diego (UCSD). “Our study strongly suggests that the association between testosterone levels and death is not simply due to some acute illness.”


Androgen deficiency in elderly men is thought to underlie many of the symptoms and diseases of aging. Dr. Laughlin and her colleagues conducted a prospective population-based study of 794 men aged 50 to 91 years who had serum testosterone levels measured at baseline (1984-1987) and were followed for mortality through July 2004. The participants have been members of the Rancho Bernardo Heart and Chronic Disease Study since the 1970s. At the beginning of the 1980s, almost one third of these men had suboptimal serum testosterone levels for their age.


Testosterone levels were 22% lower for the 143 men who met the criteria for the metabolic syndrome; these levels were inversely related to plasma interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP) levels, both markers of inflammation. During an average 18 year follow-up, 538 deaths were documented. Baseline testosterone levels did not differ for those who did and did not die, before or after adjusting for age, BMI, and waist girth.


The 229 men whose testosterone level was below 250 ng/dL—the study definition for low testosterone—had a 33% greater risk of death compared with men who had higher testosterone levels, after adjusting for age, BMI, waist girth, and lifestyle factors. This association was independent of diabetes and prevalent CVD, but it was attenuated when adjusted for the presence of the metabolic syndrome and eliminated by further adjustment for IL-6 and hsCRP. Adjustment for serum creatinine levels or weight loss did not influence the results. Men with low testosterone were three times more likely to have the metabolic syndrome than men with higher testosterone levels.


“As far as mechanism of action is concerned, we just don’t know yet,” Dr. Laughlin told Renal & Urology News. “We do think it has to do with central obesity and the metabolic abnormalities that go along with that.” She presented study results here at the The Endocrine Society’s 89th annual meeting.


While the study lends support to the belief that supplemental hormone therapy may help older men with low testosterone levels, those who practice weight control and increase their physical activity may also live longer, according to the investigators.


“It’s very possible that lifestyle determines what level of testosterone a patient has,” said principal investigator Elizabeth Barrett-Connor, MD, Distinguished Professor of Family and Preventive Medicine and chief of the division of epidemiology at UCSD.  “It may be possible to alter the testosterone levels by lowering obesity. We are very excited about these findings, which have important implications, but we are not ready to say that men should go out and get testosterone to prolong their lives.”