Metabolic Syndrome Modifies Testosterone, Mortality Link in Older Men

Metabolic syndrome (MetS) modifies the association between testosterone and mortality in older men, according to a study recently published in the Journal of the Endocrine Society.

Researchers led by Marianne Canonico, PhD, of the Université de Versailles St-Quentin-en-Yvelines, Center for Research in Epidemiology and Population Health, INSERM, in Versailles, France, point out that there have been several controversial epidemiological studies that looked at the association of low plasma total and bioavailable testosterone with all-cause mortality in older men, and that the results are inconsistent. “Although some studies show an increased risk of death among men with the lowest testosterone levels, others found no association,” the authors write. “More recent studies also yielded inconsistent findings.”

They go on to write that studies that did show a noteworthy association of low testosterone with mortality were performed in older men, and that a previous study suggested the link between low testosterone and mortality could be restricted to men with MetS. “Based on these observations,” the authors write, “we hypothesized that the association of testosterone and mortality in men may be modified by MetS.”

The researchers used data from the Three-City Cohort (3C), a large ongoing French prospective cohort that is looking at the association between vascular factors and dementia. The 3C study includes 3,650 men over 65 years old from three French cities: Bordeaux, Dijon, and Montpellier. Hormone was measured in a random subsample of 444 men, and the researchers used International Diabetes Federation criteria to determine MetS. Of these 444 men, 106 has MetS at baseline, and 166 died during the 12-year follow-up. “There was a significant interaction between testosterone level and MetS for all-cause mortality (P = 0.002 and P = 0.008 for total and bioavailable testosterone, respectively),” the authors write. “Among men with MetS, a decrease in one standard deviation of testosterone was associated with higher mortality risk.” What’s more, the researchers found no association between testosterone and mortality in men without MetS.

The authors note that their findings are consistent with some of the previous data and inconsistent with other previous findings. But they write that these “results are in agreement with the hypothesis that differences in MetS prevalence across epidemiological studies may partly explain inconsistent findings on the relation of testosterone with mortality in men.”

Based on these findings, the authors conclude that low testosterone is associated with increased all-cause mortality in men with MetS, but not in men without MetS, which, again, could explain the inconsistencies among previous studies. “Our data suggest that the response to testosterone therapy in men may depend on the presence of MetS or its components,” the authors write. “It would be therefore important to take MetS status into account when examining outcomes related to testosterone level. If confirmed, these results may help clinicians to detect individuals at higher risk of death and requiring intensive medical monitoring.”

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