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Low testosterone increases mortality risk in metabolic syndrome
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Older men with metabolic syndrome and low levels of total and bioavailable testosterone are more likely to die of any cause over 12 years vs. men without metabolic syndrome, according to findings from a prospective study in France.
“Studies that reported a significant association of low testosterone with mortality were usually performed in older men who are more likely than younger men to have low HDL cholesterol levels, dyslipidemia or abdominal obesity, three important components of [metabolic syndrome],” Nasser Laouali, MSc, of the Center for Research in Epidemiology and Population Health at Paris-Saclay University, France, and colleagues wrote in the study background. “In addition, a previous study suggested that the association of low plasma testosterone and mortality could be restricted to men with [metabolic syndrome]. Based on these observations, we hypothesized that the association of testosterone and mortality in men may be modified by [metabolic syndrome].”
Laouali and colleagues analyzed data from 444 men aged at least 65 years not using hormone antagonists or related agents from the ongoing French Three-City cohort study, a prospective analysis assessing the association between vascular factors and dementia (mean age, 74 years). Participants provided fasting blood samples at baseline and underwent interviews five times every 2 to 3 years. Researchers measured total testosterone and bioavailable testosterone and assessed individual metabolic syndrome components, including the presence of central obesity, elevated triglyceride level (> 1.7 mmol/L), reduced HDL cholesterol (< 1.03 mmol/L), high blood pressure (systolic 130 mm Hg; diastolic 85 mm Hg) or elevated fasting plasma glucose ( 5.6 mmol/L). Researchers analyzed the association of testosterone with all-cause mortality in men with and without metabolic syndrome using a Cox regression model, and they conducted separate analyses among men with metabolic syndrome by defining subgroups of men with each metabolic syndrome component.
Within the cohort, 106 men had metabolic syndrome (23.9%). During a mean follow-up of 12 years, 166 men died.
Overall, total and bioavailable testosterone were not associated with all-cause mortality in an adjusted model that included metabolic syndrome, according to researchers. However, they observed an interaction between total and bioavailable testosterone and metabolic syndrome on mortality risk (P = .002 and .008, respectively).
In men without metabolic syndrome, researchers did not observe an association between total and bioavailable testosterone and mortality. However, among men with metabolic syndrome, researchers observed a linear trend between testosterone levels and mortality risk. For each 1-standard deviation decrease in total and bioavailable testosterone in men with metabolic syndrome, HR for mortality risk was 1.78 (95% CI, 1.13-2.78) and 1.83 (95% CI, 1.17-2.86), respectively.
In analyzing each component of metabolic syndrome, researchers observed statistically significant or borderline significant interactions between each component with total and bioavailable testosterone on all-cause mortality. Results persisted after excluding men who died in the first 2 or 4 years of follow-up.
“These results are in agreement with the hypothesis that differences in [metabolic syndrome] prevalence across the epidemiological studies may partly explain inconsistent findings on the relation of testosterone with mortality in men,” the researchers wrote.
Metabolic syndrome status should be considered when examining outcomes related to testosterone level, they wrote.
“If confirmed, these results may help clinicians to detect individuals at higher risk for death and requiring intensive medical monitoring,” the researchers wrote. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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