Trajectories of Dehydroepiandrosterone Sulfate Predict Mortality in Older Adults: The Cardiovascular Health Study

Background. Dehydroepiandrosterone sulfate (DHEAS) has been proposed as an antiaging hormone, but its importance is unclear. Assessment of an individual's ability to maintain a DHEAS set point, through examination of multiple DHEAS levels over time, may provide insight into biologic aging. Methods. Using Cox proportional hazard models, we examined the relationship between DHEAS trajectory patterns and all-cause death in 950 individuals aged >65 years who were enrolled in the Cardiovascular Health Study and had DHEAS levels measured at three to six time points. Results. Overall, there was a slight decline in DHEAS levels over time (-0.013 mu g/mL/y). Three trajectory components were examined: slope, variability, and baseline DHEAS. When examined individually, a steep decline or extreme variability in DHEAS levels was associated with higher mortality (p <.001 for each), whereas baseline DHEAS level was not. In adjusted models including all three components, steep decline (hazard ratio [HR] 1.75, confidence interval [CI] 1.32-2.33) and extreme variability (HR 1.89, CI 1.47-2.43) remained significant predictors of mortality, whereas baseline DHEAS level remained unpredictive of mortality (HR 0.97 per standard deviation, CI 0.88-1.07). The effect of trajectory pattern was more pronounced in men than in women. Individuals with both a steep decline and extreme variability in DHEAS levels had a significantly higher death rate than those with neither pattern (141 vs 48 deaths per 1,000 person-years, p <.001). Conclusions. Our data show significant heterogeneity in the individual trajectories of DHEAS levels and suggest that these trajectories provide important biologic information about the rate of aging, whereas the DHEAS level itself does not.