Dehydroepiandrosterone Sulfate and Mortality in Middle-Aged and Older Men and Women—A J-shaped Relationship

Abstract

Abstract Context The relationship between dehydroepiandrosterone sulfate (DHEAS) and mortality is of scientific and public health interest, yet it remains poorly understood. Objective We examined the association between DHEAS and mortality from cancer, cardiovascular disease, and all causes in middle-aged and older men and women. Methods DHEAS was measured in stored serum samples collected from 1994 to 1998 from a case-cohort nested within EPIC-Heidelberg, that included 7370 men (mean age = 55.0) and women (mean age = 52.4 years). Median follow-up for incident mortality events was 17.7 years. All deaths due to cancer (n = 1040), cardiovascular diseases (n = 598), and all causes (n = 2407) that occurred in EPIC-Heidelberg until end of 2014 were included. Results The association between DHEAS and mortality was nonlinear such that both participants in the lowest (Q1) and highest (Q5) sex- and 5-year age-group specific quintiles of DHEAS were at increased hazard ratios (HR) of mortality from cardiovascular [Q1: HR = 1.83 (95% CI: 1.33-2.51), Q5: 1.39 (1.00-1.94)], cancer [Q1: 1.27 (1.01-1.60), Q5: 1.27 (1.02-1.60)] and all causes [Q1: 1.51 (1.25-1.82), Q5: 1.31 (1.08-1.58)], compared with participants in Q3. In men and women with below-median DHEAS levels, doubling of DHEAS was associated with lower hazards of cardiovascular [0.87, (0.78-0.96)], cancer [0.90, (0.83-0.97)], and total mortality [0.89, (0.83-0.95)]. In contrast, a doubling in DHEAS among participants with above-median levels was associated with 1.20, (1.01-1.42), 1.28, (1.01-1.62), and 1.19 (1.03-1.37) higher hazards of mortality from cancer, cardiovascular, and all causes, respectively. Conclusion In this large population-based study, DHEAS showed a J-shaped association with mortality. Both participants with lowest and highest levels experienced higher hazards of mortality from cancer, cardiovascular disease, and all causes.