Dehydroepiandrosterone and Its Sulfate Predict the 5-Year Risk of Coronary Heart Disease Events in Elderly Men

Study Questions:

The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the sulfate DHEA-S, is the most abundant steroid hormone in human blood. Its levels decline dramatically with age. Are serum DHEA and DHEA-S predictors of major coronary heart disease (CHD) and/or cerebrovascular disease events in a large cohort of elderly men?


Gas/liquid chromatography-mass spectrometry was used to analyze baseline levels of DHEA and DHEA-S in the prospective, population-based MrOS (Multicenter Osteoporotic Fractures in Men Study), which was conducted in Sweden (2,416 men, ages 69-81 years). Complete cardiovascular clinical outcomes were available from national Swedish registers.


Mean age was 75.4 years, with mean DHEA 1.79 ng/ml and DHEA-S 0.71 µg/ml. During the 5-year follow-up, 302 participants experienced a CHD event and 225 a cerebral vascular event. Both DHEA and DHEA-S levels were inversely associated with the age-adjusted risk of a CHD event; hazard ratio and 95% confidence interval per standard deviation increase was 0.82 (0.73-0.93) and 0.86 (0.77-0.97), respectively. By contrast, DHEA-S showed no statistically significant association with the risk of cerebral vascular events. The association between DHEA and CHD risk remained significant after adjustment for traditional cardiovascular risk factors and serum total testosterone and estradiol, C-reactive protein, and renal function and was unchanged after exclusion of the first 2.6 years of follow-up to reduce reverse causality.


The authors concluded that low serum levels of DHEA and its sulfate predict an increased risk of CHD, but not cerebral vascular disease events in elderly men.


Adrenal-derived DHEA-S has been a popular assay in the aging population, as has the practice of supplements, despite no well-conducted randomized trials. Nonhuman evidence suggests it may modulate lipid/glucose metabolism, systemic inflammation, and endothelial function. As with so many population-based studies that have relatively accurate death and cardiovascular event data from death and hospital discharge registries, the baseline data for smoking, diabetes, hypertension, and myocardial infarction was self-reported, which introduces a positive outcome bias. Of note, DHEA but not DHEA-S levels were highly influenced by time of blood sampling and renal function. As the authors suggested, properly designed clinical trials are needed to evaluate the cardiometabolic effects, safety, and efficacy of DHEA supplementation among clearly defined cohorts.

Clinical Topics: Prevention, Hypertension, Smoking

Keywords: Sulfates, Inflammation, Myocardial Infarction, Follow-Up Studies, Estradiol, Dehydroepiandrosterone, Risk Factors, Smoking, Chromatography, Liquid, C-Reactive Protein, Sweden, Confidence Intervals, Hypertension, Mass Spectrometry, Diabetes Mellitus, Testosterone

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