Low serum levels of the adrenal sex hormone dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) predicted increased risk for coronary heart disease in elderly men, according to a new study.1
However, DHEA and DHEA-S levels were not predictive of cerebrovascular events.
This prospective, population-based study followed 2,416 men aged 69 to 81 years (mean age, 75.4 years; mean BMI, 26.1) enrolled in the Osteoporotic Fractures in Men study in Sweden.
During a median follow-up of 5.2 years, 302 participants had a coronary heart disease (CHD) event and 225 had a cerebrovascular event, the researchers reported.
The levels of both DHEA and DHEA-S were inversely associated with the age-adjusted risk for a CHD event. Per standard deviation (SD) increase, the hazard ratios (HRs) were 0.82 (95% CI, 0.73-0.93) and 0.86 (95% CI, 0.77-0.97), respectively.
No statistically significant association was noted between cerebrovascular events and levels of DHEA or DHEA-S.
The association between DHEA and CHD risk remained significant even after adjustment for traditional cardiovascular (CV) risk factors, serum total testosterone and estradiol, C-reactive protein and renal function. Further, after the first 2.6 years of follow-up were excluded to reduce reverse causality, the association remained unchanged.
In an accompanying editorial, Nadia R. Sutton, MD, MPH, and David J. Pinsky, MD, both of the University of Michigan Health System in Ann Arbor, stated that this study has several strengths.2
It is the largest prospective trial to date that evaluated the relationship between DHEA and DHEA-S levels and CHD and cerebrovascular events. Additionally, the association between lower DHEA and DHEA-S levels “appeared to be maintained even after accounting for the recognized confounders of DHEA and DHEA-S levels of age and diurnal variation, and after adjusting for other CVD risk factors,” they wrote.
Another strength noted was the adjustment for renal function. As Sutton and Pinsky explained, even after this variable was accounted for, the association between DHEA and DHEA-S levels and CHD outcomes persisted.
Further, by measuring both DHEA and DHEA-S, the study “showed a more pronounced negative relationship between mortality and DHEA than that with DHEA-S,” the editorialists noted. They explained that DHEA could be a more important predictor of outcomes despite its low plasma concentrations relative to DHEA-S.
The editorial mentions that the same research group used a largely overlapping cohort of elderly Swedish men and found that DHEA and DHEA-S predicted all-cause and CV mortality in those aged younger than 75 years but not for those aged older than 75 years.3
Sutton and Pinsky questioned if the association between DHEA and DHEA-S and CHD events persists in men older than age 75 years. They suggest that this would be an important consideration for its use as a biomarker for this age group.
Overall, this study suggests that DHEA may be useful as a biomarker to predict future CHD events. The researchers, however, note the need for larger trials of DHEA therapy in people who are elderly or who have low levels of DHEA and DHEA-S. They also suggest that drugs targeting DHEA synthesis, which may lower DHEA levels, may have adverse effects on CHD risk.
This study is trying to understand the role of hormonal changes with aging and risk for cardiovascular disease. However, DHEA is a prohormone that is made by the adrenal gland and somewhat by the ovary and testes. With age, DHEA and DHEA-S, which is the long half-life stable form, decrease as the adrenal gland makes less prohormones. Both DHEA and DHEA-S can be converted to testosterone and then to estradiol in different tissues.
Strengths of the article are the use of gas and liquid chromatography-mass spectrometry assays and the size of the population studied.
The findings of the study were associative and not causative. It is interesting that a drop in DHEA was correlated with CHD but not CVD. This may be just a marker of aging or illness rather than any cause and effect. The fact that the hormonal changes were not consistent across different vascular diseases suggests the association is weak.
In regards to clinical practice, this article indicates that research is ongoing to examine the role of hormones in the normal aging process and risk for vascular disease. The article does not have clear-cut take-home messages, as it offers no data to suggest that taking DHEA would alter the CHD risk.
Margaret E. Wierman, MD
Vice President for Clinical Science, The Endocrine Society
Professor of Medicine, Physiology and Biophysics
University of Colorado School of Medicine
Chief of Endocrinology
Denver VA Medical Center
- Tivesten A et al. J Am Coll Cardiol. 2014;64(17):1801-1810.
- Sutton NR and Pinsky DJ. J Am Coll Cardiol. 2014;64(17):1811-1812.
- Ohlsson C et al. J Clin Endocrinol Metab. 2010;95:4406-4414.