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DHEAS Levels and Mortality in Disabled Older Women: The Women's Health and Aging Study I

¹ Division of Endocrinology, Diabetes and Metabolism and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia.
² Division of Geriatric Medicine and Gerontology and Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, Maryland.
³ Clinical Research Branch, National Institute on Aging, Baltimore, Maryland.
⁴ Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland.

Address correspondence to Anne R. Cappola, MD, ScM, Division of Endocrinology, Diabetes, and Metabolism, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 718 Blockley, 423 Guardian Dr., Philadelphia, PA 19104-6021. E-mail: acappola{at}cceb.med.upenn.edu

Background. Dehydroepiandrosterone sulfate (DHEAS) is an endogenously produced sex steroid that has been hypothesized to have anti-aging effects. Low DHEAS levels are associated with mortality in older men, but the relationship between DHEAS levels and mortality in women is not clearly defined.

Methods. The relationship between serum DHEAS level and 5-year mortality was analyzed in a cohort of 539 disabled women aged 65–100 years enrolled in the Women's Health and Aging Study I (WHAS I). Using Cox proportional hazard models, we calculated multivariate-adjusted mortality risks by DHEAS quartiles and by DHEAS continuously, allowing for a nonlinear relationship. We also examined cause-specific mortality.

Results. We found a U-shaped relationship between DHEAS level and mortality. After adjusting for multiple covariates, women in the top and bottom DHEAS quartiles had a more than 2-fold higher 5-year mortality than did those in the middle quartiles (hazard ratio, 2.15; 95% confidence interval [CI], 1.17–3.98 for the top quartile and 2.05; 95% CI, 1.27–3.32 for the bottom quartile, each compared to the third quartile). Women with higher DHEAS levels tended to have greater cancer mortality, whereas those with lower DHEAS tended to have greater cardiovascular mortality.

Conclusion. Disabled older women with either low or high levels of DHEAS are at greater risk for death than are those with intermediate levels. More research is needed to determine if targeted dehydroepiandrosterone supplementation would provide clinical benefit to disabled older women.