DHEA and mortality: what is the nature of the association?
Although very little is known about the importance of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) in human physiology and pathophysiology, emerging observations imply pivotal roles of DHEA/-S. One such observation is the association between serum DHEA/-S levels and mortality risk. In this review, we focus on the literature addressing DHEA/-S and mortality with the aim to describe and discuss patterns and potential underlying mechanisms. Although the literature reports somewhat inconsistent results, we conclude that several larger population-based studies support an association between low DHEA/-S and risk of death, at least in elderly men. In women, the association may not be present; alternatively, there may be a U-shaped association. In men, most available evidence suggests an association with cardiovascular (CV) mortality rather than cancer mortality. Further, there are biologically plausible mechanisms for an effect of DHEA/-S on the development of CV disease. On the other hand, there is also strong evidence supporting that any disease may lower DHEA/-S. Thus, the cause-effect relation of this association is less clear. Future studies may employ a mendelian randomization approach using genetic determinants of DHEA-S levels as predictors of clinical outcomes, to delineate the true nature of the association between DHEA/-S and mortality.
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: claes.ohlsson@medic.gu.se.
Claes
C
Ohlsson
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: liesbeth.vandenput@medic.gu.se.
Liesbeth
L
Vandenput
Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Bruna Stråket 16, S-413 45 Gothenburg, Sweden. Electronic address: asa.tivesten@medic.gu.se.
Asa
A
Tivesten
D000311:Adrenal Glands / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism*; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000401:mortality; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
D006728:Hormones; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate
Dehydroepiandrosterone; Dehydroepiandrosterone sulfate; Mortality