Ohlsson Claes, Vandenput Liesbeth, Tivesten Asa
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Bruna Stråket 16, S-413 45 Gothenburg, Sweden.
J Steroid Biochem Mol Biol. 2015 Jan;145:248-53. doi: 10.1016/j.jsbmb.2014.03.006. Epub 2014 Apr 2.
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.
尽管人们对脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEA-S）在人体生理和病理生理中的重要性知之甚少，但新出现的观察结果表明DHEA/-S具有关键作用。其中一个观察结果是血清DHEA/-S水平与死亡风险之间的关联。在本综述中，我们聚焦于探讨DHEA/-S与死亡率的文献，旨在描述和讨论其模式及潜在的潜在机制。尽管文献报道的结果有些不一致，但我们得出结论，至少在老年男性中，几项较大规模的基于人群的研究支持低DHEA/-S与死亡风险之间存在关联。在女性中，这种关联可能不存在；或者，可能存在U型关联。在男性中，大多数现有证据表明与心血管（CV）死亡率相关，而非癌症死亡率。此外，DHEA/-S对心血管疾病发展产生影响存在生物学上合理的机制。另一方面，也有强有力的证据支持任何疾病都可能降低DHEA/-S。因此，这种关联的因果关系尚不清楚。未来的研究可能采用孟德尔随机化方法，将DHEA-S水平的遗传决定因素用作临床结局的预测指标，以阐明DHEA/-S与死亡率之间关联的真实性质。
