Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, England, UK.
European Journal of Endocrinology (Impact Factor: 4.07). 05/2010; 163(2):285-92. DOI: 10.1530/EJE-10-0299
Source: PubMed


The aim of the present analyses was to examine the association between cortisol, DHEA sulphate (DHEAS) and the cortisol:DHEAS ratio and mortality.
This was a prospective cohort analysis.
Participants were 4255 Vietnam-era US army veterans. From military service files, telephone interviews and a medical examination, occupational, socio-demographic and health data were collected. Contemporary morning fasted cortisol and DHEAS concentrations were determined. Mortality was tracked over the subsequent 15 years. The outcomes were all-cause, cardiovascular disease, cancer, other medical mortality and external causes of death. Cox proportional hazard models were tested, initially with adjustment for age, and then with adjustment for a range of candidate confounders.
In general, cortisol concentrations did not show an association with all-cause or cause-specific mortality. However, in age-adjusted and fully adjusted analyses, DHEAS was negatively related to all-cause, all cancers and other medical mortality; high DHEAS concentrations were protective. The cortisol:DHEAS ratio was also associated with these outcomes in both age-adjusted and fully adjusted models; the higher the ratio, the greater the risk of death.
DHEAS was negatively associated, and the ratio of cortisol to DHEAS was positively associated with all-cause, cancer and other medical cause mortality. Further experimental study is needed to elucidate the mechanisms involved in these relationships.

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    • "In various scientific disciplines, log-transformation has been proposed as a solution for the asymmetry problem of ratios (e.g.,Aitchison, 1982;Aitchison and Egozcue, 2005;Björklund, 1990;Keene, 1995;Smith, 1999;Webster, 1992;Weltje, 2012). Moreover, a number of endocrine studies have already pursued this approach to address the concern of non-normally distributed hormone ratios (e.g.,Kupchak et al., 2014;Markopoulou et al., 2009;Pajer et al., 2006;Phillips et al., 2010;Schloms et al., 2014;Young et al., 2002). Concretely, log-transformation of a ratio means that the logarithm of the ratio is used instead of the raw ratio. "
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    ABSTRACT: Hormone ratios have become increasingly popular throughout the neuroendocrine literature since they offer a straightforward way to simultaneously analyze the effects of two interdependent hormones. However, the analysis of ratios is associated with statistical and interpretational concerns which have not been sufficiently considered in the context of endocrine research. The aim of this article, therefore, is to demonstrate and discuss these issues, and to suggest suitable ways to address them. In a first step, we use exemplary testosterone and cortisol data to illustrate that one major concern of ratios lies in their distribution and inherent asymmetry. As a consequence, results of parametric statistical analyses are affected by the ultimately arbitrary decision of which way around the ratio is computed (i.e., A/B or B/A). We suggest the use of non-parametric methods as well as the log-transformation of hormone ratios as appropriate methods to deal with these statistical problems. However, in a second step, we also discuss the complicated interpretation of ratios, and propose moderation analysis as an alternative and oftentimes more insightful approach to ratio analysis. In conclusion, we suggest that researchers carefully consider which statistical approach is best suited to investigate reciprocal hormone effects. With regard to the hormone ratio method, further research is needed to specify what exactly this index reflects on the biological level and in which cases it is a meaningful variable to analyze.
    No preview · Article · Nov 2015 · Psychoneuroendocrinology
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    • "For example, cortisol has significant interactions with testosterone which influence immunological responses to hepatitis B vaccination in humans (Rantala et al., 2012). Additionally, DHEA exerts interactive properties, acting as an anti-glucocorticoid in rodent experimentation (Ben-Nathan et al., 1992) and is related to disease and health outcomes in humans (Arlt et al., 2006; Phillips et al., 2010a,b). Exploring the immunological interactions between DHEA and cortisol would yield a greater understanding of how HPA activation mediates immune function. "
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    ABSTRACT: Objectives: Human immune function is strongly influenced by variation in hormone concentrations. The adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) are thought to be beneficial to immune function and disease resistance, but physiologically interact with testosterone and cortisol. We predict that DHEA and DHEA-S will interact with these other hormones in determining immunological outcomes. Understanding the interactive effects of these hormones will aid in understanding variability in immunocompetence and clarify discrepancies in human studies of androgen–immune interactions. Methods: Thirty-eight participants collected morning saliva over three days, from which concentrations of DHEA, DHEA-S, testosterone, and cortisol were measured, as well as salivary bacteria killing ability to measure innate immune function. From blood collection, serum was collected to measure innate immune function via a hemolytic complement assay, and whole blood collected and processed to measure proliferative responses of lymphocytes in the presence of mitogens. Results: DHEA was negatively correlated with T cell proliferation, and positively correlated with salivary bacteria killing in male participants. Additionally, using regression models, DHEA-S was negatively associated with hemolytic complement activity, but interaction variables did not yield statistically significant relationships for any other outcome measure. Conclusions: While interactions with other hormones did not significantly relate with immune function measures in this sample, DHEA and DHEA-S did differentially impact multiple branches of the immune system. Generally characterized as immunosupportive in action, DHEA is shown to inhibit certain facets of innate and cell-mediated immunity , suggesting a more complex role in regulating immunocompetence.
    Full-text · Article · Mar 2015 · American Journal of Human Biology
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    • "Cortisol is a glucocorticoid hormone secreted by the adrenal gland in response to pituitary secretion of adrenal corticotrophic hormone, which itself is stimulated by corticotrophin releasing hormone from the hypothalamus; together these form the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol plays key roles in the stress response and is also immunosuppressive [38]. Neuronal cells within the HPA axis contain multiple cytokine receptors, particularly for IL-1, IL-6 and TNF [39], and it has been demonstrated in human beings in vivo that injection of IL-6 or TNF induces a marked change in HPA axis [40]. "
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    ABSTRACT: Inflammaging is characterized by the upregulation of the inflammatory response that occurs with advancing age; its roots are strongly embedded in evolutionary theory. Inflammaging is believed to be a consequence of a remodelling of the innate and acquired immune system, resulting in chronic inflammatory cytokine production. Complex interrelated genetic, environmental and age-related factors determine an individual’s vulnerability or resilience to inflammaging. These factors include polymorphisms to the promoter regions of cytokines, cytokine receptors and antagonists, age-related decreases in autophagy and increased adiposity. Anti-inflammaging describes the upregulation of the hypothalamic-pituitary axis in response to inflammaging, leading to higher levels of cortisol, which in turn may be detrimental, contributing to less successful ageing and frailty. This may be countered by the adrenal steroid dehydroepiandrosterone, which itself declines with age, leaving certain individuals more vulnerable. Inflammaging and anti-inflammaging have both been linked with a number of age-related outcomes, including chronic morbidity, functional decline and mortality. This important area of research offers unique insights into the ageing process and the potential for screening and targeted interventions.
    Full-text · Article · May 2013
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