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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    • "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.
    American Journal of Human Biology 03/2015; 27(6). DOI:10.1002/ajhb.22724 · 1.70 Impact Factor
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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.
    05/2013; DOI:10.1186/2046-2395-2-8
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    • "This study confirms consistent inverse associations between the measures of physical capability (such as grip strength and walking speed) and mortality in older populations well documented in the literature [28]. Our data are also consistent with those documenting a positive effect of HbA1c and CRP and an inverse effect of DHEAS on mortality by all causes and CV conditions [29-35]. However, there are not many studies on the mortality effect of these three relatively new biomarkers. "
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    ABSTRACT: Background Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality. Methods This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths. Main outcome: prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models. Results Biomarkers significantly predict future death above and beyond demographic and self-reported health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP), glycated hemoglobin (HbA1c), and dehydroepiandrosterone sulfate (DHEAS). Strikingly, high blood pressure (BP) and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects. Conclusions This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow), are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in other settings: despite the continued medical focus on drugs for BP and cholesterol, high levels of BP and cholesterol have little predictive value of mortality in this elderly population.
    Population Health Metrics 06/2012; 10(1):11. DOI:10.1186/1478-7954-10-11 · 2.11 Impact Factor
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