Dehydroepiandrosterone Sulphate Ratio Research Articles

Unemployment is associated with lower cortisol awakening and blunted dehydroepiandrosterone responses

Previous research has investigated the endocrinological consequences of unemployment as a likely pathway behind chronic stress and negative health outcomes. Despite these early attempts at delineating the neuroendocrine consequences of the chronic stress experienced by the unemployed, identifying a consistent and stable effect has remained elusive. Here we sought to strengthen existing knowledge into the effect of the stress of employment status on cortisol by improving on the methodological weaknesses of earlier studies and extend this line of enquiry by measuring the steroid hormone Dehydroepiandrosterone-Sulfate (DHEAS). Saliva samples were collected from unemployed and employed participants at four time points across two days. As expected, unemployed people reported higher stress, lower social support and lower self-esteem. Unexpectedly, the unemployed showed lower overall cortisol output, a likely consequence of a higher cortisol awakening response (CAR) in the employed. However, they also had a higher DHEA output across the day, albeit the diurnal pattern across the day was more dysregulated compared to that seen in those employed with a blunted response evident in the evening; the cortisol:DHEAS ratio was also lower in the unemployed group. Further, these hormone differences were correlated with self-esteem and stress. Taken together these results suggest that the relationship between employment status and endocrine responses is far more complicated than previously thought. We have shown for the first time that unemployed people have a lower CAR, but also show a blunted DHEA response relative to those employed and we suggest that this may be a feature of chronic stress exposure or perhaps dependent on the prevailing socio-economic context.

Bereavement reduces neutrophil oxidative burst only in older adults: role of the HPA axis and immunesenescence.

BackgroundThe effect of the chronic stress of bereavement on immunity is poorly understood. Previous studies have demonstrated negative effects on immunity in older adults, and those who report higher depressive symptoms. The aim of the present study was to compare the effect of bereavement on neutrophil function in healthy young and old adults, also assessing serum levels of the stress hormones, cortisol and dehydroepiandrosterone sulphate (DHEAS). 41 young (mean age 32 years) and 52 older adults (mean age 72 years), bereaved and non-bereaved, took part in the study. They completed questionnaires on socio-demographic and health behaviour characteristics, as well as psychosocial variables, and provided a blood sample for analysis of neutrophil function (phagocytosis and reactive oxygen species (ROS) production) and stress hormone analysis.ResultsBereaved participants in both age groups reported more symptoms of depression and anxiety than controls and scored moderately highly on bereavement-specific questionnaires for these symptoms. Despite this, young bereaved participants showed robust neutrophil function when compared to age-matched non-bereaved controls, and comparable stress hormone levels, while reduced neutrophil ROS production and raised stress hormone levels (cortisol:DHEAS ratio) were seen in the older bereaved group compared to their age-matched controls.ConclusionsReduced neutrophil function among older bereaved participants may be the result of the inability to maintain stress hormone balance, specifically the cortisol:DHEAS ratio.

Depressive symptoms are associated with reduced neutrophil function in hip fracture patients.

Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p=.001) or controls (p=.004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.

Depression following hip fracture is associated with increased physical frailty in older adults: the role of the cortisol: dehydroepiandrosterone sulphate ratio.

BackgroundHip fracture in older adults is associated with depression and frailty. This study examined the synergistic effects of depression and hip fracture on physical frailty, and the mediating role of the cortisol:dehydroepiandrosterone sulphate (DHEAS) ratio.MethodsThis was an observational longitudinal study of patients with a hip fracture carried out in a hospital setting and with follow up in the community.Participants were 101 patients aged 60+ years (81 female) with a fractured neck of femur.Measurements of the ability to carry out activities of daily living (ADL), cognitive function, physical frailty and assays for serum cortisol and DHEAS were performed six weeks and six months post-hip fracture. Depressed and non-depressed groups were compared by ANOVA at each time point.ResultsHip fracture patients who developed depression by week six (n = 38) had significantly poorer scores on ADL and walking indices of frailty at both week six and month six, and poorer balance at week six. The association with slower walking speed was mediated by a higher cortisol:DHEAS ratio in the depressed group.ConclusionDepression following hip fracture is associated with greater physical frailty and poorer long term recovery post-injury. Our data indicate that the underlying mechanisms may include an increased cortisol:DHEAS ratio and suggest that correcting this ratio for example with DHEA supplementation could benefit this patient population.

Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease

BackgroundBiomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening.Methods(1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups.Results1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3β ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC.ConclusionSeveral metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-013-0766-5) contains supplementary material, which is available to authorized users.

Relationship Between IGF-1 and Cortisol/ DHEA-S Ratio in Adult Men With Diabetic Metabolic Syndrome Versus Non-Diabetic Metabolic Syndrome

Background : Metabolic syndrome (MS) is a strong risk factor for cardiovascular disease and type 2 diabetes mellitus. Previous studies have suggested that low i nsulin like growth factor-1 (IGF-1) , low dehydroepiandrosterone sulfate (DHEA-S) and high cortisol are significant correlates of MS. The aim of the present study was to examine the relationships between serum IGF-1, cortisol, DHEA-S and cortisol/ DHEA-S ratio in adult men with MS either diabetic or non-diabetic. Methods : One hundred adult men were enrolled in this study, divided into three groups: group 1 included 30 patients with diabetic MS, group 2 included 30 patients with non-diabetic MS and group 3 included 40 age and sex-matched controls. Anthropometric measurements, Homeostasis model assessment of insulin resistance (HOMA), lipid profile, IGF-1, cortisol, DHEA-S and cortisol/ DHEA-S ratio were assessed. Results : IGF-1 and DHEA-S levels were significantly lower while serum cortisol and cortisol/ DHEA-S ratio were higher in both diabetic MS and non-diabetic MS adult men than healthy con trols; they were also significantly different in the diabetic than in non-diabetic adult men with MS. IGF-1 was significantly and independently correlated with waist circumference, blood pressure, fasting blood glucose, HOMA, cortisol, DHEA-S and cortisol/ DHEA-S ratio. Cortisol/ DHEA-S ratio was significantly and independently correlated with blood pressure, fasting blood glucose, insulin, HOMA, triglyceride, high density lipoprotein cholesterol, cortisol and DHEA-S. Conclusion : IGF-1 concentration is reduced and cortisol/ DHEA-S ratio is increased along with insulin resistance in adult men with diabetic MS. IR may be responsible for multiple multihormonal dysregulation in MS. doi:10.4021/jem43w

Neutrophil function and cortisol:DHEAS ratio in bereaved older adults

Bereavement is a common life event for older adults and is associated with increased risk of morbidity and mortality, though the underlying reasons for this link are poorly understood. Although physical and emotional stressors and ageing are known to suppress immunity, few studies have explored the impact of bereavement upon immunity in the older population. We therefore hypothesised that the emotional stress of bereavement would suppress immune function, specifically neutrophil bactericidal activity, in older adults. A between-subjects design was used to examine the effect of recent bereavement (<2months) on neutrophil function in elders. Participants were 24 bereaved and 24 age- and sex-matched non-bereaved controls all aged 65+years. Neutrophil phagocytosis of Escherichia coli (E. coli) and stimulated superoxide production were assessed. Cortisol and dehydroepiandrosterone-sulphate (DHEAS) levels were determined in serum to assess potential mechanisms. Depressive and anxiety symptoms were measured by questionnaire. Neutrophil superoxide production was significantly reduced among the bereaved when challenged with E. coli (p=0.05), or phorbol 12-myristate 13-acetate (p=0.009). Further, the bereaved group had a significantly higher cortisol:DHEAS ratio compared to controls (p=0.03). There was no difference in neutrophil phagocytosis between the two groups. The psychological questionnaire results showed that the bereaved had significantly greater depressive and anxiety symptoms than the non-bereaved. The emotional stress of bereavement is associated with suppressed neutrophil superoxide production and with a raised cortisol:DHEAS ratio. The stress of bereavement exaggerates the age-related decline in HPA axis and combines with immune ageing to further suppress immune function, which may help to the explain increased risk of infection in bereaved older adults.

Cortisol, dehydroepiandrosterone sulphate, their ratio and hypertension: evidence of associations in male veterans from the Vietnam Experience Study

Although clinical observations implicate cortisol in hypertension, the epidemiological evidence is less compelling. Little is known about the relationship between dehydroepiandrosterone sulphate (DHEAS) and hypertension, and nothing about the association with the cortisol:DHEAS ratio. The present analyses of data obtained from Vietnam-era US veterans examined the associations between cortisol, DHEAS, their ratio and hypertension. Participants were 4180 male veterans. From military files, telephone interviews and a medical examination, sociodemographic and health data were collected. At medical examination, a fasted morning blood sample was collected to assay serum cortisol and DHEAS, blood pressure measured and body mass index (BMI) determined. Hypertension was defined by having one of the following: a reported physician diagnosis, taking antihypertensive medication, an average systolic blood pressure ≥ 140 mm Hg and an average diastolic blood pressure ≥ 90 mm Hg. Cortisol and the cortisol:DHEAS ratio were positively associated with hypertension (P < 0.001), whereas DHEAS was negatively associated; the latter relationship was attenuated to non-significance (P = 0.06) in models that adjusted for age, sociodemographics, place of service, health behaviours and BMI. The present analyses provide confirmation of a positive association between cortisol and the cortisol:DHEAS ratio and population hypertension.

Relationship Between IGF-1 and Cortisol/ DHEA-S Ratio in Adult Men With Diabetic Metabolic Syndrome Versus Non-Diabetic Metabolic Syndrome

Background : Metabolic syndrome (MS) is a strong risk factor for cardiovascular disease and type 2 diabetes mellitus. Previous studies have suggested that low i nsulin like growth factor-1 (IGF-1) , low dehydroepiandrosterone sulfate (DHEA-S) and high cortisol are significant correlates of MS. The aim of the present study was to examine the relationships between serum IGF-1, cortisol, DHEA-S and cortisol/ DHEA-S ratio in adult men with MS either diabetic or non-diabetic. Methods : One hundred adult men were enrolled in this study, divided into three groups: group 1 included 30 patients with diabetic MS, group 2 included 30 patients with non-diabetic MS and group 3 included 40 age and sex-matched controls. Anthropometric measurements, Homeostasis model assessment of insulin resistance (HOMA), lipid profile, IGF-1, cortisol, DHEA-S and cortisol/ DHEA-S ratio were assessed. Results : IGF-1 and DHEA-S levels were significantly lower while serum cortisol and cortisol/ DHEA-S ratio were higher in both diabetic MS and non-diabetic MS adult men than healthy con trols; they were also significantly different in the diabetic than in non-diabetic adult men with MS. IGF-1 was significantly and independently correlated with waist circumference, blood pressure, fasting blood glucose, HOMA, cortisol, DHEA-S and cortisol/ DHEA-S ratio. Cortisol/ DHEA-S ratio was significantly and independently correlated with blood pressure, fasting blood glucose, insulin, HOMA, triglyceride, high density lipoprotein cholesterol, cortisol and DHEA-S. Conclusion : IGF-1 concentration is reduced and cortisol/ DHEA-S ratio is increased along with insulin resistance in adult men with diabetic MS. IR may be responsible for multiple multihormonal dysregulation in MS. J Endocrinol Metab. 2011;1(4):188-195 doi: https://doi.org/10.4021/jem43w

Major depressive disorder, generalised anxiety disorder, and their comorbidity: Associations with cortisol in the Vietnam Experience Study

The aim of these analyses was to examine the association of cortisol, dehydroepiandrosterone sulphate (DHEAS), and the cortisol:DHEAS ratio with the diagnoses of major depressive disorder (MDD), generalised anxiety disorder (GAD), and their comorbidity. This was a cross-sectional study. Participants were 4256 Vietnam era US army veterans. From military service files, telephone interviews, and a medical examination, occupational, socio-demographic, and health data were collected. One-year prevalence of MDD and GAD was determined through a diagnostic interview schedule based on the DSM-IV criteria. Contemporary morning fasted cortisol and DHEAS concentrations were determined. Analyses of covariance were run, first with adjustment for age and then additionally adjusting for a range of candidate confounders. In fully adjusted analyses, there was evidence of lower basal cortisol levels in individuals with MDD and co-morbid MDD and GAD than those with GAD alone or no diagnosis. This suggests that MDD and its comorbidity can also be characterised by low as well as high cortisol levels. A profitable line of future research might be to examine cortisol and DHEAS levels in more representative samples including older participants and women with and without MDD, GAD, and other psychiatric diagnoses.

Sugar alters the level of serum insulin and plasma glucose and the serum cortisol:DHEAS ratio in female migraine sufferers

Early work has highlighted that a large percentage of migraineurs may have an altered glucidic methabolis due to carbohydrate-induced hyperinsulinism. The aim of this study was to assess the effect of sucrose on biomarkers of energy metabolism and utilization in migraineous females. A total of 16 participants (8 = Migraine, 8 = Non-migraine) at the mid-point of their menstrual cycle underwent a 15-h fast prior to ingesting 75 g sucrose dissolved in 175 g water. Blood sampling for the assessment of serum insulin, serum cortisol and serum dehydroepiandrosterone sulfate (DHEAS) and plasma glucose was conducted upon arrival at 09:00 h and then at regular 15-min intervals across a 150-min experimental period. The results showed a significant alteration in serum insulin and plasma glucose following sucrose ingestion in the migraine and non-migraine groups. In addition, significant group differences were observed in the level of serum insulin, serum DHEAS, and the cortisol:DHEAS ratio with migraine participants on average recording a higher sucrose-induced serum insulin level and lower DHEAS level and cortisol:DHEAS ratio when group data was compared. It was concluded that while sucrose consumption may potentiate serum insulin in migraineurs this does not result in the development of sucrose-induced hypoglycemia in migraine or non-migraine participants.

Affectionate Communication Received from Spouses Predicts Stress Hormone Levels in Healthy Adults

Recent research on the communication of affection illuminates its implications for mental and physical health. In particular, affectionate communication has been shown to covary with healthy hormonal variation and accelerated recovery from stress. The present study focuses on the association between marital affection and hormonal markers of stress regulation, including cortisol, dehydroepiandrosterone-sulfate (DHEA-S), and their ratio. Twenty healthy adults and spouses provided independent reports of their propensity for verbal, nonverbal, and support-based expressions of affection prior to providing saliva samples that were assayed for cortisol and DHEA-S. As hypothesized, spouses’ reports of verbal, nonverbal, and supportive affection significantly predicted participants’ waking cortisol levels, cortisol change, and cortisol:DHEA-S ratio. Participants’ own reports of affection were predictive of cortisol:DHEA-S ratio for verbal affection behaviors only, and were not predictive of participants’ waking cortisol, cortisol change, or DHEA-S. In addition, spouses’ reports of verbal, nonverbal, and supportive affection predicted participants’ evening cortisol levels. Results illustrate that affectionate communication from one's spouse is related to hormonal stress regulation and suggest the possibility that interventions designed to increase affectionate behavior in romantic relationships may have stress-ameliorating physiological effects.

Menopausal transition: A possible risk factor for brain pathologic events

Background and objective Incidence and prevalence of Alzheimer's disease (AD) are higher in postmenopausal women than in age-matched men. Since at menopause the endocrine system and other biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegedly neuroprotective (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic (e.g. related to glucocorticoid and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders. Subjects and methods Along with this aim, we evaluated the gene expression levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs), interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly playing a key role in the proinflammatory events associated with AD, in a population of 209 healthy subjects (73M, 106F, 20–91-year old) and 85 AD patients (36M, 49F, 65–89-year old). Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells (1) are easily obtainable by a simple blood sampling, (2) express many molecules and multiple receptors which are under the same regulatory mechanisms as those operative in the brain and (3) some of them, e.g. monocytes, share many functions with microglial cells. Results In healthy men all the study parameters were quite stable during lifespan. In women, instead, at menopausal transition, some changes that may predispose to neurodegeneration occurred. In particular, there was (1) an up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol (E 2); (2) an increase of HGRα:HGRβ ratio, indicative of an augmented cortisol activity on HGRα not sufficiently counteracted by the inhibitory HGRβ function; (3) a reduced CD36 expression, directly related to the increased cortisol activity; and (4) an augmented plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of both sexes, the expression of the study parameters was similar to that found in sex- and age-matched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events. Conclusions Menopausal transition is a critical phase of women's life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part, on the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers, such as beta-amyloid deposition.

Do burned-out and work-engaged employees differ in the functioning of the hypothalamic-pituitary-adrenal axis?

The central aim of the present study was to examine differences in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis between 29 burned-out, 33 work-engaged, and 26 healthy reference managers, as identified with the Maslach Burnout Inventory-General Survey and the Utrecht Work Engagement Scale. All of the managers were employed in a large Dutch telecommunications company. Salivary cortisol was sampled on three consecutive workdays and one nonworkday to determine the cortisol awakening response. Salivary dehydroepiandrosterone-sulfate (DHEAS), a cortisol counterbalancing product of the HPA axis, was measured on these days 1 hour after managers awakened. The dexamethasone suppression test was used to investigate the feedback sensitivity of the HPA axis. The morning cortisol levels were higher on the workdays than on the nonworkday, but this effect did not differ between the three groups. The burned-out, work-engaged, and reference groups did not differ in the cortisol and DHEAS levels, the slope of the cortisol awakening response, and the cortisol : DHEAS ratio. The work-engaged group showed a stronger cortisol suppression in response to the dexamethasone suppression test than the other two groups, the finding suggesting higher feedback sensitivity among work-engaged managers. Burned-out and work-engaged managers only differ marginally in HPA-axis functioning.

Adrenocortical function in hospitalised patients with active pulmonary tuberculosis receiving a rifampicin-based regimen—a pilot study

To assess whether adrenocortical function was compromised in patients with active tuberculosis (TB) during the first 5 days of therapy with either a rifampicin-based or ciprofloxacin-based regimen. Patients were randomised into two groups of 10 each. Adrenocortical function was compared in both groups by the measurement of biochemical indices, electrolytes, osmolality and pituitary-adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 mug adrenocorticotropin hormone (ACTH) stimulation tests. Department of Medicine, Johannesburg Hospital. Twenty hospitalised patients who were diagnosed with TB. Respiratory rate, pulse rate and blood pressure were recorded, and urinary sodium and osmolality were measured. Serum ACTH, cortisol, dehydroepiandrosterone- sulphate (DHEA-S) and aldosterone were assayed. None of the patients demonstrated biochemical evidence of overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any biochemical indices, electrolytes, hormones or calculated osmolality. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol/ DHEA-S ratio. In the ciprofloxacin group, cortisol responses to ACTH stimulation on day 1 were not significantly lower than on day 5. In the rifampicin group, cortisol concentrations decreased at each time point on day 5 compared with day 1 (p = 0.001). However, a significantly higher mean incremental rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental cortisol rise of < 250 nmol/l after ACTH stimulation on day 1. Rifampicin did not additionally impair adrenocortical function during the initial period of therapy. The high cortisol/DHEA-S ratio might be of clinical relevance.

Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity

The detrimental effect of stress on the immune response increases with age, though the mechanisms responsible are not fully understood. The physiological response to stress is regulated in part by the adrenocortical system. Adrenal hormones dehydroepiandrosterone sulphate (DHEAS) and cortisol have opposing effects on the innate immune system, DHEAS enhances while cortisol suppresses immunity and the molar ratio of cortisol to DHEAS increases with age. We found that elderly hip fracture patients produced a robust neutrophilia after injury, but circulating neutrophils showed an impaired antibacterial response. We therefore proposed that adrenocortical hormones mediate the heightened immunosuppression seen in the elderly after injury. We examined neutrophil function and adrenocortical hormone levels in elderly (> 65 years) hip fracture patients and age-matched healthy controls. Thirteen out of 35 elderly patients acquired infections following hip fracture. Neutrophil superoxide production was lower in elderly hip fracture patients compared with controls (P < 0.005) and lower in patients who acquired infection following injury compared with those who did not (P < 0.05). Serum cortisol:DHEAS ratio was higher in elderly hip fracture patients (0.56 +/- 0.38) compared with either age-matched controls (0.36 +/- 0.21; P < 0.05) or young fracture patients (0.087 +/- 0.033; P < 0.0001). Moreover, cortisol: DHEAS was increased in elderly patients who succumbed to infection compared with those who did not (0.803 +/- 0.42 vs. 0.467 +/- 0.28; P < 0.02). In vitro cortisol significantly decreased neutrophil superoxide generation (P < 0.05) and this was prevented by coincubation with DHEAS. We propose that increased cortisol:DHEAS ratios may contribute to reduced immunity following physical stress in the elderly.