Association Of Dehydroepiandrosterone Sulfate Research Articles

P433. Association of DHEAS, an Indicator of Adrenarchal Development, With Brain Function During an Inhibitory Control Task in Prepubertal Children

The pubertal transition is associated with increased cognitive control. Adrenarche, the activation of the adrenal androgenic endocrine system, plays an important role in puberty. However, the impact of adrenal androgens, including dehydroepiandrosterone sulfate (DHEAS), on neurodevelopment has been difficult to disambiguate from that of gonadal hormones. To investigate adrenarche-specific changes in prepubertal brain function, we studied typically-developing children who were carefully documented to be prepubertal, and thus had no puberty-related increases in gonadal hormones, to examine the impact of DHEAS on brain activation associated with inhibitory control.

Association of dehydroepiandrosterone sulfate, birth size, adiposity and cardiometabolic risk factors in 7-year-old children.

Low birth size (BS) and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in childhood, insulin acting as a mediator, despite contradictory findings. To further explore these issues, we studied the associations between DHEAS, BS, adiposity, maternal characteristics, and cardiometabolic risk indicators, in participants of Generation XXI, a population-based birth cohort. A sample of 700 children (mean age 7.1 yr) was randomly selected. Data on maternal characteristics, BS, body mass index (BMI), waist-to-height ratio, body fat (dual-energy X-ray absorptiometry), insulin, lipid profile, and high-sensitivity C-reactive protein were analyzed in relation to DHEAS. DHEAS was negatively associated with BS and positively associated with all adiposity indicators, with no sex differences. DHEAS was positively associated with insulinemia independently of the child's BS or BMI. No significant association was found between DHEAS, maternal characteristics, lipid profile, or high-sensitivity C-reactive protein. Including insulin in the model did not affect the association between BS and DHEAS but reduced the magnitude of the BMI effect by 24% for boys and 30% for girls. Higher DHEAS levels at 7 years old were associated with lower BS and higher adiposity. DHEAS levels were positively associated with insulinemia independently of BS or BMI. Low birth weight and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in prepuberty. Insulin has been suggested as a mediator, despite previous studies failing to show an association between DHEAS and insulin levels. In a randomly selected population of 700 7-year-old children from the Generation XXI birth cohort, higher DHEAS levels were associated with a lower birth size and higher adiposity, with no sex differences. DHEAS was positively related to insulinemia independently of the child's birth size or body mass index. No association was found between DHEAS and other cardiometabolic risk factors.

Protective Role of DHEAS in Age-related Changes in Bone Mass and Fracture Risk.

Dehydroepiandrosterone sulfate (DHEAS) from the adrenal cortex substantially decreases with age, which may accelerate osteoporosis. However, the association of DHEAS with bone mineral density (BMD) and fracture is inconclusive. We conducted a Mendelian randomization (MR) analysis to investigate the role of DHEAS in age-related changes in BMD and fracture risk. Single nucleotide polymorphisms (SNPs) associated with serum DHEAS concentrations were used as instrumental variables (4 SNPs for main analysis; 4 SNPs for men and 5 SNPs for women in sex-related analysis). Summary statistics were obtained from relevant genome-wide association studies. A log-transformed unit (µmol/L) increase in serum DHEAS concentrations was associated with an SD increase in estimated BMD at the heel (estimate, 0.120; 95% CI, 0.081-0.158; P = 9 × 10-10), and decreased fracture (odds ratio, 0.989; 95% CI, 0.981-0.996; P = 0.005), consistent with dual-energy X-ray absorptiometry-derived BMD at the femoral neck and lumbar spine. Their associations remained even after adjusting for height, body mass index, testosterone, estradiol, sex hormone-binding globulin, and insulin-like growth factor 1. The association of DHEAS with fracture remained after adjusting for falls, grip strength, and physical activity but was attenuated after adjusting for BMD. The MR-Bayesian model averaging analysis showed BMD was the top mediating factor for association of DHEAS with fracture. The association between DHEAS and BMD was observed in men but not in women. DHEAS was associated with increased BMD and decreased fracture. DHEAS may play a protective role in decreasing fracture risk, mainly by increasing bone mass.

Association of DHEA, DHEAS, and cortisol with childhood trauma exposure and post-traumatic stress disorder

There has been a great deal of interest in the role of the neuroendocrine hormones of the hypothalamic-pituitary-adrenal (HPA) axis in the expression of stress-related psychopathology such as post-traumatic stress disorder (PTSD). This investigation examined the association of PTSD and childhood maltreatment with three key HPA axis hormones: cortisol, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). Regression analyses were undertaken on a sample of 43 participants with and 57 participants without PTSD. Results demonstrated that after controlling for age, sex, and PTSD status, exposure to childhood maltreatment was significantly associated with cortisol secretion [F(4,95)=11.68, ΔR(2)=0.11, P=0.0009] and cortisol/DHEA ratio [F(4,95)=6.20, ΔR(2)=0.05, P=0.01]. PTSD status was not associated with any of these neuroendocrine variables. Findings are discussed in the context of the complexity of the relationship of these neuroendocrine variables with trauma exposure and trauma-related psychopathology. It is suggested that DHEA(S) or cortisol/DHEA(S) ratios may not be biomarkers of specific forms of psychopathology per se, but that, instead, the severity and developmental timing of trauma may set the HPA axis in ways that are reflected in interactions among these neuroendocrine hormones. In adulthood, these HPA axis hormones may continue to be dynamically affected by personal and environmental resources.

Higher Serum Dehydroepiandrosterone Sulfate Levels Are Protectively Associated with Depressive Symptoms in Men, But Not in Women: A Community-Based Cohort Study of Older Japanese

Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese. A community-based cohort study. Kurabuchi Town, Gunma Prefecture, Japan. A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ2 = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women.

Association of dehydroepiandrosterone sulfate, serum lipids, C-reactive protein and body mass index with age-related macular degeneration

The present study was designed to evaluate the associations between exudative age-related macular degeneration (AMD) and the serum concentrations of C-reactive protein (CRP), dehydroepiandrosterone sulfate (DHEAS), and lipids as well as the relationship between exudative AMD and body mass index (BMI). This cross-sectional study included of 141 healthy control subjects (70 males and 71 females with a mean age of 71.01 ± 3.84 years) and 142 exudative AMD patients (70 males and 72 females with a mean age of 70.92 ± 3.60 years). BMI and the serum concentrations of CRP, DHEAS, and lipids were measured in both groups. The data were statistically analysed using the Mann-Whitney U test, Chi squared test, independent sample t test, Cramer's V, point biserial correlation and logistic regression analysis. BMI values and serum concentrations of CRP, total cholesterol, and low-density lipoprotein (LDL) cholesterol were significantly higher in exudative AMD patients compared with normal controls (p values were 0.001, <0.001, 0.005 and <0.001, respectively). The serum concentrations of DHEAS were not significantly different between the controls and the exudative AMD patients for the subgroups of either gender (p values in males and females were 0.785 and 0.159, respectively). A logistic regression analysis revealed that the BMI and serum concentration of CRP moderately contributed to the predictive ability of the model (odds ratios were 1.205 and 1.179, respectively). Elevated total cholesterol concentrations and LDL cholesterol concentrations, BMI values and serum concentrations of CRP were associated with exudative AMD. However, no association between the serum DHEAS concentration and exudative AMD was established.

Serum Dehydroepiandrosterone Sulfate and Adverse Health Outcomes in Older Men and Women

Low serum dehydroepiandrosterone sulfate (DHEAS) is common in older persons with poor health. The geriatric syndrome of physical frailty is associated with a higher risk of developing fatal and nonfatal health outcomes. However, the association of DHEAS with frailty is uncertain. This study investigated the association of serum DHEAS with frailty and its related adverse outcomes in 416 men and 504 women aged ≥65 years from an Italian prospective population-based cohort study. At baseline, frailty status was defined according to the physical phenotype, and serum DHEAS was measured in a fasting venous blood sample. After 4 years, subjects were reassessed for incident frailty and occurrence of nonfatal frailty-related outcomes (hospital admission, nursing home placement, disability, falls, and fractures). All-cause mortality after 8 years was also recorded. Incident frailty was inversely associated with baseline log-transformed DHEAS in men (odds ratio [OR]=0.35, 95% confidence interval [CI] 0.14-0.88, p=0.026) but not in women. Independent of baseline frailty status, women in the lowest DHEAS quartile compared to the upper three quartiles had a higher risk of hospital admission (OR=0.44, 95% CI 0.21-0.91, p=0.027) and nursing home placement (OR=0.27, 95% CI 0.08-0.95, p=0.041). Baseline log-transformed serum DHEAS was also inversely associated with mortality risk, but limited to women with concurrent frailty (hazard ratio [HR]=0.27, 95% CI 0.11-0.68, p=0.005) or preexisting major diseases (HR=0.57, 95% CI 0.33-0.98, p=0.041). These findings suggest that DHEAS is associated with incident frailty in older men and with fatal and nonfatal frailty-related adverse outcomes in older women.

Association of dehydroepiandrosterone sulfate and testosterone deficiency with bone turnover in men with inflammatory bowel disease.

We investigated the coexistence of dehydroepiandrosterone sulfate (DHEAS) and testosterone deficiency in men with inflammatory bowel disease (IBD) and their relationship with bone homeostasis. In 45 men with IBD (25 with ulcerative colitis, 20 with Crohn's disease) the testosterone and DHEAS levels were examined in relationship to bone mineral density, osteocalcin levels, and urinary deoxypyridinoline excretions. We detected osteoporosis in 10 and osteopenia in 22 patients at the lumbar spine and/or femoral neck. Lower testosterone levels were measured in 20. Lower DHEAS levels were present in 23 patients; these had higher deoxypyridinoline excretion and lower lumbar spine and femoral neck BMD T scores than patients with normal DHEAS. DHEAS and BMD were correlated at the lumbar spine and the femoral neck. Associations remained significant after adjustment for age, weight, steroid use, and inflammatory activity. No independent effect of testosterone deficiency was detected on bone parameters. DHEAS deficiency may contribute to the bone loss of men with IBD. This putative action of DHEAS on bone turnover is contrary to the common effect of testosterone deficiency and steroid therapy.

Association of dehydroepiandrosterone sulfate with serum HDL-cholesterol concentrations in post-menopausal Japanese women

Objectives: Positive association between serum dehydroepiandrosterone sulfate (DHEAS) and high-density lipoprotein (HDL) cholesterol has been observed in men but not women. We aimed to examine the cross-sectional relationships of DHEAS, estradiol (E 2), and sex hormone-binding globulin (SHBG) to serum lipid concentrations in post-menopausal Japanese women. Methods: A total of 56 post-menopausal Japanese women were derived from female residents in Takayama City in Japan. The information on body size, disease history, reproductive history, diet, and physical activity were obtained by a self-administered questionnaire. Results: DHEAS was significantly and positively correlated with HDL-cholesterol after controlling for age and body mass index (BMI) ( r=0.28). There was no correlation between DHEAS and total-cholesterol ( r=−0.02). E 2 was not significantly correlated with total- and HDL-cholesterol and triglyceride. However, SHBG-unbound E 2 was significantly positively correlated with HDL-cholesterol ( r=0.34) and negatively correlated with triglyceride ( r=−0.27) after controlling for age and BMI. SHBG was negatively correlated with triglyceride, although the correlation was not statistically significant ( r=−0.22). Conclusion: These data suggest favorable effect of DHEAS as well as E 2 and SHBG on lipid profile in Japanese post-menopausal women.

Dehydroepiandrosterone, dehydroepiandrosterone sulfate, obesity, waist-hip ratio, and noninsulin-dependent diabetes in postmenopausal women: the Rancho Bernardo Study.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels were determined in morning specimens from 659 fasting postmenopausal women who were not using estrogen therapy or antidiabetic medication. All women had concurrent oral glucose tolerance tests and measurements of body mass index (BMI) and waist-hip ratio (WHR). DHEA levels were weakly and inversely associated with BMI but not with WHR or glucose tolerance status. DHEAS levels were not associated with BMI but were positively associated with WHR, diabetes, and impaired glucose tolerance. In analyses adjusted for or stratified by WHR, the DHEAS association with abnormal carbohydrate tolerance was reduced but still independent of fat distribution. Because this was a cross-sectional study, it was not possible to determine whether DHEAS levels were raised by central obesity or vice versa. At a minimum, these data strongly suggest that the positive association of DHEAS with both central obesity and abnormal glucose tolerance does not support the thesis that DHEAS protect against diabetes or obesity in older women as had been suggested by animal studies.

Dehydroepiandrosterone sulfate, incidence of myocardial infarction, and extent of atherosclerosis in men.

Antiatherogenic effects of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) have been suspected for more than 30 years, yet the available evidence to support or refute such effects in humans is inconclusive. The hypothesis has not been adequately tested in large-scale epidemiological studies. The present study used a cohort of men initially free of clinically detectable coronary heart disease, stroke, and cancer to compare DHEAS levels measured in sera obtained in 1968-1971 between 238 cases who had definite coronary heart disease during the subsequent 18 years and 476 age-matched controls who survived the follow-up period and remained free of clinically detectable coronary heart disease. In a separate study, the relation of DHEAS levels to extent of atherosclerosis was examined among 82 cohort men who died during the follow-up period and had protocol autopsies. Age-adjusted DHEAS levels were lower among fatal cases of coronary heart disease than among controls (94.7 versus 106.9 micrograms/dl, respectively; p < 0.05). After adjustment for eight coronary risk factors, the odds ratio for fatal coronary heart disease comparing a 100-micrograms/dl difference in DHEAS level was 0.46 (95% confidence intervals, 0.19-1.07). In contrast, age-adjusted DHEAS levels did not significantly differ between nonfatal cases of myocardial infarction and controls (107.2 versus 106.9 micrograms/dl, respectively). Furthermore, DHEAS levels were not related to extent of atherosclerosis at autopsy. These findings do not support a role of DHEAS in the development of nonfatal myocardial infarction or the progression of atherosclerosis. The association of DHEAS with fatal coronary heart disease and possibly with death from all causes merits further investigation. These findings suggest continued skepticism that DHEAS has an important role in coronary disease etiology or prevention.