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PloS One 2014Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and...
Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load) or 1-back (working memory load) task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min. Under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to less processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level.
Topics: Adult; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Electrophysiological Phenomena; Female; Humans; Hydrocortisone; Memory, Short-Term; Young Adult
PubMed: 25105970
DOI: 10.1371/journal.pone.0104869 -
Journal of Lipid Research Dec 2004A new sample preparation method coupled to GC-MS analysis was developed and validated for quantification of sulfate esters of pregnenolone (PREG-S) and...
A new sample preparation method coupled to GC-MS analysis was developed and validated for quantification of sulfate esters of pregnenolone (PREG-S) and dehydroepiandrosterone (DHEA-S) in rat brain. Using a solid-phase extraction recycling protocol, the results show that little or no PREG-S and DHEA-S (<1 pmol/g) is present in rat and mouse brain. These data are in agreement with studies in which steroid sulfates were analyzed without deconjugation. We suggest that the discrepancies between analyses with and without deconjugation are caused by internal contamination of brain extract fractions, supposed to contain steroid sulfates, by lipoidal forms of PREG and DHEA (L-PREG and L-DHEA, respectively). These derivatives can be acylated very efficiently with heptafluorobutyric anhydride and triethylamine, and their levels in rodent brain (approximately 1 nmol/g) are much higher than those of their unconjugated counterparts. They are distinct from fatty acid esters, and preliminary data do not favor structures such as sulfolipids or sterol peroxides. Noncovalent interactions between steroids and proteolipidic elements, such as lipoproteins, could account for some experimental data. Given their abundance in rodent brain, the structural characterization and biological functions of L-PREG and L-DHEA in the central nervous system merit considerable attention.
Topics: Animals; Brain; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Gas Chromatography-Mass Spectrometry; Male; Pregnenolone; Rats; Rats, Sprague-Dawley
PubMed: 15342680
DOI: 10.1194/jlr.M400244-JLR200 -
Archives of Disease in Childhood Oct 2021There is increasing evidence that patterns of pubertal maturation are associated with different patterns of health risk. This study aimed to explore the associations... (Observational Study)
Observational Study
BACKGROUND
There is increasing evidence that patterns of pubertal maturation are associated with different patterns of health risk. This study aimed to explore the associations between anthropometric measures and salivary androgen concentrations in pre-adolescent children.
METHODS
We analysed a stratified random sample (N=1151) of pupils aged 8-9 years old from 43 primary schools in Melbourne, Australia from the Childhood to Adolescence Transition Study. Saliva samples were assayed for dehydroepiandrosterone (DHEA), DHEA-sulfate and testosterone. Anthropometric measures included height, weight, body mass index (BMI) and waist circumference. Associations between (1) anthropometric measures and each androgen, and (2) hormone status with obesity and parental report of pubertal development were investigated using linear regression modelling with general estimating equations.
RESULTS
Greater height, weight, BMI and waist circumference were positively associated with higher androgen concentrations, after adjusting for sex and socioeconomic status. Being overweight or obese was associated with higher testosterone and DHEA concentrations compared with the normal BMI category. Those who were obese were more likely (OR=2.7, 95% CI 1.61 to 4.43, p<0.001) to be in the top tertile of age-adjusted androgen status in both sexes.
CONCLUSION
This study provides clear evidence for an association between obesity and higher androgen levels in mid-childhood. The adrenal transition may be a critical time period for weight management intervention strategies in order to manage the risk for metabolic problems in later life for high-risk individuals.
Topics: Adrenarche; Biomarkers; Body Height; Body Mass Index; Body Size; Body Weight; Child; Child Development; Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Obesity; Puberty; Saliva; Testosterone; Waist Circumference
PubMed: 33931399
DOI: 10.1136/archdischild-2020-319341 -
Journal of the American College of... Nov 1990Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with...
Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis.
Topics: Adult; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sex Factors; Stroke Volume
PubMed: 2146310
DOI: 10.1016/s0735-1097(10)80334-1 -
Aging Cell Aug 2004Evolutionary pressure has selected individuals with traits that allow them to survive to reproduction, without consideration of the consequences for the post-child... (Review)
Review
Evolutionary pressure has selected individuals with traits that allow them to survive to reproduction, without consideration of the consequences for the post-child rearing years and old age. In the 21st century, society is populated increasingly by the elderly and with the falling birth rate and improved health care this trend is set to continue for the foreseeable future. To minimize the potential burden on health services one would hope that 'growing old gracefully' should also mean 'growing old healthily'. However, for too many the aging process is accompanied by increasing physical and mental frailty producing an elevated risk of physical and psychological stress in old age. Stress is a potent modulator of immune function, which in youth can be compensated for by the presence of an optimal immune response. In the elderly the immune response is blunted as a result of the decline in several components of the immune system (immune senescence) and a shifting to a chronic pro-inflammatory status (the so-called 'inflamm-aging' effect). We discuss here what is known of the effects of both stress and aging upon the innate immune system, focusing in particular upon the age-related alterations in the hypopituitary-adrenal axis. We propose a double hit model for age and stress in which the age-related increase in the cortisol/sulphated dehydroepiandrosterone ratio synergizes with elevated cortisol during stress to reduce immunity in the elderly significantly.
Topics: Adrenal Cortex; Adrenal Medulla; Aged; Aging; Animals; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Glucocorticoids; Humans; Immunity, Innate; Neurosecretory Systems; Stress, Physiological; Stress, Psychological; Wounds and Injuries
PubMed: 15268748
DOI: 10.1111/j.1474-9728.2004.00103.x -
The European Respiratory Journal Jun 2018
Topics: Connective Tissue Diseases; Dehydroepiandrosterone; Estrogens; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary
PubMed: 29954927
DOI: 10.1183/13993003.01058-2018 -
The European Respiratory Journal Jun 2018
Topics: Connective Tissue Diseases; Dehydroepiandrosterone; Female; Heart Diseases; Humans; Hypertension, Pulmonary; Peptidyl-Dipeptidase A
PubMed: 29929959
DOI: 10.1183/13993003.00848-2018 -
Hormones (Athens, Greece) Sep 2022Dehydroepiandrosterone sulfate (DHEAS) is observed to be decreased in sepsis and inflammatory conditions. In the present study, we assessed the levels of DHEAS and...
PURPOSE
Dehydroepiandrosterone sulfate (DHEAS) is observed to be decreased in sepsis and inflammatory conditions. In the present study, we assessed the levels of DHEAS and cortisol and the DHEAS/cortisol ratio and their association with inflammatory markers in patients with COVID-19.
METHODS
The study recruited 76 RT-PCR-positive COVID-19-positive patients and 79 healthy controls. The blood samples were collected and were analyzed for cortisol and DHEAS.
RESULTS
We observed decreased levels of DHEAS and DHEAS/cortisol ratio and increased levels of cortisol in cases when compared with controls. DHEAS and DHEAS/cortisol ratio showed a decreasing trend with the increase in disease severity.
CONCLUSION
The present study is the first of its kind comparing DHEAS levels and DHEAS/cortisol ratio in COVID-19 patients and control subjects. DHEAS, with its inhibitory effect on IL6 and activation of Tregs, may play a crucial role in immune defense mechanisms against COVID-19.
Topics: COVID-19; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans; Hydrocortisone; Pilot Projects
PubMed: 35804262
DOI: 10.1007/s42000-022-00382-x -
The Cochrane Database of Systematic... Nov 2015Infertility is a condition affecting 10% to 15% of couples of reproductive age. It is generally defined as "the failure to achieve a clinical pregnancy after 12 months... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infertility is a condition affecting 10% to 15% of couples of reproductive age. It is generally defined as "the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse". The treatment of infertility may involve manipulation of gametes or of the embryos themselves. These techniques are together known as assisted reproductive technology (ART). Practitioners are constantly seeking alternative or adjunct treatments, or both, in the hope that they may improve the outcome of assisted reproductive techniques. This Cochrane review focusses on the adjunct use of synthetic versions of two naturally-produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction.DHEA and its derivative testosterone are steroid hormones proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation, leading to greater oocyte yields and, in turn, increased chance of pregnancy.
OBJECTIVES
To assess the effectiveness and safety of DHEA and testosterone as pre- or co-treatments in subfertile women undergoing assisted reproduction.
SEARCH METHODS
We searched the following electronic databases, trial registers and websites up to 12 March 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the Web of Science, PubMed and OpenSIGLE. We also carried out handsearches. There were no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing DHEA or testosterone as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted relevant data and assessed them for risk of bias. We pooled studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. There were no data for the intended groupings by dose, mode of delivery or after one/more than one cycle.We assessed the overall quality of the evidence for the main findings using the GRADE working group methods.
MAIN RESULTS
We included 17 RCTs with a total of 1496 participants. Apart from two trials, the trial participants were women identified as 'poor responders' to standard IVF protocols. The included trials compared either testosterone or DHEA treatment with placebo or no treatment.When DHEA was compared with placebo or no treatment, pre-treatment with DHEA was associated with higher rates of live birth or ongoing pregnancy (OR 1.88, 95% CI 1.30 to 2.71; eight RCTs, N = 878, I² statistic = 27%, moderate quality evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 15% and 26%. However, in a sensitivity analysis removing trials at high risk of performance bias, the effect size was reduced and no longer reached significance (OR 1.50, 95% CI 0.88 to 2.56; five RCTs, N = 306, I² statistic = 43%). There was no evidence of a difference in miscarriage rates (OR 0.58, 95% CI 0.29 to 1.17; eight RCTs, N = 950, I² statistic = 0%, moderate quality evidence). Multiple pregnancy data were available for five trials, with one multiple pregnancy in the DHEA group of one trial (OR 3.23, 95% CI 0.13 to 81.01; five RCTs, N = 267, very low quality evidence).When testosterone was compared with placebo or no treatment we found that pre-treatment with testosterone was associated with higher live birth rates (OR 2.60, 95% CI 1.30 to 5.20; four RCTs, N = 345, I² statistic = 0%, moderate evidence). This suggests that in women with an 8% chance of live birth with placebo or no treatment, the live birth rate in women using testosterone will be between 10% and 32%. On removal of studies at high risk of performance bias in a sensitivity analysis, the remaining study showed no evidence of a difference between the groups (OR 2.00, 95% CI 0.17 to 23.49; one RCT, N = 53). There was no evidence of a difference in miscarriage rates (OR 2.04, 95% CI 0.58 to 7.13; four RCTs, N = 345, I² = 0%, low quality evidence). Multiple pregnancy data were available for three trials, with four events in the testosterone group and one in the placebo/no treatment group (OR 3.09, 95% CI 0.48 to 19.98; three RCTs, N = 292, very low quality evidence).One study compared testosterone with estradiol and reported no evidence of a difference in live birth rates (OR 2.06, 95% CI 0.43 to 9.87; one RCT, N = 46, very low quality evidence) or miscarriage rates (OR 0.70, 95% CI 0.11 to 4.64; one RCT, N = 46, very low quality evidence).The quality of the evidence was moderate, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in some trials.
AUTHORS' CONCLUSIONS
In women identified as poor responders undergoing ART, pre-treatment with DHEA or testosterone may be associated with improved live birth rates. The overall quality of the evidence is moderate. There is insufficient evidence to draw any conclusions about the safety of either androgen. Definitive conclusions regarding the clinical role of either androgen awaits evidence from further well-designed studies.
Topics: Abortion, Spontaneous; Adult; Androgens; Dehydroepiandrosterone; Estradiol; Female; Humans; Infertility, Female; Live Birth; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Testosterone
PubMed: 26608695
DOI: 10.1002/14651858.CD009749.pub2 -
Alcohol (Fayetteville, N.Y.) Mar 2015The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug... (Comparative Study)
Comparative Study
The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under a FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or acamprosate under that schedule. Experiment 2 showed that ethanol intake was relatively independent of the interval of reinforcement in the food-maintained component, and Experiment 3 showed that naltrexone was the most effective drug at the doses tested when the interval for food reinforcement was low and maintained under a variable-interval schedule.
Topics: Acamprosate; Alcohol Drinking; Alcoholism; Animals; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Eating; Ethanol; Male; Naltrexone; Pregnanolone; Rats; Rats, Long-Evans; Self Administration; Taurine
PubMed: 25620274
DOI: 10.1016/j.alcohol.2014.07.024