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Examination of the variability of stress biomarkers among people living with dementia and their family caregivers can provide evidence of stress reactions and corresponding self-regulation capacities, but no such research has been conducted to date. The aim of this study was to examine day-to-day variability patterns of salivary biomarkers in dyads of people living with dementia and their family caregivers and to investigate differences in variability patterns between music intervention and control groups. This study involved secondary analysis of data collected during a two-group, non-randomized open trial examining the effects of an 8-week music intervention on physiological stress markers. A total of 5791 salivary samples from 34 dyads were used to analyze the variability of morning and evening cortisol and of morning dehydroepiandrosterone sulfate (DHEA-S). The variability indices employed were the intra- and inter-individual standard deviation, coefficient of variation, and intra-class correlation coefficient. We found that family caregivers in the music intervention group had significantly greater coefficients of variation for all three biomarker endpoints than those in the control group. Our findings provide evidence that stress biomarkers in family caregivers with functional self-regulation capacities may be more likely to respond to music intervention. However, stress biomarkers in people living with dementia may not be responsive to music intervention, possibly due to their dysfunctional self-regulation capacities. Future stress biomarker studies involving dyads of people living with dementia and family caregivers should consider biomarker variability patterns in determining the effectiveness of behavioral interventions. [ABSTRACT FROM AUTHOR]

Introduction: Effective treatment of papillary thyroid carcinoma (PTC) is total thyroidectomy which is followed by radioactive iodine therapy (RIT) to ablate pathologic thyroid remnants and treat metastatic tumors. However, there are concerns about possible side effects of RIT on different hormones that are important in different aspects including the immune defense system, cardiovascular system, pregnancy, and reproductive health. This study aimed to assess the impact of RIT on reliable hormonal markers levels including dehydroepiandrosterone sulfate (DHEA-S) and dihydrotestosterone (DHT) in men as well as progesterone and prolactin in women undergoing treatment for PTC. Material and Methods: 60 patients (30 male and 30 female) who underwent total thyroidectomy due to PTC and aged 25-50 were selected using convenient sampling. Blood samples were collected from each PTC patient before and 60 days after RIT. DHEA-S, DHT, progesterone, and prolactin concentrations were quantified using an enzyme-linked immunosorbent assay kit. The paired t-test was conducted to compare hormonal marker levels before and after RIT. Results: Our data revealed significant decreases in DHEA-S and DHT levels between pre- and post-RIT (P< 0.001). In contrast, progesterone and prolactin levels increased significantly after RIT (P< 0.001). Conclusion: The levels of DHEA-S, DHT, progesterone, and prolactin, which reflect testicular and ovarian reserves, were found to change after RIT. The levels of DHEA-S, DHT, progesterone, and prolactin, which reflect testicular and ovarian reserves, were found to change 60 days after RIT. Despite its benefits in treating PTC, RIT can have serious adverse effects including changes in the serum levels of sexual hormones. [ABSTRACT FROM AUTHOR]

Human ATP-binding cassette transporter C11 (ABCC11) is a membrane protein exhibiting ATP-dependent transport activity for a variety of lipophilic anions including endogenous substances and xenobiotics such as anti-cancer agents. Accumulating evidence indicates that ABCC11 wild type is responsible for the high-secretion phenotypes in human apocrine glands including wet type of earwax and the risk of axillary osmidrosis. Also, a less-functional variant of ABCC11 was reportedly associated with a risk for drug-induced toxicity in humans. Thus, functional change in ABCC11 may affect individual's constitution and drug toxicity, which led us to reason that functional validation of genetic variations in ABCC11 should be of importance. Therefore, in addition to p.G180R (a well-characterized non-functional variant of ABCC11), we studied cellular expression and function of 10 variants of ABCC11. In this study, ABCC11 function was evaluated as an ATP-dependent transport of radio labeled-dehydroepiandrosterone sulfate using ABCC11-expressing plasma membrane vesicles. Except for p.G180R, other 10 variants were maturated as an N-linked glycoprotein and expressed on the plasma membrane. We found that six variants impaired the net cellular function of ABCC11. Among them, p.R630W was most influential. Including this identification of a significantly-dysfunctional variant, our findings will extend our understanding of genetic variations and biochemical features of ABCC11 protein. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether ascorbic acid (AA) supplementation can lower plasma levels of Cortisol and dehydroepiandrosterone‐sulphate (DHEA‐S) in patients diagnosed with functional hypercortisolemia due to unspecified chronic stress. Study includes data from 69 female with elevations in the cortisol and DHEA‐S levels. Duration of follow‐up was 2 months. Patients were divided into 3 groups. Group I included patients 23 with elevated cortisol, Group II—patients 24 with elevated levels of both hormones, Group III‐ patients 22 with normal cortisol and increased DHEA‐S. Each group was randomly divided into two subgroups. The first subgroup was prescribed 1000 mg daily oral dose of AA. The diet of the second subgroup were left unaltered. All patients have their hormones levels re‐examined 2 months later. After 2 months of AA supplementation the mean levels of elevated plasma cortisol and DHEA‐S decreased. In Group I the level of cortisol fell from 780 ± 57–446 ± 26 nmol/L, p = 0.000065 in Group II from 657 ± 47–515 ± 29 nmol/L, p = 0.005. The elevated levels of DHEA‐S have also declined in patients from AA‐treated subgroups (from 13.9 ± 1.6–9.9 ± 1.2, p = 0.0007 in Group II, and from 12.8 ± 1.0–7.8 ± 1.4, p = 0.003 in Group III). In untreated subgroups changes in hormone levels were insignificant. The study shows that female patients with functional hypercortisolemia or elevated levels of DHEA‐S can be treated with AA to bring level of these hormones closer to a normal range. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between sex hormones and the risk of pulmonary fibrosis by conducting a meta-analysis of previously published studies. Methods: We executed a comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases to locate pertinent studies published up to April 2024. We included studies that reported the association between sex hormones and the risk of pulmonary fibrosis. Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of 10 articles, encompassing 1371 patients, were finally incorporated in this meta-analysis. Based on the evaluation of the included studies, it was observed that the levels of dehydroepiandrosterone sulfate (DHEA-S) (pooled SMD: −0.72, 95% CI: −1.21 to −0.24, p < 0.001), testosterone (pooled SMD: −1.25, CI: −2.39 and −0.11, p < 0.001) and estrogen (pooled SMD: −0.56, 95% CI: −0.96 to −0.15, p < 0.001) were significantly lower in patients with pulmonary fibrosis, whereas the levels of luteinizing hormone (LH) remained unaffected. Publication bias was ruled out through funnel plots. Conclusion: This meta-analysis indicates that reduced levels of DHEA-S, testosterone, estrogen may serve as potential risk factors for pulmonary fibrosis. There is a pressing need for additional studies to confirm this association and explore the underlying biological mechanisms. Clinicians should recognize the potential influence of sex hormones in the etiology of pulmonary fibrosis and consider this aspect during the patient management process. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have demonstrated that interleukin-6 (IL-6) and serum dehydroepiandrosterone sulfate levels are negatively correlated. Low DHEA-S levels may be associated with severe disease and clinically ailing patients in the context of infectious diseases. Individuals infected with Coronavirus disease who exhibit elevated levels of IL-6 may undergo a cytokine storm, which can result in severe manifestations and a dismal prognosis. Objectives: To examine the relationship between DHEA-S and Il-6 in patients exhibiting severe manifestations of COVID-19. Subjects and Methods: A case-control investigation with 79 patients, ranging in age from 36 to 74 years, who were admitted to the hospital due to severe COVID-19 disease. A control group of 72 ostensibly healthy individuals was also included in the study. Using the ELISA method, the concentrations of IL-6 and DHEA-S in the serum of both groups were determined. The statistical analyses involved the application of the Pearson correlation coefficient and the T-test. None of the authors present any conflicts of interest. Results: With a Pearson correlation coefficient (r) of -0.8349, the study revealed a highly significant negative correlation (P < 0.0001) between the mean IL-6 level (64.369 pg/ml ± 2.6237) and the mean DHEA-S level (1.2728 ng/ml ± 1.7005) in the study group. An exceptionally significant statistical disparity was also identified when IL-6 and DHEA-S levels were compared between the study and control groups. Conclusions: In severely infected COVID-19 patients inverse correlation between the levels of IL-6 and DHEA-S indicates that DHEA-S deficiency may play a role in cytokine storm formation for these patients.

Subclinical Cushing syndrome is a condition of mild autonomous cortisol excess (MACE) that lacks typical features of Cushing syndrome but is associated with many complications. It represents a common hormonal dysfunction among patients with adrenal incidentaloma (AI), defined as unexpected masses or lesions found in the adrenal glands during radiological examinations of the chest or abdomen unrelated to adrenal gland assessment. The study evaluated the accuracy of dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone sulfate ratio (calculated by dividing the DHEA-S value by the age and sex-adjusted normal range of DHEA-S) in detecting MACE in AI patients. A cross-sectional study was conducted from April 2021 to July 2022 at the Faiha Specialized Diabetes, Endocrine, and Metabolism Centre (FDEMC) in Basrah, southern Iraq, involving 38 AI patients. Comprehensive laboratory and radiological evaluations were performed, including tests for adrenocorticotropic hormone (ACTH), renin, aldosterone, aldosterone/renin ratio (ARR), metanephrine, normetanephrine, cortisol, DHEA-S, and the 1-mg overnight dexamethasone suppression test (1-mg ONDST). Among the AI patients, 14% had MACE. Both DHEA-S ≤75 µg/ dL and a DHEA-S ratio ≤1.7 exhibited a sensitivity of 80% each, with specificities of 73.3% and 76.6%, respectively, in diagnosing MACE in individuals aged ≤65 years. The negative predictive values were 95.7% and 95.8%, respectively. Low DHEA-S and DHEA-S ratio had high sensitivity and specificity in predicting MACE among AI patients aged ≤65 years, with strong negative predictive value. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa. Design/Methods: We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model. Results: We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa. Conclusions: Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome. [ABSTRACT FROM AUTHOR]

Background: Stress-related biomarkers have the potential to provide objective measures of whether interventions directed at people with dementia (PWD) and their family caregivers (FCG) are successful. The use of such biomarkers has been limited by logistical barriers to sample collection. Objective: Explore saliva concentration of steroid hormones in dementia care dyads during a music intervention. Methods: Consecutive PWD attending a memory evaluation center and their FCG were allocated to either an intervention-with-music or a non-intervention control group. All were living at home. Stress biomarkers, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) samples were collected by the PWD and their FCG, in the morning and evening, 5 days a week, for 8 consecutive weeks. Biomarker concentrations of the intervention and the control groups were compared at week 8, in an intention-to-treat approach with adjustment for baseline value. Results: Twenty-four PWD in the intervention group and 10 in the control group, and their FCG were included in the analyses. The mean number of morning saliva collections was similar in the intervention and the control groups, ranging from 4.3 to 4.9 per participant weekly during the first 7 weeks, declining to 3.3 during week 8. Median log morning cortisol (pg/mL) among caregivers was lower in the intervention group than in the control group (8.09 vs. 8.57, P = 0.0133). Conclusion: This study demonstrates that music intervention was associated with lower morning saliva cortisol concentrations for FCGs.

Background: Infertility is the inability to get pregnant after engaging in unprotected sexual activity for at least a year. Obesity and overweight are terms used to describe abnormal or excessive weight growth that is harmful to one’s health. Objectives: The aim of this study was to measure the androgen receptor (AR), total and free testosterone, and dehydroepiandrosterone sulfates (DHEA-S) levels in the serum of Iraqi women who were having trouble getting pregnant and study the change of these parameters in the case of obesity and infertility. Materials and Methods: The case–control group was made up of 45 additional, presumably healthy women, whereas the sick group was made up of 45 obese infertile women. A study was carried out in the Babylon teaching hospital for maternity and children in Hilla city and private clinics from July to January 2022. An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the serum concentrations of DHEA-S, total testosterone, and free testosterone (ELISA). SPSS software was used to conduct the statistical analysis. Results: A considerable drop in total testosterone and AR levels, infertile women exhibited significantly greater serum levels of free testosterone and DHEA-S than the control group (P > 0.05). Conclusion: Infertile women had considerably lower serum levels of total testosterone and ARs and significantly higher serum levels of free testosterone and DHEA-S. On the basis of the results of this investigation, obesity participates in the pathogenesis of infertility.

Non-suicidal self-injury (NSSI) is a significant public health issue that particularly affects female adolescents usually emerging during puberty, with a subsequent reduction and even remission in the phenomenon later in life. The dysregulation of the hormonal stress response, particularly cortisol and dehydroepiandrosterone sulfate (DHEA-S), whose levels increase markedly during pubertal adrenarche, has been associated with the development and maintenance of a wide range of emotional disorders. Our study aims to investigate whether different cortisol-DHEA-S response patterns could be associated with the main motivational moderators to engage NSSI as well as with urgency and motivation to stop NSSI in a sample of female adolescents. We found significant correlations between stress hormones and several factors that support and sustain NSSI, specifically: cortisol levels and distressing/upsetting urge (r = 0.39 and a p = 8.94 × 10−3) and sensation seeking (r = −0.32 and a p = 0.04), as well as cortisol/DHEA-s ratio and external emotion regulation (r = 0.40 and a p = 0.01) and desire to stop NSSI (r = 0.40 and a p = 0.01). Cortisol and DHEA-S may play a role in NSSI through the regulation of stress responses and affective states. Such results could have implications for the development of new and improved treatment and prevention plans for NSSI. [ABSTRACT FROM AUTHOR]

Background/Objective: Variants in PAPSS2 (3′-phosphoadenosine 5′-phosphosulfate synthetase 2) present with varying degrees of brachyolmia (short trunk, platyspondyly, mild long-bone abnormalities). Our objective is to present the phenotype of male and female siblings with the same novel inactivating variant in PAPSS2. Case Report: A Jordanian female (case 1), born to consanguineous parents, was referred at 10 years of age for short stature (SS). She had a normal laboratory workup, including normal growth hormone stimulation testing. Spinal x-rays done for clinical scoliosis revealed platyspondyly. She attained an adult height of 143.5 cm (-3 SD). Years later, her brother (case 2) was referred at 21 months of age for SS. His laboratory workup and bone age were normal. His growth velocity declined at 6 years of age, but normal growth factors did not suggest growth hormone deficiency. When he returned during puberty, disproportionate body measurements were noted. A skeletal survey revealed platyspondyly, increasing suspicion of growth plate pathology. Exome sequencing in the family revealed a homozygous variant, p.His496Pro (H496P) in PAPSS2 (NM_004670.3:c.1487A>C). Both parents carried the same variant. Discussion: PAPSS2 assists with the sulfonation of dehydroepiandrosterone (DHEA) to DHEA sulfate and the sulfonation of proteoglycans in the cartilage, necessary for endochondral bone formation. PAPSS2-inactivating variants present with skeletal dysplasia and elevated DHEA levels. Conclusion: This novel variant in PAPSS2 manifested with mild brachyolmia but disproportionate SS in male and female siblings. Biochemical phenotype with low circulating DHEA sulfate and high DHEA levels reflect a sulfonation defect.

Background: Stress-related biomarkers have the potential to provide objective measures of whether interventions directed at people with dementia (PWD) and their family caregivers (FCG) are successful. The use of such biomarkers has been limited by logistical barriers to sample collection. Objective: Explore saliva concentration of steroid hormones in dementia care dyads during a music intervention. Methods: Consecutive PWD attending a memory evaluation center and their FCG were allocated to either an intervention-with-music or a non-intervention control group. All were living at home. Stress biomarkers, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) samples were collected by the PWD and their FCG, in the morning and evening, 5 days a week, for 8 consecutive weeks. Biomarker concentrations of the intervention and the control groups were compared at week 8, in an intention-to-treat approach with adjustment for baseline value. Results: Twenty-four PWD in the intervention group and 10 in the control group, and their FCG were included in the analyses. The mean number of morning saliva collections was similar in the intervention and the control groups, ranging from 4.3 to 4.9 per participant weekly during the first 7 weeks, declining to 3.3 during week 8. Median log morning cortisol (pg/mL) among caregivers was lower in the intervention group than in the control group (8.09 vs. 8.57, P = 0.0133). Conclusion: This study demonstrates that music intervention was associated with lower morning saliva cortisol concentrations for FCGs. [ABSTRACT FROM AUTHOR]

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient's status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe etiologies, clinical findings, and compare anthropometric properties and biochemical characteristics of children with Precocious Puberty (PP). Materials and Methods: In this single-center study, 367 patients of whom medical records were reviewed diagnosed as premature thelarche (PT), premature adrenarche (PA), Central PP (CPP), and peripheral PP (PPP). The diagnosis was based on clinical, laboratory, and radiologic investigations and their follow-up. Results: During six years, 349 girls (%95,1) and 18 boys (%4,9) diagnosed as PP. The most common etiologies were CPP;127 (%34,6), PT;117 (%31,9), PA;112(%30,5) and PPP 11(%3), respectively. CPP group had significantly higher levels of height, weight, body mass index (BMI) and obesity/overweight incidence, estradiol (E2), basal luteinizing hormone (LH), peak LH, and peak LH/folliclestimulating hormone (FSH) ratio and higher uterine dimensions compared to the PT group while the PT group had significantly higher levels of peak FSH compared to the CPP group. It is impossible for the laboratory results to exactly match in each case with CPP, and the cases should be evaluated along with other clinical findings. Conclusion: Our study detected an increase in the frequency of girls referred to with PP signs. However, most children with PP were revealed as an incomplete type with a very low incidence of endocrine pathology. The complexity of pathogenesis in PP should lead us to be cautious about the consequences of PP in patients andevaluate their complaints, physical findings, and laboratory work-up seriously, such as a piece of a puzzle. [ABSTRACT FROM AUTHOR]

OBJECTIVE To compare the serum levels of cortisol, and the sulfated form of dehydroepiandrosterone (DHEA-S) and their ratio in patients with schizophrenia and healthy control subjects, and to evaluate their association with the response to antipsychotic treatment. METHOD In this clinical prospective study, 60 patients with schizophrenia and 40 healthy age- and sex-matched control subjects participated. Clinical evaluation of patients was conducted using the Positive and Negative Symptom Scale (PANSS), and a questionnaire on socio-demographic and clinical data was used. All the patients had experienced an acute exacerbation of the illness (PANSS: P1 and P3 ≥4). Serum levels of cortisol, DHEA-S, and their ratio, were measured at baseline in all participants and after 3 and 6 weeks of antipsychotic treatment in the patients with schizophrenia. For the purposes of the study, the patients were divided into two subgroups: responders and non-responders to antipsychotic medication. RESULTS Patients with schizophrenia had significantly higher mean serum cortisol and DHEA-S levels than subjects in the control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with non-responders. Elevated serum cortisol levels were associated with a positive response to antipsychotic therapy. The subgroup of responders showed greater reduction of the PANSS positive and negative scale scores at all three assessment points. CONCLUSIONS Elevated serum cortisol levels may have predictive value for a positive response to antipsychotic medication in the context of acute schizophrenia exacerbation. [ABSTRACT FROM AUTHOR]

Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

Background: Evidence for disturbances in HPA activation and abnormal HPA regulatory mechanisms in schizophrenia is accumulating. Aim: To compare serum levels of cortisol, DHEA-S and their ratio between patients with schizophrenia and healthy controls and among patients before and after treatment with different types of antipsychotics. Material and methods: In this clinical prospective study, 60 patients with schizophrenia and 40 healthy age and sex matched control subjects were included. All patients experienced an acute exacerbation of the illness (PANSS: P1 and P3 ≥ 4). Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. Serum levels of cortisol, DHEA-S and their ratio were measured at baseline in all participants and after 3 and 6 weeks, respectively, of the antipsychotic treatment with different types of antipsychotics in patients with schizophrenia. Results: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels in comparison to the control group. There was no significant difference in serum levels of cortisol, DHEA-S and their ratio between patients treated with different types of antipsychotics (typical/atypical). Serum levels of the analyzed hormones significantly reduce during the 6-week period of examination in both subgroups treated with different types of antipsychotics. Conclusion: Elevated serum cortisol and DHEA-S in schizophrenic patients might be associated with their role in the pathophysiology of the disorder. There is no significant difference in serum levels of cortisol, DHEA-S and their ratio among the patients treated with different types of antipsychotics. [ABSTRACT FROM AUTHOR]

Objective: Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR. Materials and methods: DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (35% of the females >40 years old and associated with significantly reduced ZR cell number (ba sed on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis. Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.

Abstract Background Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones. Methods We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n = 148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis. Results Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS

To analyze the association of circulating dehydroepiandrosterone sulfate (DHEA-S) levels with cardiovascular outcomes in patients with chronic Chagas cardiomyopathy (CCM) diagnosis. DHEA-S is among the main endogenous steroid hormones. Some studies have suggested a relevant role of this hormone in infections and the setting of CCM. Nevertheless, no study has evaluated the prognostic role of DHEA-S in CCM patients. Prospective cohort study. Patients with CCM and reduced ejection fraction were included. We explored the association of DHEA-S levels with NT-proBNP levels and echocardiographic variables using linear regression models. Next, by using Cox Proportional Hazard models, we examined whether levels of DHEA-S could predict a composite outcome (CO) including all-cause mortality, cardiac transplantation, and implantation of a left ventricular assist device (LVAD). Seventy-four patients were included (59% males, median age: 64 years). After adjustment for confounding factors, high DHEA-S levels were associated with better LVEF, lower left atrium volume, end-systolic volume of the left ventricle and lower NT-proBNP levels. 43% of patients experienced the CO during a median follow-up of 40 months. Increased levels of DHEA-S were associated with a lower risk of developing the CO (HR 0.43; 95%CI 0.21-0.86). Finally, adding DHEA-S to the multivariate model did not improve the prediction of the CO, but substituting NT-proBNP in the model with DHEA-S showed similar performance. In patients with CCM, higher DHEA-S levels were associated with lower mortality, heart transplantation, and LVAD implantation. Further larger studies are required to confirm our results and assess causality. Central illustration. In the present study, lower circulating dehydroepiandrosterone sulfate (DHEA-S) levels were associated with a higher risk of adverse major cardiovascular outcomes (cardiovascular mortality, LVAD implantation, and heart transplantation) in patients with Chronic Chagas Cardiomyopathy (CCM). Several mechanisms may explain the potential protective role of DHEA-S in CCM, either by direct or indirect processes. T. cruzi can impair dehydroepiandrosterone and DHEA-S synthesis in the adrenal glands by direct invasion of the adrenal tissue and/or by promoting the release of proinflammatory cytokines such as TGF-β. [Display omitted] • Chronic Chagas Cardiomyopathy (CCM) is characterized by a high morbimortality. • In CCM patients, DHEA-S levels were associated with better LVEF and lower NT-proBNP. • Increased DHEA-S levels were associated with a lower risk of mortality. • DHEA-S predictive value was independent of LVEF and NT-proBNP. • DHEA-S may be useful as a biomarker for mortality prediction in CCM patients. [ABSTRACT FROM AUTHOR]

We and other research groups have previously described that levels of the anabolic hormone dehydroepiandrosterone sulfate (DHEA-S) are lowered in individuals who report prolonged stress. We have also shown that the DHEA-S production capacity during acute stress is attenuated in individuals reporting high prolonged stress. This study aimed to further investigate the DHEA and DHEA-S production capacity in relation to prolonged stress. Eighty-one healthy participants in the age 20-50 years old were included in the study and divided into a low stress (n=45) and a high stress group (n=36) according their response to a single question regarding perceived stress during the preceding month. They underwent the Trier Social Stress Test while blood samples were drawn before, during and after the stress test. The concentration of DHEA, DHEA-S, cortisol and ACTH was measured. The results showed that the high stress group exhibited a significantly lower response of DHEA-S (40% lower) than the low stress group, while DHEA, cortisol and ACTH responses did not differ between the groups. Reduced DHEA-S production may constitute one of the links between stress and poor health. [ABSTRACT FROM AUTHOR]

Context: Cortisol and dehydroepiandrosterone‐sulfate (DHEA‐S) are indispensable hormones for normal pregnancy. It is unclear if these hormones, specifically DHEA‐S can offer value for predicting poor birth outcome. Objective: To compare prenatal cortisol and DHEA‐S levels among pregnant women with normal or poor birth outcome. Methods: Plasma and saliva were collected prospectively from women in second‐third trimester of pregnancy. Women with normal birth outcome (NBO) (n = 501) included live birth, no pregnancy complications and ≥2.5 kg infant birth weight. Women with poor birth outcome included adverse birth outcome (ABO) (n = 50) or low birth weight outcome (LBW) (n = 147). Enzyme‐linked immunosorbent assay was performed to measure hormone concentrations in plasma and saliva. Results: Circulatory‐DHEA‐S levels in pregnant women with ABO were higher than women with NBO (p =.043). Among ABO, only stillbirth cases demonstrated significant increase in circulatory‐DHEA‐S levels (p =.006). Circulatory and salivary cortisol/DHEA‐S ratio was lower among women with stillbirth (p =.004) and ABO outcome (p =.043) respectively compared with women with NBO. Consistently, increased odds of ABO were observed in pregnant women with highest circulatory‐DHEA‐S levels (odds ratio quartile score 1 vs. 4, 2.79, p =.027) and lowest salivary cortisol/DHEA‐S ratio (score 4 vs. 2, 2.83, p =.025). Increased odds of stillbirth outcome were observed in pregnant women with highest circulatory‐DHEA‐S levels (odds ratio quartile score 1 vs. 4, 8.47, p =.046) and lowest circulatory cortisol/DHEA‐S ratio (score 4 vs. 1, 4.803, p =.048). Associations remained significant after adjusting for confounders. Women with LBW did not demonstrate significant changes in cortisol or DHEA‐S levels. Conclusion: Prenatal measurement of DHEA‐S or cortisol/DHEA‐S ratio may offer significant value for predicting adverse birth, specifically stillbirth outcome. [ABSTRACT FROM AUTHOR]

Context: The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multistep enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers.Evidence Acquisition: Selective literature search using "steroid," "sulfat*," "adrenal," "transport," "mass spectrometry" and related terms in different combinations.Evidence Synthesis: A recent study highlighted the tissue abundance of estrogen sulfates to be of prognostic impact in adrenocortical carcinoma tissue samples using matrix-assisted laser desorption ionization mass spectrometry imaging. General mechanisms of sulfate uptake, activation, and transfer to substrate steroids are reasonably well understood. Key aspects of this pathway, however, have not been investigated in detail in the adrenal; these include the regulation of substrate specificity and the secretion of sulfated steroids. Both for the adrenal and targeted peripheral tissues, steroid sulfates may have relevant biological actions beyond their cognate nuclear receptors after desulfation. Impaired steroid sulfation such as low DHEAS in Cushing adenomas is of diagnostic utility, but more comprehensive studies are lacking. In bioanalytics, the requirement of deconjugation for gas-chromatography/mass-spectrometry has precluded the study of steroid sulfates for a long time. This limitation may be overcome by liquid chromatography/tandem mass spectrometry.Conclusions: A role of steroid sulfation in the pathophysiology of adrenal tumors has been suggested and a diagnostic utility of steroid sulfates as biomarkers is likely. Recent analytical developments may target sulfated steroids specifically. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare tumor, and some histological variants (oncocytic, myxoid, and sarcomatoid ACCs) have been reported in addition to the conventional ACC. Among these subtypes, oncocytic ACC is histologically characterized by the presence of abundant eosinophilic granular cytoplasm in the carcinoma cells owing to the accumulation of mitochondria, which generally yields high 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Herein, we report the case of a 21-year-old woman with oncocytic ACC with low FDG uptake on PET scan. Her circulating levels of androgens were high, and androgen-synthesis enzymes were detected in carcinoma cells. The patient also had hypocholesterolemia. However, glucose transporter 1 (GLUT1) was not detected in the tumor, which was considered to account for the low FDG uptake by the tumor. To the best of our knowledge, this is the first case of low FDG uptake by oncocytic ACC without GLUT1 expression. Additionally, since hypocholesterolemia was reported in 3 previous reports of androgen-producing tumors, a possible correlation between androgenicity in adrenal tumors and the development of hypocholesterolemia could be postulated; however, further investigations are needed for clarification. This case highlights important information regarding the diversity of ACC and its impact on hypocholesterolemia. [ABSTRACT FROM AUTHOR]

During pregnancy, circulatory cortisol levels increase, remaining steady over the second-third trimester. In contrast, profile of salivary cortisol during pregnancy is debatable, more influenced by factors like time of sample collection in the day. Circulatory DHEA-S decrease by at least 50% over the second-third trimester of pregnancy. However, profile of salivary DHEA-S is unclear. Objective was to determine changes in salivary cortisol and DHEA-S in healthy pregnant women, compared to non-pregnant women during late morning-early afternoon sampling to avoid fluctuations associated with other times. Pregnant women in their second-third trimester prospectively (n=500) and non-pregnant women (n=133) were enrolled in study with informed consent. Live birth outcome with no pregnancy complications and≥2.5 Kg infant birth weight were included. Concentrations of salivary cortisol and DHEA-S were determined through ELISA assays. Compared to non-pregnant women, pregnant women demonstrated significant increases in salivary cortisol [median (interquartile range)=4.2 (5.1) nmol/l vs. 17.2 (13.9) nmol/l, p<0.001] and salivary DHEA-S median (interquartile range)=2.7 (2.9) nmol/l vs. 3.8 (3.2) nmol/l, p<0.001). Consistently, quartile scores representing higher levels of salivary cortisol and DHEA-S concentrations demonstrated significant association with pregnancy. Quartile scores representing higher salivary cortisol/DHEA-S ratio demonstrated significant association with pregnancy. Study suggests the indicated time range of saliva sampling might best parallel the established profile of circulatory cortisol in pregnant women. However, unlike cortisol, study indicates that the salivary DHEA-S profile is distinct from the well-known profile of circulatory DHEA-S during pregnancy. A combinatorial approach involving both salivary and circulatory compartments could provide comprehensive picture of DHEA-S and hypothalamus-pituitary-adrenal axis during pregnancy. [ABSTRACT FROM AUTHOR]

17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care. [Display omitted] • E2 increased in healthy asbestos-exposed subjects and MPM patients. • DHEA-S-androstenedione-E2 signature score increased in asbestos-exposed subjects. • The signature differentiates subjects exposed to asbestos from those not exposed. • DHEA-S-androstenedione-E2 as biomarkers of MPM risk and early diagnosis of MPM. [ABSTRACT FROM AUTHOR]

Abstract Background Locomotive syndrome (LS) is associated with weakness and loss of function in the musculoskeletal organs. We aimed to determine the association between LS components and blood parameters in middle-aged and elderly individuals. Methods We included 223 middle-aged and elderly individuals in this study (104 men and 119 women; age: 40–85 years). All participants were asked to fast for at least 3 h before the venous blood samples were obtained and the hemoglobin, total protein, glycated hemoglobin (HbA1c), growth hormone, albumin and lipid profile were measured. Three functional tests, the stand-up test, the two-step test, and the 25-question geriatric locomotive function scale (GLFS) were used to assess the risk of LS. Walking speed was assessed by the 10-m walking test. Maximal isometric muscle strengths of the knee extensors were examined, and the weight bearing index (knee extension strength/body weight) was calculated. To assess an independent association between blood parameters and LS, the area under the receiver operating characteristic curve analysis (area under the curve, sensitivity, and specificity) and a binary logistic regression analysis were performed with adjustment for age. Results Of the 223 subjects, 119 (53.3%) fulfilled the diagnostic criteria for LS (including a two-step test score

Menopause is the last menstrual period associated with a decline in ovarian steroid secretion and follicular loss. Hormone profile changes during menopause include a decrease in the production of estrogen, dehydroepiandrosterone (DHEA), and prolactin (PRL), and an increase in thyroid-stimulating hormone (TSH) and cortisol. Herbal medicines are considered as alternatives to hormone therapy. The studies on postmenopausal women have shown that Elaeagnus angustifolia L. (called “Senjed” in Persian) has some efficacy in improving sex hormone and lipid profiles, joint pain, and cardiovascular function, as the decrease in luteinizing hormone, low-density lipoprotein, and heart rate was significant. The aim of the present study was to evaluate the effects of E. angustifolia on TSH, DHEA-S, PRL, and cortisol levels and their ratios in postmenopausal women. It is assumed that the eventual effects of hormones on the brain and other tissues are determined by the balance between interdependent hormones. In the present randomized double-blinded placebo-controlled trial (https://en.irct.ir/search/result?query=IRCT20170227032795N4), fifty-eight postmenopausal women were randomly assigned to one of two medicinal herb (15 g of the whole E. angustifolia fruit powder) and placebo (7.5 g isomalt + 7.5 g cornstarch) groups. After 10 weeks of the treatment, the serum levels of TSH, DHEA-S, PRL, cortisol hormones, and their ratios were measured. The increase in the TSH, and cortisol levels, and cortisol/DHEA-S ratio and the decrease in prolactin and DHEA-S and the PRL/TSH, PRL/cortisol, and DHEA-S/TSH ratios after E. angustifolia consumption were significant only based on within-group but not on the between-group analysis. Based on between-group analyses, the changes in the hormone profile were not significant in the placebo group. According to Iranian tradition and folklore, E. angustifolia fruit is a symbol of female fertility. Therefore, its consumption is highly recommended to maintain health in the elderly, especially women. However, the observed outcomes about the effect of E. angustifolia on menopause were not completely in line with the Iranian folklore. E. angustifolia consumption did not significantly affect the hormone profile and ratios at the end of the ten-week trial, possibly due to the small sample size, short time, and the fact that our participants were postmenopausal women.

Menopause is the last menstrual period associated with a decline in ovarian steroid secretion and follicular loss. Hormone profile changes during menopause include a decrease in the production of estrogen, dehydroepiandrosterone (DHEA), and prolactin (PRL), and an increase in thyroid-stimulating hormone (TSH) and cortisol. Herbal medicines are considered as alternatives to hormone therapy. The studies on postmenopausal women have shown that Elaeagnus angustifolia L. (called "Senjed" in Persian) has some efficacy in improving sex hormone and lipid profiles, joint pain, and cardiovascular function, as the decrease in luteinizing hormone, low-density lipoprotein, and heart rate was significant. The aim of the present study was to evaluate the effects of E. angustifolia on TSH, DHEA-S, PRL, and cortisol levels and their ratios in postmenopausal women. It is assumed that the eventual effects of hormones on the brain and other tissues are determined by the balance between interdependent hormones. In the present randomized double-blinded placebo-controlled trial (https://en.irct.ir/search/result?query=IRCT20170227032795N4), fifty-eight postmenopausal women were randomly assigned to one of two medicinal herb (15 g of the whole E. angustifolia fruit powder) and placebo (7.5 g isomalt + 7.5 g cornstarch) groups. After 10 weeks of the treatment, the serum levels of TSH, DHEA-S, PRL, cortisol hormones, and their ratios were measured. The increase in the TSH, and cortisol levels, and cortisol/DHEA-S ratio and the decrease in prolactin and DHEA-S and the PRL/TSH, PRL/cortisol, and DHEA-S/TSH ratios after E. angustifolia consumption were significant only based on within-group but not on the between-group analysis. Based on between-group analyses, the changes in the hormone profile were not significant in the placebo group. According to Iranian tradition and folklore, E. angustifolia fruit is a symbol of female fertility. Therefore, its consumption is highly recommended to maintain health in the elderly, especially women. However, the observed outcomes about the effect of E. angustifolia on menopause were not completely in line with the Iranian folklore. E. angustifolia consumption did not significantly affect the hormone profile and ratios at the end of the ten-week trial, possibly due to the small sample size, short time, and the fact that our participants were postmenopausal women. [ABSTRACT FROM AUTHOR]

The rationale was to explore the efficacy/sensitivity of using morning and evening cortisol levels as biomarkers for stress reduction in persons with dementia (PWDs) and their family caregivers (FCGs) participating in a music intervention program. Thirty-two PWD and their FGC were recruited to an 8-week, home-based music intervention program. Daily home-based collection of saliva samples took place at bedtime and upon awakening. Cortisol was analyzed in the morning and evening saliva samples and DHEA-s in the morning samples. Trends over 40 workdays (15–40 observations per subject) were assessed using linear regression analysis. Twenty-three PWD (72% of invited, 16 men and 7 women, age 69–93) and 24 caregivers (75%, 8 men and 16 women, age 37–90) completed the intervention for at least 6 weeks and were included in the analysis. One-fourth of the PWD and FCG had decreasing evening cortisol, accompanied by decreasing morning cortisol levels. In one-fourth of the participants the ratio between cortisol and DHEA-S in the morning samples was improved, indicating improved balance between energy mobilization and regeneration. Several participants showed no significant endocrine change. There was a statistically significant (two-sided test) correlation within the PWD-caregiver dyads in evening cortisol trend and a statistically significant decrease (two-sided test) in the morning-evening cortisol slope for the FCG group. Reduction in stress, as measured by evening cortisol, was observed in a substantial number of the participants. Recording endocrine stress is helpful for the unbiased assessment of the intervention. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the effect of repeated hot thermal stress and cold water immersion on the endocrine system of young adult men with moderate and high levels of physical activity (PA). The research was conducted on 30 men aged 19-26 years (mean: 22.67 ± 2.02) who attended four sauna sessions of 12 min each (temperature: 90-91°C; relative humidity: 14-16 %). Each sauna session was followed by a 6-min cool-down break during which the participants were immersed in cold water (10-11°C) for 1 min. Testosterone (TES), cortisol (COR), dehydroepiandrosterone sulfate (DHEA-S), and prolactin (PRL) levels were measured before and after the sauna bath. The participants' PA levels were evaluated using the International Physical Activity Questionnaire. Serum COR levels decreased significantly (p < .001) from 13.61 to 9.67 μg/ml during 72 min of sauna treatment. No significant changes (p >.05) were noted in the concentrations of the remaining hormones: TES increased from 4.04 to 4.24 ng/ml, DHEA-S decreased from 357.5 to 356.82 μg/ml, and PRL decreased from 14.50 to 13.71 ng/ml. After sauna, a greater decrease in COR concentrations was observed in males with higher baseline COR levels, whereas only a minor decrease was noted in participants with very low baseline COR values (r =-0.673, p <.001). Repeated use of Finnish sauna induces a significant decrease in COR concentrations, but does not cause significant changes in TES, DHEA-S, or PRL levels. Testosterone concentrations were higher in men characterized by higher levels of PA, both before and after the sauna bath. [ABSTRACT FROM AUTHOR]

Abstract Background In a previous randomized controlled trial, we found that sitting isometric yoga improves fatigue in patients with chronic fatigue syndrome (CFS) who are resistant to conventional therapy. The aim of this study was to investigate possible mechanisms behind this finding, focusing on the short-term fatigue-relieving effect, by comparing autonomic nervous function and blood biomarkers before and after a session of isometric yoga. Methods Fifteen patients with CFS who remained symptomatic despite at least 6 months of conventional therapy practiced sitting isometric yoga (biweekly 20 min practice with a yoga instructor and daily home practice) for eight weeks. Acute effects of sitting isometric yoga on fatigue, autonomic function, and blood biomarkers were investigated after the final session with an instructor. The effect of a single session of sitting isometric yoga on fatigue was assessed by the Profile of Mood Status (POMS) questionnaire immediately before and after the session. Autonomic nervous function (heart rate (HR) variability) and blood biomarkers (cortisol, DHEA-S, TNF-α, IL-6, IFN-γ, IFN-α, prolactin, carnitine, TGF-β1, BDNF, MHPG, and HVA) were compared before and after the session. Results Sitting isometric yoga significantly reduced the POMS fatigue score (p

Objective Identifying biomarkers is a priority in translational chronic pain research. Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are adrenocortical steroids in the blood with neuroprotective properties that also produce sex hormones. They may capture key sex-specific neuroendocrine mechanisms of chronic pain. Design Cross-sectional study. Methods Using data from 1,216 community-dwelling adults aged 34–84 from the Midlife in the United States (MIDUS) cohort, we examined blood DHEA and DHEA-S levels in association with chronic pain in men and women, adjusting for demographics, chronic diseases, medications including opioids, and psychosocial factors. If an association was found, we further explored dose-response relationships by the number of pain locations and the degree of pain interference. Results In women, chronic pain was associated with 0.072 lower (95% confidence interval [CI], –0.127 to –0.017) log10 DHEA-S µg/dL, with pain in one to two locations associated with 0.068 lower (95% CI, –0.131 to –0.006) and in three or more locations 0.071 lower (95% CI, –0.148 to 0.007) log10 DHEA-S (P for trend = 0.074). Furthermore for women, low-interference pain was associated with 0.062 lower (95% CI, –0.125 to –0.000), whereas high-interference pain was associated with 0.138 lower (95% CI, –0.233 to –0.043) log10 DHEA-S (P for trend = 0.004). Chronic pain was not associated with DHEA or DHEA-S levels in men or DHEA levels in women. Conclusions Chronic pain and its functional interference correspond to lower blood DHEA-S levels in women. [ABSTRACT FROM AUTHOR]

Context: Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events.Objective: Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults.Design: DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events: 18 years for DHEA-S level; 5.5 years for DHEA-S change.Setting: General community.Participants: Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years).Main Outcome Measure: Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events.Results: DHEA-S below the 15th sex-specific percentile of the study population (men: 55.4 µg/dL; women: 27.4 µg/dL) was associated with increased HF hospitalization (men: hazard ratio [HR] 1.30, 95% confidence interval [CI], 1.07-1.58; women: HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men: 70.0 µg/dL; women: 37.1 µg/dL) was associated with increased death (men: HR 1.12, 95% CI, 1.01-1.25; women: HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD.Conclusions: Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Context: Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes.Objective: To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).Design: Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years.Setting: General community.Participants: 4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation [SD] 5.7) and 62.8 (5.5) years, respectively.Exposure: Plasma sex hormone levels were measured at visit 4 (1996-1998).Main Outcome Measures: Incident HF events were identified through hospital discharge codes and death certificates.Results: The Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant.Conclusion: In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex. [ABSTRACT FROM AUTHOR]

Objective: Adrenocortical cancer (ACC) is one of the rare endocrine system cancers that are aggressive. Despite surgical treatment, the mortality rate is quite high. This study aimed to examine prognostic factors affecting survival in patients with ACC, the role of dehydroepiandrosterone sulfate (DHEA-S), and the maximum standard uptake (SUVmax) values on predicting mortality through the single-center data. Material and Methods: A total of 21 patients who were diagnosed with adrenal cancer and followed from a single center were included in the study. Patients who survived follow-ups were included in the survived group (n=6), and those who died were included in the dead group (n=15). The demographic, anatomical, pathological, and clinical characteristics of the patients were analyzed. Positron emission tomography-computerized tomography imaging and SUVmax values of adrenal masses were compared. The effect of all these data on survival was examined. Results: The mortality rate among patients with ACC was 71%. According to the Kaplan-Meier survival analysis, the average life expectancy was 23.66±2.79 (95% CI=18.18-29.13) months. The mass size of the survived and dead groups was 9.2±3.82 cm and 10.84±4.74 cm, respectively. The production rate of adrenal hormone was higher in the dead group (p<0.01; 80%). Moreover, the DHEA-S level and SUVmax values were statistically significantly higher in the dead group (p<0.001; p<0.05, respectively). Although no metastases were observed in the survived group during follow-ups after the operation, distant metastases were observed in 8 people from the dead group (53%; p<0.05). Conclusion: The mortality rate was very high in ACC despite surgical and medical treatments. The higher DHEA-S and SUVmax values may indicate that the overall survival duration was low. [ABSTRACT FROM AUTHOR]

Background: Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones.Methods: We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n = 148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis.Results: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS < 70 μg/dL and cortisol/DHEA-S ratio ≥ 0.2. Multiple regression analysis showed that low albumin (< 4.0 g/dl) (odds ratio [OR] = 5.79, p < 0.001), low aspartate aminotransferase (AST) activity (< 25 IU/L) (OR = 4.34, p = 0.009), and low body mass (BM) (< 53 kg) (OR = 3.85, p = 0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM.Conclusions: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients. [ABSTRACT FROM AUTHOR]

• No significant difference observed in DHEA-S levels before and after the first and second doses of vaccination. • IL-2 and IFN-γ levels significantly increased in PBMC supernatant two weeks after both initial and booster vaccinations. • Serum IgM levels significantly rose two weeks after the first dose, while IgG levels increased significantly after both the first and second doses. • FRNT50 titer significantly elevated two weeks post both initial and booster doses, indicating heightened neutralizing antibody response. • DHEA-S levels showed no significant correlation with IL-2, IFN-γ, IgM, IgG, and FRNT50 levels before and after vaccinations. • No intense unwanted clinical presentations observed post-vaccination. Dehydroepiandrosterone sulfate (DHEA-S) has been associated with an immunomodulatory function. This study aims to explore the relationship between serum levels of DHEA-S and the immune responses triggered by the Oxford–AstraZeneca COVID-19 vaccine in individuals candidate for vaccination. Serum levels of DHEA-S, cytokine release, antibody production and virus neutralization potential were assessed in 50 male and 50 female subjects before and 2 weeks after vaccination with Oxford–AstraZeneca COVID-19 vaccine. Level of DHEA-S before and 2 weeks after first and second dose of vaccination was not different significantly. Levels of Interleukin (IL)-2 and Interferon (IFN)-γ were significantly higher in the supernatant of peripheral blood mononuclear cells (PBMCs) obtained from subjects 2 weeks after both first and second dose of vaccination compared to before vaccination. Serum levels of IgM 2 weeks after first dose of vaccination was significantly higher compared to before first dose of vaccination. However, serum levels of IgG 2 weeks after first and second dose of vaccination were significantly higher compared to before first and second dose of vaccination. The 50 % focus reduction neutralization test (FRNT 50) titer was significantly higher 2 weeks after both first and second dose of vaccination compared to before vaccination. Levels of DHEA-S did not have significant correlation with levels of IL-2, IFN-γ, IgM and IgG, and FRNT 50 before and after first and second dose of vaccination. Vaccination did not result in intense unwanted clinical presentations. DHEA-S is not involved in the quality of protective immune response during Oxford-AstraZeneca COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate fertility hormone levels in adolescent girls and ten years older women with menstrual irregularities and with or without polycystic ovaries on ultrasound examination. Methods: The study population consisted of 276 patients aged 12-18 years and 469 patients aged 22-28 years who had menstrual irregularities with or without polycystic ovaries on ultrasound examination. All subjects underwent a comprehensive medical assessment including documentation of the detailed history, physical and gynecological examination, measurement of the essential laboratory variables, and measurement of the fertility hormone levels. Results: Within 745 patients (mean age: 21.4± 4.8), 276 patients were aged 12-18 years (group 1) and 469 patients were aged 22-28 years (group 2). Dehydroepiandrosterone sulfate (DHEA-S) (237.7 (2 2.6 -721.5) vs. 162.5 (2.4-660.7) respectively; p 2 in group 1 and 74 subjects (15.8%) with LH/FSH ratio > 2 in group 2 (p

Objective: The aim of this study was to investigate the impact of adrenal hyperandrogenism on insulin resistance and lipid profile in women with polycystic ovary syndrome (PCOS). Patients and methods: We studied 372 women with PCOS according to the NIH criteria. 232 age- and BMI-matched women served as controls in order to define adrenal hyperandrogenism (DHEA-S >95th percentile). Then, patients with PCOS were classified into two groups: with adrenal hyperandrogenism (PCOS-AH, n = 108) and without adrenal hyperandrogenism (PCOS-NAH, n = 264). Anthropometric measurements were recorded. Fasting plasma glucose, insulin, lipid profile, sex hormone-binding globulin (SHBG) and androgen (TT, Δ4A, DHEA-S) concentrations were assessed. Free androgen index (FAI) and homeostatic model assessment-insulin resistance (HOMA-IR) index were calculated. Results: Women with PCOS-AH were younger than PCOS-NAH (P < 0.001), but did not differ in the degree and type of obesity. No differences were found in HOMA-IR, total cholesterol, HDL-c, LDL-c and triglyceride concentrations (in all comparisons, P > 0.05). These metabolic parameters did not differ between the two groups even after correction for age. Women with PCOS-AH had lower SHBG (29.2 ± 13.8 vs 32.4 ± 11.8 nmol/L, P = 0.025) and higher TT (1.0 ± 0.2 vs 0.8 ± 0.4 ng/mL, P = 0.05) and Δ4A (3.9 ± 1.2 vs 3.4 ± 1.0 ng/mL, P = 0.007) concentrations, as well as FAI (14.1 ± 8.0 vs 10.2 ± 5.0, P < 0.001). These results were confirmed by a multiple regression analysis model in which adrenal hyperandrogenism was negatively associated with age (P < 0.001) and SHBG concentrations (P = 0.02), but not with any metabolic parameter. Conclusions: Women with PCOS and adrenal hyperandrogenism do not exhibit any deterioration in insulin resistance and lipid profile despite the higher degree of total androgens.

Context: Sulfate is critical in the biotransformation of multiple compounds via sulfation. These compounds include neurotransmitters, proteoglycans, xenobiotics, and hormones such as dehydroepiandrosterone (DHEA). Sulfation reactions are thought to be rate-limited by endogenous sulfate concentrations. The gene, SLC13A1, encodes the sodium-sulfate cotransporter NaS1, responsible for sulfate (re)absorption in the intestines and kidneys. We previously reported two rare, non-linked, nonsense variants in SLC13A1 (R12X and W48X) associated with hyposulfatemia (P = 9 × 10−20). Objective: To examine the effect of serum sulfate concentration and sulfate-lowering genotype on DHEA homeostasis. Design: Retrospective cohort study. Setting: Academic research. Patients: Participants of the Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study and the Amish Hereditary and Phenotype Intervention (HAPI) Study. Main outcome measures: DHEA, DHEA-S, and DHEA-S/DHEA ratio. Results: Increased serum sulfate was associated with decreased DHEA-S (P = 0.03) and DHEA-S/DHEA ratio (P = 0.06) in males but not females. Female SLC13A1 nonsense variant carriers, who had lower serum sulfate (P = 9 × 10−13), exhibited 14% lower DHEA levels (P = 0.01) and 7% higher DHEA-S/DHEA ratios compared to female non-carriers (P = 0.002). Consistent with this finding, female SLC13A1 nonsense variant carriers also had lower total testosterone levels compared to non-carrier females (P = 0.03). Conclusions: Our results demonstrate an inverse relationship between serum sulfate, and DHEA-S and DHEA-S/DHEA ratio in men, while also suggesting that the sulfate-lowering variants, SLC13A1 R12X and W48X, decrease DHEA and testosterone levels, and increase DHEA-S/DHEA ratio in women. While paradoxical, these results illustrate the complexity of the mechanisms involved in DHEA homeostasis and warrant additional studies to better understand sulfate's role in hormone physiology.

Objective: To evaluate the relationship between age- and gender-adjusted dehydroepiandrosterone sulfate (DHEA-S) levels and low-dose adrenocorticotropic hormone (ACTH) stimulation in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, in patients who were at risk of HPA insufficiency, including those currently being treated with glucocorticoids. Methods: Forty-six participants with a suspicion of secondary adrenal insufficiency were recruited from the Diabetes and Endocrinology Clinic at Ramathibodi Hospital, Mahidol University, Bangkok. Low-dose (1 μg) ACTH stimulation was performed in every participants, and serum DHEA-S was measured at baseline before ACTH injection. Results: Individuals with normal age- and gender-specific DHEA-S levels had baseline serum cortisol and peak cortisol levels higher than those with reduced DHEA-S. Normal age- and gender-specific DHEA-S levels predicted intact HPA function with a sensitivity of 87.1%, a specificity of 86.7%, a positive predictive value of 93.1%, and a negative predictive value of 76.5%. To account for the age and gender dependency of DHEA-S, the DHEA-S ratio was calculated by measured DHEA-S divided by the lower limit of the respective reference range for all participants. A DHEA-S ratio of more than 1.78 had 100% sensitivity regarding intact HPA function. Area under the receiver operating characteristic [ROC] curve was 0.920. (95% CI, 0.844–0.997). Conclusion: Normal age- and gender-specific DHEA-S level or a DHEA-S ratio of more than 1.78 are valuable markers of HPA integrity. Serum DHEA-S may be a candidate for a less costly approach where ACTH stimulation is unavailable.

Patients with poor ovarian response (POR) to exogenous gonadotropins stimulation for assisted reproductive technology (ART) have decreased circulating androgens during spontaneous cycles. The Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) is a 4-tier stratification of women with POR to controlled ovarian stimulation (COH) based on age and biomarkers of ovarian reserve has been proposed to maximize the clinical management of this group for ART. The aim of the present study was to characterize the levels of androgens during COH in follicular fluid (FF) and serum in POSEIDON subgroups and compared them with women of normal ovarian response. Sixty nine consecutive patients undergoing ART were included and testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), estradiol, sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) were measured in serum and FF collected at the time of oocyte pick-up. The number of retrieved oocytes was registered for each patient for their allocation to the respective POSEIDON subgroup. The control group comprised 19 women and the POSEIDON group 1 (age < 35, normal ovarian reserve biomarkers) n = 14, group 2 (age ≥ 35, normal ovarian reserve biomarkers) n = 8, group 3 (age < 35, poor ovarian reserve biomarkers) n = 6 and group 4 (age ≥ 35, poor ovarian reserve biomarkers) n = 22. Serum levels of total testosterone, androstenedione and DHEA-S were not different in group 1 vs. control but significantly decreased in group 3 vs. control. DHEA-S in FF was also significantly decreased in group 3 vs. control. In addition, serum testosterone was decreased in groups 2 and 4 vs. control; and serum androstenedione and estradiol were reduced in group 4 vs. control. No differences were observed for estradiol, SHBG and IGF-1 in FF. Finally, a high correlation between serum and FF DHEA-S was observed when data from samples of all groups were pooled. Group 1 did not show hypoandrogenemia however group 3 had low levels of all measured androgens in serum and DHEA-S in FF. Such differences might help to better characterize and/or improve the clinical management of women with POR according to their respective POSEIDON stratification.