Serum Dehydroepiandrosterone Sulfate Research Articles

Androgen synthesis cell-specific CREBZF deficiency alters adrenal cortex steroid secretion and develops behavioral abnormalities in adult male mice.

The global challenge of male infertility is escalating, notably due to the decreased testosterone (T) synthesis in testicular Leydig cells under stress, underscoring the critical need for a more profound understanding of its regulatory mechanisms. CREBZF, a novel basic region-leucine zipper transcription factor, regulates testosterone synthesis in mouse Leydig cells invitro; however, further validation through invivo experiments is essential. Our study utilized Cyp17a1-Cre to knock out CREBZF in androgen-synthesis cells and explored the physiological roles of CREBZF in fertility, steroid hormone synthesis, and behaviors in adult male mice. Conditional knockout (cKO) CREBZF did not affect fertility and serum testosterone level in male mice. Primary Leydig cells isolated from CREBZF-cKO mice showed impaired testosterone secretion and decreased mRNA levels of Star, Cyp17a1, and Hsd3b1. Loss of CREBZF resulted in thickening of the adrenal cortex, especially X-zone, with elevated serum corticosterone and dehydroepiandrosterone levels and decreased serum dehydroepiandrosterone sulfate levels. Immunohistochemical staining revealed increased expression of StAR, Cyp11a1, and 17β-Hsd3 in the adrenal cortex of CREBZF-cKO mice, while the expression of AR was significantly reduced. Along with the histological changes and abnormal steroid levels in the adrenal gland, CREBZF-cKO mice showed higher anxiety-like behavior and impaired memory in the elevated plus maze and Barnes maze, respectively. In summary, CREBZF is dispensable for fertility, and CREBZF deficiency in Leydig cells promotes adrenal function in adult male mice. These results shed light on the requirement of CREBZF for fertility, adrenal steroid synthesis, and stress response in adult male mice, and contribute to understanding the crosstalk between testes and adrenal glands.

Serum Dehydroepiandrosterone sulfate (DHEA-S) level and its potential impact on immune responses and symptom severity after Oxford-AstraZeneca COVID-19 vaccination

BackgroundDehydroepiandrosterone 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. MethodsSerum 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. ResultsLevel 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 (FRNT50) 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 FRNT50 before and after first and second dose of vaccination. Vaccination did not result in intense unwanted clinical presentations. ConclusionDHEA-S is not involved in the quality of protective immune response during Oxford-AstraZeneca COVID-19 vaccination.

The Correlation Between Interleukin -6 and Dehydroepiandrosterone Sulfate in Patients with Severe COVID-19

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.

Multiparametric arterial spin-labeling and diffusion-weighted imaging of phenotyping of polycystic ovaries

BackgroundPolycystic ovarian syndrome [PCO] is a worldwide endocrine disorder affecting women of reproductive age. Diagnosis and differentiation of PCO phenotypes are crucial for disease prognosis, fertility outcome, and treatment planning. This study aims to assess arterial spin labeling perfusion (ASL) and diffusion-weighted imaging (DWI) derived metrics in the diagnosis of PCO, differentiation of its phenotypes, and correlation of these metrics with laboratory measurements.ResultsASL and DWI of the pelvis were performed on 72 PCO patients and another 20 age-matched control group. Two observers measured the blood flow (BF) and ADC in the ovarian stroma. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), and body mass index (BMI) were calculated. BF values were significantly higher in PCO patients than in control cases (P = 0.001), with area under the curve (AUC) of (0.94 and 0.89) and accuracy of (96% and 92%) for both observers, respectively. Also, BF values were significantly higher in classic than in non-classic PCO cases (P = 0.001), with AUC of (0.92 and 0.90) and accuracy of (91%) for both observers, respectively. ADC values were significantly lower in PCO patients than in control cases (P = 0.001), with AUC of (0.85 and 0.84) for the first observer and second observer, respectively. ADC values were significantly lower in classic PCO patients than in non-classic patients (P = 0.001), with AUC of (0.85 and 0.84) and accuracy of (77% and 81%) for both observers, respectively. Combined values of BF and ADC showed an accuracy of 91% and 86% for differentiating patient from control cases for both observers, respectively, and an accuracy of 92% for differentiating classic from non-classic PCO phenotypes. A significant correlation was found between ADC, BF metrics, and both serum testosterone and DHEAS levels (P < 0.05).ConclusionsCombination of ASL and ADC can be used in PCO diagnosis and can help in the differentiation of its phenotypes. Serum levels of testosterone and DHEAS have a significant correlation with ADC and BF metrics.

Urinary Androgens Provide Additional Evidence Related to Metabolism and Are Correlated With Serum Androgens in Girls.

Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative. To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics. Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations. The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5β-androstane-3α,11β-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%. The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens.

Bone density in patients with nonfunctional adrenal incidentaloma

Aims: Adrenal incidentalomas (AI) are adrenal masses that are detected incidentally in imaging studies performed for different reasons in people who do not have any complaints suggestive of adrenal gland disease. The overall prevalence, approximately just over 4%, increases with age. AI is detected in approximately 10% of people over the age of 70. In this context, we thought that CT imaging, which is already used in the diagnosis and follow-up of AI, can contribute to the evaluation of muscle and bone mass without creating additional costs. Methods: In this retrospective study, 39 patients who were followed up with NFAI by the endocrinology department and 30 healthy individuals with normal adrenal imaging in the abdominal CT examination as the control group were included. Patients with chronic diseases or drug use that may affect bone and muscle mass, and individuals in the postmenopausal period were excluded in this study. Endocrine tests performed to exclude autonomous cortisol secretion, pheochromocytoma and primary hyperaldosteronism; VMA and fractionated metanephrines in 24-hour urine, cortisol values after 1 mg dexamethasone suppression test, baseline serum dehydroepiandrosterone sulfate (DHEAS) levels and plasma aldosterone (ng/dl)/renin (ng/ml/hour) ratio were measured. Autonomous cortisol production was excluded in patients with serum cortisol below 1.8 mcg/dl after 1 mg dexamethasone suppression. Results: 39 patients with NFAI and 30 healthy volunteers participated in the study. In the NFAI group, 69.2% (n= 27) were female and 30.8% (n=12) were male. In the healthy control group 63.3% (n=19) of the people were female and 37.7% (n=11) were male. There was no statistically significant difference between the two groups in terms of gender (p=061). The mean age of the NFAI group is 43 and the mean age of the control group is 49, and there was no statistically significant difference in age between the two groups (p=0.06) Conclusion: No decrease was found in BMD and paravertebral muscle mass values in the measurements made at L1-3 vertebral level with CT in NAFI patients. Further studies are needed in a larger patient population where the results are evaluated together with the femur and vertebral BMD measurements by DXA method, and muscle strength and performance are evaluated in addition to muscle mass in terms of sarcopenia.

Effects of Blue Light on Puberty and Ovary in Female Rats

This study was designed to examine the effect of blue light exposure and exposure time on puberty in an animal model. Eighteen 21-day-old female Sprague Dawley rats were divided into three equal groups which were: control group (CG); blue light-6 hours (BL-6); and blue light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The animals in BL-6 and BL-12 were exposed to blue light of wavelength 450-470 nm and intensity of 0.03 uW/cm2 for 6 and 12 hours, respectively. Exposure to blue light continued until the first signs of puberty. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), leptin and melatonin were measured. Subsequently the ovaries and uterus were examined histomorphologically. The median day of puberty start was 38, 32 and 30 for the CG, BL-6, and BL-12 groups, respectively (p=0.001). FSH, testosterone, DHEA-S, and leptin concentrations of all groups were similar. However, LH and estradiol concentrations in BL-6 were higher compared to CG (p=0.02). There was a negative correlation between blue light exposure, exposure time, and melatonin concentrations (r=-0.537, p=0.048). Ovarian tissue was compatible with puberty in all groups. As blue light exposure time increased, capillary dilatation and edema in the ovarian tissue increased. Prolonged exposure was associated with polycystic ovary-like (PCO) morphological changes and apoptosis in granulosa cells. These results suggest that exposure to blue light and the duration of exposure induced earlier puberty in female rats. As the duration of blue light exposure increased, PCO-like inflammation, and apoptosis were detected in the ovaries.

The impact of menopause and serum DHEA-S level on the severity of Covid-19

ObjectivesWe aimed to demonstrate the difference between premenopausal and postmenopausal women in respect of the clinical course and outcomes of Covid-19. We investigated the epidemiological and hormonal factors which influence the severity of the disease. Study designThis observational cross-sectional study included the female patients admitted to a Covid-19 outpatient clinic between July 2020 and June 2021 and diagnosed with a positive polymerase chain reaction test. Blood samples were obtained to determine the serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, total testosterone and dehydroepiandrosterone sulfate. Main outcome measureOur primary outcome was the poor clinical course of the disease in postmenopausal women. Our secondary outcome was the contribution of hormonal status to the clinical course of the disease. ResultsOur cohort consisted of 253 female patients (85 with mild, 125 with moderate and 43 with severe disease; 101 at the premenopausal and 152 at the postmenopausal stage). There was a statistically significant difference between the patients in different severity groups regarding clinical data and serum levels of luteinizing hormone, follicle stimulating hormone, estradiol and dehydroepiandrosterone sulfate. Being one year younger decreased the odds of having severe Covid-19 0.338-fold relative to the group with mild disease. A decrease in the serum dehydroepiandrosterone sulfate level was associated with a 2.604-fold increase in the odds of having severe Covid-19 relative to the group with mild disease. Being postmenopausal increased the odds of having severe disease compared with mild disease by 2.687-fold. ConclusionsThe prognosis of Covid-19 is more favorable in premenopausal women compared with postmenopausal women. Age, postmenopausal status and serum levels of dehydroepiandrosterone sulfate are important predictors of the severity of Covid-19 for women.

Dehydroepiandrosterone Sulfate, an Adrenal Androgen, Is Inversely Associated with Prevalence of Dynapenia in Male Individuals with Type 2 Diabetes.

Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia.

Sex-Specific Total Testosterone and Dehydroepiandrosterone Sulfate Status in Noncritically Ill Hospitalized Patients with Coronavirus Disease 2019: A Cross-Sectional Study.

In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently been linked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce. The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemical features. This cross-sectional observational study was done in the COVID-19 unit of a University hospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase- polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncture before receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescent microparticle immunoassay. Diagnosis and classification of COVID-19 were done according to World Health Organization's interim guidance. Age- and sex-specific laboratory reference values were used to classify the TT and DHEAS status of the patients. Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the females had high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal, and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity of COVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS (P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytes ratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034). In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected and correlated with severity markers in males.

The relationship between basal serum dehydroepiandrosterone sulfate (DHEAS) levels and the response to ovarian stimulation in in-vitro fertilization cycles

The relationship between basal serum dehydroepiandrosterone sulfate (DHEAS) levels and the response to ovarian stimulation in in-vitro fertilization cycles

Biomarkers in Body Fluids as Indicators of Skeletal Maturity: A Systematic Review and Meta-analysis.

This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment. A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software. A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2). Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.

Sex steroid hormones and allergic diseases in children: a pilot birth cohort study in the Japan Environment and Children’s Study cohort

BackgroundNumerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children.MethodsThe present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children’s Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases.ResultsAfter adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases.ConclusionsThe current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1(IGF-1) significantly correlated with serum DHEAS levels in either sex.

Anorexia nervosa and adrenal hormones: a systematic review and meta-analysis.

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. 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. 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. 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.

Sex Hormones associated with Temporomandibular Pain on Palpation in Male Adolescents - Results of the Epidemiologic LIFE Child Study.

This study aimed to investigate whether the sex steroid precursor hormone dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), and testosterone (TT) are associated with temporomandibular (TM) pain on palpation in male adolescents. Out of the LIFE Child study dataset containing 1,022 children and adolescents aged 10 to 18 years (496 males, 48.5%), we used a subsample of 273 male adolescents (mean age: 13.8 ± 2.3 years) in advanced pubertal development (PD) to analyze the association between hormones and TM pain. The Tanner scale was applied to describe the stage of PD. Pain on palpation of the temporalis and masseter muscles and the TM joints (palpation pain) was assessed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Serum levels of sex hormones (DHEA-S, SHBG, TT) were determined using standardized laboratory analyses. Free TT was estimated from the ratio between TT and SHBG (free androgen index = FAI). We calculated the risk of perceived positive palpation pain for male participants as a function of hormone levels (DHEA-S, FAI) taking into account age and body mass index (BMI). Among more developed (Tanner stage 4-5) male adolescents, 22.7% (n=62) reported palpation pain in the TM region. In these participants, FAI levels were approximately half that of individuals without such pain (p<0.01). DHEA-S levels were about 30% lower in the pain group (p<0.01). In multivariable regression analyses, the odds ratio (OR) for pain on palpation decreased to 0.75 (95% confidence interval [CI]: 0.57-0.98) per 10 units of FAI level compared to those without pain, after controlling for the effects of age and adjusted BMI. We observed the same effect for this subgroup per unit of DHEA-S serum level (OR=0.71; 95% CI: 0.53-0.94). At subclinical lower levels of serum free TT and DHEA-S, male adolescents are more likely to report pain on standardized palpation of the masticatory muscles and/or TM joints. This finding supports the hypothesis that sex hormones may influence pain reporting.

Effects of 2-Year Physical Activity and Dietary Intervention on Adrenarchal and Pubertal Development: The PANIC Study.

Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations. To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children. We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs. The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin. A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.

Changes in Brain Structure Associated with Adrenarche in Typically Developing Prepubertal Children

Adrenarche is marked by increases in neuroactive adrenal androgens, including dehydroepiandrosterone sulfate (DHEAS). However, the specific impact of DHEAS on neurodevelopment is difficult to disambiguate from that of gonadal hormones as both systems overlap in maturational trajectories. Here, we investigate the relationship between DHEAS concentrations and gray matter volume in prepubertal children studied prior to increases in gonadal hormones (i.e., gonadarche). Fasting morning blood samples and neuroimaging data were collected on ninety-two healthy children (55 boys, 8.6±.3years; 37 girls, 8.6±.3years) ascertained by physical examination to be prepubertal. Children underwent structural T1-weighted MRI in a 3 T scanner, and serum DHEAS concentrations were measured with liquid chromatography-tandem mass-spectrometry. A whole-brain, voxel-wise multivariate-model analysis (AFNI) was used to examine log-transformed DHEAS effects on gray matter volume, controlling for sex and total brain volume. Post-hoc non-parametric correlations were conducted in SPSS. There was an effect of DHEAS on gray matter volume in the right superior frontal gyrus, anterior cingulate cortex, and right amygdala (p’s<0.001). Post-hoc analyses showed that DHEAS correlated positively with gray matter volume in the right superior frontal gyrus (p=0.002) and anterior cingulate cortex (p=0.003), but negatively in the right amygdala (p=0.001). Our results identified an association between serum DHEAS and gray matter volume prior to gonadarche and support previous studies documenting associations between DHEA and cortical thickness in prepubertal children. These data suggest that DHEA(S) may play a role in extending the window of neurodevelopmental plasticity commonly associated with gonadarche.

Prospective Study of Associations Between Testosterone, Mortality, and Health Outcomes Among Adults Undergoing Hemodialysis

Prospective Study of Associations Between Testosterone, Mortality, and Health Outcomes Among Adults Undergoing Hemodialysis

Relationship between Serum Cortisol, Dehydroepiandrosterone Sulfate (DHEAS) Levels, and Natural Killer Cell Activity: A Cross-Sectional Study.

The adrenal steroid hormones, cortisol and dehydroepiandrosterone sulfate (DHEAS), are associated with the immune system in opposite actions. This study aimed to investigate the relationship between cortisol and DHEAS serum concentrations, their ratio (CDR), and natural killer cell activity (NKA). This cross-sectional study included 2275 subjects without current infection or inflammation in the final analyses. NKA was estimated by measuring the amount of interferon-gamma (IFN-γ) released by activated natural killer cells; low NKA was defined as IFN-γ level < 500 pg/mL. Cortisol, DHEAS levels, and CDRs were categorized by quartiles in men, premenopausal women, and postmenopausal women. Compared with the lowest quartile as reference, the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for low NKA of the highest cortisol and CDR group were 1.66 (1.09-2.51) and 1.68 (1.11-2.55) in men, 1.58 (1.07-2.33) and 2.33 (1.58-3.46) in premenopausal women, and 2.23 (1.28-3.87) and 1.85 (1.07-3.21) in postmenopausal women. Only in premenopausal women, the highest DHEAS group showed significantly lower risk of low NKA (OR: 0.51, 95% CI: 0.35-0.76). HPA axis activation indicated as high cortisol level, CDR was significantly associated with low NKA, while high DHEAS levels were inversely associated with low NKA in premenopausal women.