Higher Dehydroepiandrosterone Sulfate Research Articles

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.

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.

Association of size for gestational age and dehydroepiandrosterone sulfate with cardiometabolic risk in central precocious puberty girls.

The aim of this study was to assess whether size for gestational age and dehydroepiandrosterone sulfate (DHEAS) are associated with cardiometabolic risk in central precocious puberty (CPP) girls. The retrospective study included 443 patients with newly diagnosed CPP. Subjects were categorized by birth weight for gestational age (appropriate [AGA], small [SGA], and large [LGA] for gestational age) and serum DHEAS concentration (high [≥75th percentile] and normal [<75th percentile] DHEAS). Cardiometabolic parameters were examined. Composite cardiometabolic risk (CMR) score was calculated based on BMI, blood pressure, glucose, insulin, triglyceride, and HDL cholesterol. Non-obesity CMR score was computed, omitting the value from BMI. Logistic regression models, general linear models, and partial correlation analyses were used to evaluate associations. Propensity score matching was performed for sensitivity analyses. Overall, 309 patients (69.8%) were born AGA, 80 (18.1%) were born SGA, and 54 (12.2%) were born LGA. Compared with AGA counterparts, CPP girls born SGA were more prone to have elevated HbA1c (adjusted OR = 4.54; 95% CI, 1.43-14.42) and low HDL cholesterol (adjusted OR = 2.33; 95% CI, 1.18-4.61). In contrast, being born LGA was not associated with increased risk for any glucose or lipid derangements. Despite the fact that elevated CMR score was more common among individuals born LGA than AGA (adjusted OR = 1.84; 95% CI, 1.07-4.35), no significant difference was found on non-obesity CMR score (adjusted OR = 0.75; 95% CI, 0.30-1.88). When controlling for age, birth weight SDS, and current BMI-SDS, individuals with high DHEAS exhibited higher HDL cholesterol and apolipoprotein A-1 concentrations and lower triglyceride level and non-obesity CMR score. Furthermore, DHEAS correlated positively with HDL cholesterol and apolipoprotein A-1 and negatively with triglyceride, prominently in girls born SGA, after adjustments for the three abovementioned confounders. Sensitivity analyses corroborated the findings. Among CPP girls, those born SGA were more likely to possess cardiometabolic risk factors compared to their AGA peers. The difference we observed in cardiometabolic risk between individuals born LGA and AGA was driven by BMI. High DHEAS was associated with favorable lipid profile in CPP girls, even in subjects born SGA.

Low Total Testosterone Levels in Men with Newly Diagnosed Early-Onset Type 2 Diabetes: A Cross-Sectional Study in China.

There is a bidirectional interaction between circulating testosterone and blood glucose levels. We aim to investigate the testosterone levels in men with early-onset type 2 diabetes (T2DM). A total of 153 drug naive men with T2DM were enrolled in the study. Early- (n = 63) and late-onset (n = 90) T2DM was classified according to age 40 years old. Clinical characteristics and plasma for biochemical criterions were collected. Gonadal hormones were measured using chemiluminescent immunometric assay. The concentrations of 3β- and 17β-HSD were determined using ELISA. Compared with men with late-onset T2DM, those with early-onset T2DM had lower serum total testosterone (TT), sex hormone-binding globulin (SHBG), and FSH, but higher dehydroepiandrosterone sulfate (DHEA-S) level (p < 0.05). The mediating effect analysis showed that the decreased TT levels in patients with early-onset T2DM were associated with the higher HbA1c, BMI, and triglyceride in these patients (both p < 0.05). The early-onset of T2DM directly correlated with increased DHEA-S (both p < 0.01). The 3β-HSD concentration in the early-onset T2DM group was lower than that in the late-onset T2DM group (11.07 ± 3.05 vs. 12.40 ± 2.72 pg/mL, p = 0.048) and was positively correlated with fasting C-peptide, while negatively correlated with HbA1c and fasting glucagon (p all < 0.05). Patients with early-onset T2DM showed inhibition of conversion from DHEA to testosterone, which may attribute to the low level of 3β-HSD and high blood glucose in these patients.

High DHEAS in girls and metabolic features throughout pubertal maturation.

An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high dehydroepiandrosterone sulphate(DHEAS [HD]) at the adrenarche determines the risk of metabolic syndrome during puberty, taking into account body mass index (BMI) and birth weight. Prospective observational. Five hundred four girls from the Growth and Obesity Chilean Cohort Study were followed from birth through puberty. At age ~7, subjects were classified by DHEAS concentrations into the HD(>75th percentile) or normal DHEAS (ND,≤75th percentile) subgroups. Anthropometrics, semiannual clinical pubertal stagingand hormonal and metabolic levels. The relationships among DHEAS at age ~7, metabolic syndrome, and each of its components independently, were analyzed by linear and logistic regression models during puberty and 1-year postmenarche, adjusted by confounders. Girls with HD at 7 years exhibited higher BMI, more central fatand higher serum androgen andinsulin like growth factor (IGF)-I levels throughout puberty. Also, girls with HD had a greater prevalence of hyperglycemia at B2 and B4 breast stages, and of low HDL at B4. At 1 year after menarche, HD girls had a higher prevalence of metabolic syndrome, and those with BMI > 1 SD score had a higher metabolic score and insulin levels than ND girls with similar BMI. Our observations suggest that girls with HD at the age of adrenarche may be at greater risk for metabolic syndrome at adolescence, especially in those who are overweight or obese. Our results emphasize the importance of lifestyle interventions for childhood overweight and obesity among girls with HD.

Circulating DHEA-S levels and major cardiovascular outcomes in chronic Chagas cardiomyopathy: A prospective cohort study

ObjectiveTo analyze the association of circulating dehydroepiandrosterone sulfate (DHEA-S) levels with cardiovascular outcomes in patients with chronic Chagas cardiomyopathy (CCM) diagnosis. BackgroundDHEA-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. MethodsProspective 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). ResultsSeventy-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. ConclusionsIn 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.

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

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

Effect of Mindfulness-Based Stress Reduction on dehydroepiandrosterone-sulfate in adults with self-reported stress. A randomized trial.

Long‐term stress can lead to long‐term increased cortisol plasma levels, which increases the risk of numerous diseases. Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone‐sulfate (DHEAS), together DHEA(S), have shown to counteract some of the effects of cortisol and may be protective during stress. The program “Mindfulness‐Based Stress Reduction” (MBSR) has shown to have positive effects on stress. The present study examined a possible effect of MBSR on DHEAS in plasma compared to a waiting list and a locally developed stress reduction program (LSR) in people with self‐reported stress. The study was a three‐armed randomized controlled trial conducted in a municipal health care center in Denmark. It included 71 participants with self‐reported stress randomized to either MBSR (n = 24) or LSR (n = 23), or a waiting list (n = 24). Blood samples were collected at baseline and at 12 weeks follow‐up to estimate effects of MBSR on DHEAS. The effect of MBSR on DHEAS was statistically significant compared to both the waiting list and LSR. We found a mean effect of 0.70 µmol/L (95% confidence interval [CI] = 0.18–1.22) higher DHEAS in the MBSR group compared with the waiting list group and a mean effect of 0.54 µmol/L (95% CI = 0.04–1.05) higher DHEAS in the MBSR group compared with the LSR group. Findings indicate an effect on DHEAS of the MBSR program compared to a waiting list and LSR program in people with self‐reported stress. However, we consider our findings hypothesis‐generating and validation by future studies is essential.

Abstract #1003768: Non Classic Congenital Adrenal Hyperplasia Due to Late Onset 3 Beta-Hydroxysteroid Dehydrogenase Deficiency Diagnosed as a Work Up of Infertility and Adrenal Adenoma

3 Beta-Hydroxysteroid Dehydrogenase (3B-HSD) deficiency is a rare form of Congenital Adrenal Hyperplasia (CAH). It is an autosomal recessive disease leading to varying degrees of enzymatic defects. Presented is a case of late onset type 2 3B-HSD deficiency, diagnosed as a work up of infertility, adrenal adenoma, and high dehydroepiandrosterone sulfate (DHEA-S) levels.

Dehydroepiandrosterone sulphate (DHEAS) concentrations stringently regulate fertilisation, embryo development and IVF outcomes: are we looking at a potentially compelling 'oocyte-related factor' in oocyte activation?

Erratic oocyte-activation affects fertilization and embryo development. Dehydro-epiandrosterone sulphate (DHEAS) is present in theca/cumulus-granulosa cells, regulates the same calcium-pumps that cause calcium-oscillations in mice and its levels are altered in women with no or low fertilization rates. Yet no study has explored correlation of DHEAS with oocyte-activation. We proposed to implicate DHEAS as an oocyte-related factor in oocyte-activation by demonstrating that rectification of deviated (both lower/and higher than normal) DHEAS concentrations to normal post-treatment improves fertilization, embryo development rates. Prospective Closed-Cohort. Recruited n = 750 (150 women/subgroup) in previously classified Low(A), Average/Control(B), High(C) D3-serum DHEAS groups. 50% women in both A and C groups received 3-months exposure to oral DHEAS and Metformin respectively. Also measured Follicular-fluid DHEAS levels. Compared embryologic, clinical outcomes: DHEAS untreated (A1) vs. treated (A2); metformin untreated (C1) vs. treated (C2) and A1/A2/C1/C2 against normal-control-B group. Also compared serum vs. FF-group results. Significantly improved embryologic, clinical parameters in treated A2/C2 compared to untreated A1/C1 subgroups respectively. Post-treated improved parameters in A2/C2 were comparable with, whereas untreated A1/C1 sub-groups had significantly lower values than, normal-control B-group. Parameters differed significantly between Low, Medium, High FF-DHEAS groups. Results in serum vs. FF: A1 vs. LowFF, C1 vs. HighFF and A2/C2/B vs. MediumFF were comparable. Odds of fertilization, live-births increased in post-treatment A2/C2 subgroups. Fertilization rates strongly correlated with FF-DHEAS. Rectification of deviated DHEAS levels post-treatment significantly improves outcomes, comparable with those exhibited by normal-control DHEAS thresholds. DHEAS is the most promising endogenous oocyte-related factor influencing embryologic, clinical IVF outcomes possibly by affecting oocyte-activation.

Cross-Sectional and Longitudinal Effects of PCB Exposure on Human Stress Hormones in the German HELPcB Surveillance Program.

Multiple pathological associations are attributed to PCBs (polychlorinated biphenyls). Research shows a positive association of PCBs with dehydroepiandrosterone sulfate (DHEAS) concentration but the results on the stress hormone cortisol have been inconsistent so far. This study is the first to examine not only the cross-sectional but also the longitudinal effects of PCB exposure on the stress hormones DHEAS and cortisol. Over a period of three years, 112 former employees occupationally exposed to PCBs were tested for their body burden with different types of PCBs (lower and higher chlorinated, dioxin-like and hydroxylated) and for their stress hormone concentration. Highly exposed employees showed a significantly higher risk for higher DHEAS values. Multiple linear regression analysis revealed a positive relationship between the exposure to lower chlorinated PCBs and DHEAS. Mixed models also revealed a significantly positive correlation between lower chlorinated PCBs with DHEAS when controlled for a cross-section. However, an effect for cortisol was not found. These results suggest a causal pathophysiological relationship between PCB exposure and DHEAS concentration, but not with cortisol. The health consequences of high DHEAS concentrations are discussed.

Elevated maternal androgen is associated with dysfunctional placenta and lipid disorder in newborns of mothers with polycystic ovary syndrome

To investigate the placental morphology alterations and identify the clinical characteristics of women with polycystic ovary syndrome (PCOS) and their newborns. Pregnant women with PCOS (n = 12) and pregnant women without PCOS (n = 11) were recruited. Then, the placenta, maternal blood and cord blood were collected after delivery. Clinical observational study. Not applicable. In the present study, pregnant women with PCOS and healthy pregnant women were recruited from the clinic of the Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, China, between February 2015 and October2015. None. A proteomic analysis was performed on the placenta in women with PCOS and healthy women. The maternal testosterone, androstenedione, dehydroepiandrosterone sulfate, free androgen index, cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A-I levels were significantly higher in the PCOS group than in the control group, and the offspring in the PCOS group had higher dehydroepiandrosterone sulfate, high-density lipoprotein, and cholesterol levels, when compared with the control group. The placenta in the PCOS group demonstrated infarction, calcification, and a greater intervillous space, when compared with the control group. A higher level of estrogen receptor-β protein was observed in the placenta of women with PCOS, when compared with women without PCOS. A total of 258 proteins in the placenta were identified to be significantly different, when the PCOS and control groups were compared, and fibronectin 1 exhibited the closest relationship with other differential proteins. The overexposure to hyperandrogenism and hyperlipidemia affects the functions of the placenta, which are associated with the development of metabolic disorders in newborns.

Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia

BackgroundDepending on CYP21A2 genotype, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to biochemical alterations (including hyperandrogenism, hypocortisolism, and hypoaldosteronism) and a wide spectrum of phenotypic disease manifestation. The latter include life-threatening salt-wasting crises, prenatal virilization of genitalia in women (classic CAH [C-CAH]) as well as milder forms of the disease exclusively presenting with hirsutism, acne or reduced fertility (nonclassic CAH [NC-CAH]), and could influence sexual function and identity. AimThe present study evaluated sexual function, gender identification, and partner preference in women with C-CAH and NC-CAH. MethodsIn a cross-sectional cohort analysis, 35 female patients with CAH were divided into 2 groups: C-CAH (salt-wasting/simple virilizing; n = 17) and NC-CAH (n = 18) according to genotype and phenotype. Sexual function and sexual distress were assessed using established questionnaires, including the Female Sexual Function Index. Phenotype (defined by signs of hyperandrogenism) was assessed clinically (Ferriman-Gallwey score) and with the ovulatory function index. CYP21A2 genotype was determined by Sanger sequencing and multiplex ligation-dependent probe amplification. Sexual function was also separately analyzed in the context of clinical signs of androgenization in women with (n = 13) and without acne (n = 22). OutcomesThe study outcomes were sexual function and sexual distress in relation to genotype, clinical signs of androgenization, and biochemical parameters. ResultsWomen with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress, as well as biochemical evidence of hyperandrogenism (higher dehydroepiandrosterone sulfate and lower SHBG) and a trend toward more clinical signs of hyperandrogenism (hirsutism). Indicators of in utero and childhood androgen excess as well as the presence of acne in all patients were related to lower sexual function and higher sexual distress. Clinical signs of hyperandrogenism correlated well with cardiovascular and metabolic risk factors. Clinical TranslationWomen with NC-CAH and women with clinical signs of hyperandrogenism demonstrated higher distress compared to women with C-CAH and women without clinical signs of hyperandrogenism, respectively, regarding different aspects of sexual function. ConclusionsThese data underline the importance of early diagnosis and therapy initiation, especially in patients with NC-CAH.Schernthaner-Reiter MH, Baumgartner-Parzer S, Egarter HC, et al. Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia. J Sex Med 2019;16:1529–1540.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8–13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8–13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8–13, 14–18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8–13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8–13, but lower odds of progressing to the next stage at 14–18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development.

Dehydroepiandrosterone Sulfate and Free Testosterone but not Estradiol are Related to Muscle Strength and Bone Microarchitecture in Older Adults.

The study aimed to elucidate the relationship between sex steroids and muscle mass, muscle strength, and trabecular bone score (TBS) in a community-dwelling aged population. We analyzed 922 men > 60years of age and 1244 postmenopausal women. Weak muscle strength was defined as hand grip strength < 26kg for men and < 18kg for women, whereas degraded bone microarchitecture was defined as a TBS ≤ 1.2. The mean age was 70.2 ± 6.8years for men and 71.2 ± 6.7years for women. Participants within higher dehydroepiandrosterone sulfate(DHEAS) and free testosterone (FT) tertiles were likely to be younger, have greater muscle mass, and have stronger hand grip strength. Based on logistic regression models, men within the lowest FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted odds ratio [OR] 2.28; 95% confidence interval [CI] 1.33-3.91). Women within the lowest DHEAS and FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted OR for DHEAS 1.42; 95% CI 1.02-1.99; adjusted OR for FT 1.77, 95% CI 1.26-2.48). Moreover, men within the lowest FT tertile exhibited degraded bone microarchitecture compared to those in the highest tertile (adjusted OR 2.57, 95% CI 1.46-4.51). However, estradiol was not related to muscle strength or bone microarchitecture in both sexes. In conclusion, in aged men, serum FT was closely associated with muscle strength and bone microarchitecture and in postmenopausal women, serum DHEAS and FT were related to muscle strength.

Adrenarcheal Timing Longitudinally Predicts Anxiety Symptoms via Amygdala Connectivity During Emotion Processing

This study aimed to examine longitudinally whether adrenarcheal timing (adrenarcheal hormone levels independent of age) and tempo (change in hormone levels over time) were associated with amygdala functional connectivity and how this in turn related to anxiety symptoms in the transition from childhood to adolescence. Participants were 64 children (34 girls) who completed the Spence Children's Anxiety Scale and saliva collections to measure levels of testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate at two time points (mean age 9.5 years at time 1 [T1], 12.2 years at time 2 [T2]). Participants also viewed fearful and calm facial expressions while undergoing functional magnetic resonance imaging scanning at both time points. Amygdala functional connectivity was assessed with psychophysiological interaction analysis and modeled longitudinally with the Multivariate and Repeated Measures MATLAB toolbox. Controlling for age, higher dehydroepiandrosterone sulfate at T1 was related to an increase in amygdala to inferior frontal gyrus connectivity over time (T1 to T2) in boys, but the opposite pattern was found in girls. Dehydroepiandrosterone at T1 showed a positive association with amygdala connectivity to several lateral prefrontal areas and the anterior cingulate across time. Higher dehydroepiandrosterone at T1 was indirectly related to more anxiety symptoms at T2, controlling for symptoms at T1, via more positive amygdala to inferior frontal gyrus connectivity. Changes in hormone levels did not relate to changes in amygdala connectivity (from T1 to T2). The results suggest that amygdala to prefrontal cortex connectivity may be a mechanism through which early adrenarcheal timing predicts the development of anxiety symptoms during adrenarche.

Role of the Androgen Receptor Gene CAG Repeat Polymorphism on the Sequence of Pubertal Events and Adiposity in Girls with High Dehydroepiandrosterone Sulfate Level.

The androgen receptor (AR) harbors a variable repeat number of glutamine residues codified by (CAG)n, which seems to inversely affect AR transcriptional activity. We assessed whether (CAG)n affects the sequence of the androgen-sensitive pubertal events and body composition in prepubertal girls. Nested case-control study within the Growth and Obesity Cohort Study of 1196 low-middle income children (approximately 50% girls) from a university clinic in Santiago, Chile. Cases were girls with high dehydroepiandrosterone sulfate (DHEAS; >42μg/dL; HD) at age 7.0 (±0.4) years (n=58). On follow-up, 32 of them had thelarche (TB2) before the age of pubarche (PH2) and 26 had PH2 before the age of TB2. As controls, 107 age-matched girls with normal DHEAS (≤42μg/dL; ND) were selected. Methylation-weighted mean (CAG)n (mw[CAG]n) was calculated through X-chromosome methylation-sensitive enzyme restriction and polymerase chain reaction followed by automated capillary electrophoresis in peripheral blood DNA. Girls with HD and PH2 before the age of TB2 showed a trend to higher frequency (7/26, 26.9%) of mw(CAG)n <20 compared with ND girls (12/107; 11.2%; P=.087). Accordingly, a direct correlation between age of PH2 and mw(CAG)n was observed in HD (r=0.352; P=.007) and in ND girls (r=0.207; P=.033). Moreover, HD girls with mw(CAG)n less than 20 had lower waist circumference and waist/height ratio than HD girls with mw(CAG)n from 20 to less than 25 (P=.027 and P=.012, respectively) at age of DHEAS determination. Our results suggest that a greater transcriptional activity of theAR, given by short number of CAG repeats, might favor the onset of pubarche and reduce central adiposity in prepubertal girls with HD.

Quantification of fetal steroids in nails of neonates to quantify prenatal stress and growth restriction

This study assesses the impact of prenatal stress and intrauterine growth restriction (IUGR) on the dehydroepiandrosterone (DHEA) and dehydroepiandrosteronesulfate (DHEAS) concentrations in nails of newborns.Nail samples were gained from 56 newborn infants. The concentration of DHEA and DHEAS was measured by liquid chromatography/tandem mass spectrometry. Prenatal stress was assessed by the Prenatal Distress Questionnaire and by the Life Experience Survey.Prenatal stress was not associated with infant nail DHEA or DHEAS concentrations. The concentration of DHEA and DHEAS was decreased in infants with IUGR (DHEA: p = 0.037, DHEAS p < 0.01). Nail-DHEAS increased with gestational age (p < 0.01).In this study prenatal life event stress or pregnancy specific stress do not correlate with higher DHEA or DHEAS concentrations in nails of newborns. Concentration of DHEAS is rather affected by length of gestation. Our approach is an easily applicable method to assess intrauterine life with the potential to give insights in the activity of fetal hormone systems and mechanism underlying fetal programming.

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension.

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL-1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.

Associations of Dehydroepiandrosterone Sulfate With Cardiometabolic Risk Factors in Prepubertal Children.

Premature adrenarche (PA) has been associated with overweight and insulin resistance, but the associations of serum dehydroepiandrosterone sulfate (DHEAS) concentration with other cardiometabolic risk factors are uncertain. To examine the associations of serum DHEAS concentration with several cardiometabolic risk factors in children. Cross-sectional data from the Physical Activity and Nutrition in Children Study. Population sample of 207 girls and 225 boys aged 7.6 ± 0.4 years. Cardiometabolic risk factors by serum DHEAS concentration. DHEAS correlated positively with body mass index standard deviation score, body fat percentage, lean body mass, high-sensitivity C-reactive protein (hs-CRP), and alanine aminotransferase (ALT) when adjusted for age and sex. The associations of DHEAS with hs-CRP and ALT disappeared when adjusted also for body fat percentage. When further adjusted for birth weight SD score, DHEAS correlated negatively with low-density lipoprotein (LDL) cholesterol and LDL/high-density lipoprotein (HDL) cholesterol ratio. LDL cholesterol was lower in children with DHEAS ≥40 µg/dL than in those with DHEAS <40 µg/dL, adjusted for age, sex, and body fat percentage (86.5 vs 92.3 mg/dL, P = 0.029). This association strengthened after further adjustment for birth weight SD score (85.3 vs 92.3 mg/dL, P = 0.012). Higher DHEAS is not associated with an increased cardiometabolic risk in prepubertal children. Instead, it may be protective, evidenced by an association with lower LDL cholesterol and LDL/HDL cholesterol ratio. The increased cardiometabolic risk in PA shown in many studies may be due to low birth weight and childhood overweight associated with PA.