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Objective: The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population. Participants: Ninety-eight young, healthy, underweight women participated in this study. Design: To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively. Results: Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR. Conclusions: Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels. [ABSTRACT FROM AUTHOR]

The relationship between stress and behavior can help us to understand how physiological adaptations shape primate societies. Most studies have focused on glucocorticoids (GC) as stress biomarkers, but other extrinsic and intrinsic factors can influence GC levels and confound the results. To overcome this issue, including analyses of dehydroepiandrosterone-sulfate (DHEAS), a GC antagonist, can be useful in evaluating overall adrenal function in response to biological, social, and environmental factors. Our goal was to evaluate the effect of reproductive state, social behavior, ambient temperature, and season (mating and non-mating) on DHEAS levels and the ratio between GC metabolites and DHEAS (GCM:DHEAS) in 11 free-ranging, female, Japanese macaques (Macaca fuscata) (7 pregnant/lactating, 4 nonpregnant/nonlactating) from Jigokudani Monkey Park (Japan). We validated and measured fecal DHEAS levels in 354 samples by enzyme immunoassay and calculated GCM:DHEAS by using previously reported data for GC metabolites. We tested the effects of reproductive state, dominance rank, social behavior, season, and ambient temperature on adrenal steroids using Generalized Linear Mixed-Effect Models. We found that pregnant and lactating females had higher DHEAS levels than nonpregnant/nonlactating females and that DHEAS levels were higher during the mating season. Temperature was positively correlated with GCM:DHEAS. Dominant females had higher DHEAS levels and lower GCM:DHEAS than subordinate females. We suggest that the high DHEAS to GC ratio in high-ranking females explains why they have better body condition than low-ranking females despite high GCM levels. This study confirms that including DHEAS provides valuable information for evaluating the stress response in primates. [ABSTRACT FROM AUTHOR]

Background Prevailing experimental and epidemiological evidence supports the role of circulating endogenous sex steroid hormones in the pathogenesis of ovarian carcinogenesis by dysregulation of cell differentiation, proliferation, and apoptosis but is scarce and inconclusive. Objectives This article evaluates the role of circulating levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and androgens (testosterone, dehydroepiandrosterone-sulfate [DHEA-S]) for the risk of epithelial ovarian cancer in a case–control approach using samples collected in advance of clinical diagnosis. Materials and Methods A total of 100 epithelial ovarian cancer (EOC) patients and 100 healthy female controls were consequently enrolled in this hospital-based case–control study. Serum FSH, LH, testosterone, and DHEA-S were measured based on the principle of electrochemiluminescence immunoassay. Suitable descriptive statistics were used for different variables. Results Median values of FSH (58.9 vs. 45.5 IU/L, p = 0.02) and DHEA-S (163.43 vs. 142.2 ug/dL, p = 0.03) were significantly high in EOC patients compared with controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH and DHEA-S concentrations, and the results revealed that the highest third tertile of FSH (> 72.6 IU/L; OR = 3.0, confidence interval [CI] = 1.24–7.29, p trend = 0.04) and DHEA-S (> 194.2 ug/dL; OR = 3.8, CI = 1.26–11.61, p trend = 0.03) were significantly associated with increased risk of ovarian cancer in postmenopausal and premenopausal women, respectively. The statistically significant trend observed for FSH in postmenopausal women, remained only for the subgroup with menopause duration greater than 10 years (OR = 5.9, CI = 1.33–26.66, p trend = 0.04). FSH and DHEA-S concentrations and ovarian cancer risk were internally consistent with groups defined by oral contraceptive pill use, hormone replacement therapy, and smoking. However, no evidence was found for the association between serum LH and testosterone level with the occurrence of ovarian tumorigenesis. Conclusion Prediagnostic circulating concentration of FSH and DHEA-S unveiled a significant positive association with augmented risk of EOC, thus might serve as a predictive marker for the susceptibility to ovarian carcinogenesis and should be added in the screening profile of EOC for early recognition and scheduling necessary interventions/management strategies.

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are important estrogen precursors, secreted mainly by the adrenal cortex. At late gestation, both DHEA and DHEAS (DHEA(S)) are produced at high concentrations in some species due to the developing fetal adrenal gland. Failure in DHEAS increase during late gestation can indicate fetal death, which prompts its use as a biomarker of pregnancy and fetal health in wildlife. Here, we review the most common non-invasive biomarkers of reproduction in wildlife, the molecular mechanisms of DHEAS synthesis and action during gestation, in addition to the advantages and limitations of incorporating DHEA(S) in these studies. Using previously published data, we tested the specificity and sensitivity of fecal DHEAS as a predictor of successful gestation in four captive primate species (orangutans (Pongo pygmaeus), siamangs (Symphalangus syndactylus), Japanese macaques (Macaca fuscata), and howler monkeys (Alouatta caraya)). Using data from non-pregnant/non-lactating females, we set a threshold on fecal DHEAS levels for detecting successful pregnancy per species, controlling for age and housing condition (social vs single). We found that DHEAS had 100% specificity for all species (non-pregnant samples were below the threshold for pregnancy), and 100% sensitivity for Japanese macaques housed individually, and for orangutan and siamangs (all samples from successful pregnancies were above the threshold, and all samples from stillbirth were below the threshold). However, the sensitivity was 80% in howler monkeys and 50% in Japanese macaques housed socially. Our preliminary results indicate that, while DHEAS is a promising biomarker of fetal health, it is limited to late gestation and to some species. We suggest increasing the sample size to calculate the pregnancy threshold per species and to test multiple samples from the same individual when using this method.

Background. Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown. Methods. We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks. Results. DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees. [ABSTRACT FROM AUTHOR]

The regulation of DHEA-sulfate by steroid sulfotransferase (SULT) and steryl-sulfatase (STS) enzymes is a vital process for the downstream formation of many steroid hormones. DHEA-sulfate is the most abundant steroid hormone in the human body; thus, DHEA-sulfate and its hydrolyzed form, DHEA, continue to be evaluated in numerous studies, given their importance to human health. Yet, a basic question of relevance to the reproductive-age female population—whether the two steroid hormones vary across the menstrual cycle—has not been addressed. We applied a validated, multi-step protocol, involving realignment and imputation of study data to early follicular, mid-late follicular, periovulatory, and early, mid-, and late luteal subphases of the menstrual cycle, and analyzed DHEA-sulfate and DHEA serum concentrations using ultraperformance liquid chromatography tandem mass spectrometry. DHEA-sulfate levels started to decrease in the early luteal, significantly dropped in the mid-luteal, and returned to basal levels by the late luteal subphase. DHEA, however, did not vary across the menstrual cycle. The present study deep-mapped trajectories of DHEA and DHEA-sulfate across the entire menstrual cycle, demonstrating a significant decrease in DHEA-sulfate in the mid-luteal subphase. These findings are relevant to the active area of research examining associations between DHEA-sulfate levels and various disease states. [ABSTRACT FROM AUTHOR]

Objective: The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population., Participants: Ninety-eight young, healthy, underweight women participated in this study., Design: To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively., Results: Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR., Conclusions: Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sato, Tamura, Kaga, Yamasaki, Kadowaki, Sugimoto, Nakagata, Someya, Nishida, Kawamori and Watada.)

Background: Work-related stress is a critical area of research in civil aviation, given the potential for severe consequences when airline pilots (APs) are overwhelmed or unable to perform optimally. While pilots are traditionally considered to be exposed to various stressors, the impact of specific occupational characteristics on stress in the aviation industry remains inadequately understood. Considering that biomarkers are increasingly being utilized as objective measures of stress in human research, this cross-sectional study investigated the association between occupational variables and serum levels of cortisol and dehydroepiandrosterone sulfate (DHEAS) as stress biomarkers in commercial APs., Methods: A total of 120 male APs completed a survey assessing the following work-related characteristics: position (captain vs. first officer), years of experience, total flight hours, flight hours in the preceding year, inter-flight rest duration, and flight route length. Serum cortisol and DHEAS concentrations were determined from venous blood samples obtained between 08:00 and 09:00 a.m., following a minimum eight-hour fasting period. The biomarker data were analyzed in relation to the aforementioned occupational characteristics., Results: The mean serum cortisol and DHEAS concentrations in the entire cohort were 8.5±2.1 µg/dL and 214.6±96.4 µg/dL, respectively. There were no significant differences in the levels of the two stress hormones in relation to position, years of experience, total flight hours, flight hours in the preceding year, or flight route length. However, an inter-flight rest period of less than one hour was significantly associated with elevated serum cortisol (P<0.01) and reduced DHEAS levels (P<0.001) compared to longer rest durations. Notably, a stepwise decrease in DHEAS concentrations was observed for rest periods of <1 hour, 1-4 hours, 4-24 hours, and >24 hours. After adjustment for potential confounders in multivariable analyses, a rest period of <1 hour remained independently associated with both serum cortisol (odds ratio [OR]=1.09, 95% confidence interval [CI]=1.04-1.13, P<0.01) and DHEAS (OR=0.94, 95% CI=0.92-0.97, P<0.001)., Conclusions: Serum stress hormones in APs are associated with short inter-flight rest periods. Optimization of rest durations may contribute to improved pilot well-being and performance. Further research is warranted to determine ideal rest period lengths and develop interventions to mitigate the potential adverse effects of abbreviated rest periods between flights., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Studio Minoretti issued approval 2021/07SH. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Minoretti et al.)

Background Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown. Methods We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks. Results DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees.

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation. [ABSTRACT FROM AUTHOR]

We investigated the extent to which individual differences in activity of the hypothalamic pituitary adrenal axis (HPA) are associated with depressive symptoms among newlywed couples. Participants were 218 couples (M age 28.4 years; 94% White) who provided 5 saliva samples (later assayed for cortisol and DHEA-S) before and after participation in a discussion of a major area of disagreement in their relationship. Depressive symptoms were assessed initially, and approximately 19- and 37-months later. Results revealed an interactive effect suggesting that concordant levels of cortisol and DHEA-S (either both high or both low) were concurrently and prospectively associated with higher depression scores. Interestingly, this interactive effect was observed for wives only - not for husbands. These observations underscore contemporary theoretical assumptions that the expression of the association between HPA activity and depression is dependent on factors related to the interaction between characteristics of the person and features of the social environment, and moderated by co-occurring variation in endocrine milieu.

The regulation of DHEA-sulfate by steroid sulfotransferase (SULT) and steryl-sulfatase (STS) enzymes is a vital process for the downstream formation of many steroid hormones. DHEA-sulfate is the most abundant steroid hormone in the human body; thus, DHEA-sulfate and its hydrolyzed form, DHEA, continue to be evaluated in numerous studies, given their importance to human health. Yet, a basic question of relevance to the reproductive-age female population—whether the two steroid hormones vary across the menstrual cycle—has not been addressed. We applied a validated, multi-step protocol, involving realignment and imputation of study data to early follicular, mid-late follicular, periovulatory, and early, mid-, and late luteal subphases of the menstrual cycle, and analyzed DHEA-sulfate and DHEA serum concentrations using ultraperformance liquid chromatography tandem mass spectrometry. DHEA-sulfate levels started to decrease in the early luteal, significantly dropped in the mid-luteal, and returned to basal levels by the late luteal subphase. DHEA, however, did not vary across the menstrual cycle. The present study deep-mapped trajectories of DHEA and DHEA-sulfate across the entire menstrual cycle, demonstrating a significant decrease in DHEA-sulfate in the mid-luteal subphase. These findings are relevant to the active area of research examining associations between DHEA-sulfate levels and various disease states.

Non-invasive measures of stress are crucial for captive and conservation management programs. The adrenal hormone dehydroepiandrosterone-sulfate (DHEAS) has recently been adopted as a stress marker, but there is little investigation of its relationship to glucocorticoids (GC), well-known indicators of stress. This study examined the influence of age, reproductive state and environment on GC and DHEAS levels in orangutans, to test whether the GC/DHEAS ratio can provide an index of stress response in primates. We measured fecal GC (fGC) and fecal DHEAS (fDHEAS) concentrations in 7 captive orangutans from zoological parks in Japan and 22 wild orangutans from Danum Valley Conservation Area, Malaysia. We found that in a stressful condition (transportation), fDHEAS levels increased 2 days after the fGC response, which occurred 1 day after the stressor. One pregnant female had elevated levels of both hormones, and a higher fGC/fDHEAS ratio than baseline. Females in the first year of lactation had fGC levels and the fGC/fDHEAS ratio significantly higher than both baseline and females in the second and subsequent years of lactation. There was no effect of age on fGC levels, but the fGC/fDHEAS ratio was higher in infants than adults and adolescents. fDHEAS concentrations were lower in infants than juveniles, adolescents and adults, a phenomenon known as adrenarche, shared with humans and other great apes. We suggest that changes in DHEAS during orangutan life history are associated with changes in the dynamics of maintaining homeostasis that vary with age and reproductive state. The GC/DHEAS ratio index is useful to evaluate age-related abilities of responding to stressful challenges. [ABSTRACT FROM AUTHOR]

Abstract Background Previous reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity. Methods We conducted a longitudinal observational analysis of a subgroup of women from the Study of Women’s Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2. Results Compared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (β 9.180, p < 0.0001) and E1 (β 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (β 28.80, p = 0.061) and A4 (β 0.2556, p = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (β 0.0764, p = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time. Conclusion This report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI.

In dogs, the phase from mating to the end of weaning lasts about 120 days and encompasses many aspects that, interacting, contribute to increase the allostatic load. The coat and claws, useful for long-term change assessments, have the advantage of being collectable without invasiveness. In the present study, the Cortisol (C) and Dehydroepiandrosterone-sulfate (DHEA-S) concentration monthly changes in the coat and claws were studied in female dogs from mating to the end of weaning to assess Hypothalamic–Pituitary–Adrenal (HPA) axis activation during pregnancy and the post-partum period. The results from 15 Dobermann Pinscher female dogs showed a trend of increase of the coat C from mating to 60 days post-partum, with significant changes between mating and parturition-60 days post-partum (p < 0.01) and between the 30-day pregnancy diagnosis (PD) and 30–60 days post-partum (p < 0.05). The claws C trend showed significant increases between mating and 30–60 days post-partum (p < 0.05) and between the PD and 60 days post-partum (p < 0.01). DHEA-S in both matrices showed non-significant changes. The results suggest that maternity could play a pivotal role in the HPA axis activation, with a subsequent chronic secretion of C determining an increase in the allostatic load in the mothers. Neither maternal parity nor litter size played a significant role in the accumulation of C and DHEA-S in both matrices.

Highlights • Overall, morning and 24 h cortisol was significantly lower in PTSD than controls (trauma-exposed and non-trauma exposed controls). • No clear pattern of dysregulation was found across investigated moderators. • Guidelines regarding standardized assessment of hormone parameters are needed. Abstract Posttraumatic stress disorder (PTSD) is often associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Previous findings are inconsistent, possibly due to trauma exposure of controls or different hormone measurement methods. We investigated cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) in adults with clinical PTSD under basal or challenged conditions (Prospero registration no. CRD42016041690). A search of PubMed, Scopus, Medline, PsycINFO, Pilots/ProQuest , and Web of Science resulted in 108 included studies (N = 6484). Morning and 24 h cortisol were significantly lower in PTSD than in controls (g = −0.21; 95% CI: −0.42–(−0.01); g = −0.31; CI: −0.60–(−0.03)). Significant cortisol increases occurred after awakening in PTSD (g = 0.40; CI: 0.13–0.67) and in non-exposed controls (g = 0.96; CI: 0.59–1.33). Evening DHEA was significantly higher in PTSD than in non-exposed controls (g = 0.58; CI: 0.17–0.99). All groups showed large cortisol suppression effects after dexamethasone administration. Overall, the potential moderators investigated did not reveal a consistent pattern of HPA alterations. [ABSTRACT FROM AUTHOR]

Highlights • There is considerable diversity in study and hormone assessment designs. • Changes from pre- to post-test in basal cortisol and in the CAR were not significant. • The primary studies found significant changes only in subgroups. • Consistent use of established hormone parameters (CAR, slope, AUC) is essential. • Further guidelines for standardized hormone sampling procedures are needed. Abstract Posttraumatic stress disorder (PTSD) has been associated with dysregulation of the hypothalamic–pituitary– adrenal (HPA) axis. Research over the past years has investigated potential changes of these alterations in the context of psychotherapy. Yet, no systematic review has been conducted. To summarize the current state of research on psychotherapy and HPA hormones, namely cortisol, dehydroepiandrosterone and its sulfate form (DHEA(S)), we searched for studies investigating predictions or changes in hormones over treatment course within the databases PubMed, Scopus, Medline, PsychINFO, Pilots/ProQuest, and Web of Science, and in the grey literature up to May 2018. Controlled and uncontrolled trials investigating adult samples with a clinical status of PTSD were eligible for inclusion. Twelve studies (428 participants) were included. Study quality was overall sufficient. Hormone assessment designs differed considerably. Treatment efficacy on PTSD symptom reduction was mostly high, but predictions of pre-treatment hormone concentrations on treatment efficacy were largely non-significant. Changes from pre- to post-test in basal cortisol (g = −0.07, 95% CI = −0.36; 0.21) and in the cortisol awakening response (g = −0.07, 95% CI = −0.48; 0.35) were also non-significant. Future studies require comparable designs and need to be sufficiently powered to be able to detect potential associations with HPA regulation. [ABSTRACT FROM AUTHOR]

Summary: Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH.Introduction: One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing’s syndrome (CS), and nonfunctional AI (NFAI).Methods: We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women).Results: After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (β = −0.133, P = 0.045) and women (β = − 0.140, P = 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (β = − 0.252, P < 0.001), but not men. This inverse association of cortisol/DHEA-S ratio in women remained statistically significant after adjusting for the serum cortisol level after 1 mg DST (β = − 0.221, P = 0.008). Compared with women with NFAI, women with SH had 2.2% lower TBS (P = 0.040). Deteriorated bone microstructure (TBS < 1.230) was associated with the serum cortisol level after 1 mg DST (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.04-4.53) and cortisol/DHEA-S ratio (OR, 2.05; 95% CI, 1.03-4.08).Conclusions: Subtle cortisol excess in both genders and reduced DHEA-S, especially in women, may contribute to impaired bone quality in Asian patients with SH. [ABSTRACT FROM AUTHOR]

Abstract Introduction Gender-affirming hormone treatment is known to affect adrenal androgen levels in adult individuals with gender dysphoria (GD). This may be clinically relevant because the adrenal gland plays a critical role in many different metabolic processes. Aim This study aims to assess the effects of gonadotropin-releasing hormone analogs (GnRHa) treatment and gender-affirming hormone treatment on adrenal androgen levels in adolescents with GD. Methods In this prospective study, dehydroepiandrosterone-sulfate (DHEAS) and androstenedione values were measured every 6 months during 2 years of GnRHa treatment only, and 2 years of GnRHa combined with gender-affirming hormone treatment (estradiol or testosterone) in 73 transgirls and 54 transboys. To determine trends in adrenal androgen levels a linear mixed model was used to approximate androgen levels. Main Outcome Measures DHEAS and androstenedione levels were the main outcome measures. Results DHEAS levels rose in transboys during GnRHa treatment, which may represent the normal increase during adolescence. In transgirls no change in DHEAS levels during GnRHa treatment was found. Gender-affirming hormone treatment did not affect DHEAS levels in either sex. In transboys androstenedione levels decreased during the first year of GnRHa treatment, which may reflect reduced ovarian androstenedione synthesis, and rose during the first year of gender-affirming hormone treatment, possibly due to conversion of administered testosterone. In transgirls androstenedione levels did not change during either GnRHa or gender-affirming hormone treatment. Clinical Implications No deleterious effects of treatment on adrenal androgen levels were found during approximately 4 years of follow-up. Strengths & Limitations This is one of the largest cohort of adolescents with GD, treated using a uniform protocol, with standardized follow-up. The lack of a control group is a limitation. Conclusion The changes in androstenedione levels during GnRHa and gender-affirming hormone treatment in transboys may not be of adrenal origin. The absence of changes in androstenedione levels in transgirls or DHEAS levels in either sex during gender-affirming hormone treatment suggests that gender-affirming hormone treatment does not significantly affect adrenal androgen production. Schagen SEE, Lustenhouwer P, Cohen-Kettenis PT, et al. Changes in Adrenal Androgens During Puberty Suppression and Gender-Affirming Hormone Treatment in Adolescents With Gender Dysphoria. J Sex Med 2018;15:1357–1363. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone-sulfate (DHEAS) is the main steroid product of the primate fetal adrenal during mid to late gestation and it plays a major role in providing estrogens needed for parturition. We tested the hypothesis that this hormone can indicate fetal health status and attempted to use fecal DHEAS (fDHEAS) to predict pregnancy outcome in Japanese macaques. The subjects were 16 adult females and 3 neonatal Japanese macaques living in captivity at the Primate Research Institute, Kyoto University. We classified females that gave birth to healthy infants as successful and females that gave birth to dead infants as stillbirth (late fetal loss) and miscarriage (early fetal loss). The remaining females did not become pregnant and were used as controls. We collected fecal samples from all cycling, pregnant, and post-pregnant females as well as the three neonates for analysis of fDHEAS, fecal estrogen (fE) and fecal progesterone (fP) by enzyme immunoassay. We found that fE and fP increased during gestation in both successful and stillbirth groups, but increased only during the first two months in the female that had a miscarriage. Levels of fDHEAS only increased in the second half of gestation in successful pregnancies. Neonates had extremely elevated concentrations of fDHEAS in comparison to post-parturition females, which confirms that DHEAS metabolites are a product of the fetal adrenal. Low DHEAS levels could be a marker of an unsuccessful pregnancy in primates. Monitoring fDHEAS levels can be useful in zoos and institute management and can be applied to wild and free-ranging populations. [ABSTRACT FROM AUTHOR]

Several studies have suggested that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may enhance working memory and attention, yet current evidence is still inconclusive. The balance between both forms of the hormone might be crucial regarding the effects that DHEA and DHEAS exert on the central nervous system. To test the hypothesis that higher DHEAS-to-DHEA ratios might enhance working memory and/or involuntary attention, we studied the DHEAS-to-DHEA ratio in relation to involuntary attention and working memory processing by recording the electroencephalogram of 22 young women while performing a working memory load task and a task without working memory load in an audio-visual oddball paradigm. DHEA and DHEAS were measured in saliva before each task. We found that a higher DHEAS-to-DHEA ratio was related to enhanced auditory novelty-P3 amplitudes during performance of the working memory task, indicating an increased processing of the distracter, while on the other hand there was no difference in the processing of the visual target. These results suggest that the balance between DHEAS and DHEA levels modulates involuntary attention during the performance of a task with cognitive load without interfering with the processing of the task-relevant visual stimulus. [ABSTRACT FROM AUTHOR]

Cardiovascular stress reactivity is a predictor of atherosclerosis and cardiac events. Dehydroepiandrosterone (DHEA) protects against cardiovascular diseases, but results among previous studies have been inconsistent. We investigated the association between dehydroepiandrosterone-sulfate (DHEA-s) and cardiovascular stress reactivity in Japanese women and men. Among 979 healthy Japanese subjects (641 women and 338 men), serum levels of DHEA-s, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, heart rate variability, and peripheral blood flow were measured under rest and two types of task. Mean differences in measured variables during tasks and a post-task period were calculated as changes in stress reactivity. Variables of stress reactivity were adjusted for multiple potential confounding factors. In women, DHEA-s levels showed positive associations with changes in SBP and DBP (standardized beta = 0.12, p = 0.020; 0.17, 0.002, respectively). Stratification by menopausal status and other lifestyle factors (e.g., smoking status, alcohol consumption) were conducted. Significant positive associations remained in pre-menopausal (standardized beta = 0.13, p = 0.037; 0.18, 0.005), non-smoking (0.12, 0.010; 0.18, <0.001), and non-drinking women (0.14, 0.021; 0.21, 0.001), and women without a medical history (0.15, 0.020; 0.20, 0.001). In men, there was no significant association between DHEA-s levels and changes in stress reactivity. DHEA-s levels were positively associated with high blood-pressure reactivity to stress in women, and being menopausal, smoking, and alcohol consumption modified this association. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may have mood enhancement effects: higher DHEAS concentrations and DHEA/cortisol ratio have been related to lower depression scores and controlled trials of DHEA administration have reported significant antidepressant effects. The balance between DHEAS and DHEA has been suggested to influence brain functioning. We explored DHEAS, DHEA, cortisol, DHEA/cortisol and DHEAS/DHEA ratios relations to the processing of negative emotional stimuli at behavioral and brain levels by recording the electroencephalogram of 21 young women while performing a visual task with implicit neutral or negative emotional content in an audio–visual oddball paradigm. For each condition, salivary DHEA, DHEAS and cortisol were measured before performing the task and at 30 and 60 min intervals. DHEA increased after task performance, independent of the implicit emotional content. With implicit negative emotion, higher DHEAS/DHEA and DHEA/cortisol ratios before task performance were related to shorter visual P300 latencies suggesting faster brain processing under a negative emotional context. In addition, higher DHEAS/DHEA ratios were related to reduced visual P300 amplitudes, indicating less processing of the negative emotional stimuli. With this study, we could show that at the electrophysiological level, higher DHEAS/DHEA and DHEA/cortisol ratios were related to shorter stimulus evaluation times suggesting less interference of the implicit negative content of the stimuli with the task. Furthermore, higher DHEAS/DHEA ratios were related to reduced processing of negative emotional stimuli which may eventually constitute a protective mechanism against negative information overload. [ABSTRACT FROM AUTHOR]

Summary Individual differences in the psychobiology of the stress response have been linked to behavior problems in youth yet most research has focused on single signaling molecules released by either the hypothalamic–pituitary–adrenal axis or the autonomic nervous system. As our understanding about biobehavioral relationships develops it is clear that multiple signals from the biological stress systems work in coordination to affect behavior problems. Questions are raised as to whether coordinated effects should be statistically represented as ratio or interactive terms. We address this knowledge gap by providing a theoretical overview of the concepts and rationales, and illustrating the analytical tactics. Salivary samples collected from 446 youth aged 11–12 were assayed for salivary alpha-amylase (sAA), dehydroepiandrosterone-sulfate (DHEA-s) and cortisol. Coordinated effect of DHEA-s and cortisol, and coordinated effect of sAA and cortisol on externalizing and internalizing problems (Child Behavior Checklist) were tested with the ratio and the interaction approaches using multi-group path analysis. Findings consistent with previous studies include a positive association between cortisol/DHEA-s ratio and internalizing problems; and a negative association between cortisol and externalizing problems conditional on low levels of sAA. This study highlights the importance of matching analytical strategy with research hypothesis when integrating salivary bioscience into research in behavior problems. Recommendations are made for investigating multiple salivary analytes in relation to behavior problems. [ABSTRACT FROM AUTHOR]

The ability to determine hormonal profiles of primate populations using non-invasive techniques can help to monitor physical fitness, stress, and physiological responses to environmental changes. We investigated fecal glucocorticoids (fGC) and DHEAS concentrations in captive Japanese macaques ( Macaca fuscata) in relation to environmental, biological, and social factors. The subjects were female Japanese monkeys from 4 months to 31 years old housed in captivity (27 in social groups and 12 in single cages). Fecal samples were collected from all females, and behavioral data from the social groups during the mating season and the following birth season. Hormonal concentrations were analyzed by enzyme immunoassay. Our results revealed that both fGC and fecal DHEAS concentrations are higher in females housed indoors in single cages than in those living outdoors in social groups. We also found that fGC concentrations were higher in the cycling females during the mating (winter) season than the lactating females in the birth (spring) season. Age was negatively associated to both fGC and fecal DHEAS levels, but the relationship between age and fecal DHEAS was more evident in females housed indoors in single cages than in females housed in outdoor social groups. We did not observe any association of dominance rank with either fecal DHEAS or fGC. This study showed that measurement of fecal DHEAS and fGC can be a good method to assess stress in Japanese macaques. These findings provide insights about the physiology of these two adrenal hormones in female Japanese macaques, which can be applied to wild populations and is fundamental for captive management and conservation biology. Am. J. Primatol. 76:1084-1093, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Rationale: Hypothalamic-pituitary-adrenal (HPA) axis hormones have neuroactive metabolites with receptor activity similar to ethanol. Objectives: The present study related HPA hormones in naïve monkeys to ethanol self-administration. Methods: Morning plasma adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone (DOC), aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were measured longitudinally in male rhesus macaques ( Macaca mulatta) induced to drink ethanol followed by access to ethanol (4 % w/ v, in water) and water 22 h/day for 12 months. Results: During ethanol access, DOC increased among non-heavy (average intake over 12 months ≤3.0 g/kg/day, n = 23) but not among heavy drinkers (>3.0 g/kg/day, n = 9); aldosterone was greater among heavy drinkers after 6 months. The ratio of DOC/aldosterone decreased only among heavy drinkers after 6 or12 months of ethanol self-administration. ACTH only correlated significantly with DHEA-S, the ratio of cortisol/DHEA-S and DOC after the onset of ethanol access, the former two just in heavy drinkers. Baseline hormones did not predict subsequent ethanol intake over 12 months, but baseline DOC correlated with average blood-ethanol concentrations (BECs), among all monkeys and heavy drinkers as a group. During ethanol access, aldosterone and DOC correlated and tended to correlate, respectively, with 12-month average ethanol intake. Conclusions: Ethanol self-administration lowered ACTH and selectively altered its adrenocortical regulation. Mineralocorticoids may compensate for adrenocortical adaptation among heavy drinkers and balance fluid homeostasis. As DOC was uniquely predictive of future BEC and not water intake, to the exclusion of aldosterone, GABAergic neuroactive metabolites of DOC may be risk factors for binge drinking to intoxication. [ABSTRACT FROM AUTHOR]

Highlights: [•] DHEAS promoted MIN6 cells insulin secretion for 24h. [•] AMPK activity may partly play an important role in regulating insulin secretion in DHEAS-treated MIN6 cells. [•] Increased insulin secretion via AMPK inhibition is accompanied by ACC-1 upregulation. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined the potential influence of age and season on fecal DHEAS concentrations among female Japanese macaques. [•] DHEAS concentration was negatively correlated with age. [•] Season had no effect on DHEAS concentrations. [•] Elevated neonatal DHEAS is possibly a residue from fetal adrenal secretion. [ABSTRACT FROM AUTHOR]

Background and aims: Serum dehydroepiandrosterone-sulfate (DHEAS), the most abundant adrenal steroid hormone, may predict aging status and longevity in humans. The aims of this study are to clarify the fundamental properties of serum DHEAS as a biomarker for health in middle-aged men. Methods: We investigated correlations of serum DHEAS with age or conventional health indices (body mass index, blood pressure, and 12 serum/blood tests) and associations of serum DHEAS with lifestyle factors (smoking, drinking, exercise, sleep) in 384 healthy men aged 30-49 years, randomly selected from voluntary attendees at a checkup. Results: Serum DHEAS had an inverse and stronger correlation with age (Spearman's r=-0.320, p<0.001) than with any conventional health indices used here. Regardless of age and BMI adjustments, serum DHEAS had a weak correlation with serum uric acid (crude Spearman's r=0.198, p<0.001), and its correlations with other conventional health indices were weaker or non-significant. Serum DHEAS rose in parallel with increased smoking and alcohol intake (p for trend <0.001 in both), but had no significant relationships with exercise or sleep. Conclusions: Serum DHEAS reflects age better than health status evaluated by conventional health indices, and may increase with cigarette smoking and alcohol drinking in middle-aged healthy men. [ABSTRACT FROM AUTHOR]

Abstract: Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are the most abundant steroids circulating in human blood. DHEA stimulates endothelial cells to release high amounts of nitric oxide in the circulation. Nitric oxide activates guanylyl cyclase in platelets thus decreasing the responsiveness of these cells to physiological agonists. However, the impact of DHEA-S and DHEA on platelet function and their possible role in modulating the response of human platelets to physiological agonists were not yet investigated. Here, DHEA-S, but not DHEA, inhibited in vitro thrombin-dependent platelet aggregation in a dose-dependent manner. DHEA-S exerted this effect by decreasing thrombin-dependent dense granule secretion, and so impairing the positive feed-back loop provided by ADP. Furthermore, DHEA-S inhibited thrombin-dependent activation of Akt, ERK1/2, and p38 MAP kinase. Although both DHEA-S and DHEA directly activated in platelets the inhibitory cGMP/PGK/VASP pathway, these events were not responsible for the inhibitory action of DHEA-S in platelets. In addition DHEA-S acted in synergism with nitric oxide in inhibiting platelet aggregation. In conclusion DHEA-S inhibited platelet activation caused by a mild stimulus without completely hampering platelet functionality and thus DHEA-S may participate in the physiological mechanisms that maintain circulating platelets in a resting state. The role played by DHEA-S could be relevant mainly when the functionality of the vascular endothelium is compromised. [Copyright &y& Elsevier]

Aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen receptor-positive breast cancer, are associated with an increased risk of musculoskeletal symptoms. The underlying cause of the symptoms is often attributed to estrogen depletion, yet all women treated with AIs have low estrogen levels and only a subset develop symptoms. Concentrations of circulating androgens may be mediating factors contributing to these side effects. The purpose of this study was to examine changes in androgen concentrations among women initiating AI therapy and to determine if concentrations are associated with musculoskeletal symptoms. Data were analyzed from a cohort study of 74 breast cancer patients for whom AI therapy was planned. Questionnaire data on symptoms were collected and blood was drawn prior to AI therapy (baseline) and then again at 3 and 6 months after baseline. Blood was assayed for testosterone, androstenedione, dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Free testosterone index (FTI) values were calculated using testosterone and SHBG measurements. The results showed that concentrations of all of the androgens increased over the study period, with statistically significant differences from baseline concentrations observed for the FTI at 3 and 6 months and for DHEAS at 6 months . Additionally, breast cancer patients with new onset or worsening of pain over the study period had a significantly smaller change in mean DHEAS concentration from baseline to 3 months ( P = 0.04) and a marginally significant smaller change in mean DHEAS concentration from baseline to 6 months ( P = 0.1) compared to those who reported no pain at all time points or no worsening of pain across the study period. Changes in testosterone, androstenedione, and the FTI were not associated with the onset or worsening of pain during the study period. Findings from this study suggest that higher DHEAS concentrations are associated with less AI-associated pain and should be further investigated. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone-sulfate (DHEA-S) are involved in age-related diseases such as cardiovascular disease and diabetes mellitus, the association of these hormones with serum adiponectin level is still unclear. Objective and methods: To investigate the association between serum IGF-I and DHEA-S versus adiponectin, we conducted a cross-sectional study of 348 Japanese men with type 2 diabetes mellitus and examined their relationships. Serum total adiponectin level was measured by an ELISA kit. Results: Simple correlation analysis showed that patients'' age and duration of diabetes were negatively correlated with IGF-I and DHEA-S (p<0.01) and positively with adiponectin (p<0.01), while body mass index (BMI) was positively correlated with IGF-I and DHEA-S (p<0.001) and negatively with adiponectin (p<0.001). IGF-I was negatively correlated with adiponectin (r=−0.25, p<0.001) and DHEA-S was negatively correlated with adiponectin and HbA1c (r=−0.17, p=0.003 and r=−0.12, p=0.027, respectively). In multiple regression analysis adjusted for age, duration of diabetes, BMI, and serum creatinine, HbA1c was negatively associated with IGF-I and DHEA-S (β=−0.12, p=0.036 and β=−0.22, p<0.001, respectively). Adiponectin was negatively associated with IGF-I (β=−0.15, p=0.013), but not DHEA-S. Moreover, this association was still significant after additional adjustment for HbA1c (β=−0.18, p=0.005). Conclusions: Present cross-sectional study for the first time showed a negative association of serum IGF-I with serum adiponectin in Japanese men with type 2 diabetes independent of age, duration of diabetes, BMI, renal function, and HbA1c. [Copyright &y& Elsevier]

Steroid biosynthesis is initiated with transportation of cholesterol along with steroidogenic acute regulatory protein (StAR) into the mitchondria and is achieved with several steroidogenic enzymes. It has been reported that Ca2+ channel blockers (CCBs), such as azelnidipine, efonidipine and nifedipine, suppress the biosynthesis of aldosterone and cortisol, but the overall effects of CCBs on steroid biosynthesis remain to be clarified. The present study was designed to evaluate the effects of CCBs on the expression of steroidogenic enzymes and the production of adrenal androgen, dehydroepiandrosterone sulfate (DHEA-S) that has anti-atherosclerotic actions. NCI-H295R human adrenocortical carcinoma cells and HepG2 human hepatoma cells were cultured for 24 hours with or without a CCB (amlodipine, efonidipine, nifedipine, azelnidipine R(-)-efonidipine, verapamil or diltiazem). HepG2 hepatoma cells were used to confirm the effects of CCBs on the expression of StAR. In fact, efonidipine and nifedipine increased the expression of StAR in HepG2 cells. Efonidipine and nifedipine, but not other examined CCBs, also increased the N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP)-induced StAR mRNA, which relects the action of adrenocorticotropic hormone, and efonidipine and R(-)-efonidipine enhanced the dbcAMP-induced DHEA-S production in NCI-H295R adrenocortical carcinoma cells. Therefore, efonidipine and nifedipine might increase the expression of StAR and, in turn, efonidipine enhanced the dbcAMP-induced DHEA-S production, independent of Ca2+ channel blockade. These results indicate that such effects are not associated with Ca2+ influx. Moreover, only efonidipine enhanced the angiotensin II-induced expression of StAR mRNA (P < 0.01 vs. angiotensin II alone). In conclusion, efonidipine might exert an additional action beyond anti-hypertensive actions. [ABSTRACT FROM AUTHOR]

Abstract: Stress and anxiety are commonly thought to be detrimental to sexual function. Several studies in both the human and animal literature, however, have found that inducing anxiety can enhance sexual function in women. The mechanisms that explain a negative relationship between physical and psychological stress and sexual functioning are well documented, but little is known about how stress or anxiety might have a facilitatory effect on sexual arousal. As an initial step in exploring the relationship between anxiety and sexual arousal, the present study examined the role of the autonomic nervous system, and the adrenal hormones cortisol and dehydroepiandrosterone-sulfate (DHEA-S) in response to a sexual film, an anxiety-inducing film, and a humorous film. Nineteen premenopausal women (mean age 24.4years) who were free from sexual difficulties came into the lab on three separate days. At each session they were shown an anxiety-inducing, sexually arousing, or humorous (control) film while their physiological arousal was measured. They also provided saliva samples before and after each film. Cortisol significantly decreased, while DHEA-S increased in the sexual and humorous conditions. Neither hormone changed significantly in the anxiety-inducing condition. Autonomic nervous system activity measured by heart rate and heart rate variability did not change in response to the sexual or anxiety-inducing films, but heart rate variability increased significantly in response to the humorous film. The cortisol/DHEA-S ratio at the post-sexual film time point was significantly negatively correlated with genital arousal (measured by vaginal pulse amplitude). Anxiety-inducing films did not result in a physiological stress response, which can explain why they do not impair sexual function. [Copyright &y& Elsevier]

Abstract: Dehydroepiandrosterone sulfate is classically seen as an inactive reservoir for the production of dehydroepiandrosterone. Steroid sulfatase is the enzyme that catalyzes the hydrolysis of dehydroepiandrosterone sulfate to dehydroepiandrosterone, which can then be further metabolized to other steroid hormones. Recent studies, however, indicate that dehydroepiandrosterone sulfate can mediate biological effects without being converted to dehydroepiandrosterone. This study aims to evaluate whether dehydroepiandrosterone sulfate itself influences the differentiation of PC-12 cells or if its desulfation to dehydroepiandrosterone is required. dehydroepiandrosterone and dehydroepiandrosterone sulfate both influence the differentiation of chromaffin PC-12 cells. Blocking steroid sulfatase activity and thereby the conversion of dehydroepiandrosterone sulfate to dehydroepiandrosterone by the enzyme blocker estrone sulfamate showed that the effect of dehydroepiandrosterone sulfate is independent of its conversion to dehydroepiandrosterone. Dehydroepiandrosterone sulfate, similar to dehydroepiandrosterone, reduced nerve growth factor-induced neurite outgrowth of PC-12 cells and the expression of synaptosomal-associated membrane protein of 25kDa, increased the expression of chromogranin A and significantly increased dopamine release of PC-12 cells. In addition, dehydroepiandrosterone sulfate, dehydroepiandrosterone and membrane impermeable dehydroepiandrosterone-BSA all significantly reduced NGF-induced MAPK ERK1/2 signaling after 5min. In summary, this study provides evidence that dehydroepiandrosterone sulfate, independent of its conversion to dehydroepiandrosterone, directs PC-12 cells’ differentiation to a neuroendocrine direction. Furthermore, employing membrane-impermeable dehydroepiandrosterone-BSA indicates the involvement of plasma-membrane bound receptors. [Copyright &y& Elsevier]

Background: Dehydroepiandrosterone-sulfate (DHEA-S) has been described as a protector agent against obesity-related pathologies, although the mechanism of action is still unknown. We have shown that DHEA-S acts on adipose tissue (AT), altering the fatty acid (FA) profile in rodents. Thus, we could hypothesize that some of the beneficial effects shown by DHEA-S in humans are related to a modification of the human AT-FA profile. The present study examines this question and whether this effect is tissue-dependent. Methods: Paired visceral and subcutaneous AT biopsies were obtained from 20 patients who had undergone bariatric surgery. These samples were subjected to primary adipose culture and incubated for 24 h with 1 μM DHEA-S. The FA profile of both control and treated samples were analyzed by gas chromatography. Results: A reduction in total saturated fatty acids (SFA), the n−6 family of polyunsaturated fatty acids (PUFA) and the n−6/ n−3 PUFA ratio was observed after DHEA-S treatment, whereas monounsaturated fatty acids (MUFA) increased. In addition, DHEA-S altered the percentage of several individual FA, decreasing palmitic acid and increasing vaccenic acid in both AT. All estimated desaturase activity ratios slightly increased after DHEA-S treatment, although only the increase of delta-6-desaturase index in both depots reached statistical significance. No depot-specific action of DHEA-S was found between subcutaneous and visceral AT. Conclusions: In vitro, DHEA-S modifies the AT-FA composition towards a better metabolic profile to a similar extent in the subcutaneous and visceral adipose depots, in both of which a decrease in SFA and increased MUFA are observed after treatment. This effect could help to explain the beneficial effects attributed to DHEA-S. Further studies, however, are required to determine whether the effect of DHEA-S on adipose tissue in vitro is conserved in vivo. [ABSTRACT FROM AUTHOR]

Abstract: A significant role for hormones in regulating the balance of Th1- and Th2-associated cytokines with a role in modulating diseases has been accumulating. Previously, we reported that dehydroepiandrosterone (DHEA), the most abundant steroid hormone synthesized by the adrenal cortex, markedly reduced the blood and tissue parasites in experimentally Trypanosoma cruzi-infected rats. Based on these findings, the main purpose of this study was to investigate the effect of dehydroepiandrosterone-sulfate ester (DHEA-S) therapy alone or in combination with benznidazole (BNZ) (recommended in Brazil for the treatment of T. cruzi infection) will be effective during the acute phase of two different lineages of T. cruzi strains: type I (Y strain) and type II (Bolivia strain) of T. cruzi. Administration of either DHEA-S or BNZ alone or in combination significantly reduced the Y strain parasite load as compared with untreated. Furthermore treatment with DHEA-S resulted in Bolivia strain clearance. This protective effect of DHEA-S was associated with the host''s immune response, as evidence by enhanced levels of interferon-gamma and interleukin-2. DHEA-S treatment also increased peritoneal macrophages levels and nitrite production. DHEA-S treatment was effective in reducing the mortality rate as compared to BNZ alone or to combiner DHEA-S+BNZ treatment of T. cruzi Bolivia strain infected animals. These findings suggest that hormonal therapy may have a protective effect in the treatment of T. cruzi infection. [Copyright &y& Elsevier]

Inhaled dehydroepiandrosterone-3-sulfate (DHEAS), but not dehydroepiandrosterone (DHEA), possesses anti-inflammatory activity in in vitro assays and in models of allergen and lipopolysaccharide challenges. We postulated whether an inhaled suspension of DHEAS delivered via nebulizer would improve asthma control in moderate-to-severe asthma patients. We also characterized the safety profile of an inhaled suspension of DHEAS. Patients receiving at least 500 μg of fluticasone equivalent plus long-acting beta-agonists (LABA) entered a 5-week run-in where the dose of inhaled corticosteroids was reduced to 200 μg of fluticasone plus LABA per day. Patients were randomized to 70 mg of DHEAS or placebo if their Asthma Control Questionnaire (ACQ) score was ≥2.0 and their FEV1 ≥ 50%. When compared with control, a statistically significant improvement in ACQ in 6 weeks of treatment with 70 mg of DHEAS was observed. The median improvement in ACQ was -0.72 and -0.43 for the active and placebo groups, respectively (p = 0.0389); the percentage of patients with at least minimally clinically important difference of -0.50 from baseline was significantly greater in the DHEAS group versus the placebo, (59.4% versus 45.7%; p = 0.0236). Asthma symptom scores, the proportion of symptom-free days and symptom nights, although not statistically significant, had positive trends supporting the improvement in ACQ. Fewer patients were withdrawn from the study for respiratory events on DHEAS compared with placebo. There were few adverse events and no changes in sex hormones despite increases in circulating levels of DHEAS. An inhaled suspension of DHEAS delivered via nebulizer improved asthma control scores in subjects with poorly controlled moderate-to-severe asthma. Australian New Zealand Clinical Trials Registry ANZCTR.org.au Identifier: 012607000192482 [ABSTRACT FROM AUTHOR]

Objective: Increased plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) have been demonstrated in post-traumatic stress disorder (PTSD), but the documented beneficial effects of these steroids in enhancing mood and cognition, as well as neuroprotection, suggest their presence in PTSD may be associated with defensive rather than maladaptive effects. Method: We, therefore, examined plasma DHEA, DHEAS, cortisol, and the DHEA/cortisol ratio in 40 male veterans with or without PTSD, and determined their relationships to PTSD symptom severity and symptom improvement. Results: The PTSD group showed significantly higher plasma DHEA and non-significantly higher DHEAS levels as well as a significantly lower cortisol/DHEA ratio, controlling for age. Regression analyses demonstrated that DHEA and DHEAS levels could be predicted by symptom improvement and coping, whereas the cortisol/DHEA ratio was predicted by severity of childhood trauma and current symptom severity. Conclusion: That greater symptom improvement was related to DHEA levels may suggest for a role for these hormones in modulating recovery from PTSD. [ABSTRACT FROM AUTHOR]