Higher Dehydroepiandrosterone Research Articles

Sex-specific association of serum dehydroepiandrosterone and its sulfate levels with osteoporosis in type 2 diabetes.

This study is to investigate the relation between serum dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels and the risk of osteoporosis in patients with T2DM. This cross-sectional study involved 938 hospitalized patients with T2DM. Linear regression models were used to explore the relationship between DHEA and DHEAS and the BMD at different skeletal sites. Multinominal logistic regression models and the restricted cubic spline (RCS) were used to evaluate the associations of DHEA and DHEAS with the risks of osteopenia and/or osteoporosis. In postmenopausal women with T2DM, after adjustment for confounders including testosterone and estradiol, DHEA showed a significant positive correlation with lumbar spine BMD (P = 0.013). Moreover, DHEAS exhibited significant positive correlations with BMD at three skeletal sites: including femoral neck, total hip, and lumbar spine (all P < 0.05). Low DHEA and DHEAS levels were associated with increased risk of osteopenia and/or osteoporosis (all P < 0.05) and the risk of osteoporosis gradually decreased with increasing DHEAS levels (P overall = 0.018, P-nonlinear = 0.559). However, DHEA and DHEAS levels in men over the age of 50 with T2DM were not associated with any of above outcomes. In patients with T2DM, independent of testosterone and estradiol, higher DHEA and DHEAS levels are associated with higher BMD and lower risk of osteopenia/osteoporosis in postmenopausal women but not men over the age of 50.

High Pretreatment DHEA Is Associated with Inferior Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer.

Background: Sex difference in the immune response may influence patients' response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC). Method: Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort. Result: Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7-43); p < 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89-23.35); p < 0.0001]. Conclusions: High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs.

Unveiling the spectrum: A cross-sectional exploration of hirsutism causes in women.

Hirsutism is a common endocrine disorder and its etiology varies from benign and idiopathic disorders to serious malignant diseases. Hirsutism creates negative impact on quality of life and considerable effects on fertility. Our objective was to determine the various causes of hirsutism in women presenting at two endocrine clinics. This cross-sectional study was conducted at Baqai Institute of Diabetology and Endocrinology, Karachi and at Jinnah hospital, Lahore from August 2020 to December 2021 women between 12-45 years of age with complains of hirsutism were included in the study. Severity of Hirsutism was evaluated using modified Ferriman-Gallwey score (FG). Patients with modified FG score of 8 or more were considered having hirsutism. The study had 113 patients with a mean age of 15.50+7.29 years with 89% having moderate hirsutism (FG score 16-25). Polycystic ovaries was the most common cause of hirsutism. Common sites for hirsutism included back (83%), arms (74%), buttocks (70%), and upper abdomen (47%). High BMI (p-value <0.01) and high Dehydroepiandrosterone levels were positively associated with the severity of hirsutism (p-value of 0.006.). The various causes of hirsutism identified were polycystic ovaries, followed by idiopathic, thyroid dysfunction, congenital adrenal hyperplasia, and hyperprolactinemia; therefore, all women presenting with hirsutism should be evaluated for potential serious and curable etiologies, before embarking on a treatment plan.

Comparative steroid profiling of newborn hair and umbilical cord serum highlights the role of fetal adrenals, placenta, and pregnancy outcomes in fetal steroid metabolism

Previous steroid hormone studies concerning pregnancy and newborns have mainly focused on glucocorticoids; wider steroid profiles have been less commonly investigated. Here, we performed a comparative analysis of 17 steroids from newborn hair and umbilical cord serum at the time of delivery. The study participants (n = 42, 50% girls) were a part of the Kuopio Birth Cohort and represent usual Finnish pregnancies. The hair and cord serum samples were analyzed with liquid chromatography high resolution mass spectrometry and triple quadrupole tandem mass spectrometry, respectively. We detected high individual variations in steroid hormone concentrations in both sample matrices. The concentrations of cortisol (F), corticosterone (B), estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), 11β-hydroxyandostenedione (11bOHA4), 5α-androstanedione (DHA4), and 17α-hydroxypregnenolone (17OHP5) correlated positively between cord serum and newborn hair samples. In addition, F and 11bOHA4 concentrations correlated positively with each other in both newborn hair and cord serum samples. The cortisone-to-cortisol ratio (E/F) was significantly higher in cord serum than in newborn hair samples reflecting high placental 11βHSD2 enzyme activity. Only minor sex differences in steroid concentrations were observed; higher testosterone (T) and 11-deoxycortisol (S) with lower 11bOHA4 in male cord serum, and higher DHEA, androstenedione (A4) and 11bOHA4 in female newborn hair samples. Parity and delivery mode were the most significant pregnancy- and birth-related parameters associating with F and some other adrenocortical steroid concentrations. This study provides novel information about intrauterine steroid metabolism in late pregnancy and typical concentration ranges for several newborn hair steroids, including also 11-oxygenated androgens.

The Role of Puberty and Hormones in Psychopathology Symptoms Severity and Directionality in Male Adolescents across Development

Externalizing and internalizing psychopathology affect both male and female adolescents; however, symptoms tend to present differently according to gender. Internalizing symptoms in particular may go undetected in males, although internalizing and externalizing symptoms often co-occur. We investigated the role of puberty and hormones in males on the development of symptom severity (overall behavior problems) and directionality (preponderance of internalizing vs. externalizing symptoms) from middle childhood to early adolescence. At time 1, mean age was 7.44 years (SD = 0.96, N = 1711), time 2 M age = 13.16 years, SD = 1.26, N = 348, and time 3 M age = 14 years, SD = 1.34, N = 387. Data on Tanner staging, the Pubertal Development Scale, pubertal hormones [dehydroepiandrosterone (DHEA), testosterone], and a range of internalizing and externalizing symptom measures were collected. Growth curve models examined the role of pubertal status, timing, and hormones on male adolescents’ symptom severity trajectory and symptom preponderance (directionality). Earlier pubertal timing predicted higher symptom severity (p=0.004). As they aged, while controlling for puberty, adolescents showed a preponderance of externalizing symptoms (p=0.042). High DHEA level was associated with lowered symptom severity (p=0.031), while high testosterone level was associated with elevated symptom severity (p=0.009) and showed a preponderance of externalizing symptoms (p=0.044). Findings suggest that some male adolescents are more vulnerable to changes during puberty and as they matured. Future research is needed to investigate risk factors that put some male adolescents at more risk for increasing psychopathology symptoms across development.

Exploring profiles of hormone exposure: Associations with cognition in a population-based cohort of early adolescents

Testosterone, dehydroepiandrosterone (DHEA), and estradiol are the main hormonal markers of puberty. Previous research has explored links between these hormones and cognition with little consideration of how hormonal patterns may co-occur and together, influence cognitive processes. The current study uses a novel approach to capture this heterogeneity, using latent profile analysis (LPA) to generate empirically-derived hormone profiles in a population-level dataset of adolescents. We analyzed basal salivary testosterone, DHEA, and estradiol data from 10,816 youth (48.1% female, Mage = 9.91, SDage =.63) using LPA in the Adolescent Brain Cognitive Development (ABCD) study and examined whether hormone profiles differentially predicted cognition assessed two years later. Eight profiles were identified, primarily representing differences in hormone levels (e.g., Low Hormones, High Hormones), but also discordance (e.g., High Estradiol). There were limited sociodemographic differences, but youth in higher hormone profiles had better inhibitory control, visuospatial processing, and decision-making skills, even after adjusting for age, income, race/ethnicity, and pubertal status. For example, girls in the High Estradiol profile had better visuospatial processing skills compared to all other girls and girls in the High DHEA profile as well as boys in the High Hormone profile made significantly fewer risky decisions than youth in the Low Hormone profiles. Higher hormone levels may predict better cognition over time in early adolescence. Further, this work suggests that pubertal hormone profiles likely reflect distinct physiological phenomena with unique cognitive consequences that may not be observed by studying individual hormone levels or subjective pubertal status.

A high serum dehydroepiandrosterone concentration is a predictor of candidates for active surveillance in men with serum prostate-specific antigen < 10 ng/mL

BackgroundThere is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy.MethodsA systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC–MS/MS) just before biopsy. Patient’s age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses.ResultsThe median patient’s age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively.ConclusionThe study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.

Profiles of diurnal cortisol and DHEA regulation among children: Associations with maltreatment experiences, symptomatology, and positive adaptation.

Person-centered methods represent an important advance in the simultaneous examination of multiple indicators of neuroendocrine functioning and may facilitate a more nuanced understanding of the impact of child maltreatment on hypothalamic-pituitary-adrenal axis dysregulation. The aims of the present study were threefold: (a) identify naturally occurring patterns of diurnal cortisol and dehydroepiandrosterone (DHEA) regulation among a sample of N = 1,258 children with and without histories of maltreatment, (b) investigate which neuroendocrine profiles characterize children with exposure to maltreatment, and (c) examine which profiles are related to adaptive outcomes and symptomatology among children. Cortisol and DHEA were sampled three times per day (9 a.m., 12 p.m., and 4 p.m.) across 5 and 2 days, respectively. Four profiles of cortisol and DHEA regulation were identified. Among females, a pattern marked by high cortisol and low DHEA was associated with more pervasive maltreatment experiences. Furthermore, we found evidence of adaptive interpersonal resilience such that children with maltreatment exposure who evidenced this pattern of high cortisol and low DHEA were viewed as more likeable than maltreated children with other neuroendocrine patterns. Finally, results pointed to higher levels of internalizing symptoms among children who displayed a profile marked by average cortisol and high DHEA.

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.

Neurobiological effects of a probiotic-supplemented diet in chronically stressed male Long-Evans rats: Evidence of enhanced resilience.

Probiotics that regulate the microbiome-gut-brain axis and provide mental health benefits to the host are referred to as psychobiotics. Preclinical studies have demonstrated psychobiotic effects on early life stress-induced anxiety- and depression-related behavior in rodents; however, the specific mechanisms remain ill-defined. In the current study, we investigated the effects of probiotic supplementation on neurobiological responses to chronic stress in adult male Long-Evans rats. Twenty-four rats were randomly assigned to probiotic (PB) or vehicle control (VEH) groups, then to either chronic unpredictable stress (CUS) or no-stress control (CON) conditions within each group (n = 6/subgroup). We hypothesized that PB supplementation would reduce markers of anxiety and enhance emotional resilience, especially in the CUS animals. In the cognitive uncertainty task, a nonsignificant trend was observed indicating that the PB-supplemented animals spent more time oriented toward the food reward than VEH animals. In the open-field task, CUS-PB animals spent more time in the center of the arena than CUS-VEH animals, an effect not observed between the two CON groups. In the swim task, the PB animals, regardless of stress assignment, exhibited increased floating, suggesting a conserved response in a challenging context. Focusing on the endocrine measures, higher dehydroepiandrosterone (DHEA)-to-corticosterone fecal metabolite ratios, a correlate of emotional resilience, were observed in PB animals. Further, PB animals exhibited reduced microglia immunoreactivity in the basolateral amygdala, possibly indicating a neuroprotective effect of PB supplements in this rodent model. These results provide evidence that PB supplementation interacts with stress exposure to influence adaptive responses associated with endocrine, neural, and behavioral indices of anxiety.

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.

The effect of kangaroo care on modulate chronic stress response in preterm infants and mothers

To assess stress experienced during Neonatal Intensive Care Unit (NICU) stay, we analyzed fingernail Cortisol (CORT) and Dehydroepiandrosterone (DHEA) levels and ratios in mothers and preterm infants (PI); compared hormones levels/ratio (CORT and DHEA) in kangaroo care (KC) versus standard care (SC) groups and examined relationships between PI hormone levels total days spent in the NICU. Mothers and their infants were recruited in the NICU, included levels I-IV and kangaroo care unit, within one week of infant birth in hospitals in Brazil. At 3 months after birth, mothers provided 3-month growth clippings from all ten digits of their own and their infants’ fingernails. CORT and DHEA were measured using enzyme immunoassays (mothers) and high-performance-liquid-chromatography-with-mass-spectrometry (infants). Sample: n = 59 mothers (KC = 30/SC = 29) and 63 infants (KC = 32/SC = 31). Data were analyzed using non-parametric/parametric comparative statistics. NICU stay ranged from 3–103 days. For mothers in Kangaroo and Standard Care the CORT, DHEA levels and DHEA:CORT ratio (DC) ratio did not differ. Infants in KC had higher DHEA (p = 0.003) and a higher DC ratio (p = 0.011) than SC infants. Even though KC infants stayed in the NICU for a greater number of days than infants in SC, they had higher mean level of DHEA, and DC ratio, suggesting that KC played a role in promoting their stress regulatory capacities and may mitigate toxic effects of chronic hypercortisolemia. However, for mothers, KC did not reduce chronic stress compared to that in women in the SC condition. Further research warranted.

DHEA-pretreatment attenuates oxidative stress in kidney-cortex and liver of diabetic rabbits and delays development of the disease

In view of reported discrepancies concerning antioxidant activity of dehydroepiandrosterone (DHEA), a widely used dietary supplement, the current investigation was undertaken to evaluate the antioxidant properties of DHEA in both kidney-cortex and liver of alloxan (ALX)-induced diabetic rabbits, as this diabetogenic compound exhibits the ROS-dependent action. ALX was injected to animals following 7 days of DHEA administration. Four groups of rabbits were used in the experiments: control, DHEA-treated control, diabetic and DHEA-treated diabetic. Our results show for the first time, that in kidney-cortex DHEA resulted in normalization of hydroxyl free radicals (HFR) levels and restoration of catalase (CAT) and glutathione peroxidase (GPx) activities to near the control values, while in liver DHEA prevented the malondialdehyde (MDA) accumulation and normalized glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH) activities. Moreover, in both kidney-cortex and liver DHEA supplementation prevented GSSG elevation accompanied by a decrease in GSH/GSSG ratio. Although DHEA attenuated oxidative stress in both kidney-cortex and liver of ALX-induced diabetic rabbits and significantly delayed the onset of diabetes in time, it did not protect against the final development of diabetes. In conclusion, the current investigation underscores the complexity of the antioxidant action of DHEA. The data are of clinical interest since DHEA supplementation could prevent the deleterious effects of ROS and delay, or even prevent the onset of many diseases. However, in view of the reported pro-oxidant effects of high DHEA doses, the potential use of this agent as a supplement needs a careful evaluation.

DHEA Moderates the Impact of Childhood Trauma on the HPA Axis in Adolescence

Background: Trauma can lead to long-term downregulation of the hypothalamic pituitary adrenal (HPA) axis. However, dehydroepiandrosterone (DHEA) has neuroprotective effects that may reduce the need for downregulation of the axis in response to stress. Furthermore, high DHEA/cortisol ratios are often conceptualized as better markers of DHEA’s availability than DHEA alone, as ratios account for the coupling of DHEA and cortisol in response to stress. Objectives: In this study, we explored if DHEA and DHEA/cortisol ratios moderated the association between childhood maltreatment and the HPA axis stress response. Methods: The sample consisted of 101 adolescents (ages 12–16) who completed the Child Trauma Questionnaire (CTQ) and the Trier Social Stress Test (TSST). Cortisol was modeled using saliva samples at 8 time points throughout the TSST. Cortisol and DHEA ratios were examined at baseline and 35 min after stress initiation. Results: Childhood maltreatment was associated with less steep cortisol activation slope and peak cortisol levels, but DHEA and DHEA/cortisol ratios moderated this effect. At high levels of DHEA, the impact of childhood maltreatment on cortisol peak levels was no longer significant. In contrast, high DHEA/cortisol ratios were associated with an intensification of the impact of childhood maltreatment on peak levels. Conclusions: Results suggest that DHEA can limit the blunting of the HPA axis in response to childhood maltreatment. However, this protective effect was not reflected in high DHEA/cortisol ratios as predicted. Therefore, high DHEA and high DHEA/cortisol ratios may reflect different, and potentially opposite, processes.

The Stress of Caring-Resilience and HPA-Axis Activity in Hair Samples of Youth Residential Caregivers.

Background: Professional caregivers in youth residential care institutions experience frequent verbal and physical aggression as well as multiple stressors as part of their everyday work, leading to high levels of burnout and staff turnover. Resilience might buffer against psychophysiological stress response and therefore be crucial for well-being in professional caregivers.Objectives: We aimed to investigate if measures related to resilience [sense of coherence (SoC), self-efficacy and self-care] and attachment security of caregivers were cross-sectionally associated with stress markers in hair samples [cortisol and dehydroepiandrosterone (DHEA)].Method: Participants (n = 134; 64.2% women) reported on individual resilience measures and provided hair samples for cortisol and DHEA assays. Attachment was assessed in a subsample using the Adult Attachment Projective Picture System (AAP, n = 69). Linear regression models were fitted to estimate the association between resilience measures and the Cortisol:DHEA ratio, cortisol and DHEA, controlling for gender and age.Results: SoC was associated with a lower Cortisol:DHEA ratio (β = −0.36, p < 0.001), driven by a positive association between SoC and DHEA levels (β = 0.28, p = 0.002). Self-care was also associated with lower Cortisol:DHEA ratios (β = −0.24, p = 0.005), due to self-care being associated with higher DHEA (β = 0.21, p = 0.016). HPA-axis measures were not associated with self-efficacy nor with attachment patterns in a subsample.Conclusions: Our findings imply that youth residential care institutions might benefit from programs focusing on enhancing SoC and self-care practices. Fostering a meaningful, comprehensible and manageable professional climate in caregiving environments and implementing self-care in routine practices might enhance not only well-being but also physical health of professional caregivers and in this way buffer adverse health effects of chronic stressors.

Association of dioxin in maternal breast milk and salivary steroid hormone levels in preschool children: A five-year follow-up study of a Vietnam cohort

Recent studies have found elevated dioxin levels inside some former US military air bases in Vietnam, known as hotspots. The aim of the present study was to evaluate the association of dioxin exposure and steroid hormone in preschool children in Vietnam. In 2010, 2011, 52 primiparae mother–infant pairs in the hotspot and 52 pairs in a non-exposure region were enrolled. For the final analysis, 26 vs 26 pairs were selected, who participated at all three surveys. Univariable and multivariable linear regressions were used to evaluate associations between hormone and dioxin congeners. Geometric mean total TEQ of PCDD/DFs in the hotspot were significantly higher than in the non-exposure region, 8.7 and 3.4 pg TEQ/g lipid, respectively. In the hotspot, salivary dehydroepiandrosterone (DHEA) was significantly higher in 1-year-old children (Boys = 123 pg/mL, Girls = 120 pg/mL) than in the non-exposure region (Boys = 28 pg/mL, Girls = 27 pg/mL). In contrast, DHEA was significantly lower in 5-year-old children (Boys = 70 pg/mL, Girls = 106 pg/mL) in the hotspot than in the non-exposure region (Boys = 496 pg/mL, Girls = 654 pg/mL). Salivary testosterone was significantly lower in the hotspot (Boys = 1.9 pg/mL, Girls = 1.9 pg/m; Boys = 1.0 pg/mL, Girls = 1.1 pg/mL, respectively) than in the non-exposure region (Boys = 3.7 pg/mL, Girls = 3.8 pg/m; Boys = 5.7 pg/mL, Girls = 7.0 pg/mL, respectively) at 3 years and 5 years of age. Higher levels of highly chlorinated dioxins in breast milk were associated with higher DHEA in 1-year-old and lower DHEA and testosterone levels in 5-year-old children. Our findings indicated that dioxins were associated with changes of DHEA and testosterone levels in preschool Vietnamese children.

Prenatal and Postnatal Hair Steroid Levels Predict Post-Partum Depression 12 Weeks after Delivery.

Background: Within three to six months after delivery, 13%–19% of women suffer from post-partum depression (PPD), understood as a dysfunctional adaptation to the postpartum condition and motherhood. In the present cross-sectional study, we compared the hair steroid levels of women 12 weeks before and after delivery and with or without PPD. Method: The present study was a cross-sectional study conducted twelve weeks after delivery. At that time, 48 women (mean age: 25.9 years) with PPD and 50 healthy controls (mean age: 25.2 years) completed questionnaires on depressive symptoms. Further, at the same time point, 6 cm lengths of hair strands were taken, providing samples of hair steroids 12 weeks before and 12 weeks after delivery in order to analyze hair steroids (cortisol, cortisone, progesterone, testosterone, and dehydroepiandrosterone (DHEA)). Results: Compared to those of women without PPD, hair steroid levels (cortisol, cortisone, progesterone) were significantly lower in women with PPD both before and after delivery. Lower prenatal cortisone and progesterone levels predicted higher depression scores 12 weeks after delivery. Lower prenatal levels of cortisol and progesterone and higher levels of DHEA, and postnatal lower levels of cortisol, cortisone, and progesterone, along with higher levels of DHEA predicted PPD-status with an accuracy of 98%. Conclusions: PPD is associated with blunted hair cortisol, cortisone, and progesterone secretions both pre- and postpartum. Such blunted steroid levels appear to reflect a stress responsivity that is less adaptive to acute and transient stressors. It follows that prenatally assessed low hair cortisol and progesterone levels, along with high DHEA levels, are reliable biomarkers of post-partum depression 12 weeks after delivery.

Novel associations between sex hormones and diabetic vascular complications in men and postmenopausal women: a cross-sectional study

BackgroundAssociations between sex hormones and vascular remodeling have been extensively studied, but the results vary widely among different races and sex. We aimed to investigate whether total testosterone (TT), estrogen (E2), and dehydroepiandrosterone (DHEA) associate with macrovascular complications and diabetic kidney disease (DKD) among community-dwelling patients with diabetes.MethodsA total of 4720 participants with type 2 diabetes were recruited from Shanghai, China. Common carotid artery (CCA) plaques and diameter were assessed by ultrasound. Cardiovascular disease (CVD) was defined by prior diagnosis of coronary heart disease, myocardial infarction or stroke. DKD was defined according to the ADA Guidelines.Results(1) In men, TT was negatively associated with CCA diameter (regression coefficient (β) − 0.044, 95% CI − 0.087, 0). E2 levels were positively associated with CVD and CCA plaque prevalence (OR 1.151, 95% CI 1.038, 1.277 and OR 1.13, 95% CI 1.017, 1.255, respectively). DHEA was negatively associated with CVD (OR 0.809, 95% CI 0.734, 0.893). In postmenopausal women, TT levels were negatively associated with CCA diameter (β − 0.046, 95% CI − 0.083, − 0.010) and positively associated with CVD (OR 1.154, 95% CI 1.038, 1.284). (2) In both men and postmenopausal women, TT levels were negatively associated with the albumin/creatinine ratio and DKD (β − 0.098, 95% CI − 0.154, − 0.043 and OR 0.887, 95% CI 0.790, 0.997 vs. β − 0.084, 95% CI − 0.137, − 0.031 and OR 0.822, 95% CI 0.731, 0.924, respectively) and DHEA levels were positively associated with DKD (OR 1.167, 95% CI 1.038, 1.313 vs. OR 1.251, 95% CI 1.104, 1.418, respectively).ConclusionsOur study indicates that macrovascular complications were associated with low TT, DHEA and high E2 in men and with high TT in postmenopausal women. DKD was associated with low TT and high DHEA levels in both genders. Sex hormone replacement therapy requires careful and comprehensive consideration.Trial registration ChiCTR1800017573, http://www.chictr.org.cn. Registered 04 August 2018

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.