Dehydroepiandrosterone Sulfate Concentrations Research Articles

Age-dependent changes in visceral adiposity are associated with decreased plasma levels of DHEA-S in sigma-1 receptor knockout male mice

The sigma-1 receptor (S1R) is involved in intracellular lipid synthesis and transport. Recent studies have shown that its genetic inactivation impairs adipogenic differentiation in vitro. This study investigated the role of S1R in adipose tissue physiology and metabolic health using adult and old WT and S1R KO mice.Visceral fat mass was increased in adult, but not old S1R-KO male mice compared to that of WT mice, despite having similar body weights, food intake, and energy expenditure. The average adipocyte size was 64 % larger in adult KO mice than in adult WT mice. Adult S1R-KO mice showed reduced plasma dehydroepiandrosterone sulfate (DHEA-S) and elevated fasting plasma leptin concentrations. Lipidomic analysis revealed alterations in plasma metabolite concentrations, particularly reduced levels of sphingomyelins, ceramides, phosphatidylcholines, lysophosphatidylcholines, and cholesteryl esters in adult mice. Decreased expression of Pparγ, Adipoq, and Atgl was detected in visceral white adipose tissue (vWAT) isolated from adult KO mice. Additionally, Fabp4 and Adipoq expression levels were significantly lower in KO adipose-derived stromal cells than in WT adipose-derived stromal cells. A fivefold increase in the mitochondrial fatty acid oxidation rate and a 43 % increase in electron transfer coupling capacity were detected in adult S1R-KO vWAT.In summary, our investigation revealed an age-dependent association between increased visceral adiposity and decreased plasma levels of DHEA-S in S1R-deficient male mice. These findings underscore the potential role of S1R in regulating metabolic processes in adipose tissue and suggest that DHEA-S is a potential mediator of adiposity changes in the absence of S1R.

The state of the hypothalamic-pituitary-adrenal system in workers exposed to electric and magnetic fields of industrial frequenc

Introduction. Electric and magnetic fields of industrial frequency are an integral part of production processes, and their effect on the human body is of increasing interest both among scientists and among specialists in the field of medicine and occupational safety. In recent decades, there has been growing concern about the potential impact of these areas on the health of workers, especially those who are exposed to prolonged exposure in the course of their professional activities. In this context, we pay special attention to the neuroendocrine system, which plays a key role in regulating many physiological processes, including metabolism, stress reactions and maintaining homeostasis. The study of the fundamentals of the neuroendocrine system and the mechanisms of the effect of electromagnetic fields on the body not only contributes to the deepening of scientific knowledge in the field of biomedical research, but also has practical significance in ensuring occupational safety and improving working conditions in industrial enterprises, allowing to identify possible health consequences and develop effective measures to protect workers from negative bioeffects. The study aims to research the effects of electric and magnetic fields of industrial frequency on the functional state of the hypothalamic-pituitary-adrenal system of employees of electric grid facilities. Materials and methods. Specialists examined 144 employees of the main group engaged in the repair and operation of electric grid facilities and 40 employees of the control group who were not exposed to electromagnetic fields of industrial frequency. We determined the concentration of adrenocorticotropic hormone, cortisol and dehydroepiandrosterone sulfate in blood serum samples and calculated the ratio of dehydroepiandrosterone sulfate to cortisol. Results. Workers exposed to the combined effects of electric and magnetic fields of industrial frequency had a lower (p<0.05) level of adrenocorticotropic hormone (1.9 [0.5; 3.9] pg/ml) and dehydroepiandrosterone sulfate (5.8 [3.7; 8.4] mmol/l) in the blood compared with the group of workers exposed to magnetic fields industrial frequency fields (4.4 [2.1; 12.9] pg/ml; 9.8 [6.3; 14.5] mmol/l) and to the control group (6.4 [4.0; 19.8] pg/ml; 7.8 [4.7; 13.3] mmol/l), respectively. The scientists also revealed in the group of workers exposed to combined exposure in the field, the association of a low ratio of dehydroepiandrosterone sulfate and cortisol with the development of cardiovascular diseases and feedback from work experience (p<0.05). Limitations. The study is limited by the number of people surveyed (144 employees). Conclusion. The results of the study indicate the hypoactivity of the hypothalamic-pituitary-adrenal system induced by exposure to electric and magnetic fields of industrial frequency, manifested by a decrease in the level of adrenocorticotropic hormone, dehydroepiandrosterone sulfate and its relationship to cortisol in workers exposed to combined effects of electric and magnetic fields of industrial frequency. Ethics. The work complies with ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting Scientific medical research with human participation" as amended in 2000 and the "Rules of Clinical Practice in the Russian Federation" approved by Order of the Ministry of Health of the Russian Federation dated 04/01/2016 No. 200n. We received informed consent from each examined person to participate in the study, approved in accordance with the established procedure by the local Ethics Committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics Committee No. 17 dated 12/16/2015).

Clinical and diagnostic evidence of benign endometrial pathology in postmenopausal patients

The objective: to study clinical and diagnostic features of the benign endometrial conditions in the postmenopausal women.Materials and method. 64 postmenopausal patients with various severity of postmenopausal vaginal bleeding were examined. All patients underwent clinical, radiological, laboratory and histological examinations, reproductive history data and body mass index indicators were evaluated. Of them 33 persons were diagnosed with complex endometrial hyperplasia without atypia, 16 women – endometrial polyp and 15 women – hyperplasia with atypia. Routine gynecological examination including abdominal and pelvic examination following transvaginal ultrasound examination for the determination of the uterine and ovarian volume as well, as the endometrial thickness were conducted. Patients included in the study underwent computer tomography and magnetic resonance imaging as indicated. All patients with endometrial pathology underwent endometrial biopsy by standard dilatation and curettage or Pipelle-biopsy with histological examination of the obtained material. The concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), estradiol, estrone, progesterone, prolactin, and testosterone were determined in blood serum.Results. It was confirmed that in 87,5% of cases endometrial hyperplasia manifested with vaginal bleeding. Endometrial thickness in examined persons ranged from 14.1±1.6 mm in patients with atypical endometrial hyperplasia to 21.3±4.8 mm in patients with complex endometrial hyperplasia without atypia. The study of blood levels of hormones found that postmenopausal patients with endometrial hyperplasia have lower FSH concentration, LH/FSH ratio, estradiol, testosterone levels, with significantly high values of prolactin, DHEA-S and estrone. During the postmenopausal period, hyperplasia was developed in 10% of cases by the presence of bleeding, and 86.2% of cases by the presence of blood spotting. Conclusions. The study suggests that high body mass index, numerous artificial abortions, high blood levels of estrone, DHEA-S and prolactin as well as increased thickness of endometrium influence the frequency of endometrial hyperplasia in postmenopausal women.

Short Rest Between Flights Is Associated With Increased Serum Stress Hormone Levels in Airline Pilots: A Cross-Sectional Study.

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. 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. 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). 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.

Alcohol intake and endogenous sex hormones in women: Meta-analysis of cohort studies and Mendelian randomization.

The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984). Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively). Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.

#1298 Combination of clinical frailty score and biomarkers as mortality predictor in hemodialysis patients

Abstract Background and Aims Frailty is common among hemodialysis (HD) patients. Its assessment is usually based on clinical criteria. In the present work, we evaluated the interest of combining clinical frailty score and biomarkers to predict mortality of chronic HD patients. Three biomarkers were assessed: myostatin, insulin-like growth factor-1 (IGF-1) and dehydroepiandrosterone sulfate (DHEA-S) Method Prevalent HD patients were enrolled from September 2016 to October 2017 in two centers in Liège, Belgium in this observational prospective study and followed up for 5 years. Myostatin, IGF-1 and DHEA-S levels were measured at baseline. Frailty was assessed using Fried's five points frailty score (≥3 indicates frailty). The ability to predict mortality was assessed by calculating areas under the curve (AUC). AUCs were compared by Hanley &amp; McNeil test. Results We included 125 HD patients with the following characteristics: median age was 67 [53; 78] years; 60% of men; 41% of diabetic and median dialysis vintage of 30 [16; 54] months. Among them, 46% were classified as “Frail” according to Fried. The median follow up was 49 [19; 60] months (Table 1). The ability (AUC) of Fried score, myostatin, IGF-1 and DHEA-S to predict mortality was significant and comparable: 0.72 (95% CI: 0.63 to 0.80), 0.72 (95% CI: 0.64 to 0.80), 0.68 (95% CI: 0.59 to 0.76) and 0.73 (95% CI: 0.64 to 0.80), respectively (Fig. 1). Combining (by logistic regression) one biomarker with Fried score improved significantly the AUC with myostatin (AUC = 0.79, 95% CI: 0.71 to 0.86, p = 0.0049), IGF-1 (AUC = 0.78, 95% CI: 0.70 to 0.85, p = 0.0099) and DHEA-S (AUC = 0.79, 95% CI: 0.71 to 0.86, p = 0.0018) compared to Fried score alone. Compared to biomarker alone, the combination also improved significantly AUC for myostatin and IGF-1 (p = 0.035 and p = 0.011 respectively) but not for DHEA-S. The combination of several biomarkers with Fried score did not significantly improve mortality prediction compared to the combination of a single biomarker with Fried score. Conclusion The study suggests that combining Fried frailty score with either myostatin, IGF-1 or DHEA-S concentration improves the prediction of five-year mortality in chronic HD patients.

Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor

BackgroundLevels of sulfated Dehydroepiandrosterone (DHEA-S) are unknown in people with Cystic Fibrosis (pwCF). DHEA-S is reported to have an inverse association with inflammation and warrants evaluation in pwCF. MethodsWe compared differences in DHEA-S and other hormones between pwCF (n = 180) and without CF (n = 180) and DHEA-S association with percent predicted forced expiratory volume in one second (ppFEV1). We also evaluated DHEA-S levels in people with CF on elexacaftor-tezacaftor-ivacaftor (ETI) (n = 145). ResultsPwCF (not on ETI) had lower DHEA-S levels compared to healthy non-CF controls. DHEA-S levels in individuals with CF on ETI were similar to those without CF. Lower DHEA-S levels were associated with lower ppFEV1. ConclusionsPwCF (not on ETI) have lower levels of DHEA-S than people without CF or people with CF on ETI. Additional studies are needed to investigate the impact of DHEA-S on the health of pwCF and mechanisms involved.

Effect of SGLT2 Inhibitors on Improving Glucolipid Metabolism and Reproductive Hormone Status in Overweight/Obese Women with PCOS: A Systematic Review and Meta-Analysis.

Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle leading to reproductive and metabolic abnormalities. Metformin improves the symptoms of PCOS by increasing insulin sensitivity but is not therapeutically optimal. Recent studies have reported that sodium-glucose co-transporter protein receptor inhibitors improve insulin resistance and reduce the weight of patients with PCOS. We performed a meta-analysis to assess the influence of sodium-glucose co-transporter protein-2 (SGLT2) inhibitors on anthropometric, glycolipid metabolism and reproductive outcomes after therapy of overweight/obese women with PCOS. We searched the relevant literature published up to April 2023. Information on the effect of SGLT2 inhibitors on overweight/obese patients with PCOS was extracted independently by two reviewers. Review Manager 5.3 was used for meta-analysis. Five randomized controlled trials that met our criteria were retrieved. Our meta-analysis demonstrated that in overweight/obese patients with PCOS, SGLT2 inhibitors treatment was significantly superior to metformin treatment in terms of reducing body weight (P = 0.02, I2 = 36%), decreasing dehydroepiandrosterone sulfate concentrations [SMD = -0.42, 95% CI (-0.76, -0.07), I2 = 22%, P = 0.02], and reducing the incidence of nausea [RR = 0.35, 95% CI (0.21, 0.60), I2 = 71%, P = 0.0001]. SGLT2 inhibitors are a possible alternative therapy for treating overweight/obese women with PCOS who do not respond favorably to metformin treatment. However, further large randomized controlled trials and cost-effectiveness analyses are warranted to guide the implementation of SGLT2 inhibitors treatment in this population.

Effects of Blue Light on Puberty and Ovary in Female Rats

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

Postpartum hair cortisol, dehydroepiandrosterone sulfate and their ratio in beef cows: Exploring association with parity and conception outcome

Hair steroid measurement has received increasing attention for monitoring hypothalamic-pituitary-adrenal axis function, as it offers the advantages of being noninvasive, fast, and able to indicate steroid concentrations over long periods. The objects of the study were to evaluate cortisol (C) and dehydroepiandrosterone sulfate (DHEA-S) hair concentrations and their ratio (C/DHEA-S) in beef cows from calving to 100 days (d) postpartum (pp) and to assess possible differences related to parity (primiparous vs multiparous) and conception outcome (pregnant vs not pregnant). Hair samples were collected from 6 primiparous and 5 multiparous pregnant beef cows by clipping the coat at calving (T0) and every 20 d for 5 times (T1-T5), collecting only the regrown hair. Starting from the 6th-week pp, cows were submitted to artificial insemination at spontaneous estrus; by 100 d pp, 7 cows were pregnant and 4 were not pregnant. Statistical analysis showed higher hair C concentrations in the 11 cows at calving (T0) compared to all the subsequent samplings except for T1, and higher C concentrations at T1 compared to T3, T4, and T5. These results indicate that hair C concentrations in beef cows are affected by sampling time, with a decrease from calving, as reported in other matrices. When exploring changes within parity groups, no differences were found in the multiparous among sampling times, while hair C concentrations at T0 and T1 tended to be higher than at T2 (0.01 ≤ p < 0.05) and were higher (p < 0.01) than in all the subsequent samplings (T3, T4 and T5) within the primiparous group. Higher hair C concentrations were found at T0 and T1 in the primiparous compared to multiparous (p < 0.01), suggesting that primiparous cows undergo a greater stress level before and around parturition compared to multiparous, probably due to the novelty of the calving experience. No differences were detected in C hair concentrations according to conception outcome (pregnant versus not pregnant) in each sampling time. Hair DHEA-S concentrations were neither affected by time nor by parity or conception outcome. Differences in the C/DHEA-S ratio were found at T1, with higher C/DHEA-S in the multiparous compared to primiparous cows (p < 0.001), and a tendency for higher ratio in the not pregnant compared to the pregnant (0.01 ≤ p < 0.05). These results support the choice of hair as a valuable biological matrix when investigating long-time periods such as postpartum in cows and suggest an enhanced immunoprotective effect of DHEA-S in the postpartum of primiparous cows, and in cows that get pregnant within 100 d postpartum.

Minipuberty in Sons of Women with Low Vitamin D Status during Pregnancy.

Minipuberty is a transient phase of reproductive axis activation during the first several months of life, playing an important role in the development of reproductive organs in boys. Low 25-hydroxyvitamin D levels during pregnancy are associated with an increased risk of neonatal complications. An inadequate gestational vitamin D status is hypothesized to affect the postnatal activation of the hypothalamic-pituitary-gonadal axis. The purpose of our study was to assess whether a low vitamin D status during pregnancy determines the course of minipuberty in boys. The study included three groups of male infants born to women with different vitamin D statuses: sons of women with vitamin D deficiency (group 1), sons of women with vitamin D insufficiency (group 2), and male offspring of females with normal 25-hydroxyvitamin D levels (group 3 (the reference group)). Concentrations of testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, progesterone, and 17-hydroxyprogesterone in saliva, as well as concentrations of gonadotropins in urine, were assayed monthly from postnatal months 1 to 6, and once every 2 months in the second half of the first year of life. Additionally, at each visit, penile length and testicular volume were assessed. Concentrations of testosterone, FSH, and LH, as well as penile length and testicular volume, were greater in group 1 than in groups 2 and 3. In turn, group 2 was characterized by higher FSH levels and a greater testicular volume than group 3. Peak concentrations of LH and testosterone were observed earlier in group 1 than in the remaining groups. The obtained results suggest that a low vitamin D status during pregnancy may have a stimulatory impact on reproductive axis activity and on the early postnatal development of male genital organs, correlating with the severity of hypovitaminosis D.

Determinants of Bone Mineral Density in Iranian Women with Polycystic Ovary Syndrome.

Whether the endocrine aberrations caused by polycystic ovary syndrome (PCOS) might influence bone density in women of reproductive age is controversial. The present study aimed to compare PCOS women to a control group matched in terms of age and body mass index (BMI) regarding bone indices and to clarify the potential relationship between their hormonal changes and bone density. This case-control study consisted of 61 PCOS patients, and 35 women with normal ovulatory function served as controls. Bone parameters, including bone mineral content (BMC) and bone mineral density (BMD) in addition to T- and Z-scores, were measured at the lumbar vertebrae, neck of the left femur, hip, and distal part of the radial bone, using dual-energy X-ray absorptiometry. Blood samples were taken to be tested for biochemical parameters and serum concentrations of insulin, osteocalcin, parathyroid hormone (PTH), vitamin D, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, dehydroepiandrosterone sulfate (DHEAS), and estradiol were measured. Insulin resistance was evaluated through the homeostatic model assessment of insulin resistance (HOMA-IR). The results revealed greater levels of HOMA-IR and total testosterone in PCOS women than in controls. Nevertheless, the two groups were comparable in terms of bone parameters. In the control group, BMI was the only determinant of bone density at most of the skeletal sites. Nonetheless, BMI and HOMA-IR were independently and positively associated with bone indices at the femoral neck (FN) and total hip in the PCOS group. Parathyroid hormone and vitamin D concentrations were not different in the two groups. However, phosphate levels were higher in PCOS patients (P = 0.025). Osteocalcin was inversely correlated to BMI, and both groups had a negative correlation between DHEAS and PTH. Serum phosphate was inversely and independently associated with estrogen in the PCOS group (r = -0.377, P = 0.004). Body mass index and HOMA-IR were independent and positive determinants of FN and total hip bone density in the PCOS subjects. Nonetheless, in the non-PCOS women, BMI was the only independent determinant of bone density at most of the skeletal sites. Additionally, osteocalcin was inversely correlated with BMI in both groups.

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

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

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

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

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

Incorporation of Testicular Ultrasonography and Hair Steroid Concentrations in Bull Breeding Soundness Evaluation.

Testicular ultrasonography and steroid concentrations (cortisol, dehydroepiandrosterone sulfate (DHEA-S), cortisol/DHEA-S ratio, testosterone) in hair were examined for their utility in the bull breeding soundness evaluation (BBSE). Beef and dairy bulls (n = 16; 2.7 ± 0.4 years old; body condition score 3.2 ± 0.1) of five breeds were maintained under the same conditions at an accredited semen collection center. Bulls underwent routine semen collection twice weekly for 12 weeks and semen was processed and cryopreserved. Ultrasonography and hair sampling were undertaken at the last semen collection. Bulls with homogeneous testicular parenchyma (n = 8) had a higher (p < 0.05) percentage of motile sperm post-thawing compared with bulls with heterogeneous parenchyma (n = 8). There were no differences (p > 0.05) in the hair concentrations of cortisol, DHEA-S, and testosterone between bulls with homogeneous and heterogeneous parenchyma. In bulls with homogeneous parenchyma, hair DHEA-S concentration was positively correlated with percentage motile sperm (R2 = 0.76), progressively motile sperm (R2 = 0.70), and motility yield (R2 = 0.71). The findings indicate that the integration of testicular ultrasonography and hair DHEA-S status in the BBSE could provide a more comprehensive assessment of indicative fertility in bulls. Additionally, ultrasonography can be used in the BBSE when the evaluation of semen parameters is not available.

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

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

Associations of prenatal and postnatal exposure to perfluoroalkyl substances with pubertal development and reproductive hormones in females and males: The HOME study

BackgroundPrenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce. ObjectivesWe examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years. MethodsWe studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003–2006). We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and females) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture. ResultsIn females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adolescent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males. ConclusionsWe observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea

Background Neurokinin B (NKB) belongs to the tachykinin family of proteins who’s regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. Aim To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. Materials and methods A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. Results Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. Conclusions Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA.

Assessing Dehydroepiandrosterone Sulfate (DHEAS) as a novel biomarker for monitoring estrus and successful reproduction in polar bears

Polar bears (Ursus maritimus) in the wild are under threat due to climate change, primarily loss of sea ice, and experience poor reproductive success in zoos. The polar bear is a seasonally polyestrous species that exhibits embryonic diapause and pseudopregnancy, complicating characterization of reproductive function. Fecal excretion of testosterone and progesterone have been studied in polar bears, but accurately predicting reproductive success remains difficult. Dehydroepiandrosterone (DHEA) is a steroid hormone precursor correlated with reproductive success in other species, but has not been well studied in the polar bear. The purpose of the present study was to characterize the longitudinal excretion of DHEAS, the sulfated form of DHEA, from zoo-housed polar bears using a validated enzyme immunoassay. Lyophilized fecal samples from parturient females (n = 10), breeding non-parturient females (n = 11), a non-breeding adult female, a juvenile female, and a breeding adult male were investigated. Five of the breeding non-parturient females had been previously contracepted, while six were never contracepted. DHEAS concentrations were closely associated with testosterone concentrations (p < 0.05, rho > 0.57) for all reproductive statuses. Breeding females exhibited statistically significant (p < 0.05) increases in DHEAS concentration on or near breeding dates, which were not observed outside of the breeding season, or in the non-breeding or juvenile animals. Breeding non-parturient females exhibited higher median and baseline DHEAS concentrations than parturient females over the course of the breeding season. Previously contracepted (PC) breeding non-parturient females also exhibited higher season-long median and baseline DHEAS concentrations than non-previously (NPC) contracepted breeding non-parturient females. These findings suggest that DHEA is related to estrus or ovulation in the polar bear, that there is an optimal DHEA concentration window, and concentrations exceeding that threshold may be associated with reproductive dysfunction.