Higher Dehydroepiandrosterone Levels Research Articles

Before Low Serum Cortisol Can Be Attributed to SARS-Cov-2 Infection, Alternative Causes Must Be Ruled Out

We read with interest Banu et al.,’s article about a cross-sectional study of adrenal function using blood levels of cortisol and adrenocorticotropic hormone (ACTH) in 91 patients with acute SARS-CoV-2 infection. It was found that 27% of patients with severe COVID-19, 26% with mild COVID-19 and 4% with moderate COVID-19 had adrenal insufficiency. Decreased cortisol reserve was found in 6.6% of all patients. It was concluded that the adrenocortical response was impaired in a significant number of non-critically ill COVID-19 patients, with the percentage being highest in patients with severe COVID-19 disease.1 The study is impressive, but some points should be discussed. The major limitation of the study is that imaging of the pituitary gland and hypothalamus was not performed. To rule out pituitary adenoma, hypophysitis, pituitary apoplexy, pituitary abscess, sellar tuberculoma, or hypothalamic stroke or bleeding, magnetic resonance imaging (MRI) of the pituitary gland and the hypothalamus with contrast agent must be performed. Like any other infection, SARS-CoV-2 infection can trigger the appearance of symptoms of a pituitary pathology.2 A second limitation is that imaging of the suprarenal glands was not performed. To assess whether there was adrenal atrophy, adenoma, ischemia, bleeding, or carcinoma, adrenal imaging is mandatory. 3 A third limitation is that current medication was not reported. Several medications are known to affect serum cortisol levels, making it imperative to know all medications regularly taken by the included patients. Ketoconazole, isilodrostat, vitamin D and omega-3 fatty acids in particular are known to be able to reduce cortisol levels in the blood.4 A fourth limitation is that no ACTH stimulation test was performed to determine whether primary or secondary suprarenal insufficiency was present. Determining cortisol levels alone without ACTH stimulation testing is not reliable with regard to cortical adrenal function. A fifth limitation is that serum dehydroepiandrosterone (DHEA) levels were not measured. Since DHEA is the antagonist of cortisol and decreases with age, it is conceivable that high levels of DHEA promoted the reduction of serum cortisol.5 Since low thyroxine levels may be associated with low cortisol levels,6 it would also be desirable to know whether thyroid function was normal or abnormal in the included patients. In summary, the excellent study has limitations that should be addressed before drawing final conclusions. Clarifying the weaknesses would strengthen the conclusions and could improve the study. Serum cortisol levels may be low not only due to SARS-CoV-2 infection but also due to several other causes. Before adrenal insufficiency can be attributed solely to inadequate cortical cortisol production, the entire hypothalamic-pituitary-adrenal axis must be thoroughly examined.

Hair steroid before and after COVID-19 in preschoolers: the moderation of family characteristics

BackgroundFrequent or prolonged exposure to stressors may jeopardize young children’s health. The onset of the COVID-19 pandemic, coupled with disruptions in daily routines and social isolation resulting from public health preventive measures, have raised concerns about its potential impact on children’ experienced stress, particularly for young children and vulnerable families. However, whether the pandemic was accompanied by changes in physiological stress remains unknown as perceived stress is not a good proxy of physiological stress. This study examined if preschoolers showed increasing hair steroid concentrations following the onset of the COVID-19 pandemic and whether family characteristics may have exacerbated or buffered these changes. Methods136 preschoolers (2–4 years) provided hair for steroid measurement (cortisol, dehydroepiandrosterone (DHEA), cortisone, cortisol-to-DHEA ratio, cortisol-to-cortisone ratio) in October-November 2019 (T0) and in July-August 2020 (T1). A 2-centimeter hair segment was analyzed, reflecting steroid production over the two months leading up to collection. Family income, conflict resolution and lack of cohesion, as well as parents’ COVID-19 stress were reported by parents. Linear mixed models for repeated measures and Bayes factors were used. ResultsNo significant changes were noted from before to after the onset of the COVID-19 pandemic for most hair steroids. However, a moderating role of family conflict resolution was noted. Children living with parents with a better ability to resolve conflicts had lower levels of DHEA compared to those who had more difficulty managing conflicts. Additionally, lower levels of family cohesion and income were linked to some steroids, especially DHEA, suggesting that these factors may relate to children’s physiological stress. Finally, boys had higher DHEA levels than girls. ConclusionOur findings suggest that stress biomarkers were comparable from before to during the COVID-19 pandemic. This observation holds true despite the pandemic being perceived by many as a novel, unpredictable, and potentially threatening event. Findings further suggest that family characteristics are associated with hair steroid, especially DHEA, which deserves further investigation.

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.

Психоэндокринные характеристики курсантов ОВД

&lt;p style="text-align: justify;"&gt;The characteristics of 79 cadets of the Ministry of Internal Affairs (mean age &amp;mdash; 20.3&amp;plusmn;2.3 years) were studied: 26.6% male and 73.4% female. Signs of stress, coping, level of anxiety and depression were studied. Stressful stimuli were presented by showing images of dangerous situations and incidents, as well as loud, negatively socially colored sounds. The levels of cortisol and dehydroepiandrosterone (DHEA) in saliva before and after presentation of stressful stimuli were determined. It was revealed that male cadets are characterized by high levels of cortisol and DHEA before stress, with a decrease after presentation. The group of female cadets was characterized by normal hormone indices. Profiles of reaction to stress were formed. Two pro-files were identified in the group of male cadets. The first one corresponded to destructive ways of coping with stress, depression and anxiety expression, normal dynamics of hormone indices after stress; the second one &amp;mdash; low level of anxiety and depression, high level of coping planning-solving problems, decrease of cortisol and DHEA level after stress. For female cadets, 3 profiles were distinguished. The first was characterized by the absence of signs of stress, positive reassessment of stress, normal dynamics of hormones; the second &amp;mdash; low level of stress, non-expressiveness of coping escape and increase of hormones after stress; the third &amp;mdash; expression of signs of stress, coping self-control, and decrease of hormones after stress.&lt;/p&gt;

The associations of hair cortisol and DHEA with posttraumatic stress disorder symptoms in refugees

BackgroundExposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. AimThe aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. MethodsAdult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. Results115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. ConclusionsThis study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. EthicsThe study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665).

DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA.

Malaria is the most lethal parasitic disease worldwide; the severity of symptoms and mortality are higher in men than in women, exhibiting an evident sexual dimorphism in the immune response; therefore, the contribution of 17β-estradiol and testosterone to this phenomenon has been studied. Both hormones differentially affect several aspects of innate and adaptive immunity. Dehydroepiandrosterone (DHEA) is the precursor of both hormones and is the sexual steroid in higher concentrations in humans, with immunomodulatory properties in different parasitic diseases; however, the involvement of DHEA in this sexual dimorphism has not been studied. In the case of malaria, the only information is that higher levels of DHEA are associated with reduced Plasmodium falciparum parasitemia. Therefore, this work aims to analyze the DHEA contribution to the sexual dimorphism of the immune response in malaria. We assessed the effect of modifying the concentration of DHEA on parasitemia, the number of immune cells in the spleen, cytokines, and antibody levels in plasma of CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). DHEA differentially affected the immune response in males and females: it decreased IFN-γ, IL-2 and IL-4 concentrations only in females, whereas in gonadectomized males, it increased IgG2a and IgG3 antibodies. The results presented here show that DHEA modulates the immune response against Plasmodium differently in each sex, which helps to explain the sexual dimorphism present in malaria.

Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project

Background & AimsIncidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. MethodsConcentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. ResultsHigher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). ConclusionsHigher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implicationsThis study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.

CortiLove: A pilot study on hair steroids in the context of being in love and separation

While romantic infatuation and separation influence psychological and physiological functioning, the hypothalamic-pituitary-adrenal axis with its biomarkers cortisol, dehydroepiandrosterone (DHEA), and progesterone central for coping and distress has been scarcely researched in this context. In particular, endocrine hair analyses assumed to be more valid than saliva or blood assessments for studying long-term processes have not yet been conducted in the context of romantic love. Thus, 101 female subjects in phases of infatuation (n = 16), separation (n = 14), long-term relationships (n = 40), and singlehood (n = 31) reported psychological distress and provided 1 cm hair samples for the assessment of long-term integrated cortisol, DHEA, and progesterone over the last month. Separated, infatuated, and single women exhibited higher cortisol levels than those in a long-term relationship (all ps ≤ .031), while self-reported distress was only evident in separated individuals. Further, no group differences for progesterone (p = .602), but higher DHEA levels in the separation (p = .009) and single group (p = .016) compared to the long-term relationship group were detected. This is the first study showing that compared to women in long-term relationships, infatuation, separation, and single groups exhibit higher levels of physiological, but not necessarily self-reported indicators of distress. These findings, albeit on a very small and preliminary sample, are discussed in the context of the stress-buffering effect of relationships, and provide important starting points for bigger, more balanced studies combining multimodal self-report and biological markers in psychological research of romantic love.

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.

Quantification of Hair Corticosterone, DHEA and Testosterone as a Potential Tool for Welfare Assessment in Male Laboratory Mice.

Simple SummaryMice is the most used species in the biomedical research laboratory setting. Scientists are constantly striving to find new tools to assess their welfare, in order to ameliorate husbandry conditions, leading to a better life and scientific data. Steroid hormones can provide information regarding different behavioral tracts of laboratory animals but their quantification often require stressful sampling procedures. Hair represents a good, less invasive, alternative in such scenario and is also indicative of longer timespan due to hormones’ accumulation. The aim of the work was to quantify steroid hormones in the hair of male laboratory mice and to look for differences imputable to age and housing conditions (pairs VS groups). Age influenced all analysed hormones by increasing testosterone and dehydroepiandrosterone (DHEA) levels and decreasing corticosterone. When comparing animals housed in pairs VS groups, the only difference found was a higher level of DHEA in mice housed in groups. Due to the nature of DHEA, this finding may suggest that group housing may be beneficial for social interaction. In conclusion, it seems that hair hormones quantification may be a good tool for welfare assessment in laboratory mice and may help in refining husbandry.Steroids, providing information regarding several biological patterns including stress and sexual behavior, have been investigated in different matrices in laboratory mice. Data regarding hair quantification, indicative of longer timespans when compared to blood and saliva, are lacking. The aim of the work was to analyze the hormonal hair profile of laboratory male mice and to investigate potential relationships with age and housing, as a potential tool for welfare assessment. Fifty-six adult male C57BL/6J and C57BL/6OlaHsd substrain mice were included in the study, housed in pairs or groups. Testosterone (T) and dehydroepiandrosterone (DHEA) were quantified by radioimmunoassay, corticosterone (CORT) by ELISA. Mean hormone levels were 6.42 pg/mg for T, 23.16 pg/mg for DHEA and 502.1 pg/mg for CORT. Age influenced all hormones by significantly increasing T and DHEA levels and decreasing CORT; only DHEA, significantly higher in grouped mice, was influenced by housing conditions. The influence of age indicates the need for accurate age-related reference intervals, while the higher levels of DHEA in grouped animals suggests that such housing practice may be beneficial for social interactions. In conclusion, it seems that hair hormones quantification may be a good tool for welfare assessment in laboratory mice and may help in refining husbandry.

Sex-specific associations between person and environment-related childhood adverse events and levels of cortisol and DHEA in adolescence.

Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity. We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls. A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates. Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys. We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health.

Lopinavir-Ritonavir Impairs Adrenal Function in Infants.

Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. NCT00640263.

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

OR25-6 Higher Ovarian Androgen Responses to Ambient Luteinizing Hormone and to Recombinant Human Chorionic Gonadotropin Stimulation in Late Pubertal Girls with Obesity

Our studies suggest that 60% of obese peripubertal girls have androgen excess, a precursor to polycystic ovary syndrome. Since the ovary is a major source of androgens in women, we studied steroid levels after dexamethasone (DEX) and after recombinant human chorionic gonadotropin (r-hCG) in girls to assess how obesity affects ovarian androgens during puberty. We studied 41 peripubertal girls in the mid-follicular phase (if relevant, 11 were pre-menarcheal): age 13.2 ± 3.0 (7.3-18.8) y (mean ± SD [range]); BMI Z-score 1.2 ± 1.1 (-1.08 to +2.64); Tanner breast 4.0 ± 1.3 (1-5); bone age 14.2 ± 2.9 (7.8-18) y. In early pubertal girls (Tanner 1-3), 5 were normal weight (NW, BMI%-for-age [BMI%] 5-84) and 6 overweight (OW, BMI% ≥ 85). In late pubertal girls (Tanner 4-5), 12 were NW and 18 OW. DEX (1 mg po) was given at 10 pm. At 7 am the next day, progesterone (P4), 17-OH progesterone (OHP), 17-OH pregnenolone, androstenedione (A4), dehydroepiandrosterone (DHEA), testosterone (T), estradiol (E2), and anti-mullerian hormone were measured immediately before r-hCG (25 mcg IV) was given. DEX was again given at 10 pm; hormone levels were repeated 24h after r-hCG. Free T was calculated using SHBG. Forty girls also had frequent (q 10 min) LH sampling from 7 pm-7 am. Comparisons were made using Student’s t-tests. In early pubertal girls, NW girls had higher DHEA levels after r-hCG compared to OW girls (2.46 ± 1.07 vs. 1.23 ± 0.68 ng/dL, p=0.04). In late puberty, OW girls had higher free T after DEX (19.3 ± 15.6 vs. 8.6 ± 4.1 pmol/L, p=0.03) and after r-hCG (27.2 ± 22.3 vs. 10.7 ±4.5 pmol/L, p=0.02) versus NW girls. OW girls also had higher total T levels after DEX (21.7 ± 15.2 vs. 16.7 ± 7.4 ng/dL, p=0.3) and after r-hCG (30.0 ± 20.4 vs. 21.1 ± 10.2 ng/dL, p=0.2), but did not achieve significance. SHBG was lower in OW versus NW girls in late puberty only (20.7 ± 13.4 vs. 48.0 ± 21.8 nmol/L, p=0.0002). No other hormone levels were different. Overnight mean LH was not different for NW and OW groups, for either early or late puberty. However, in late pubertal girls, 33% in OW group had mean LH values ≥ 5 (5.3-9.3) mIU/mL compared to 17% in NW group. Compared to OW girls with mean LH < 5, OW girls with mean LH ≥ 5 had higher OHP, A4, free T, and total T after DEX and after r-hCG (p ≤ 0.05 for all, except A4 after r-hCG [p=0.06]). Results suggest that OW late pubertal girls had higher free T levels after DEX, which may reflect steady-state ovarian androgen production related to ambient LH milieu. OW late pubertal girls had higher free T levels after r-hCG, which may suggest increased capacity to produce ovarian androgens in response to stimulation. In a subgroup of OW girls, obesity during late puberty was associated with higher mean LH values and higher androgen levels after DEX and r-hCG, in keeping with our earlier reports that LH levels predict free T levels in girls with obesity.

Dehydroepiandrosterone (DHEA) and its ratio to cortisol moderate associations between maltreatment and psychopathology in male juvenile offenders

This study examined whether DHEA and its ratio to cortisol moderated risk for psychopathology among incarcerated youth exposed to childhood maltreatment. Resistance to stress-related psychopathology under adversity was also examined in relation to callous-unemotional (CU) traits, a personality construct characterized by resistance to pathological anxiety and blunted reactivity to threatening stimuli. Participants were 201 ethnically heterogeneous (41.8% White, 35.3% Black, 17.2% Hispanic) adolescent boys (M age = 16.75, SD = 1.15 years) incarcerated in a juvenile detention facility in the South Eastern United States who provided four afternoon saliva samples (later assayed for DHEA and cortisol) and completed self-report questionnaires. Results indicated that childhood maltreatment was associated with greater internalizing problems at lower DHEA concentrations and at higher cortisol-to-DHEA ratios. Conversely, higher DHEA levels and lower cortisol-to-DHEA ratios were associated with greater CU traits, irrespective of maltreatment exposure. CU traits did not attenuate levels of psychopathology in maltreated youth. Findings inform biosocial models of how exposure to parental maltreatment in early life contributes to risk and resilience through mechanisms associated with adaptive environmentally sensitive biological systems and processes.

Role of DHEA and cortisol in prefrontal-amygdalar development and working memory

There is accumulating evidence that both dehydroepiandrosterone (DHEA) and cortisol play an important role in regulating physical maturation and brain development. High DHEA levels tend to be associated with neuroprotective and indirect anabolic effects, while high cortisol levels tend to be associated with catabolic and neurotoxic properties. Previous literature has linked the ratio between DHEA and cortisol levels (DC ratio) to disorders of attention, emotional regulation and conduct, but little is known as to the relationship between this ratio and brain development. Due to the extensive links between the amygdala and the cortex as well as the known amygdalar involvement in emotional regulation, we examined associations between DC ratio, structural covariance of the amygdala with whole-brain cortical thickness, and validated report-based measures of attention, working memory, internalizing and externalizing symptoms, in a longitudinal sample of typically developing children and adolescents 6–22 years of age. We found that DC ratio predicted covariance between amygdalar volume and the medial anterior cingulate cortex, particularly in the right hemisphere. DC ratio had a significant indirect effect on working memory through its impact on prefrontal-amygdalar covariance, with higher DC ratios associated with a prefrontal-amygdalar covariance pattern predictive of higher scores on a measure of working memory. Taken together, these findings support the notion, as suggested by animal and in vitro studies, that there are opposing effects of DHEA and cortisol on brain development in humans, and that these effects may especially target prefrontal-amygdalar development and working memory, in a lateralized fashion.

Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden Study.

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men. Serum DHEA and DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2516, age 69 to 81 years). Falls were ascertained every 4 months by mailed questionnaires. Associations between steroid hormones and falls were estimated by generalized estimating equations. During a mean follow-up of 2.7 years, 968 (38.5%) participants experienced a fall. High serum levels of both DHEA (odds ratio [OR] per SD increase 0.85; 95% CI, 0.78 to 0.92) and DHEAS (OR 0.88, 95% CI, 0.81 to 0.95) were associated with a lower incident fall risk in models adjusted for age, BMI, and prevalent falls. Further adjustment for serum sex steroids or age-related comorbidities only marginally attenuated the associations between DHEA or DHEAS and the likelihood of falling. Moreover, the point estimates for DHEA and DHEAS were only slightly reduced after adjustment for lean mass and/or grip strength. Also, the addition of the narrow walk test did not substantially alter the associations between serum DHEA or DHEAS and fall risk. Finally, the association with incident fall risk remained significant for DHEA but not for DHEAS after simultaneous adjustment for lean mass, grip strength, and the narrow walk test. This suggests that the associations between DHEA and DHEAS and falls are only partially mediated via muscle mass, muscle strength, and/or balance. In conclusion, older men with high DHEA or DHEAS levels have a lesser likelihood of a fall. © 2018 American Society for Bone and Mineral Research.

Brain structural connectivity during adrenarche: Associations between hormone levels and white matter microstructure

Levels of the adrenal hormones dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and testosterone, have all been linked to behavior and mental health during adrenarche, and preclinical studies suggest that these hormones influence brain development. However, little is known about how variation in these hormones is associated with white matter structure during this period of life. The current study aimed to examine associations between DHEA, DHEAS, and testosterone, and white matter microstructure during adrenarche. To avoid the confounding effect of age on hormone levels, we tested these associations in 87 children within a narrow age range (mean age 9.56 years, SD=0.34) but varying in hormone levels. All children provided saliva samples directly after waking and completed a diffusion-weighted MRI scan. Higher levels of DHEA were associated with higher mean diffusivity (MD) in a widespread cluster of white matter tracts, which was partially explained by higher radial diffusivity (RD) and partially by higher axial diffusivity (AD). In addition, there was an interaction between DHEA and testosterone, with higher levels of testosterone being associated with higher fractional anisotropy (FA) and lower MD and RD when DHEA levels were relatively high, but with lower FA and higher MD and RD when DHEA levels were low. These findings suggest that relatively early exposure to DHEA, as well as an imbalance between the adrenal hormones, may be associated with alterations in white matter microstructure. These findings highlight the potential relevance of adrenarcheal hormones for structural brain development.

Circulating androgens and SHBG during the normal menstrual cycle in two ethnic populations

The objective of this study was to study possible ethnic differences in steroid hormones and sex hormone-binding globulin (SHBG) during the menstrual cycle. Serum levels of the ovarian steroids estradiol (E2) and progesterone (P) and of follicle-stimulating hormone (FSH), luteinizing hormone (LH), SHBG, dehydroepiandrosterone (DHEA) and testosterone (T-ria) were all measured by immunoassay during the menstrual cycle in 15 Swedish and 11 West Asian regularly menstruating women. Testosterone (T-ms) was also measured by LC-MS/MS and so were 4-androstene-3,17-dione (A-4) and 17-alpha-hydroxyprogesterone (17-OHP). There were no ethnic differences in levels of ovarian steroids, gonadotrophins, A-4, 17-OHP and T-ms. DHEA were significantly higher and SHBG significantly lower in West Asian than in Swedish women. Surprisingly, T-ria was significantly higher in West Asian than in Swedish women and higher than T-ms (47% in Swedish and 107% in West Asian women). The difference (T-ria − T-ms) showed strong positive correlations to DHEA in the total and in West Asian but not in Swedish women, indicating an influence of DHEA/DHEAS metabolites on the T-ria results. In conclusion, ethnic differences in cross reacting steroids may cause erroneous results in one ethnic group by a steroid immunoassay having reasonable specificity in another. The reasons for the lower SHBG and the higher DHEA levels in West Asian women are not known. The results raise the question about establishing different reference values for certain analytes in different ethnic groups.