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Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche.Epigenetics Dec 2023Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its...
Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.
Topics: Female; Humans; Child; Adrenarche; Androgens; Pilot Projects; DNA Methylation; Dehydroepiandrosterone Sulfate; Obesity
PubMed: 37053179
DOI: 10.1080/15592294.2023.2200366 -
Frontiers in Endocrinology 2023Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic...
BACKGROUND
Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD.
METHOD
A total of 11 serum steroids in adrenal CS ( = 13) and CD ( = 15) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed.
RESULTS
The PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with -tests. The sensitivity and specificity of DHEA-S ratios <0.40 were 92.31% (95% CI 64.0%-99.8%) and 93.33% (95% CI 68.1%-99.8%), respectively, in identifying adrenal CS. The sensitivity and specificity of DHEA ratios <0.18 were 100% (95% CI 75.3%-100.0%) and 100% (95% CI 78.2%-100.0%), respectively, in identifying adrenal CS.
CONCLUSION
Our data support the clinical use of the DHEA-S and DHEA ratios in the differential diagnosis of adrenal CS and CD, especially when falsely elevated ACTH is suspected.
Topics: Humans; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Cushing Syndrome; Pituitary ACTH Hypersecretion; Chromatography, Liquid; Tandem Mass Spectrometry; Steroids; Adrenocorticotropic Hormone
PubMed: 37260439
DOI: 10.3389/fendo.2023.1158573 -
Hormones (Athens, Greece) Dec 2021The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the... (Review)
Review
The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the larynx is affected by sex hormones and may change considerably over the lifespan. In the current review, sex hormone-related voice modifications occurring during childhood, puberty, the menstrual cycle, pregnancy and senescence are described. The roles of sex hormones (including gonadotropins, testosterone, estrogen, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate) underlying physiological voice changes are discussed, the main differences between males and females are explained and clinical implications are taken into account.
Topics: Androgens; Androstenedione; Dehydroepiandrosterone; Estrogens; Female; Gonadal Steroid Hormones; Gonadotropins; Humans; Male; Pregnancy; Testosterone; Voice
PubMed: 34046877
DOI: 10.1007/s42000-021-00298-y -
The Journals of Gerontology. Series A,... Apr 2021The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress.
BACKGROUND
The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress.
METHOD
We performed a standard 250 µg ACTH stimulation test in a home-based substudy of 51 women aged 85-96 years enrolled in the Women's Health and Aging Study II who were not taking corticosteroids. We examined the cortisol and dehydroepiandrosterone (DHEA) responses at 0, 30, 60, and 120 minutes, overall and by frailty status.
RESULTS
The peak cortisol response to ACTH could not be determined, with the highest levels at the 120-minute time point. Pre- and post-ACTH stimulated cortisol levels did not differ by frailty status over this time frame, with no difference in the characteristics of the dose-response curves. Pre- and post-ACTH stimulated DHEA levels also did not differ by frailty status, though the dose-response curves suggested divergence after stimulation, with a more rapid DHEA response with increasing frailty.
CONCLUSIONS
Our data demonstrate a robust cortisol response to ACTH challenge testing, but inadequate negative feedback in old-old women, resulting in prolonged exposure to cortisol. Future studies should examine dynamic cortisol and DHEA responses in this age group, using a less potent ACTH stimulus and longer collection period.
Topics: Adrenocorticotropic Hormone; Aged, 80 and over; Dehydroepiandrosterone; Female; Frailty; Hormones; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests
PubMed: 32502234
DOI: 10.1093/gerona/glaa134 -
Cleveland Clinic Journal of Medicine Jan 2021In women, the androgens testosterone and dehydroepiandrosterone (DHEA) play important physiologic roles in reproductive tissues, mood, cognition, the breast, bone,... (Review)
Review
In women, the androgens testosterone and dehydroepiandrosterone (DHEA) play important physiologic roles in reproductive tissues, mood, cognition, the breast, bone, muscle, vasculature, and other systems. This article reviews the effects of androgens in women, as well as the indications and best-practice recommendations for the use of androgen therapy.
Topics: Androgens; Dehydroepiandrosterone; Female; Humans; Testosterone
PubMed: 33384313
DOI: 10.3949/ccjm.88a.20030 -
The Cochrane Database of Systematic... Feb 2016There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators.
OBJECTIVES
To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment.
DATA COLLECTION AND ANALYSIS
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use.
AUTHORS' CONCLUSIONS
Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
Topics: Acetylcysteine; Allopurinol; Antioxidants; Antipsychotic Agents; Ascorbic Acid; Dehydroepiandrosterone; Drug Therapy, Combination; Free Radical Scavengers; Ginkgo biloba; Humans; Oxidative Stress; Randomized Controlled Trials as Topic; Schizophrenia; Selegiline; Vitamin E; Vitamins
PubMed: 26848926
DOI: 10.1002/14651858.CD008919.pub2 -
The Journal of Steroid Biochemistry and... Jun 2019The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other...
The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other primates. The human adrenal also secretes 11-oxygenated androgens (11-oxyandrogens), including 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), of which 11OHT and 11KT are bioactive androgens. The 11-oxyandrogens, particularly 11KT, have been recognized as biologically important testicular androgens in teleost fishes for decades, but their physiological contribution in humans has only recently been established. Beyond fish and humans, however, the presence of 11-oxyandrogens in other species has not been investigated. This study provides a comprehensive analysis of a set of C steroids, including the traditional androgens and 11-oxyandrogens, across 18 animal species. As previously shown, serum DHEA and DHEAS were much higher in primates than all other species. Circulating 11-oxyandrogens, especially 11KT, were observed in notable amounts in male, but not in female trout, consistent with gonadal origin in fish. The circulating concentrations of 11-oxyandrogens ranged from 0.1 to 10 nM in pigs, guinea pigs and in all the primates studied (rhesus macaque, baboon, chimpanzee and human) but not in rats or mice, and 11OHA4 was consistently the most abundant. In contrast to fish, serum 11KT concentrations were similar in male and female primates for each species, despite significantly higher circulating testosterone in males, suggesting that 11KT production in these species is not testis-dependent and primarily originates from adrenal-derived 11-oxyandrogen precursors.
Topics: Androgens; Animals; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Male; Species Specificity; Testosterone
PubMed: 30959151
DOI: 10.1016/j.jsbmb.2019.04.005 -
Hormones and Behavior Mar 2024The cumulative negative effects of prolonged Hypothalamic-Pituitary-Adrenal axis (HPA axis) activation are associated with several age-related diseases. Some...
The cumulative negative effects of prolonged Hypothalamic-Pituitary-Adrenal axis (HPA axis) activation are associated with several age-related diseases. Some psychological traits such as optimism and pessimism have been shown to be related to both health and the stress response, although their relationship with the HPA axis is inconclusive. More stable HPA axis biomarkers, such as hair samples of cortisol (HC) and dehydroepiandrosterone (HDHEA), would help to clarify the association between these psychological traits and HPA axis functioning. The main aim of this study was to test the relationships between optimism and pessimism and chronic stress biomarkers measured in hair (HC and HDHEA). Additionally, a secondary objective was to explore sex differences in HC and HDHEA levels and their relationship with these psychological traits. We measured optimism, pessimism, and their combination (dispositional optimism) using the Life Orientation Test Revised (LOT-R) and chronic stress biomarkers (HC and HDHEA) in 119 healthy participants (46 men and 73 women) between 56 and 81 years old who belonged to a university program. Regression analyses controlling for perceived stress and BMI indicated that higher dispositional optimism was related to lower HC and HC:HDHEA (β = -0.256, p = .008 and β = -0.300, p = .002, respectively). More specifically, higher pessimism was related to higher HC (β = 0.235; p = .012) and HC:HDHEA (β = 0.240; p = .011), whereas higher optimism was associated with a lower HC:HDHEA(β = -0.205; p = .031). Moderation analyses showed no sex differences. To date, this is the first study to investigate the link between these traits and HC and HDHEA in older people. Our results confirm that positive and negative expectations about the future (i.e. optimism and pessimism) may play an important role in health due to their relationship with the HPA axis. They also strengthen the idea that the negative effects of pessimism have a greater weight than the protective effects of optimism in their relationship with HPA axis regulation.
Topics: Humans; Male; Female; Aged; Middle Aged; Aged, 80 and over; Hydrocortisone; Pessimism; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Biomarkers; Hair; Dehydroepiandrosterone
PubMed: 38194858
DOI: 10.1016/j.yhbeh.2023.105474 -
Journal of Autoimmunity Nov 2016Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Current treatment strategies rely heavily on corticosteroids, which are in turn responsible... (Review)
Review
Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Current treatment strategies rely heavily on corticosteroids, which are in turn responsible for a significant burden of morbidity, and immunosuppressives which are limited by suboptimal efficacy, increased infections and malignancies. There are significant deficiencies in our immunosuppressive armamentarium, making immunomodulatory therapies crucial, offering the opportunity to prevent disease flare and the subsequent accrual of damage. Currently available immunomodulators include prasterone (synthetic dehydroeipandrosterone), vitamin D, hydroxychloroquine and belimumab. These therapies, acting via numerous cellular and cytokine pathways, have been shown to modify the aberrant immune responses associated with SLE without overt immunosuppression. Vitamin D is important in SLE and supplementation appears to have a positive impact on disease activity particularly proteinuria. Belimumab has specific immunomodulatory properties and is an effective therapy in those with specific serological and clinical characteristics predictive of response. Hydroxychloroquine is a crucial background medication in SLE with actions in many molecular pathways. It has disease specific effects in reducing flare, treating cutaneous disease and inflammatory arthralgias in addition to other effects such as reduced thrombosis, increased longevity, improved lipids, better glycemic control and blood pressure. Dehydroeipandrosterone is also an immunomodulator in SLE which can have positive effects on disease activity and has bone protective properties. This review outlines the immunologic actions of these drugs and the clinical evidence supporting their use.
Topics: Adjuvants, Immunologic; B-Lymphocytes; Combined Modality Therapy; Dehydroepiandrosterone; Disease Management; Humans; Hydroxychloroquine; Immunologic Factors; Immunomodulation; Immunotherapy, Adoptive; Lupus Erythematosus, Systemic; Stem Cell Transplantation; Vitamin D
PubMed: 27371107
DOI: 10.1016/j.jaut.2016.06.010 -
Biomolecules Nov 2022Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone,... (Review)
Review
Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). These steroids modulate the development and function of immune response cells. Androgens are generally attributed to immunosuppressive effects; however, this is not always the case. Variations in the concentrations of these hormones induce differences in the innate, humoral, and cell-mediated immune response, which is concentration dependent. The androgens at the highest concentration in the organism that bind to the androgen receptor (AR) are DHEA and testosterone. Therefore, in this work, we review the effects of DHEA and testosterone on the immune response. The main findings of this review are that DHEA and testosterone induce similar but also opposite effects on the immune response. Both steroids promote the activation of regulatory T cells, which suppresses the Th17-type response. However, while testosterone suppresses the inflammatory response, DHEA promotes it, and this modulation is important for understanding the involvement of androgens in infectious (bacterial, viral and parasitic) and autoimmune diseases, as well as in the sexual dimorphism that occurs in these diseases.
Topics: Testosterone; Dehydroepiandrosterone; Androgens; Dihydrotestosterone; Adaptive Immunity
PubMed: 36551196
DOI: 10.3390/biom12121768