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Vitamins and Hormones 2023Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA) and its sulfated metabolite DHEA-S are the most abundant circulating steroids and are precursors for active...
Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA) and its sulfated metabolite DHEA-S are the most abundant circulating steroids and are precursors for active sex steroid hormones, estradiol and testosterone. DHEA has a broad range of reported effects in the central nervous system (CNS), cardiovascular system, adipose tissue, kidney, liver, and in the reproductive system. The mechanisms by which DHEA and DHEA-S initiate their biological effects are diverse. DHEA and DHEA-S may directly bind to plasma membrane (PM) receptors, including a DHEA-specific, G-protein coupled receptor (GPCR) in endothelial cells; various neuroreceptors, e.g., aminobutyric-acid-type A (GABA(A)), N-methyl-d-aspartate (NMDA) and sigma-1 (S1R) receptors (NMDAR and SIG-1R). DHEA and DHEA-S directly bind the nuclear androgen and estrogen receptors (AR, ERα, or ERβ) although with significantly lower binding affinities compared to the steroid hormones, e.g., testosterone, dihydrotestosterone, and estradiol, which are the cognate ligands for AR and ERs. Thus, extra-gonadal metabolism of DHEA to the sex hormones must be considered for many of the biological benefits of DHEA. DHEA also actives GPER1 (G protein coupled estrogen receptor 1). DHEA activates constitutive androstane receptor CAR (CAR) and proliferator activated receptor (PPARα) by indirect dephosphorylation. DHEA affects voltage-gated sodium and calcium ion channels and DHEA-2 activates TRPM3 (Transient Receptor Potential Cation Channel Subfamily M Member 3). This chapter updates our previous 2018 review pertaining to the physiological, biochemical, and molecular mechanisms of DHEA and DHEA-S activity.
Topics: Humans; Endothelial Cells; Androgens; Testosterone; Dehydroepiandrosterone Sulfate; Estradiol
PubMed: 37717999
DOI: 10.1016/bs.vh.2022.12.002 -
Endocrinology and Metabolism Clinics of... Mar 2021
Topics: Androgens; Dehydroepiandrosterone; Female; Humans; Testosterone
PubMed: 33518191
DOI: 10.1016/j.ecl.2020.12.004 -
Reproductive Biology and Endocrinology... Jul 2023Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is still a serious challenge and the scientific evidence of some adjuvant therapies remains controversial.
AIM
Based on previous evidence, the purpose of this systematic review and network meta-analysis was to evaluate the effects of DHEA, CoQ10, GH and TEAS on pregnancy outcomes in POR patients undergoing in vitro fertilization and embryo transplantation (IVF-ET). In addition, we aimed to determine the current optimal adjuvant treatment strategies for POR.
METHODS
PubMed, Embase, The Cochrane Library and four databases in China (CNKI, Wanfang, VIP, SinoMed) were systematically searched up to July 30, 2022, with no restrictions on language. We included randomized controlled trials (RCTs) of adjuvant treatment strategies (DHEA, CoQ10, GH and TEAS) before IVF-ET to improve pregnancy outcomes in POR patients, while the control group received a controlled ovarian stimulation (COS) regimen only. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The surface under the cumulative ranking curve (SUCRA) was used to provide a pooled measure of cumulative ranking for each outcome.
RESULTS
Sixteen RCTs (2323 women) with POR defined using the Bologna criteria were included in the network meta-analysis. Compared with the control group, CoQ10 (OR 2.22, 95% CI: 1.05 to 4.71) and DHEA (OR 1.92, 95% CI: 1.16 to 3.16) had obvious advantages in improving the clinical pregnancy rate. CoQ10 was the best in improving the live birth rate (OR 2.36, 95% CI: 1.07 to 5.38). DHEA increased the embryo implantation rate (OR 2.80, 95%CI: 1.41 to 5.57) and the high-quality embryo rate (OR 2.01, 95% CI: 1.07 to 3.78) and number of oocytes retrieved (WMD 1.63, 95% CI: 0.34 to 2.92) showed a greater advantage, with GH in second place. Several adjuvant treatment strategies had no significant effect on reducing the cycle canceling rate compared with the control group. TEAS was the least effective of the four adjuvant treatments in most pooled results, but the overall effect appeared to be better than that of the control group.
CONCLUSION
Compared with COS regimen, the adjuvant use of CoQ10, DHEA and GH before IVF may have a better clinical effect on the pregnancy outcome of POR patients. TEAS needs careful consideration in improving the clinical pregnancy rate. Future large-scale RCTs with direct comparisons are needed to validate or update this conclusion.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022304723.
Topics: Female; Pregnancy; Humans; Network Meta-Analysis; Ovulation Induction; Reproductive Techniques, Assisted; Fertilization in Vitro; Pregnancy Rate; Dehydroepiandrosterone
PubMed: 37464357
DOI: 10.1186/s12958-023-01119-0 -
Obstetrics and Gynecology Sep 2023To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of...
OBJECTIVE
To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM).
DATA SOURCES
MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators.
METHODS OF STUDY SELECTION
We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group.
TABULATION, INTEGRATION, AND RESULTS
Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO 2 ) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO 2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function.
CONCLUSION
Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.
Topics: Female; Humans; Hyaluronic Acid; Menopause; Vagina; Estrogens; Testosterone; Dehydroepiandrosterone
PubMed: 37543737
DOI: 10.1097/AOG.0000000000005288 -
Reproductive Biomedicine Online Mar 2024Many women undergoing IVF take supplements during treatment. The purpose of this review was to systematically review these nutritional supplements. The therapies studied... (Review)
Review
Many women undergoing IVF take supplements during treatment. The purpose of this review was to systematically review these nutritional supplements. The therapies studied are dehydroepiandrosterone (DHEA), melatonin, co-enzyme Q10 (CoQ1O), carnitine, selenium, vitamin D, myo-inositol, omega-3, Chinese herbs and dietary interventions. A literature search up to May 2023 was undertaken. The data suggest that a simple nutritional approach would be to adopt a Mediterranean diet. With regards to supplements to treat a potential poor ovarian response to ovarian stimulation, starting DHEA and COQ-10 before cycle commencement is better than control therapies. Furthermore, medication with CoQ10 may have some merit, although it is unclear whether its place is for older women, for those with a poor response to ovarian stimulation or for poor embryonic development. There appears a benefit for some IVF outcomes for the use of melatonin, although it is unclear what group of patients would derive the benefit and the appropriate dosing regimen. For women with polycystic ovary syndrome, there may be a benefit to the use of myo-inositol, although again the dosing regimen is unclear. Furthermore, the place of vitamin D supplementation has yet to be clarified, and supplementation with omega-3 free fatty acids may lead to improvements in clinical and embryological IVF outcomes.
Topics: Pregnancy; Humans; Female; Aged; Melatonin; Fertilization in Vitro; Dietary Supplements; Inositol; Vitamin D; Dehydroepiandrosterone; Ovulation Induction
PubMed: 38184959
DOI: 10.1016/j.rbmo.2023.103770 -
Ageing Research Reviews Sep 2020Musculoskeletal disorders related to ageing are one of the most common causes of mortality and morbidity among elderly individuals worldwide. The typical constitutive... (Review)
Review
Musculoskeletal disorders related to ageing are one of the most common causes of mortality and morbidity among elderly individuals worldwide. The typical constitutive components of the musculoskeletal system, including bone, muscle, and joints, gradually undergo a process of tissue loss and degeneration as a result of life-long mechanical and biological stress, ultimately leading to the onset of a series of age-related musculoskeletal diseases, including osteoporosis (OP), sarcopenia, and osteoarthritis (OA). Dehydroepiandrosterone (DHEA), a precursor of androgen secreted mainly by the adrenal gland, has attracted much attention as a marker for senescence due to its unique age-related changes. This pre-hormone has been publicly regarded as an "antidote for ageing" because of its favourable effect against a wide range of age-related diseases, such as Alzheimer disease, cardiovascular diseases, immunosenescence and skin senescence, though its effect on age-related musculoskeletal diseases has been explored to a lesser extent. In the present review, we summarized the action of DHEA against OP, sarcopenia and OA. Extensive detailed descriptions of the pathogenesis of each of these musculoskeletal disorders are beyond the scope of this review; instead, we aim to highlight the association of changes in DHEA with the processes of OP, sarcopenia and OA. A special focus will also be placed on the overlapping pathogeneses among these three diseases, and the molecular mechanisms underlying the action of DHEA against these diseases are discussed or postulated.
Topics: Aged; Aging; Dehydroepiandrosterone; Humans; Musculoskeletal Diseases; Osteoporosis; Sarcopenia
PubMed: 32711158
DOI: 10.1016/j.arr.2020.101132 -
Nature Chemical Biology Nov 2022Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM)...
Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a G trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2. The cryo-EM structures of DHEA-ADGRG2-G provided interaction details for DHEA within the seven transmembrane domains of ADGRG2. Collectively, our data provide a structural basis for the activation and signaling of ADGRG2, as well as characterization of steroid hormones as ADGRG2 ligands, which might be used as useful tools for further functional studies of the orphan ADGRG2.
Topics: Humans; Male; Cryoelectron Microscopy; Dehydroepiandrosterone Sulfate; Desoxycorticosterone; Ligands; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 35982227
DOI: 10.1038/s41589-022-01084-6 -
Methods in Enzymology 2023The enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), encoded by the gene HSD3B1, plays an essential role in the peripheral conversion of 3β-OH, Δ-steroids to...
The enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), encoded by the gene HSD3B1, plays an essential role in the peripheral conversion of 3β-OH, Δ-steroids to 3-keto, Δ-steroids. In human physiology, the adrenal produces dehydroepiandrosterone (DHEA) and DHEA-sulfate, which are major precursors for the biosynthesis of potent androgens and estrogens. DHEA is converted by 3βHSD1 and subsequently is converted by steroid-5α-reductase to potent androgens or by aromatase to estrogens. Assessment of 3βHSD1 is therefore critical under various conditions. In this chapter, we detail several approaches to assessing 3βHSD1. First, we describe a genotyping protocol for the identification of a common missense-encoding variation that regulates 3βHSD1 cellular metabolic activity. This protocol distinguishes between the HSD3B1(1245A) and the HSD3B1(1245C) allele which have lower and higher metabolic activity, respectively. Second, we detail mass spectrometry approaches to determining 3βHSD1 activity using stable isotope dilution. Third, we describe methods for using tritiated DHEA and high performance liquid chromatography coupled with a beta-RAM to also determine 3βHSD1 activity. Together, we provide multiple methods of directly assessing 3βHSD1 activity or anticipated 3βHSD1 activity.
Topics: Humans; Androgens; Estrogens; Multienzyme Complexes; Dehydroepiandrosterone; Steroids
PubMed: 37802584
DOI: 10.1016/bs.mie.2023.04.002 -
The Journal of Clinical Endocrinology... May 2023The relationship between dehydroepiandrosterone sulfate (DHEAS) and mortality is of scientific and public health interest, yet it remains poorly understood.
CONTEXT
The relationship between dehydroepiandrosterone sulfate (DHEAS) and mortality is of scientific and public health interest, yet it remains poorly understood.
OBJECTIVE
We examined the association between DHEAS and mortality from cancer, cardiovascular disease, and all causes in middle-aged and older men and women.
METHODS
DHEAS was measured in stored serum samples collected from 1994 to 1998 from a case-cohort nested within EPIC-Heidelberg, that included 7370 men (mean age = 55.0) and women (mean age = 52.4 years). Median follow-up for incident mortality events was 17.7 years. All deaths due to cancer (n = 1040), cardiovascular diseases (n = 598), and all causes (n = 2407) that occurred in EPIC-Heidelberg until end of 2014 were included.
RESULTS
The association between DHEAS and mortality was nonlinear such that both participants in the lowest (Q1) and highest (Q5) sex- and 5-year age-group specific quintiles of DHEAS were at increased hazard ratios (HR) of mortality from cardiovascular [Q1: HR = 1.83 (95% CI: 1.33-2.51), Q5: 1.39 (1.00-1.94)], cancer [Q1: 1.27 (1.01-1.60), Q5: 1.27 (1.02-1.60)] and all causes [Q1: 1.51 (1.25-1.82), Q5: 1.31 (1.08-1.58)], compared with participants in Q3. In men and women with below-median DHEAS levels, doubling of DHEAS was associated with lower hazards of cardiovascular [0.87, (0.78-0.96)], cancer [0.90, (0.83-0.97)], and total mortality [0.89, (0.83-0.95)]. In contrast, a doubling in DHEAS among participants with above-median levels was associated with 1.20, (1.01-1.42), 1.28, (1.01-1.62), and 1.19 (1.03-1.37) higher hazards of mortality from cancer, cardiovascular, and all causes, respectively.
CONCLUSION
In this large population-based study, DHEAS showed a J-shaped association with mortality. Both participants with lowest and highest levels experienced higher hazards of mortality from cancer, cardiovascular disease, and all causes.
Topics: Male; Middle Aged; Humans; Female; Aged; Dehydroepiandrosterone Sulfate; Cardiovascular Diseases; Proportional Hazards Models; Neoplasms; Dehydroepiandrosterone
PubMed: 36477484
DOI: 10.1210/clinem/dgac716 -
Clinical Chemistry Dec 2023Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the... (Review)
Review
BACKGROUND
Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the different phases of life and regulate important developmental and maturational processes. Androgen excess or deficiency can therefore present at various ages in various ways.
CONTENT
The diagnostic approach for atypical genitalia, premature pubarche, delayed pubertal onset or progression, and hirsutism or virilization, including measurement of androgens (testosterone, androstenedione, 17-OHprogesterone, dehydroepiandrosterone, and dihydrotestosterone) is discussed in the current review. Androgens can be measured in serum, saliva, urine, or dried blood spots. Techniques to measure androgens, including immunoassays and LC-MS, have their own advantages and pitfalls. In addition, pre- and postanalytical issues are important when measuring androgens.
SUMMARY
During clinical interpretation of androgen measurements, it is important to take preanalytical circumstances, such as time of blood withdrawal, into account. As immunoassays have major drawbacks, especially in samples from women and neonates, concentrations measured using these assays should be interpreted with care. Reference intervals can only be used in relation to the measurement technique and the standardization of the assay. In the near future, new androgens will probably be added to the current repertoire to further improve the diagnosis and follow-up of androgen excess or deficiency.
Topics: Infant, Newborn; Female; Humans; Androgens; Testosterone; Androstenedione; Virilism; Hirsutism; Dehydroepiandrosterone
PubMed: 37794651
DOI: 10.1093/clinchem/hvad146