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Hormones (Athens, Greece) Jun 2023Hyperandrogenism, one of the most frequent causes of anovulation in women, increases the risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS)....
PURPOSE
Hyperandrogenism, one of the most frequent causes of anovulation in women, increases the risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS). Ferroptosis, characterized by iron-dependent lipid peroxidation, has provided new insight into the progression of PCOS. 1,25-dihydroxyvitamin D3 (1,25D3) may play a role in reproduction because its receptor, VDR, which contributes to the inhibition of oxidative stress, is primarily located in the nuclei of granulosa cells. This study has therefore investigated whether 1,25D3 and hyperandrogenism affect granulosa-like tumor cells (KGN cells) through ferroptosis.
METHODS
KGN cells were treated with dehydroepiandrosterone (DHEA) or pretreated with 1,25D3. Cell viability was evaluated with the cell counting kit-8 (CCK-8) assay. The mRNA and protein expression levels of ferroptosis-related molecules, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member (SLC7A11), and long-chain acyl-CoA synthetase 4 (ACSL4), were assessed via qRT-PCR and western blot. The concentration of malondialdehyde (MDA) was measured by ELISA. The rates of reactive oxygen species (ROS) production and lipid peroxidation were assessed via photometric methods.
RESULTS
Decreased cell viability, suppression of GPX4 and SLC7A11 expression, increased expression of ACSL4, elevated levels of MDA, accumulation of ROS, and increased lipid peroxidation, which are changes representative of ferroptosis, were observed in KGN cells after treatment with DHEA. Pretreatment with 1,25D3 in KGN cells significantly prevented these changes.
CONCLUSIONS
Our findings demonstrate that 1,25D3 attenuates hyperandrogen-induced ferroptosis of KGN cells. This finding might lead to new insights into the pathophysiology and therapy of PCOS and provides new evidence for the treatment of PCOS with 1,25D3.
Topics: Humans; Female; Calcitriol; Ferroptosis; Reactive Oxygen Species; Hyperandrogenism; Polycystic Ovary Syndrome; Dehydroepiandrosterone
PubMed: 36884209
DOI: 10.1007/s42000-023-00439-5 -
Current Alzheimer Research 2020Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and...
BACKGROUND
Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease.
OBJECTIVE
The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer's disease.
METHODS
PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles.
RESULTS
We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer's disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications.
CONCLUSION
Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer's disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.
Topics: Alzheimer Disease; Animals; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans
PubMed: 32183671
DOI: 10.2174/1567205017666200317092310 -
Neuroscience and Biobehavioral Reviews May 2019Posttraumatic stress disorder (PTSD) is often associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Previous findings are inconsistent, possibly... (Meta-Analysis)
Meta-Analysis Review
Posttraumatic stress disorder (PTSD) is often associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Previous findings are inconsistent, possibly due to trauma exposure of controls or different hormone measurement methods. We investigated cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) in adults with clinical PTSD under basal or challenged conditions (Prospero registration no. CRD42016041690). A search of PubMed, Scopus, Medline, PsycINFO, Pilots/ProQuest, and Web of Science resulted in 108 included studies (N = 6484). Morning and 24 h cortisol were significantly lower in PTSD than in controls (g = -0.21; 95% CI: -0.42-(-0.01); g = -0.31; CI: -0.60-(-0.03)). Significant cortisol increases occurred after awakening in PTSD (g = 0.40; CI: 0.13-0.67) and in non-exposed controls (g = 0.96; CI: 0.59-1.33). Evening DHEA was significantly higher in PTSD than in non-exposed controls (g = 0.58; CI: 0.17-0.99). All groups showed large cortisol suppression effects after dexamethasone administration. Overall, the potential moderators investigated did not reveal a consistent pattern of HPA alterations.
Topics: Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Stress Disorders, Post-Traumatic
PubMed: 30790632
DOI: 10.1016/j.neubiorev.2019.02.005 -
International Journal of Clinical... Aug 2021Background Testosterone administration was found to have a protective effect on thyroid autoimmunity in men with autoimmune (Hashimoto's) thyroiditis. Objective The...
Background Testosterone administration was found to have a protective effect on thyroid autoimmunity in men with autoimmune (Hashimoto's) thyroiditis. Objective The present study was aimed at assessing whether oral dehydroepiandrosterone affects thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with subclinical hypothyroidism induced by Hashimoto's thyroiditis. Setting The study was conducted at Medical University of Silesia, Katowice, Poland. Method The study enrolled 32 elderly men with autoimmune hypothyroidism and low dehydroepiandrosterone-sulfate levels. Based on patient preference, the participants either received oral dehydroepiandrosterone (50 mg daily; n = 16) or remained untreated (n = 16). Apart from measuring antibody titers and hormone levels, we calculated baseline and post-treatment values of three structure parameters of thyroid homeostasis. Main outcome measure Serum titers of thyroid peroxidase and thyroglobulin antibodies. Results At baseline, there were no significant differences in the investigated parameters between both groups of men. All participants completed the study. Oral dehydroepiandrosterone increased dehydroepiandrosterone-sulfate and testosterone levels, as well as had a neutral effect on estradiol levels. The increase in dehydroepiandrosterone-sulfate correlated with treatment-induced changes in serum testosterone. Moreover, dehydroepiandrosterone reduced titers of thyroid peroxidase and thyroglobulin antibodies, decreased serum thyrotropin levels, reduced Jostel's thyrotropin index as well as increased thyroid's secretory capacity. Treatment-induced changes in thyroid antibody titers, thyrotropin levels, Jostel's thyrotropin index and thyroid's secretory capacity correlated with the increase in dehydroepiandrosterone-sulfate and testosterone levels. Conclusion The obtained results show that exogenous dehydroepiandrosterone may exert a beneficial effect on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune thyroiditis and subclinical hypothyroidism.
Topics: Aged; Autoimmunity; Dehydroepiandrosterone; Humans; Hypothyroidism; Male; Thyroid Hormones; Thyrotropin
PubMed: 33245519
DOI: 10.1007/s11096-020-01207-w -
Gynecological Endocrinology : the... Mar 2018Dehydroepiandrosterone (DHEA) supplementation might hold some promise in vitro fertilization and embryo transfer cycles. However, the results remain controversial. We... (Meta-Analysis)
Meta-Analysis Review
Dehydroepiandrosterone (DHEA) supplementation might hold some promise in vitro fertilization and embryo transfer cycles. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy of DHEA in patients for in vitro fertilization. PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of DHEA versus placebo on in vitro fertilization were included. Two investigators independently searched articles, extracted data and assessed the quality of included studies. The primary outcomes were clinical pregnancy and live birth rate. Meta-analysis was performed using random-effect model. Six RCTs involving 745 patients were included in the meta-analysis. Overall, compared with placebo, DHEA supplementation was associated with the significant increase in clinical pregnancy (OR = 1.45; 95% CI = 1.04-2.03; p = .03), live birth rate (OR = 2.70; 95% CI = 1.24-5.85; p = .01) and endometrial thickness (Std. mean difference = 0.67; 95% CI = 0.02-1.32; p = .04) but showed no influence on E on hCG day (Std. mean difference = 0.69; 95% CI = -0.46 to 1.85; p = .24), embryos transferred (Std. mean difference = 0.42; 95% CI = -0.04 to 0.88; p = .07) and miscarriage rate (OR = 0.43; 95% CI = 0.03-6.66; p = .55). DHEA supplementation could significantly improve clinical pregnancy, live birth rate, endometrial thickness and retrieved oocytes but failed to alter E on hCG day, embryos transferred and miscarriage rate.
Topics: Dehydroepiandrosterone; Embryo Transfer; Female; Fertilization in Vitro; Humans; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Treatment Outcome
PubMed: 29073790
DOI: 10.1080/09513590.2017.1391202 -
Actas Espanolas de Psiquiatria Sep 2017Aging and Alzheimer’s disease (AD) are associated with a declination of cognition and memory, whose severity increases in AD. Recent investigations point to a... (Review)
Review
Aging and Alzheimer’s disease (AD) are associated with a declination of cognition and memory, whose severity increases in AD. Recent investigations point to a greater participation of neurofibrillary tangles (NFTs) than that of senile plaques, as responsible for cognitive impairment in AD and normal aging. On the other hand, aging is related with reduced levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as testosterone (T). Basic and clinical studies give evidence that hypoandrogenism is associated with memory impairment. Accordingly, some animal studies show that the administration of these hormones improves the performance of cognitive tasks. However, effects of DHEA, DHEA-S, and T in the clinical setting, are not clear in part because of the balance between the benefits and risks of hormone therapy in aging subjects and because the cellular mechanism underlying its effects on memory in old age and related pathologies are unknown. The objective of this review is to analyze the role of DHEA, DHEA-S, and T, on memory in normal aging and in AD, and to determine whether these hormones modulate the hyperphosphorylation of tau protein, a molecular marker in AD pathology. The method used in the review included articles from the PubMed database, using the following search terms: DHEA, DHEA-S, T, memory, androgen deprivation therapy, tau protein, aging, and AD. Finally, we analyze the use of these steroids as an adjunct in the treatment of memory deficits in aging subjects and AD patients.
Topics: Aged; Aging; Alzheimer Disease; Dehydroepiandrosterone; Humans; Memory Disorders; Testosterone
PubMed: 29044447
DOI: No ID Found -
Climacteric : the Journal of the... Feb 2019The loss of sex steroids (e.g. estradiol, dehydroepiandrosterone [DHEA], progesterone) that causes menopause commonly affects a woman's general health and produces... (Review)
Review
The loss of sex steroids (e.g. estradiol, dehydroepiandrosterone [DHEA], progesterone) that causes menopause commonly affects a woman's general health and produces bothersome physical changes that may interfere with normal sexual and genitourinary functioning. Although both over-the-counter and prescription treatments are available, there remains a large unmet need, as less than 10% of women are treated. Adrenal DHEA and its sulfate are the most abundant steroids in humans. Here we review the development of intravaginal prasterone, the synthetic equivalent to endogenous DHEA. Prasterone is approved by the US Food and Drug Administration for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Prasterone has been shown to decrease the pain associated with dyspareunia, and to improve vaginal pH, as well as superficial and parabasal cell counts, while maintaining serum hormone levels within the range of those seen in normal postmenopausal women. Unlike other menopausal prescription therapies, intravaginal prasterone does not carry a boxed warning, thus allowing the clinician and patient to engage in meaningful and reassuring discussion around a new approach that treats this common, debilitating condition.
Topics: Administration, Intravaginal; Atrophy; Dehydroepiandrosterone; Dyspareunia; Female; Humans; Menopause; Randomized Controlled Trials as Topic; Vagina
PubMed: 30554531
DOI: 10.1080/13697137.2018.1535583 -
Journal of the Chinese Medical... Aug 2015The effect of dehydroepiandrosterone (DHEA) therapy on improvement of reproduction outcome is uncertain. Many earlier studies have shown conflicting results. Therefore,... (Review)
Review
The effect of dehydroepiandrosterone (DHEA) therapy on improvement of reproduction outcome is uncertain. Many earlier studies have shown conflicting results. Therefore, a review of the literature is needed to explore the role of DHEA in reproduction. We conducted a literature search of MEDLINE (Ovid) and Pub-Med (2000-June 2014) for all relevant articles that included the terms "dehydroepiandrosterone," "DHEA," and "in vitro fertilization." Among the search-identified articles, seven prospective self-controlled studies and four retrospective case-control studies showed DHEA as an adjuvant therapy able to improve in vitro fertilization outcomes in poor responders (women with diminished ovarian reserve and/or poor ovarian response). However, four randomized controlled trials did not support the benefit of DHEA therapy for poor responders. By contrast, one prospective randomized study showed that DHEA might be beneficial to reproduction in women without diminished ovarian reserve (normal responders). In summary, a review of the previously published studies does not provide clear evidence that DHEA can be a useful treatment to improve ovarian function in poor responders.
Topics: Dehydroepiandrosterone; Female; Fertilization in Vitro; Humans; Ovary; Primary Ovarian Insufficiency
PubMed: 25708822
DOI: 10.1016/j.jcma.2014.12.008 -
CNS Neuroscience & Therapeutics Sep 2022Hypoxia causes plenty of pathologies in the central nervous system (CNS) including impairment of cognitive and memory function. Dehydroepiandrosterone (DHEA) has been...
AIMS
Hypoxia causes plenty of pathologies in the central nervous system (CNS) including impairment of cognitive and memory function. Dehydroepiandrosterone (DHEA) has been proved to have therapeutic effects on CNS injuries by maintaining the homeostasis of synapses, yet its effect on hypoxia-induced CNS damage remains unknown.
METHODS
In vivo and in vitro models were established. Concentrations of glutamate and γ GABA were tested by ELISA. Levels of synapse-associated proteins were measured by western blotting. Density of dendritic protrusions of hippocampal neurons was assessed by Golgi staining. Immunofluorescence was adopted to observe the morphology of primary neurons. The novel object recognition test (NORT) and shuttle box test were used to evaluate cognition.
RESULTS
Dehydroepiandrosterone reversed abnormal elevation of glutamate levels, shortenings of neuronal processes, decreases in the density of dendritic protrusions, downregulation of synaptosome-associated protein (SNAP25), and impaired cognition caused by hypoxia. Hypoxia also resulted in notably downregulation of syntaxin 1A (Stx-1A). Overexpression of Stx-1A dramatically attenuated hypoxia-induced elevation of glutamate. Treatment with DHEA reversed the Stx-1A downregulation caused by hypoxic exposure.
CONCLUSION
Dehydroepiandrosterone may exert a protective effect on hypoxia-induced memory impairment by maintaining synaptic homeostasis. These findings offer a novel understanding of the therapeutic effect of DHEA on hypoxia-induced cognitive dysfunction.
Topics: Dehydroepiandrosterone; Glutamates; Hippocampus; Homeostasis; Humans; Hypoxia
PubMed: 35703574
DOI: 10.1111/cns.13869 -
Frontiers in Endocrinology 2023Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the evidence remains inconsistent. This study aimed to investigate the efficacy of DHEA supplementation in patients with POR/DOR undergoing IVF/ICSI.
METHODS
PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched up to October 2022.
RESULTS
A total of 32 studies were retrieved, including 14 RCTs, 11 self-controlled studies and 7 case-controlled studies. In the subgroup analysis of only RCTs, DHEA treatment significantly increased the number of antral follicle count (AFC) (weighted mean difference : WMD 1.18, 95% confidence interval(CI): 0.17 to 2.19, 0.022), while reduced the level of bFSH (WMD -1.99, 95% CI: -2.52 to -1.46, <0.001), the need of gonadotropin (Gn) doses (WMD -382.29, 95% CI: -644.82 to -119.76, 0.004), the days of stimulation (WMD -0.90, 95% CI: -1.34 to -0.47, <0.001) and miscarriage rate (relative risk : RR 0.46, 95% CI: 0.29 to 0.73, 0.001). The higher clinical pregnancy and live birth rates were found in the analysis of non-RCTs. However, there were no significant differences in the number of retrieved oocytes, the number of transferred embryos, and the clinical pregnancy and live birth rates in the subgroup analysis of only RCTs. Moreover, meta-regression analyses showed that women with lower basal FSH had more increase in serum FSH levels (b=-0.94, 95% CI: -1.62 to -0.25, 0.014), and women with higher baseline AMH levels had more increase in serum AMH levels (b=-0.60, 95% CI: -1.15 to -0.06, 0.035) after DHEA supplementation. In addition, the number of retrieved oocytes was higher in the studies on relatively younger women (b=-0.21, 95% CI: -0.39 to -0.03, 0.023) and small sample sizes (b=-0.003, 95% CI: -0.006 to -0.0003, 0.032).
CONCLUSIONS
DHEA treatment didn't significantly improve the live birth rate of women with DOR or POR undergoing IVF/ICSI in the subgroup analysis of only RCTs. The higher clinical pregnancy and live birth rates in those non-RCTs should be interpreted with caution because of potential bias. Further studies using more explicit criteria to subjects are needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD 42022384393.
Topics: Pregnancy; Humans; Female; Sperm Injections, Intracytoplasmic; Fertilization in Vitro; Pregnancy Rate; Ovulation Induction; Follicle Stimulating Hormone; Dehydroepiandrosterone
PubMed: 37361534
DOI: 10.3389/fendo.2023.1156280