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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 -
The Cochrane Database of Systematic... Oct 2007Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem autoimmune condition. Dehydroepiandrosterone (DHEA) is a naturally occurring inactive steroid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem autoimmune condition. Dehydroepiandrosterone (DHEA) is a naturally occurring inactive steroid which may possess disease activity modifying properties as well as the ability to reduce flares and steroid requirements.
OBJECTIVES
To assess the effectiveness and safety of dehydroepiandrosterone compared to placebo in the treatment of people with systemic lupus erythematosus.
SEARCH STRATEGY
We searched The Cochrane Library (Issue 2, 2006), MEDLINE, Pub Med, EMBASE, Science Citation Index and ISI Proceedings as well as searching web sites of Genelabs, FDA and EMEA. (Searches undertaken in June 2006 unless otherwise specified).
SELECTION CRITERIA
We included randomised controlled trials of at least three months duration comparing DHEA to a placebo in people with SLE.
DATA COLLECTION AND ANALYSIS
Two review authors assessed quality and extracted data.
MAIN RESULTS
From the seven RCTs identified (842 participants) to date there is 'gold' ranking evidence (www.cochranemsk.org) that DHEA: had little clinical effect on disease activity in those with mild/moderate disease (measured by SLEDAI or SLAM) but one study demonstrated evidence of stabilisation or improvement in 8.3% more patients than those treated with placebo; had a modest but clinically significant improvement in health related quality of life measured by Patient Global Assessment, estimated as 11.5% (11.5 mm on a 100 mm scale) by meta-analysis; resulted in a greater number of patients experiencing adverse events, particularly androgenic effects such as acne where patients risk was doubled when compared to placebo (RR 2.2; 95% CI 1.65 to 2.83)
AUTHORS' CONCLUSIONS
Studying effectiveness of DHEA for SLE is difficult, reflecting the problems of studying any treatment for a disease as complex as SLE. From the seven RCTs to date, there was evidence that DHEA had a modest but clinically significant impact on health related quality of life in the short term. Impact on disease activity was inconsistent, with DHEA showing no benefit over placebo in terms of change in SLEDAI in all but one of the 6 studies reporting this outcome. Long term outcomes and safety remain unstudied.
Topics: Adjuvants, Immunologic; Dehydroepiandrosterone; Humans; Lupus Erythematosus, Systemic; Randomized Controlled Trials as Topic
PubMed: 17943841
DOI: 10.1002/14651858.CD005114.pub2 -
Fertility and Sterility Apr 2002To determine the role of adrenal androgenic hormone precursors in female sexual function. (Review)
Review
OBJECTIVE
To determine the role of adrenal androgenic hormone precursors in female sexual function.
DESIGN
A review of current literature on sexual function and the androgen precursor hormone dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS).
RESULT(S)
The C(19) steroid DHEA is both an ovarian and adrenal androgen precursor hormone, whereas DHEAS is only synthesized in the adrenal cortex. Dehydroepiandrosterone sulfate secretion begins at age 10, peaks at age 20, and then wanes. Low DHEAS levels occur in men and women with adrenal insufficiency and in the elderly. Dehydroepiandrosterone, 50 mg/d, increases DHEAS levels. In women but not men, the increased DHEAS levels facilitate additional production of downstream androgens, testosterone, dihydrotestosterone, androstenedione, and androstenediol glucuronide. With the improved female androgenic profile women with adrenal insufficiency have increased sexual thoughts and fantasies as well as an enhancement in mood and well-being. In the elderly >age 65 - DHEAS levels increase in both men and women with DHEA 50 mg/d but only in women were the higher DHEAS levels accompanied by a surge in testosterone levels and in women >age 70 increased libido and enhanced sexual satisfaction as well as a 26% diminution in bone resorption, and a 10% decrease in skin pigmentation.
CONCLUSION(S)
The female adrenal androgen deficiency syndrome, characterized low serum DHEAS levels may be corrected by DHEA supplements that increase levels of DHEAS and downstream androgens of importance to female sexuality.
Topics: Adolescent; Adrenal Glands; Adult; Age Factors; Aged; Clinical Trials as Topic; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Middle Aged; Sexuality
PubMed: 12007898
DOI: 10.1016/s0015-0282(02)02987-4 -
Frontiers in Endocrinology 2023Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship...
OBJECTIVE
Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship between dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels and the risk of dyslipidemia in people with type 2 diabetes mellitus.
MATERIALS AND METHODS
The analysis included 1,927 patients with type 2 diabetes mellitus. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels were determined using lipid chromatography-tandem mass spectrometry. Multivariable analyses were performed to investigate the association between the variables and dyslipidemia.
RESULTS
The multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of dyslipidemia across DHEA tertiles were 0.39 and 0.24-0.64, respectively (p trend = 0.001). This relationship was still maintained when analyzed as a continuous variable (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; P < 0.01). However, in males with type 2 diabetes mellitus, no significant correlations were found between rising levels of dehydroepiandrosterone sulfate, androstenedione, and total testosterone and the risk of dyslipidemia (all P > 0.05). Furthermore, there was no significant association between androgen precursors and total testosterone with regard to the risk of developing dyslipidemia (all P > 0.05).
CONCLUSIONS
Serum dehydroepiandrosterone levels were substantially and adversely correlated with dyslipidemia in adult men with T2DM. These results indicated that dehydroepiandrosterone may have an essential role in the development of dyslipidemia. More prospective research is required to validate this link.
Topics: Adult; Humans; Male; Androstenedione; Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 2; Prospective Studies; Testosterone; Dyslipidemias; Risk Factors
PubMed: 38075062
DOI: 10.3389/fendo.2023.1272797 -
JBRA Assisted Reproduction Oct 2019One in six couples worldwide will experience at least one infertility problem during their reproductive years. Between 5.6% and 35.1% of women will exhibit poor ovarian... (Review)
Review
One in six couples worldwide will experience at least one infertility problem during their reproductive years. Between 5.6% and 35.1% of women will exhibit poor ovarian response. A variety of methods have been applied to improve ovarian response, including dehydroepiandrosterone. In the ovaries, dehydroepiandrosterone promotes follicular development and granulosa cell proliferation by increasing intraovarian androgen concentrations while simultaneously enhancing the level of follicular insulin-like growth factor-1, which promotes folliculogenesis. Dehydroepiandrosterone supplementation may improve in vitro fertilization outcomes and ovarian response in patients with poor ovarian response. However, a few questions still loom over the effectiveness of dehydroepiandrosterone.
Topics: Adult; Dehydroepiandrosterone; Female; Fertilization in Vitro; Humans; Infertility, Female; Ovulation Induction; Pregnancy; Pregnancy Rate; Treatment Outcome
PubMed: 31251010
DOI: 10.5935/1518-0557.20190045 -
CNS Drug Reviews 2003The physiological role of dehydroepiandrosterone (DHEA) and its sulphated ester DHEA(S) has been studied for nearly 2 decades and still eludes final clarification. The... (Review)
Review
The physiological role of dehydroepiandrosterone (DHEA) and its sulphated ester DHEA(S) has been studied for nearly 2 decades and still eludes final clarification. The major interest in DHEA derives from its unique pattern of activity. Its levels exhibit a dramatic age-related decline that supports significant involvement of DHEA(S) in the aging process. Particularly relevant to the aging process is the functional decline that involves memory and cognitive abilities. DHEA is derived mainly from synthesis in the adrenal glands and gonads. It can also be detected in the brain where it is derived from a synthesis that is independent from peripheral steroid sources. For this reason DHEA and other steroid molecules have been named "neurosteroids." Pharmacological studies on animals provided evidence that neurosteroids could be involved in learning and memory processes because they can display memory-enhancing properties in aged rodents. However, human studies have reported contradictory results that so far do not directly support the use of DHEA in aging-related conditions. As such, it is important to remember that plasma levels of DHEA(S) may not reflect levels in the central nervous system (CNS), due to intrinsic ability of the brain to produce neurosteroids. Thus, the importance of neurosteroids in the memory process and in age-related cognitive impairment should not be dismissed. Furthermore, the fact that the compound is sold in most countries as a health food supplement is hampering the rigorous scientific evaluation of its potential. We will describe the effect of neurosteroids, in particular DHEA, on neurochemical mechanism involved in memory and learning. We will focus on a novel effect on a signal transduction mechanism involving a classical "cognitive kinase" such as protein kinase C. The final objective is to provide additional tools to understand the physiological role and therapeutic potentials of neurosteroids in normal and/or pathological aging, such as Alzheimer's disease.
Topics: Administration, Oral; Adrenal Cortex; Aged; Aging; Animals; Central Nervous System; Cognition; Cytochrome P-450 Enzyme System; Dehydroepiandrosterone; Female; Humans; Male; Middle Aged; Neurosecretory Systems; Signal Transduction
PubMed: 12595910
DOI: 10.1111/j.1527-3458.2003.tb00242.x -
Rejuvenation Research Aug 2013Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as... (Review)
Review
Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as low as 10%-20% of those encountered in young individuals. This age-related decrease suggests an "adrenopause" phenomenon. Studies point toward several potential roles of DHEA, mainly through its hormonal end products, making this decline clinically relevant. Unfortunately, even if positive effects of DHEA on muscle, bone, cardiovascular disease, and sexual function seem rather robust, extremely few studies are large enough and/or long enough for conclusions regarding its effects on aging. Moreover, because it has been publically presented as a "fountain of youth" equivalent, over-the-counter preparations lacking pharmacokinetic and pharmacodynamic data are widely used worldwide. Conceptually, supplementing a pre-hormone is extremely interesting, because it would permit the human organism to adequately use it throughout long periods, increasing or decreasing end products according to his needs. Nevertheless, data on the safety profile of long-term DHEA supplementation are still lacking. In this article, we examine the potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease. We also review risks and benefits of existing protocols of DHEA supplementation.
Topics: Aging; Dehydroepiandrosterone; Humans; Syndrome
PubMed: 23647054
DOI: 10.1089/rej.2013.1425 -
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 -
Canadian Family Physician Medecin de... Jul 1999To review the evidence that supplementation with dehydro-3-epiandrosterone (DHEA) is beneficial in aging, cardiovascular disease, immune function, and cancer. (Review)
Review
OBJECTIVE
To review the evidence that supplementation with dehydro-3-epiandrosterone (DHEA) is beneficial in aging, cardiovascular disease, immune function, and cancer.
METHODS
English-language literature search using MEDLINE with subject headings DHEA, adrenal steroids, and androgens.
QUALITY OF EVIDENCE
Although some randomized, double-blind, placebo-controlled trials have been conducted, most of the evidence supporting use of DHEA for any disease state is of poor quality and consists of case reports and case-control and open-label clinical trials.
MAIN MESSAGE
Dehydro-3-epiandrosterone is available as a health food supplement and is touted as being beneficial for a variety of diseases. It might be beneficial for improving someone's sense of well-being; minor improvements in body composition have been noted for men only. No consistent relationship has been demonstrated between levels of DHEA and risk of cardiovascular disease, breast cancer, or immune function. Insufficient evidence exists to support using DHEA for acquired immune deficiency syndrome. High levels of DHEA are associated with adverse effects, such as increased risk of breast and ovarian cancer at certain ages and reduced levels of high-density lipoprotein cholesterol.
CONCLUSIONS
Current enthusiasm for using DHEA as a panacea for aging, heart disease, and cancer is not supported by scientific evidence in the literature. Given the potentially serious adverse effects, using DHEA in the clinical setting should be restricted to well-designed clinical trials only.
Topics: Adjuvants, Immunologic; Aging; Dehydroepiandrosterone; Female; Heart Diseases; Humans; Immune System; Male; Neoplasms; Preventive Medicine
PubMed: 10424272
DOI: No ID Found -
Journal of Neuroendocrinology Nov 2013Similar to humans, rhesus macaques (Macaca mulatta) are large, long-lived diurnal primates, and show similar age-related changes in the secretion of many steroid... (Review)
Review
Similar to humans, rhesus macaques (Macaca mulatta) are large, long-lived diurnal primates, and show similar age-related changes in the secretion of many steroid hormones, including oestradiol, testosterone, cortisol and dehydroepiandrosterone (DHEA). Consequently, they represent a pragmatic animal model in which to examine the mechanisms by which these steroidal changes contribute to perturbed sleep-wake cycles and cognitive decline in the elderly. Using remote serial blood sampling, we have found the circulating levels of DHEA sulphate, as well as oestradiol and testosterone, decline markedly in old monkeys. Furthermore, using the real-time polymerase chain reaction, we have shown that the genes for the enzymes associated with the conversion of DHEA to oestradiol and testosterone (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and aromatase) are highly expressed in brain areas associated with cognition and behaviour, including the hippocampus, prefrontal cortex and amygdala. Taken together, these findings suggest that the administration of supplementary DHEA in the elderly may have therapeutic potential for cognitive and behavioural disorders, although with fewer negative side effects outside of the central nervous system. To test this, we have developed a novel steroid supplementation paradigm for use in old animals; this involves the oral administration of DHEA and testosterone at physiologically relevant times of the day to mimic the circadian hormone patterns observed in young adults. We are currently evaluating the efficacy of this steroid supplementation paradigm with respect to reversing age-associated disorders, including perturbed sleep-wake cycles and cognitive decline, as well as an impaired immune response.
Topics: Aging; Animals; Brain; Circadian Rhythm; Dehydroepiandrosterone; Estradiol; Macaca mulatta; Testosterone
PubMed: 23796387
DOI: 10.1111/jne.12064