-
Mini Reviews in Medicinal Chemistry 2023Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates, which is predominantly synthesized in the adrenal cortex. A characteristic curve of... (Review)
Review
Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates, which is predominantly synthesized in the adrenal cortex. A characteristic curve of growth and decline of its synthesis during life was observed, together with the corresponding formation of its sulphate ester (DHEAS). High levels of plasma circulating DHEA are suggested as a marker of human longevity, and various pathophysiological conditions lead to a decreased DHEA level, including adrenal insufficiency, severe systemic diseases, acute stress, and anorexia. More recent studies have established the importance of DHEA in the central nervous system (CNS). A specific intranuclear receptor for DHEA has not yet been identified; however, highly specific membrane receptors have been detected in endothelial cells, the heart, kidney, liver, and the brain. Research shows that DHEA and DHEAS, as well as their metabolites, have a wide range of effects on numerous organs and organ systems, which places them in the group of potential pharmacological agents useful in various clinical entities. Their action as neurosteroids is especially interesting due to potential neuroprotective, pro-cognitive, anxiolytic, and antidepressant effects. Evidence from clinical studies supports the use of DHEA in hypoadrenal individuals and in treating depression and associated cognitive disorders. However, there is also an increasing trend of recreational DHEA misuse in healthy people, as it is classified as a dietary supplement in some countries. This article aims to provide a critical review regarding the biological and pharmacological effects of DHEA, its mechanism of action, and potential therapeutic use, especially in CNS disorders.
Topics: Animals; Humans; Dehydroepiandrosterone; Endothelial Cells; Dehydroepiandrosterone Sulfate; Brain; Steroids
PubMed: 36121077
DOI: 10.2174/1389557522666220919125817 -
Drugs Jul 2014Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal... (Review)
Review
Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a 'superhormone' and an 'anti-aging' panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25(hi) and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent/negative results of some studies. Overreliance on animal models (DHEA is essentially a human molecule), different dosing protocols with non-pharmacological doses often unachievable in humans, rapid metabolism of DHEA, co-morbidities and organ-specific differences render data interpretation difficult. Nevertheless, a growing body of evidence supports the notion that DHEA is not just an overrated dietary supplement but a useful drug for some, but not all, human diseases. Large-scale randomised controlled trials are needed to fine-tune the indications and optimal dosing protocols before DHEA enters routine clinical practice.
Topics: Adrenal Insufficiency; Aging; Animals; Bone Density; Dehydroepiandrosterone; Dietary Supplements; Humans; Hypersensitivity
PubMed: 25022952
DOI: 10.1007/s40265-014-0259-8 -
The Journal of Clinical Endocrinology... May 2022Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of... (Review)
Review
CONTEXT
Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of menopausal status. Investigators have examined their potential beneficial effects in normal women and those with DHEA-deficient states.
EVIDENCE ACQUISITION
A review of the literature from 1985 to 2021 on the potential benefits and risks of androgen prohormones in women.
EVIDENCE SYNTHESIS
Studies have examined the potential benefit of DHEA therapy for anti-aging, sexual dysfunction, infertility, metabolic bone health, cognition, and wellbeing in hormone-deficient states such as primary adrenal insufficiency, hypopituitarism, and anorexia as well as administration to normal women across the lifespan.
CONCLUSIONS
Data support small benefits in quality of life and mood but not for anxiety or sexual function in women with primary or secondary adrenal insufficiency or anorexia. No consistent beneficial effects of DHEA administration have been observed for menopausal symptoms, sexual function, cognition, or overall wellbeing in normal women. Local administration of DHEA shows benefit in vulvovaginal atrophy. Use of DHEA to improve induction of ovulation response in women with diminished ovarian reserve is not recommended. Risks of high physiologic or pharmacologic use of DHEA include androgenic and estrogenic side effects which are of concern for long-term administration.
CLINICAL CASE
A 49-year-old woman with Addison's disease who is on low dose estrogen with cyclic progesterone therapy for menopausal symptoms returns for follow-up. She is on a stable glucocorticoid replacement strategy of hydrocortisone 10 mg in the morning and 5 mg in the early afternoon and fludrocortisone 0.05 mg each morning. She has read on the internet that additional therapy with DHEA may help her overall quality of life and libido. She asks whether she should add this therapy to her regimen and at what dose.
Topics: Androgens; Anorexia; Dehydroepiandrosterone; Estrogens; Female; Hormone Replacement Therapy; Humans; Middle Aged; Quality of Life
PubMed: 35254428
DOI: 10.1210/clinem/dgac130 -
Progress in Lipid Research Jan 2023N-acylethanolamines (NAEs), including N-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), N-arachidonoylethanolamine (AEA, anandamide),... (Review)
Review
N-acylethanolamines (NAEs), including N-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), N-arachidonoylethanolamine (AEA, anandamide), N-docosahexaenoylethanolamine (DHEA, synaptamide) and their oxygenated metabolites are a lipid messenger family with numerous functions in health and disease, including inflammation, anxiety and energy metabolism. The NAEs exert their signaling role through activation of various G protein-coupled receptors (cannabinoid CB and CB receptors, GPR55, GPR110, GPR119), ion channels (TRPV1) and nuclear receptors (PPAR-α and PPAR-γ) in the brain and periphery. The biological role of the oxygenated NAEs, such as prostamides, hydroxylated anandamide and DHEA derivatives, are less studied. Evidence is accumulating that NAEs and their oxidative metabolites may be aberrantly regulated or are associated with disease severity in obesity, metabolic syndrome, cancer, neuroinflammation and liver cirrhosis. Here, we comprehensively review NAE biosynthesis and degradation, their metabolism by lipoxygenases, cyclooxygenases and cytochrome P450s and the biological functions of these signaling lipids. We discuss the latest findings and therapeutic potential of modulating endogenous NAE levels by inhibition of their degradation, which is currently under clinical evaluation for neuropsychiatric disorders. We also highlight NAE biosynthesis inhibition as an emerging topic with therapeutic opportunities in endocannabinoid and NAE signaling.
Topics: Endocannabinoids; Peroxisome Proliferator-Activated Receptors; Polyunsaturated Alkamides; Dehydroepiandrosterone
PubMed: 36150527
DOI: 10.1016/j.plipres.2022.101194 -
American Journal of Obstetrics and... Sep 2022This study aimed to present a narrative review regarding androgen production, androgens' role in folliculogenesis, and the available therapeutic approaches for androgen... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to present a narrative review regarding androgen production, androgens' role in folliculogenesis, and the available therapeutic approaches for androgen supplementation, and to perform a systematic review and meta-analysis regarding the impact of androgens (dehydroepiandrosterone/testosterone) compared with placebo or no treatment on ovarian response and pregnancy outcomes in patients with diminished ovarian reserve and/or poor ovarian responders.
DATA SOURCES
An electronic search of MEDLINE, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, the ISRCTN registry, and the World Health Organization International Clinical Trials Registry, was conducted for studies published until September 2021.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared ovarian response and/or pregnancy outcomes between the different in vitro fertilization protocols using androgens (ie, dehydroepiandrosterone and testosterone) and conventional in vitro fertilization stimulation in patients with diminished ovarian reserve and/or poor ovarian responders were included.
METHODS
The quality of each study was evaluated with the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The meta-analysis used random-effects models. All results were interpreted on the basis of intention-to-treat analysis (defined as the inclusion of all randomized patients in the denominator). Risk ratios and 95% confidence intervals were used and combined for meta-analysis.
RESULTS
No significant differences were found regarding the number of oocytes retrieved (mean difference, 0.76; 95% confidence interval, -0.35 to 1.88), mature oocytes retrieved (mean difference, 0.25; 95% confidence interval, -0.27 to 0.76), clinical pregnancy rate (risk ratio, 1.17; 95% confidence interval, 0.87-1.57), live-birth rate (risk ratio, 0.97; 95% confidence interval, 0.47-2.01), or miscarriage rate (risk ratio, 0.80; 95% confidence interval, 0.29-2.22) when dehydroepiandrosterone priming was compared with placebo or no treatment. Testosterone pretreatment yielded a higher number of oocytes retrieved (mean difference, 0.94; 95% confidence interval, 0.46-1.42), a higher clinical pregnancy rate (risk ratio, 2.07; 95% confidence interval, 1.33-3.20), and higher live-birth rate (risk ratio, 2.09; 95% confidence interval, 1.11-3.95).
CONCLUSION
Although dehydroepiandrosterone did not present a clear effect on outcomes of assisted reproductive techniques, we found a potentially beneficial effect of testosterone priming on ovarian response and pregnancy outcomes. However, results should be interpreted with caution, taking into account the low to moderate quality of the available evidence.
Topics: Androgens; Dehydroepiandrosterone; Female; Fertilization in Vitro; Humans; Live Birth; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Rate; Testosterone
PubMed: 35364061
DOI: 10.1016/j.ajog.2022.03.051 -
Ginekologia Polska 2020Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the...
Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the usefulness of DHEA in premenopausal and postmenopausal women, and the options of hormone therapy have received a large amount of attention. The effectiveness of DHEA in the premenopausal women remains unclear, while in postmenopausal women with coexisting estrogens deficiency is controversial. Despite many years of study, the use of DHEA is still controversial, especially regarding its effectiveness. The aim of present article was to evaluate DHEA specific effects on metabolic parameters, bone mineral density, insulin resistance as well as the therapeutic potential of DHEA in pre- and postmenopausal women using measures of sexual activity, cognition and well-being. The summary of this article is the position statement of expert group of the Polish Menopause and Andropause Society regarding the efficacy and safety of DHEA supplementation in women. We concluded, that currently available clinical trials and meta-analyses indicate that DHEA supplementation is effective in women with adrenal insufficiency and chronically treated with exogenous glucocorticoids, postmenopausal women with low bone mineral density and/or osteoporosis, premenopausal women with sexual disorders and low libido, and in women with vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. Currently available clinical trials also suggest that DHEA supplementation is probably effective in postmenopausal women with hypoactive sexual disorders, infertile women with diminished ovarian reserve, women suffering from depression and anxiety, and women with obesity and insulin resistance. No serious adverse effects have been reported.
Topics: Aged; Dehydroepiandrosterone; Dietary Supplements; Female; Humans; Poland; Postmenopause; Practice Guidelines as Topic; Premenopause; Societies, Medical
PubMed: 33030737
DOI: 10.5603/GP.2020.0091 -
Journal of Strength and Conditioning... Nov 2022Riechman, SE and Lee, CW. Oral contraceptive use impairs muscle gains in young women. J Strength Cond Res 36(11): 3074-3080, 2022-Many active young women use oral...
Riechman, SE and Lee, CW. Oral contraceptive use impairs muscle gains in young women. J Strength Cond Res 36(11): 3074-3080, 2022-Many active young women use oral contraceptives (OCs), yet their effects on the body composition and exercise performance have not been thoroughly studied. We examined the effects of OCs on muscle responses to a standardized resistance exercise training (RET) program. Two groups of young healthy women (18-29 years old, non-OC: n = 38, OC: n = 34) underwent 10 weeks of whole-body RET (3 days·wk -1 , 3 sets, 6-10 repetitions, at 75% of maximum strength, 13 exercises). Body composition was determined using hydrostatic weighing, and blood samples were taken before and after training to measure dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), IGF-1, and cortisol levels. There were significant differences in lean mass gains between the groups (non-OC: 3.5 ± 0.4% vs. OC: 2.1 ± 0.5% and non-OC: 1.6 ± 0.2 kg vs. OC: 1.0 ± 0.2 kg, p < 0.05). Plasma concentrations of DHEA, DHEAS, and IGF-1 were significantly lower, and cortisol levels were higher in the OC group before and after training ( p < 0.05). In addition, there were significant differences in lean mass gains depending on the androgenicity of progestin between the non-OC and medium-high groups (non-OC: 1.6 ± 0.2 kg, Low = 1.1 ± 0.2 kg, med-high = 0.3 ± 0.5 kg, p < 0.05). Oral contraceptive use impaired lean mass gains in young women after RET and was associated with lower DHEA, DHEAS, and IGF-1 and higher cortisol. The diminished lean mass gain may be related to the effect of OCs on anabolic and catabolic hormone levels or the androgenicity of progestin that may bind to androgen receptors and inhibit its function.
Topics: Adolescent; Adult; Female; Humans; Young Adult; Contraceptives, Oral; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Hydrocortisone; Insulin-Like Growth Factor I; Progestins; Receptors, Androgen; Muscle, Skeletal
PubMed: 33993156
DOI: 10.1519/JSC.0000000000004059 -
Vitamins and Hormones 2018Drug addiction has a great negative influence on society, both social and economic burden. It was widely thought that addicts could choose to stop using drugs if only...
Drug addiction has a great negative influence on society, both social and economic burden. It was widely thought that addicts could choose to stop using drugs if only they had some self-control and principles. Nowadays, science has changed this view, defining drug addiction as a complex brain disease that affects behavior in many ways, both biological and psychological. Currently there is no ground-breaking reliable treatment for drug addiction. For more than a decade we are researching an alternative approach for intervention with drug craving and relapse to its usage, using DHEA, a well-being and antiaging food supplement. In this chapter we navigate through the significant therapeutic effect of DHEA on the brain circuits that control addiction and on behavioral performance both in animal models and addicts. We suggest that an integrative program of add-on DHEA treatment may further enable to dynamically evaluate the progress of rehabilitation of an individual patient, in a comprehensive assessment. Such a program may boost and support the detoxification and rehabilitation process, and help patients regain a normal life in a shorter amount of time.
Topics: Animals; Behavior, Addictive; Dehydroepiandrosterone; Humans; Mental Disorders; Stress, Physiological; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 30029736
DOI: 10.1016/bs.vh.2018.04.001 -
Taiwanese Journal of Obstetrics &... Jul 2022
Topics: Adjuvants, Immunologic; Dehydroepiandrosterone; Female; Humans; Ovary
PubMed: 35779899
DOI: 10.1016/j.tjog.2022.04.001 -
Vitamins and Hormones 2018Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the most abundant steroid hormones in the systemic circulation of humans. Due to their abundance and... (Review)
Review
Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the most abundant steroid hormones in the systemic circulation of humans. Due to their abundance and reduced production during aging, these hormones have been suggested to play a role in many aspects of health and have been used as drugs for a multiple range of therapeutic actions, including hormonal replacement and the improvement of aging-related diseases. In addition, several studies have shown that DHEA and DHEAS are neuroprotective under different experimental conditions, including models of ischemia, traumatic brain injury, spinal cord injury, glutamate excitotoxicity, and neurodegenerative diseases. Since astrocytes are responsible for the maintenance of neural tissue homeostasis and the control of neuronal energy supply, changes in astrocytic function have been associated with neuronal damage and the progression of different pathologies. Therefore, the aim of this chapter is to discuss the neuroprotective effects of DHEA against different types of brain and spinal cord injuries and how the modulation of astrocytic function by DHEA could represent an interesting therapeutic approach for the treatment of these conditions.
Topics: Animals; Astrocytes; Brain Injuries, Traumatic; Dehydroepiandrosterone; Humans; Neurodegenerative Diseases; Neuroprotection; Spinal Cord Injuries
PubMed: 30029726
DOI: 10.1016/bs.vh.2018.01.004