Dehydroepiandrosterone - an overview | ScienceDirect Topics (original) (raw)
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Clinical uses and misuses of dehydroepiandrosterone
Emanuela Binello, Catherine M Gordon, in Current Opinion in Pharmacology, 2003
Dehydroepiandrosterone is the most abundant adrenal androgen and also functions as a neurosteroid. Serum concentrations decline with age and can serve as a prognostic factor in both critical illnesses and breast cancer progression. Evidence is accruing in support of dehydroepiandrosterone supplementation in adrenal insufficiency, hypopituitarism, osteoporosis, systemic lupus erythematosus, depression and schizophrenia. Research is ongoing at both the basic and the clinical level to elucidate mechanisms of action and establish efficacy and safety, as well as to expand new areas of potential application for this multi-faceted hormone.
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Inflammatory Bowel Disease
Alyssa M. Parian MD, ... Amy C. Brown PhD, in Integrative Medicine (Fourth Edition), 2018
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) is one of the most abundant endogenous circulating steroid hormones produced mainly within the adrenal cortex. DHEA may inhibit the activation of NF-κB and secretion of IL-6 and IL-12.172 One study found lower levels of DHEA-S (the sulfated form) in the blood and intestines of IBD patients,173 although this may have been secondary to the use of corticosteroids.174 A pilot trial by Andus et al. demonstrated an improvement in clinical activity indices in 20 IBD patients treated with 200 mg of DHEA orally for 8 weeks.172 A case report suggests that DHEA may also be useful in the treatment of pouchitis.175
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Cellular Plasticity Cascades: Targets for the Development of Novel Therapeutics for Bipolar Disorder
Carlos A. ZarateJr, ... Husseini K. Manji, in Biological Psychiatry, 2006
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) serves as a precursor for both androgenic and estrogenic steroids; together with its sulphated form (DHEA-S), it is secreted by the adrenal gland and also produced in the CNS. Thus, DHEA and DHEA-S are neuroactive steroids that have a number of effects that can be described as functional antagonism of the actions of glucocorticoids (DHEA does not directly interact with the glucocorticoid receptor, and there is no known receptor for DHEA in any tissue). It has been reported to have antidepressant efficacy in dysthymic and depressed patients (reviewed in Quiroz et al 2004).
In a recent double-blind, randomized placebo-controlled crossover study involving 23 men and 23 women with midlife-onset major or minor depression given DHEA (90–450 mg/day) for 6 weeks was found to be superior to placebo in reducing depressive symptoms (Schmidt et al 2005).
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Endocrinology of Aging and Longevity
H.M. Brown-Borg, in Reference Module in Biomedical Sciences, 2014
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) is a steroid molecule synthesized in large quantities, primarily by the adrenal cortex, and found in high concentrations relative to other steroids in the blood of humans and some nonhuman primates. Most DHEA circulates as the sulfate conjugate DHEAS. Lower primates have relatively little plasma DHEA, and other mammals secrete almost none. Both DHEA and DHEAS are metabolically transformed into biologically active estrogens and androgens in tissues. It is thought that over 90% of estrogen in postmenopausal women and 30% of total androgens in men are derived from peripheral conversion of DHEA (Labrie et al., 1995). The levels of this hormone decline with age from puberty to senescence (2–4% per year) and do so more dramatically than any other circulating steroid measured with the exception of estrogen during menopause (Orentreich et al., 1992). It has been postulated that, in large amounts, DHEA secretion may be a unique adaptation in humans contributing to their relative longevity, and that the age-related decline in DHEA contributes to senescence. However, it has been difficult to correlate endogenous human DHEA levels with age-related changes in body composition or function (including immune and cognitive function and insulin sensitivity), and only generally weak or nonsignificant relationships have been identified.
Treatment of older men and women with DHEA replacement has thus far demonstrated clinical benefits in only a few cases. One study in postmenopausal women showed improvement in self-reported physical and psychological well-being, while some reports have shown improvements in insulin sensitivity and reductions in inflammatory cytokines following administration of DHEA (Morales et al., 1994). Nonetheless, this hormone may be a reliable biomarker of aging – specifically in men – and a potential predictor of mortality (Roth et al., 2002; Mazat et al., 2001). Comparative studies suggest that the most likely function for DHEA in higher primates is as a precursor for conversion to more potent androgens, which mediate adrenarchy, a sexual signaling mechanism occurring just before puberty. The shrinkage of the DHEA-secreting tissue zone of the adrenal cortex and the resulting decrease in DHEA levels could be considered to be the postpubertal involution of an organ whose function has been fulfilled and is no longer necessary, rather than as a phenomenon of aging or senescence. There is little clinical use of DHEA–except in the case of pathologic adrenal failure, in which replacement is associated with improvements.
A genome-wide association study found some polymorphisms associated with DHEAS concentration in humans. These genes were associated with steroid metabolism and some comorbidities of aging, suggesting a wider functional role for DHEAS than once thought. At present, there is not enough evidence of antiaging activity of DHEA to recommend it as a supplement (Allolio and Arlt, 2002). Overall, it is not clear whether DHEA plays a role in regulating life span or is merely a biomarker of aging in higher primates.
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Psychosis
George M. Kapalka, in Nutritional and Herbal Therapies for Children and Adolescents, 2010
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) is a natural substance produced in the brain, as well as the adrenal glands and the gonads. DHEA, and its major metabolite, dehydroepiandrosterone-3-sulfate (DHEAS) are the most abundant steroids circulating in the human body. DHEA is metabolized to various hormones, including testosterone and estrogen. In the brain, DHEA is classified as a neurosteroid and may act as a modulator of GABA A and glutamate NMDA receptors (Medical Economics, 2008a).
DHEA has been investigated as a pharmacological compound for many decades, and has been shown to have some efficacy in the treatment of lupus, asthmatic attacks, and severe burns. Supplementation with DHEA or DHEAS has been attempted in the treatment of symptoms of schizophrenia and some have reported promising results (Strauss & Stevenson, 1955). However, subsequent double-blind trials revealed no efficacy in the treatment of psychosis (Wolkowitz & Reus, 2002), although it appears to exhibit some efficacy in treatment of depression (as discussed in Chapter 6).
Use of DHEA should be cleared with a medical professional. DHEA is usually contraindicated in children and adolescents, and use of the compound in this population should generally be avoided (Medical Economics, 2008a). Supplementation with DHEA has been associated with significant adverse effects, including dermatological problems, hirsutism, and voice changes in women (which may be permanent), cardiovascular problems, hepatitis, insulin resistance, and manic symptoms. In addition, males who use DHEA may have an increased risk of prostate cancer (Medical Economics). Consequently, the risks of DHEA supplementation, especially with children and adolescents, significantly outweigh any presumed benefits, and clinicians should avoid using this compound with pediatric patients.
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Adrenal Fatigue
Jacqueline Redmer MD, MPH, in Integrative Medicine (Fourth Edition), 2018
Dehydroepiandrosterone
Although commonly used for adrenal fatigue, there is minimal evidence to support the use of dehydroepiandrosterone (DHEA). In a study of patient with Sjogren syndrome with fatigue and documented low DHEA levels, replacement with 50 mg of DHEA had no benefit in fatigue scores over placebo.26
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Obesity
Laura L. Gathercole, ... Jeremy W. Tomlinson, in Vitamins & Hormones, 2013
5.7.3 Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) is an adrenal-derived androgen that in its sulfated form (DHEAS) the most abundant circulating adrenal steroid in humans. Despite its abundance, its true physiological role is unclear. Although lower mammals secrete almost negligible amounts of DHEA and its metabolites, exogenous administration decreases lipid accumulation in both liver and adipose tissue in rodents (McIntosh & Berdanier, 1991), and this may represent suppression of DNL in these tissues. In support of this, DHEA inhibits glucose incorporation into intracellular lipids in mice liver (Marrero, Prough, Frenkel, & Milewich, 1990) and decreases hepatic SREBP1 and ACC expression in chickens (Tang, Ma, Huang, Miao, & Zou, 2009). However, future detailed analysis is needed to define the role of DHEA in the regulation of DNL.
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Host susceptibility and resistance to Mycobacterium tuberculosis
Graham A.W. Rook, T Mark Doherty, in Tuberculosis, 2009
Dehydroepiandrosterone and its metabolites in tuberculosis
The most abundant steroid secreted by the adrenal cortex in man is dehydroepiandrosterone. Secretion is greatly decreased in TB patients.80 While this is not disease-specific because a similar fall occurs in most illnesses, it might be important. In a mouse model of pulmonary TB, dehydroepiandrosterone and a derivative, androstenediol, were protective and partly therapeutic, but not a practical therapy for humans because they are converted in the gonads into sex steroids.84 A synthetic analogue, 16α-bromoepiandrosterone (HE-2000), which has the advantage that it cannot enter sex steroid pathways, was also both protective and therapeutic in this model, and is currently in human clinical trials.85
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Alternative Therapy through Nutrients and Nutraceuticals
Jeri W. Nieves, in Osteoporosis (Fourth Edition), 2013
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) is a steroid hormone that serves as a precursor to androgens in men and estrogens in women. Serum levels of dehydroepiandrosterone-sulfate (DHEA-S) fall with age in both men and women. DHEA is heavily commercialized with claims that it is an anti-aging remedy; will increase muscle; decrease fat; and improve energy, strength, and immunity. There are data indicating an inhibition of bone resorption and serum levels of DHEA appear to relate to bone loss [33,36]. Clinical trials have conflicting or inconsistent data regarding the skeletal site and gender specific benefit of DHEA [37–42]. Although DHEA may have some skeletal benefit, the benefit may be limited to elderly individuals with low serum DHEA-S [41]. The safety concerns with the use of DHEA include that it may adversely affect liver function, and lead to acne and masculinizing effects.
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