ReviewDehydroepiandrosterone: Is There a Role for Replacement?
Section snippets
BIOCHEMISTRY AND PHYSIOLOGY OF DHEA
DHEA and DHEAS are 2 of the major C19 steroids secreted by the zona reticularis region of the adrenal glands. As with all C19 steroids, these hormones are products of cholesterol metabolism and are derived from the action of CYP11A (cytochrome P-450scc) on the inner membrane of the highly active mitochondria found in the adrenal cortex.2 In humans, DHEA and DHEAS are the most abundant circulating steroid hormones. Their role remains to be fully elucidated. DHEAS can be readily converted to
Mood and Well-being
Sex hormones are known to play an important role in mood and well-being in both sexes (Table 1). Because levels of these hormones decline with aging, there is a parallel deterioration of mental function, and DHEA replacement is thought to be of potential benefit.
As a neuroactive neurosteroid, DHEA has become more important with the discovery that both DHEA and DHEAS are produced in the brain independently and are not influenced by factors that control adrenal DHEA secretion.54 Some reports have
ADVERSE EFFECTS AND POTENTIAL LIMITATIONS OF DHEA USE
In most studies, adverse effects are common but minor. They usually occur in women and are due to the androgenic effects. The most common adverse effect is increased skin sebum production, leading to perceived “greasiness” and acne.172 However, many women previously reported that this change is beneficial and that before DHEA replacement their skin was excessively dry. This effect is reversible when DHEA is withdrawn.
Of greater concern are the reports of mild elevations in serum transaminase
AVAILABILITY OF DHEA IN THE UNITED STATES
The International Olympic Committee banned DHEA use because of its conversion to sex hormones and thus its potential to be used as a drug of abuse. The Food and Drug Administration also banned the substance until the passage of the Dietary and Supplement Health and Education Act of 1994, when this ruling was overturned. DHEA is now freely available in pharmacies and health food stores, where it is classified as a food supplement. This is despite the fact that DHEA is not a food, that DHEA does
SUMMARY AND CONCLUSIONS
DHEA and DHEAS are intriguing hormones. Their metabolites have a variety of effects on several physiological systems, and yet little is known about the role of either DHEA or DHEAS in normal physiology. It is still unclear whether aging should be classified as a DHEA-deficient state. In hypoadrenal subjects, DHEA deficiency is associated with a lower quality of life. However, these hormones are not essential for life because hypoadrenal subjects and those who have undergone adrenalectomy who
REFERENCES (177)
Aging of the human adrenal cortex
Ageing Res Rev
(2002)- et al.
Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S
Mech Ageing Dev
(2002) - et al.
Adrenal androgen secretion and biologic effects
Endocrinol Metab Clin North Am
(1991) - et al.
Role of 17 beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues
Trends Endocrinol Metab
(2000) Intracrinology
Mol Cell Endocrinol
(1991)- et al.
Specific binding and effects of dehydroepiandrosterone sulfate (DHEA-S) on skeletal muscle cells: possible implication for DHEA-S replacement therapy in patients with myotonic dystrophy
Life Sci
(1999) - et al.
Dehydroepiandrosterone activates endothelial cell nitric-oxide synthase by a specific plasma membrane receptor coupled to Gαi2,3
J Biol Chem
(2002) - et al.
The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells
J Steroid Biochem Mol Biol
(1992) - et al.
Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells
Clin Immunol Immunopathol
(1991) - et al.
Longitudinal changes in dehydroepiandrosterone concentrations in men and women
J Lab Clin Med
(1998)
Effect of oophorectomy on circulating testosterone and androstenedione levels in patients with endometrial cancer
Am J Obstet Gynecol
Ovarian hyperstimulation augments adrenal dehydroepiandrosterone sulfate secretion
Fertil Steril
The cellular and subcellular bases of immunosenescence
Adv Immunol
Serum dehydroepiandrosterone sulfate in Alzheimer's disease and in multi-infarct dementia
Biol Psychiatry
Plasma dehydroepiandrosterone sulfate in Alzheimer's disease
Biol Psychiatry
Dehydroepiandrosterone (DHEA) treatment of depression
Biol Psychiatry
Dehydroepiandrosterone treatment of midlife dysthymia
Biol Psychiatry
Simultaneous radioimmunoassay of progesterone, androst-4-enedione, pregnenolone, dehydroepiandrosterone and 17-hydroxyprogesterone in specific regions of human brain
J Steroid Biochem
The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor
Brain Res
Receptor binding and electrophysiological effects of dehydroepiandrosterone sulfate, an antagonist of the GABAA receptor
NeuroScience
Sigma1 (σ1) receptor agonists and neurosteroids attenuate B25-35-amyloid peptide-induced amnesia in mice through a common mechanism
NeuroScience
Dehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage
Brain Res Mol Brain Res
Paradoxical effects of adrenal steroids on the brain: protection versus degeneration
Biol Psychiatry
Dehydroepiandrosterone antagonizes the neurotoxic effects of corticosterone and translocation of stress-activated protein kinase 3 in hippocampal primary cultures
NeuroScience
Steroid-induced psychiatric syndromes: a report of 14 cases and a review of the literature
J Affect Disord
Biomarkers of caloric restriction may predict longevity in humans?
Science
High-flux mitochondrial cholesterol trafficking, a specialized function of the adrenal cortex
J Clin Invest
Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood
J Clin Endocrinol Metab
The hypothalamic-pituitary-adrenal axis in senescence
Marked attenuation of ultradian and circadian rhythms of dehydroepiandrosterone in postmenopausal women: evidence for a reduced 17,20-desmolase enzymatic activity
J Clin Endocrinol Metab
Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids
Proc Natl Acad Sci U S A
24-Hour secretory pattern of dehydroisoandrosterone and dehydroisoandrosterone sulfate
J Clin Endocrinol Metab
Dehydroepiandrosterone sulphate (DHEAS) in the oldest old, aged 85 and over
Ann N Y Acad Sci
The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity
J Clin Endocrinol Metab
Complete androgen blockade for the treatment of prostate cancer
Important Adv Oncol
Evidence for an influence of the ovary on circulating dehydroepiandrosterone sulfate levels
J Clin Endocrinol Metab
The hormonal activity of the postmenopausal ovary
J Clin Endocrinol Metab
Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood
J Clin Endocrinol Metab
Adrenal insufficiency
N Engl J Med
Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects
J Clin Endocrinol Metab
Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens
J Clin Endocrinol Metab
Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans
J Clin Endocrinol Metab
Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age [published correction appears in J Clin Endocrinol Metab. 1995;80:2799]
J Clin Endocrinol Metab
Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression
J Clin Endocrinol Metab
Replacement of DHEA in aging men and women: potential remedial effects
Ann N Y Acad Sci
Dehydroepiandrosterone replacement in women with adrenal insufficiency
N Engl J Med
Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial
J Clin Endocrinol Metab
Life extension
N Engl J Med
A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease
N Engl J Med
Absence of an inverse relation of dehydroepiandrosterone sulfate with cardiovascular mortality in postmenopausal women [letter]?
N Engl J Med
Cited by (61)
Anti-androgen hormonal therapy for cancer and other diseases
2020, European Journal of PharmacologyCitation Excerpt :Cancer cells expressing those mutant ARs are resistant to CYP17A1 inhibition. Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA-S) are major secretory products of adrenal gland and occur in serum in high concentration (Dhatariya and Nair, 2003). Concentration of DHEA-S inversly correlates with concentration of PSA in castrated patients with CRPC (Suzuki et al., 2018).
Genome-wide association studies on serum sex steroid levels
2014, Molecular and Cellular EndocrinologyCitation Excerpt :DHEAS levels show a significant decline with aging in both men and women, with serum levels being only 10–20% of those during early adulthood (Labrie et al., 2005). This age-related decline in serum DHEAS levels has led to the speculation that DHEAS plays a role in the aging process and common age-related disorders (Dhatariya and Nair, 2003). Low serum DHEAS levels have been associated with increased cardiovascular disease and mortality in men (Barrett-Connor et al., 1986; Ohlsson et al., 2010).
Uncertainties in endocrine substitution therapy for central hypocortisolism
2014, Handbook of Clinical NeurologyNeurosteroid, Natural and Anabolic Steroids: Physiological, Immunological and Histopathological Study on Diabetic Albino Rats
2023, Egyptian Journal of Veterinary Science(Egypt)