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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 -
Journal of the American College of... May 2015
Topics: Coronary Disease; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans; Male
PubMed: 25975482
DOI: 10.1016/j.jacc.2015.02.065 -
Molecular and Cellular Endocrinology Mar 2009Dehydroepiandrosterone (DHEA) is commonly used in the USA as a nutritional supplement for antiaging, metabolic support or other uses. Investigations into understanding... (Review)
Review
Dehydroepiandrosterone (DHEA) is commonly used in the USA as a nutritional supplement for antiaging, metabolic support or other uses. Investigations into understanding the effects of DHEA on human prostate cancer progression have posed more questions than answers and highlight the importance of communications between stromal and epithelial tuoitiuot elements within the prostate that contribute to the regulation of DHEA metabolism. Intracrine metabolism of DHEA to androgens (A) and/or estrogens (E) may occur in one cell compartment (stromal) which may release paracrine hormones or growth/inhibitory factors to the epithelial cells. Alternatively no metabolism of DHEA may occur, resulting in no harmful consequences of high levels of DHEA in prostate tissues. We herein review the tissue components involved and interactions with the prohormone, DHEA and/or resulting metabolites, including dihydrotestosterone (DHT) or 17beta-estradiol (E(2)) in an in vitro model of endocrine-immune-paracrine interactions within the prostate. This work raises questions and hypotheses concerning the role of DHEA in prostate in normal tissues, vs. preneoplastic tissues.
Topics: Dehydroepiandrosterone; Epithelium; Humans; Male; Prostate; Prostatic Neoplasms; Risk Factors; Stromal Cells
PubMed: 19013497
DOI: 10.1016/j.mce.2008.10.019 -
Neurochemistry International 2008Dehydroepiandrosterone (DHEA) is an abundant circulating prohormone in humans, with a variety of reported actions on central and peripheral tissues. Despite its... (Review)
Review
Dehydroepiandrosterone (DHEA) is an abundant circulating prohormone in humans, with a variety of reported actions on central and peripheral tissues. Despite its abundance, the functions of DHEA are relatively unknown because common animal models (laboratory rats and mice) have very low DHEA levels in the blood. Over the past decade, we have obtained considerable evidence from avian studies demonstrating that (1) DHEA is an important circulating prohormone in songbirds and (2) the enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD), responsible for converting DHEA into a more active androgen, is expressed at high levels in the songbird brain. Here, we first review biochemical and molecular studies demonstrating the widespread activity and expression of 3beta-HSD in the adult and developing songbird brain. Studies examining neural 3beta-HSD activity show effects of sex, stress, and season that are region-specific. Second, we review studies showing seasonal and stress-related changes in circulating DHEA in captive and wild songbird species. Third, we describe evidence that DHEA treatment can stimulate song behavior and the growth of neural circuits controlling song behavior. Importantly, brain 3beta-HSD and aromatase can work in concert to locally metabolize DHEA into active androgens and estrogens, which are critical for controlling behavior and robust adult neuroplasticity in songbirds. DHEA is likely secreted by the avian gonads and/or adrenals, as is the case in humans, but DHEA may also be synthesized de novo in the songbird brain from cholesterol or other precursors. Irrespective of its source, DHEA seems to be an important prohormone in songbirds, and 3beta-HSD is a key enzyme in the songbird brain.
Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Behavior, Animal; Biotransformation; Brain; Brain Chemistry; Cells, Cultured; Dehydroepiandrosterone; Gonadal Steroid Hormones; Songbirds
PubMed: 17643555
DOI: 10.1016/j.neuint.2007.05.003 -
Physiological Research 2003Dehydroepiandrosterone (DHEA) and its sulphate-bound form (DHEAS) are important steroids mainly of adrenal origin. Their physiological and pathophysiological functions... (Review)
Review
Dehydroepiandrosterone (DHEA) and its sulphate-bound form (DHEAS) are important steroids mainly of adrenal origin. Their physiological and pathophysiological functions are not yet fully identified, although a number of various possible features have been hypothesized. Most popular is the description of the "hormone of youth" as the long-term dynamics of DHEA levels are characterized by a sharp age-related decline in the late adulthood and later. Low levels of DHEA are, however, associated not only with the ageing process but also with diabetes mellitus, cardiovascular diseases and some neurological or immunological entities. In the past decade, a number of brief studies have concentrated on these relationships and also on the role of exogenous DHEA in health, disease and human well-being. This article tries to summarize some of the most important facts achieved recently.
Topics: Aged; Aging; Dehydroepiandrosterone; Female; Hormone Replacement Therapy; Humans; Male
PubMed: 12899651
DOI: No ID Found -
The Journal of Clinical Endocrinology... Nov 2023Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in...
CONTEXT
Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations.
OBJECTIVE
To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children.
METHODS
We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs.
RESULTS
The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin.
CONCLUSION
A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.
Topics: Child; Female; Humans; Male; Adrenarche; Androgens; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Puberty; Testosterone; Exercise; Diet, Healthy
PubMed: 37329220
DOI: 10.1210/clinem/dgad367 -
Cells Mar 2022Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells...
Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells (cholangiocytes) and primarily affects postmenopausal women, when their estrogen levels sharply decrease. An impaired cholangiocyte response to estrogen characterizes the terminal stage of the disease, as this is when an inefficiency of cholangiocyte proliferation, in balancing the loss of intrahepatic bile ducts, is observed. Here, we report that the estrogen precursor dehydroepiandrosterone (DHEA) and its sulfate metabolites, DHEA-S and 17 β-estradiol, enhance the proliferation of cholangiocytes and hepatocytes in vitro. Flow cytometry analysis showed that DHEA and DHEA-S decreased glyco-chenodeoxycholic acid (GCDC)-driven apoptosis in cholangiocytes. Cell viability assay (MTT) indicated that ER-α, -β, and the G-protein-coupled estrogen receptor, are involved in the protection of DHEA against oxidative stress in cholangiocytes. Finally, immunoblot analysis showed an elevated level of steroid sulfatase and a reduced level of sulfotransferase 1E1 enzymes, involved in the desulfation/sulfation process of estrogens in cirrhotic PBC, and primary sclerosis cholangitis (PSC) liver tissues, another type of chronic cholestatic and immune-mediated liver disease. Taken together, these results suggest that DHEA can prevent the deleterious effects of certain potentially toxic bile acids and reactive oxygen species, delaying the onset of liver disease.
Topics: Apoptosis; Dehydroepiandrosterone; Estrogens; Female; Hepatocytes; Humans; Liver Diseases; Oxidative Stress; Receptors, G-Protein-Coupled
PubMed: 35326489
DOI: 10.3390/cells11061038 -
Fertility and Sterility Aug 1990Genital skin samples were obtained from normal women and men to determine the extent of conversion of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT) and...
Genital skin samples were obtained from normal women and men to determine the extent of conversion of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT) and other androgen metabolites and to assess sulfatase activity. The skin samples were minced and incubated with 3H-DHEA or 3H-dehydroepiandrosterone sulfate (3H-DHEAS) in medium for 1 hour at 37 degrees C. The following metabolites of DHEA were isolated after extraction and chromatography: 5-androstene-3 beta,17 beta-diol (delta 5-diol), 5 alpha-androstane-3,17-dione (5 alpha-delta 4A), testosterone, DHT, androsterone (A), and 5 alpha-androstane-3 alpha,17 beta-diol. Although the conversion of DHEA to all the metabolites was low, the conversions were higher in men than in women. In women, conversions of DHEA to delta 5-diol and androstenedione (delta 4A) were highest, followed by conversions of DHEA to DHT and 5 alpha-delta 4A, whereas in men the formation of delta 4A and 5 alpha-delta 4A was highest, followed by delta 5-diol and A. There was a significant conversion of DHEAS to DHEA in both women and men, although the sulfatase activity was approximately six times higher in men. We conclude that despite the low conversion of DHEA to DHT, significant androgenecity may result from pathological levels of DHEAS.
Topics: Adult; Aged; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Genitalia; Humans; Male; Middle Aged; Sex Characteristics; Skin
PubMed: 2143146
DOI: No ID Found -
Clinical Interventions in Aging 2014Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency.... (Review)
Review
Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. Finally, we argue on future perspectives of such protocols as part of everyday practice.
Topics: Aging; Dehydroepiandrosterone; Estrogens; Hormone Replacement Therapy; Human Growth Hormone; Humans; Off-Label Use; Progesterone; Testosterone
PubMed: 25092967
DOI: 10.2147/CIA.S48918