DHEA - Elixir of life?
Steroid Hormones

Author: Elisabetta Robba
Date: 20/02/2012



5-Dehydroepiandrosterone (5-DHEA) is a 19-carbon endogenous steroid hormone.

It is the major steroid produced by the adrenal zona reticularis and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans.

DHEA is produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA.1

DHEA has been implicated in a broad range of biological effects in humans and other mammals. It acts on the androgen receptors both directly and through its metabolites, which include androstenediol and androstenedione, which can undergo further conversion to produce the androgen testosterone and the estrogens, including estrone, estradiol, and estriol. It is considered a neurosteroid.2


Secretion of dhea, in contrast to cortisol and aldosterone, declines with ageing; This has generated major interest in its putative role as an 'anti-ageing' hormone. However, it is not clear that the age-associated, physiological decline in DHEA secretion represents a harmful deficiency.3

    Seven studies examined measures of muscle strength. One study showed improvement in handgrip strength, one showed improvement in chest press, two showed improvement in leg press, and one showed improvement in knee extension and flexion. Nevertheless, similar numbers of studies had negative results for each of these endpoints. Five studies examined measures of physical function and performance. Only one study showed improvement in a composite score measuring physical performance; the rest reported no differences between DHEA and control for any end point. Overall, evidence is inconclusive in regards to the effect of DHEA on strength in the elderly.4
    In middle-aged men, no statistically significant effect of DHEA supplementation on lean body mass, strength, or testosterone levels was found in a randomized placebo-controlled trial.5
    Dhea prevents brain aging, enhances the cerebral metabolism and interacts with energy substrates. It improves glucose uptake in specific conditions. Thus, DHEA may affect CNS metabolism and interact with lactate, which is the most important neuronal energy substrate, on glucose uptake.6
    Dhea decreases ~80% between ages 25 and 75 years. In a preliminary study, that 6 months of DHEA replacement improved insulin action in elderly individuals. DHEA replacement improved glucose tolerance in participants who had abnormal GT initially, reduced plasma triglycerides, and the inflammatory cytokines IL6 and TNFα.7


DHEA is a naturally occurring inactive steroid which may possess disease activity modifying properties as well as the ability to reduce flares and may allow a reduction in the dose of prescription drugs needed. DHEA may also help SLE symptoms such as muscle ache and mouth ulcers. DHEA also seems to strengthen bones in SLE patients being treated with high-dose steroids (corticosteroids). Studying effectiveness of DHEA for SLE is difficult, but there is evidence that DHEA has a modest but clinically significant impact on health related quality of life in the short term. Long term outcomes and safety remain unstudied.8


p<>. The present findings suggest that, in men, low serum levels of DHEAS may be associated with coronary heart disease. However, whether DHEA supplementation has any cardiovascular benefit is not clear. Data from prospective randomised trials are needed.9


Studies have provided evidence that both estrogens and androgens can play a protective role against Alzheimer's disease (AD) related neurodegeneration. Males who become hypogonadal in later life often report problems with their memory. The results of some small clinical trials suggest that testosterone can improve cognitive function in andropause. In contrast, there is no clinical evidence to date which suggest that the hormone dihydroepiandrosterone can improve cognitive function.10


Dehydroepiandrosterone is known to have antiproliferative effects. DHEA induces growth inhibition and apoptosis in BV-2 cells and these effects are inversely associated with glucose concentrations in the medium. The incubation of BV-2 cells with DHEA under glucose deprivation (G0) led to dose- and time-dependent decrease in cellular ATP levels. The decrease in ATP preceded growth inhibition and apoptosis induced by DHEA and all these effects of DHEA were prevented by glucose added during incubation.11
Some in vitro studies have found DHEA to have apoptotic effect on cancer cell lines.12


Early evidence suggests that DHEA seems to help overweight older people who are likely to get metabolic syndrome to lose weight. But it’s not known if DHEA helps younger people to lose weight.

p<>. There is evidence that DHEA might lower some of the health risks that make overweight men and women more likely to develop metabolic syndrome. The risk factors that DHEA seems to lower are obesity, fat around the waist, and high insulin levels. There is some evidence that DHEA might improve Chronic Fatigue Syndrome symptoms.
For Schizophrenia, DHEA may be more effective in women than men.
Athletes and other people use DHEA to increase muscle mass, strength, and energy, but DHEA, classified as a controlled substance under the category of anabolic steroids13.
Is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency
There is some early evidence that DHEA might improve symptoms of Addison’s disease.


As a hormone precursor, there has been a smattering of reports of side effects possibly caused by the hormone metabolites of DHEA
Some of these include possibly serious cardiovascular effects such as heart palpitations and increased blood pressure.14
DHEA is possibly unsafe when taken by mouth during pregnancy or breast-feeding. It can cause higher than normal levels of a male hormone called androgen. This might be harmful to the baby.

Women with polycystic ovary syndrome tend to have elevated levels of DHEAS; so taking DHEA might make this condition worse.


Blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia.

Regular exercise is known to increase DHEA production in the body.

Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.15


DHEA plasma levels are so low in most animals that they are difficult to measure, hindering studies on DHEA and aging. DHEA had not yet, at the time of writing, been linked to any specific health disorder. Side effects are linked to its androgenic effects, unfavorable lipid metabolism effects, and "possible growth-stimulating effect" on hormone dependent malignancies (prostate, breast). In practice, there is currently no scientific reason to prescribe DHEA for any purpose whatsoever.16


1 Harper's illustrated Biochemistry, 27th edition, Ch.41 "The Diversity of the Endocrine system".

2 "Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity":http://www.sciencedirect.com/science/article/pii/S0960076006000392.

3 Arlt, W (2004 Sep). "Dehydroepiandrosterone and ageing.". Best practice & research. Clinical endocrinology & metabolism 18 (3): 363–80. PMID 15261843

4 Baker, WL; Karan, S, Kenny, AM (2011 Jun). "Effect of dehydroepiandrosterone on muscle strength and physical function in older adults: a systematic review.". Journal of the American Geriatrics Society 59 (6): 997–1002. PMID 21649617

5 Wallace, M. B.; Lim, J.; Cutler, A.; Bucci, L. (1999). "Effects of dehydroepiandrosterone vs androstenedione supplementation in men". Medicine and Science in Sports and Exercise 31 (12): 1788–92. doi:10.1097/00005768-199912000-00014. PMID 10613429

6 “Effects of dehydroepiandrosterone (DHEA) and lactate on glucose uptake in the central nervous system”., de Souza DK, Kucharski LC. PMID 22172926

7 _ “Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans”.Weiss EP, Villareal DT, Fontana L, Han DH, Holloszy JO_ PMID 100327

8 Crosbie, D; Black, C, McIntyre, L, Royle, PL, Thomas, S (2007 Oct 17). "Dehydroepiandrosterone for systemic lupus erythematosus.". Cochrane database of systematic reviews (Online) (4): CD005114. PMID 17943841

9 Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA. Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol. 2003 Oct;58(5):403-10. PMID 14609305

10 Fuller, SJ; Tan, RS, Martins, RN (2007 Sep). "Androgens in the etiology of Alzheimer's disease in aging men and possible therapeutic interventions.". Journal of Alzheimer's disease : JAD 12 (2): 129–42. PMID 17917157

11 Yang, N. C.; Jeng, K. C.; Ho, W. M.; Hu, M. L. (2002). "ATP depletion is an important factor in DHEA-induced growth inhibition and apoptosis in BV-2 cells". Life Sci. 70 (17): 1979–88. doi:10.1016/S0024-3205(01)01542-9. PMID 12148690

12 Schulz, S.; Klann, R. C.; Schönfeld, S.; Nyce, J. W. (1992). "Mechanisms of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis". Cancer Res. 52 (5): 1372–6. PMID 1531325

13 _S. 762: A bill to include dehydroepiandrosterone as an anabolic steroid, from http://thomas.loc.gov/cgi-bin/thomas

14 Sahelian, M.D., Ray (2005). "Honest DHEA Supplement Information". DHEA: A Practical Guide, Mind Boosters, and Natural Sex Boosters. http://www.raysahelian.com/dhea.html.

15 _19Roberts, E. (1999). "The importance of dehydroepiandrosterone sulfate in the blood of primates: a longer and healthier life?". Biochemical Pharmacology 57 (4): 329–346. _doi:10.1016/S0006-2952(98)00246-9 PMID 9933021

DHEA: the last elixir, 2002

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