Dehydroepiandrosterone, or DHEA for short, is a steroid hormone, and one considered basic or elemental in human physiology.What is a steroid? A steroid is a relatively simple molecule that has a chicken wire appearing basic skeleton of connected carbon atoms with little short chemical appendages added at various locations on the skeletal structure:
These little appendages can make various steroid molecules differ widely in function. We all know that Testosterone provides male characteristics and Estradiol, the major human estrogen, lends female characteristics. But see how similar they appear when looking at stick drawings of them:
Testosterone
Estradiol
You don’t have to be a chemist to get the impression that minor changes onto the basic steroidal ring structure result in major differences in human physiology and behavior. The main determiners of male and female function, Testosterone and Estradiol, appear to be very similar.
And there are many more steroid hormones naturally occurring in humans, such as Progesterone, Aldosterone, Cortisol, DHEA, and Calcitriol (or activated Vitamin D3). (Growth Hormone (hGH), Thyroid hormone, and Melatonin are hormones, but not steroids.)
Some pharmaceuticals have the steroid ring skeleton, but are not found anywhere in nature, such as Provera®, Norethindrone, Prednisone®, and Flonase®. Various anabolic steroids are not found in nature as well. I refer to these as “drugs” or “pharmaceuticals”, but my use of the term “hormone” is reserved for those substances naturally produced in the body.
Some “natural” steroid compounds are not found in humans naturally, but are derived from animals for use in humans. Examples are Premarin®, a brand name for conjugated equine estrogens (CEE); or various bovine adrenal gland products.
So, you can see that with minor changes, steroid molecules, whether natural & native to humans, or pharmaceuticals not found in nature have wide use, from modulation of menstrual cycles to anti-inflammation.
I prescribe only bio-identical steroid hormones. This means that the base material is derived from soy or yam, but changed in the laboratory to be exactly identical to what is produced in the human body.
As to the natural production of steroid hormones in the body, the original starting point for synthesis is always cholesterol.
Cholesterol
And if you compare this stick drawing with that of Estradiol or Testosterone, you can readily appreciate the similarity.
People who have very low levels of cholesterol, by the way, have low levels of endogenous steroid hormones as well.
The serial production of steroid hormones follows a pattern, as outlined in the following diagram.
Diagram of Steroid Synthesis
Cholesterol is the source of all steroidal hormones. Viewing this diagram, you can appreciate that both Pregnenolone and DHEA are very basic in the production of steroid hormones.
Conventional medical thought has considered Pregnenolone and DHEA to be intermediaries in the production of the sex hormones, Testosterone, Estradiol, as well as Cortisol [1]. And they are!
But more than that, Pregnenolone and DHEA have their own specific functions [2]. They are produced in the adrenal glands, but also in the ovaries and testicles. Interestingly, they are produced in the brain, as well [3,4].
In this article, I will concentrate on DHEA.
DHEA is found not only in humans, where it is by far the most common steroidal hormone [3], but is fabricated in lesser quantities in all vertebrate animals. Further, it is produced in snails, which are invertebrates [5]. It turns out that the attendant mechanisms to produce and translate steroids have been found in other invertebrates, such as starfish and sea urchins, as well as the most primitive of vertebrates [6].
Scientists have theorized that DHEA is actually basic to the formation of the most advanced living cells, those that possess a combination of a nucleus and mitochondria. The latter are the cellular energy producers. These cells are referred to as “eukaryotes.” All animals are eukaryotes [7].
If that is the case, then DHEA has been around for a long time, “a phylogenetically ancient neurotrophic factor.” [8]
It turns out that DHEA and Pregnenolone are concentrated in the brain. So, levels in the brain are higher than their levels in the serum of the blood [4]. For this reason, they are referred to as “neurosteroids” and “neurohormones” [4,9].
It has been well known for some time that DHEA has a general effect to stimulate production and maintenance of brain cells, including brain protection [1,10,8,11]. Recently, specific receptor sites, molecules that receive the DHEA molecules and relay stimulation of beneficial activity, have been identified in the human brain [1].
Further, because of its activity in brain cells and its predominant amounts in humans [3,5], DHEA has been postulated as the cause for increased brain size in human beings [12].
However, a major characteristic of DHEA, as is true with the majority of other hormones, is decrease of production with age [14]. This decrease is accompanied by age-related loss of function, including brain function.
DHEA supplementation has an effect to prevent decline and to restore function [14]. “DHEA-Sulfate concentration is independently and inversely related to death from any cause and death from cardiovascular disease in men over age 50.” [15]
DHEA production peaks at about age 20, and starts declining after age 30 years. By age 40, many individuals demonstrate blood levels significantly lower than the maximum youthful level.
But DHEA not only positively affects the brain, and heart, but affects multiple cellular functions of the endocrine and immune systems, as well [5].
Human immune function is strongly influenced by variation in hormone concentrations, but especially DHEA [13]. Benefit to immune function has been shown to occur after supplementation in the elderly [16].
“Patients receiving DHEA experienced significant improvement in mood.” [17]
Lastly, I want to emphasize the nature of the adrenal outpouring of DHEA and Cortisol during stress. When you hear about the beneficial effects of “adrenal function” during stress, “burnout”, and fatigue, what is meant is DHEA [18] Cortisol is the opposite adrenal hormone, (“The cortisol/DHEA-S ratio during the life span follows a U-shape curve”) [19,20]. That is, Cortisol is high compared to DHEA in infancy and in the elderly.
Cortisol is beneficial during stress which lasts only seconds to minutes [21]. Excess Cortisol released from the adrenal glands over days to weeks causes negative effects [22] including fatigue, weight gain, water retention, thinning of skin & hair, as well as depression [23]. Can you be depleted of Cortisol? Yes, but that occurs rarely. On the other hand, age related decline of DHEA happens to everyone sooner or later.
Bottom line: DHEA declines with age. DHEA improves immunity, lowers the effects of stress, and improves brain & heart function [24].
What are the side effects of DHEA supplementation?
Talking about my experience, I don’t see side effects in men. Some women report increased sexual interest while taking DHEA. A few women notice increased irritability.
Anytime you note side effects from a natural supplement, try taking a lower dose. Except for allergic effects, which can occur at any dose, side effects are dose related. We are looking for a sweet spot of maximum benefit with minimum problems.
Serum levels (blood testing) of DHEA provide the information about whether or not to take DHEA and how much. Further blood testing after supplementation has started can demonstrate effectiveness of the dose taken.
The typical male dose of DHEA is 50 mg daily. The female dose can vary from 5 to 50 mg, but more usually 10 to 25 mg.
Bibliography:
Compagnone NA & Mellon SH. Dehydroepiandrosterone: A potential signalling molecule for neocortical organization during development. Proc. Natl. Acad. Sci. USA, Vol. 95, pp. 4678–4683, April 1998 PMID: 9539798
Ritsner MS. The clinical and therapeutic potentials of dehydroepiandrosterone and pregnenolone in schizophrenia. Neuroscience Volume 191, Neuroactive Steroids: Focus on Human Brain, 15 September 2011, Pages 91–100. doi: 10.1016/j.neuroscience.2011.04.017 http://www.sciencedirect.com/science/article/pii/S0306452211003976
Stárka L, Dušková M, Hill M. Dehydroepiandrosterone: a neuroactive steroid. J Steroid Biochem Mol Biol. 2015 Jan;145:254-60. doi: 10.1016/j.jsbmb.2014.03.008. Epub 2014 Apr 2. PMID: 24704258
Maninger N, et al. Neurobiological and Neuropsychiatric Effects of Dehydroepiandrosterone (DHEA) and DHEA Sulfate (DHEAS). Front Neuroendocrinol. 2009 Jan; 30(1): 65–91. Published online 2008 Dec 3. doi: 10.1016/j.yfrne.2008.11.002 PMC2725024
Pediaditakis I, et al. Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors. Endocrinology. 2015 Jan;156(1):1623. doi: 10.1210/en.20141596. PMID: 25330101
Baker ME. Origin and diversification of steroids: co-evolution of enzymes and nuclear receptors. Mol Cell Endocrinol. 2011 Mar 1;334(1-2):14-20. doi: 10.1016/j.mce.2010.07.013. Epub 2010 Jul 21. PMID: 20654689
Howard JM. A Theory of the Evolution of Eukaryotes, Crossing Over and Sex. http://anthropogeny.com/Evolution%20of%20Eukaryotes,%20Crossing%20Over%20and%20Sex.htm
Lazaridis I, et al. Neurosteroid Dehydroepiandrosterone Interacts with Nerve Growth Factor (NGF) Receptors, Preventing Neuronal Apoptosis. PLoS Biol. 2011 Apr; 9(4): e1001051. Published online 2011 Apr 26. doi: 10.1371/journal.pbio.1001051 PMCID: PMC3082517
Marx, CE, et al. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. Neuroscience, Volume 191, Neuroactive Steroids: Focus on Human Brain, 15 September 2011, Pages 78–90. doi:10.1016/j.neuroscience.2011.06.076 http://www.sciencedirect.com/science/article/pii/S030645221100786X
Rahmani A, et al. Dehydroepiandrosterone Stimulates Nerve Growth Factor and Brain Derived Neurotrophic Factor in Cortical Neurons. Adv Pharmacol Sci. 2013; 2013: 506191, Published online 2013 Dec 4. doi: 10.1155/2013/506191 PMC3867952
Höllig, Anke, et al. Neuroprotective properties of dehydroepiandrosterone-sulfate and its relationship to interleukin 6 after aneurysmal subarachnoid hemorrhage: a prospective cohort study. Crit Care. 2015; 19(1): 231. Published online 2015 May 21. doi: 10.1186/s13054-015-0954-1 PMC4462180
Howard JM. Evolution of Placental Animals and Enlarged Brains. (1999) http://anthropogeny.com/Evolution%20of%20Placental%20Animals%20and%20Enlarged%20Brains.htm
Prall SP & Muehlenbein MP. Dehydroepiandrosterone and multiple measures of functional immunity in young adults. Am J Hum Biol. 2015 Nov;27(6):877-80. doi: 10.1002/ajhb.22724. Epub 2015 Mar 31. PMID: 25828095
Samaras, N, et al. Age related dehydroepiandrosterone decrease: clinical significance and therapeutic interest. Rev Med Suisse. 2015 Jan 28;11(459):3214. PMID: 25845195
Barrett-Connor E, Khaw KT, Yen SS. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986 Dec 11;315(24):1519-24. PMID: 2946952
Khorram O, Vu L, Yen SS. Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. J Gerontol A Biol Sci Med Sci. 1997 Jan;52(1):M1-7. PMID: 9008662
Qureshi NA, Al-Bedah AM. Mood disorders and complementary and alternative medicine: a literature review. Neuropsychiatr Dis Treat. 2013; 9: 639–658. Published online 2013 May 14. doi: 10.2147/NDT.S43419 PMCID: PMC3660126
Lennartsson AK, et al. Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients. PLoS One. 2015; 10(10): e0140054. Published online 2015 Oct 6. doi: 10.1371/journal.pone.0140054 PMCID: PMC4595129
Yen SS, Laughlin GA, Aging and the adrenal cortex. Exp Gerontol. 1998 Nov-Dec;33(7-8):897-910. PMID: 9951633
Bauer ME. Chronic stress and immunosenescence: a review. Neuroimmunomodulation. 2008;15(4-6):241-50. doi: 10.1159/000156467. Epub 2008 Nov 26. PMID: 19047801
Valenti G. Neuroendocrine hypothesis of aging: the role of corticoadrenal steroids. J Endocrinol Invest. 2004;27(6 Suppl):62-3. PMID: 15481804
Hechter O, Grossman A, Chatterton RT Jr. Relationship of dehydroepiandrosterone and cortisol in disease. Med Hypotheses. 1997 Jul;49(1):85-91. PMID: 9247914
https://en.wikipedia.org/wiki/Cushing%27s_syndrome
Rouzier M.D., Neal (2010-10-08). Natural Hormone Replacement For Men and Women – How to Achieve Healthy Aging 2nd Edition (Kindle Locations 504-505). Worldlink Medical. Kindle Edition.