DHEa is available over the counter in the USA- only because the FDA decreed it is very safe and has no safety issues. Unlike Australia, where it is basically banned.

Dehydroepiandrosterone (DHEA)

DHEA is made primarily by the ovaries and adrenal gland. Smaller amounts are produced in the skin and brain. DHEA is the most abundant circulating hormone. It provides protection against the effects of physical stress and inflammation.

DHEA can also increase libido and sexual arousal. It improves motivation, engenders a sense of well-being, decreases pain, and enhances immune system function.

DHEA facilitates the rapid eye movement (REM) phase of sleep, enhances memory, and assists in maintaining normal cholesterol levels. DHEA can be converted in into estrogen and testosterone through fat, muscle, bone and liver.


 Dehydroepiandrosterone (DHEA): A Misunderstood Adrenal Hormone and Spine-Tingling Neurosteroid?

    1. Sheryl G. Beck and
  1. Robert J. Handa

Author Affiliations

  1. Pediatrics Department (S.G.B.) Children’s Hospital of Philadelphia and University of Pennsylvania Philadelphia, Pennsylvania 19104 and Department of Biomedical Sciences (R.J.H.) College of Veterinary Medicine Colorado State University Fort Collins, Colorado 80523
  1. Address all correspondence and requests for reprints to: Robert Handa, College of Veterinary Medicine, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523-1617. E-mail: robert.handa@colostate.edu.

The sex steroid hormones have pronounced effects in areas of the brain that are not involved in sexual behavior or reproduction. The actions of the sex hormones have been a topic of recent research. One area of interest is their effects on hippocampal neuron spine formation. The paper by Hajszan et al. (1) presented in this issue now reports that dehydroepiandrosterone (DHEA), the adrenal hormone, also alters spine formation, and the effect may be due to its metabolism to estrogen in brain.

The adrenal cortex is the source of a variety of hormones, and the best known of these are the C21 steroids: mineralocorticoids, such as aldosterone, and glucocorticoids, such as cortisol. The C19 steroids of the adrenal gland are androgens, the most potent of this class being testosterone. However, testosterone is synthesized in only small amounts by the adrenal gland (2). Androstenedione, DHEA, and the sulfated derivative of DHEA, DHEA-sulfate (DHEAS), are the most highly circulating adrenal androgens, but these bind androgen receptors with low affinity (3) and thus are considered weak androgens. The role of adrenal androgens, particularly DHEA and DHEAS, in normal physiology has become, in recent years, the subject of intense investigation.

Maturation of the adrenal gland (adrenarche) occurs in humans well before the onset of puberty. This is characterized by the increased secretion of adrenal androgens, without corresponding increases in glucocorticoids or mineralocorticoids (4). Although androstenedione and DHEA are measurable in blood in preadrenarchal children, the amounts are low. Increases in adrenal androgen secretion typically occur in children between 6 and 8 yr of age (4) and, in adulthood, circulating levels of DHEAS are higher than those of any other steroid (5, 6). In addition, DHEA and DHEAS decrease dramatically in aging primates (5, 6). Unlike cortisol, whose secretion is regulated by the hypothalamo-pituitary axis and ACTH, there are few extraadrenal factors that are known to specifically regulate adrenal DHEA synthesis and secretion.

What is the role of DHEA in primate physiology? And can we test these hypotheses using rodent models? A number of recent studies have suggested that DHEA can have beneficial effects and suggest the possibility that DHEA is involved in a number of functions including cognitive function, metabolism, and vascular and immune function (for a review see Ref. 7).

Interestingly, rodent species do not have measurable levels of circulating DHEA when examined before sexual maturation and have very low levels subsequently (8). Thus, the rodent is a potential model in which to explore the effects of high levels of DHEA that are seen in humans without interference from changes in endogenous levels. It can be argued, however, that the lack of circulating DHEAS in rodents also makes it a poor model because treatment with DHEA is not a replacement therapy but is supraphysiological (9).

Nonetheless, given the reported effects of DHEA on primate and rodent physiology, how might these effects of DHEA be mediated at the cellular level? Binding studies demonstrated that DHEA binds the androgen receptor and the estrogen receptor, but with an affinity that is at least an order of magnitude less than that of the endogenous ligand (10, 11). Thus, the effects of DHEA do not appear to be mediated by direct binding of hormone to a currently known receptor type. A recent study by Liu and Dillon (12) has demonstrated a high-affinity G protein-coupled DHEA receptor found in endothelial cells. Such a finding will help in the search for a putative receptor mediating DHEA action.

An alternative explanation for DHEA action on cellular function is through its metabolism to other steroids that do have a high affinity for estrogen and androgen receptors. As shown in Fig. 1, DHEA can be converted to estrogen or testosterone in tissues that have the appropriate steroidogenic enzymes. This theory posits that circulating DHEA exists as a precursor pool for steroid hormone synthesis in appropriate tissues and under appropriate conditions. These steroidogenic enzymes do exist in brain areas such as the hippocampus, thus raising the possibility that DHEA can be produced de novo in brain, or can be converted to another active steroid by local cellular metabolism (13).

In the paper by Hajszan et al. (1), a role for DHEA in the growth of dendritic spines in the hippocampus is shown. Dendritic spines are small bulbous protrusions on short stalks on dendrites. Most excitatory input to the hippocampus occurs on dendritic spines. Recent studies have shown that dendritic spines are highly mobile structures that also appear and disappear over the course of days depending on synaptic inputs (14). Time-lapse images of dendritic spine movements have been made by a number of groups. An example of these can be visualized at the following web site: http://www.fmi.ch/members/andrew.matus/video.actin.dynamics.htm.

Changes in the number of dendritic spines, the size of the spine head, the length of the stalk, and synaptic appositions occur after treatment with estrogen in ovariectomized female rats (15, 16, 17), through activation of N-methyl-d-aspartate receptors (18, 19) and a decrease in γ-aminobutyric acid-mediated inhibition (20). Recent work has also implicated androgen receptors in the modulation of spine density in male rats (21). In the paper by Hajszan et al. (1), the data presented suggest that DHEA treatment increased CA1 spine synapse density, an effect that was blocked by a nonsteroidal aromatase inhibitor. The authors propose that the ability of DHEA to increase spine density is therefore mediated by the aromatization of DHEA in the brain, and could be through activation of either estrogen or androgen receptors.

Although estrogen can increase spine density in female rats, this does not seem to take place in male rats (22). In males, it appears that androgen receptor activation is the prime mechanism for spine growth (21). This raises the question of whether DHEA, a precursor for both estrogens and androgens, can work equally well in both males and females. And, if so, are the intracellular processes mediating this action similar in both sexes?

What are the implications of these results? The hippocampus is a brain region involved in learning, memory, and cognitive function, and it also shows pronounced changes during aging and in pathological disease states, such as Alzheimer’s disease, related to aging and cognition. Estrogen and DHEA have been shown to enhance memory and learning functions (23, 24, 25) and prevent damage due to anoxia (26, 27) and glutamate-induced toxicity (28, 29). DHEA levels and estrogen levels decrease during aging and have also been implicated in etiology and treatment of the damage induced by Alzheimer’s disease (30, 31, 32). The results regarding the changes in spine density in hippocampal dendrites reviewed above are intriguing, but there is still a large gap between these data and how they may be involved, or not, in the changes seen in the behaviors, anoxia, toxicity, and Alzheimer’s disease. These studies and the one reported in this issue by Hajszan et al. (1) are certainly exciting and are motivating to push forward in determining how the spine-altering effects of estrogen, androgens, and the endogenous substance DHEA may be involved in these complex processes.


  1. Hajszan T, MacLusky NJ, Leranth C 2004 Dehydroepiandrosterone increases hippocampal spine synapse density in ovariectomized female rats. Endocrinology 145:1042–1045
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  5. Muehlenbein MP, Campbell BC, Richards RJ, Svec F, Phillippi-Falkenstein KM, Murshison MA, Myers L 2003 Dehydroepiandrosterone-sulfate as a biomarker of senescence in male non-human primates. Exp Gerontol 38:1077–1085
  6. Sapolsky RM, Vogelman JH, Orentreich N, Altmann J 1993 Senescent decline in serum dehydroepiandrosterone sulfate concentrations in a population of wild baboons. J Gerontol 48:B196–B200
  7. Buvat J 2003 Androgen therapy with dehydroepiandrosterone. World J Urol 21:346–355
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  9. Dhataryiya KK, Nair KS 2003 Dehydroepiandrosterone: is there a role for replacement? Mayo Clin Proc 78:1257–1273
  10. Lu SF, Mo Q, Hu S, Garippa C, Simon NG 2003 Dehydroepiandrosterone upregulates neural androgen receptor level and transcriptional activity. J Neurobiol 57:163–171
  11. Nephew KP, Sheeler CQ, Dudley MD, Gordon S, Nayfield SG, Khan SA 1998 Studies of dehydroepiandrosterone (DHEA) with the human estrogen receptor in yeast. Mol Cell Endocrinol 143:133–142
  12. Liu D, Dillon JS 2002 Dehydroepiandrosterone activates endoethelial cell nitric-oxide synthase by a specific plasma membrane receptor coupled to Gα(i2,3). J Biol Chem 277:21379–21388
  13. Mellon SH, Vaudry H 2001 Biosynthesis of neurosteroids and regulation of their synthesis. Int Rev Neurobiol 46:33–78
  14. Matus A, Brinkhaus H, Wagner U 2000 Actin dynamics in dendritic spines: a form of regulated plasticity at excitatory synapses. Hippocampus 10:555–560
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  16. Woolley CS, Wenzel HJ, Schwartzkroin PA 1996 Estradiol increases the frequency of multiple synapse boutons in the hippocampal CA1 region of the adult female rat. J Comp Neurol 373:108–117
  17. Yankova M, Hart SA, Woolley CS 2001 Estrogen increases synaptic connectivity between single presynaptic inputs and multiple postsynaptic CA1 pyramidal cells: a serial electron-microscopic study. Proc Natl Acad Sci USA 98:3525–3530
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International Menopause Society – Press release
Hormone DHEA shows promise in helping women through menopause and towards a better sex life.
A new study has shown that the DHEA, a hormone mostly secreted by the adrenal glands, may be able to help a woman’s menopausal symptoms, as well as giving her a better sex life. This is the first controlled evidence that low doses of DHEA can help sexual function as well as menopausal symptoms, and indicates a need for larger trials to confirm the benefits of DHEA in women after the menopause. The results appear in the December edition of the peer-reviewed journal Climacteric.
The researchers, from the University of Pisa, followed a group of 48 postmenopausal women with troubling symptoms for a period of a year. 12 of the women did not wish to take any form of hormone replacement, so they were given vitamin D and calcium (to help prevent osteoporosis). The remaining 36 women were randomly split into groups as follows:
• 12 women took a low dose of the hormone DHEA (dehydroepiandrosterone)
• 12 women were given a standard Hormone Replacement Therapy (oestrogen plus progesterone)
• 12 women were given the synthetic steroid, tiboloneThroughout the trial, the women’s menopausal symptoms were measured using a standard questionnaire, the Greene Climacteric Scale.
The women’s sexual interest and activity were also measured using a standard questionnaire, the McCoy Female Sexuality Questionnaire (MFSQ). This combines a number of factors, such as sexual interest, satisfaction with frequency of sexual activity, vaginal lubrication, orgasm, and sexual partner. The MFSQ was designed to measure aspects of female sexuality likely to be affected by changing sex hormone levels. Hormone levels were also measured throughout the trial.
After 12 months, all women receiving the hormone replacements showed improvements in climacteric (menopausal) symptoms, whereas those taking vitamin D and Calcium did not show any significant improvement.
At the start of the trial, all groups had similar sexual activity. After a year of use, women taking calcium and vitamin D showed a McCoy score of 34.9, whereas women taking DHEA showed a McCoy score of 48.6, indicating that women taking DHEA had a statistically significant elevation in sexual interest and activity. The results for the HRT group were similar, and both the HRT group and the DHEA group showed a higher level of sexual intercourse in comparison to the control group. Activity was also higher with tibolone, but this was not statistically significant.
Study leader, Professor Andrea Genazzani said:
“This is the first time that a controlled trial has shown that low doses of the hormone DHEA may be able to help women deal better with menopausal symptoms, as well as helping their sex life. The work shows that DHEA has potential, especially for those women who may have problems in taking more conventional HRT. But this is a small study, a proof of concept. What we need to do now is to look at a larger study, to confirm that these initial results are valid”.
Commenting, Dr Anna Fenton (co-editor of the journal Climacteric) said: “This is an interesting result, although we must bear in mind that this is a pilot study with a small sample. Nevertheless, it does indicate that DHEA has potential as a therapy to help women deal with the physical discomfort of the menopause, as well as helping them sexually. We can’t yet say that this study means that DHEA is a viable alternative to HRT, but what we can say is that we should be looking to do larger studies to confirm these initial results”.


Arch Gen Psychiatry. 2005 Feb;62(2):154-62.

Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression.


Behavioral Endocrinology Branch, National Institute of Mental Health, Rockville, MD 20892-1276, USA. PeterSchmidt@mail.nih.gov <PeterSchmidt@mail.nih.gov>



Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants. The adrenal androgen and neurosteroid dehydroepiandrosterone (DHEA) is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects.


To evaluate the efficacy of DHEA as a monotherapy treatment for midlife-onset depression.


A double-blind, randomized, placebo-controlled, crossover treatment study was performed from January 4, 1996, through August 31, 2002. Settings The National Institute of Mental Health Midlife Outpatient Clinic in the National Institutes of Health Clinical Center, Bethesda, Md. Patients Men (n = 23) and women (n = 23) aged 45 to 65 years with midlife-onset major or minor depression participated in this study. None of the subjects received concurrent antidepressant medications. Intervention Six weeks of DHEA therapy, 90 mg/d for 3 weeks and 450 mg/d for 3 weeks, and 6 weeks of placebo.


The 17-Item Hamilton Depression Rating Scale and Center for Epidemiologic Studies Depression Scale. Additional measures included the Derogatis Interview for Sexual Functioning. Results were analyzed by means of repeated-measures analysis of variance and post hoc Bonferroni t tests.


Six weeks of DHEA administration was associated with a significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P<.01) and 6 weeks of placebo treatment (P<.01). A 50% or greater reduction in baseline Hamilton Depression Rating Scale scores was observed in 23 subjects after DHEA and in 13 subjects after placebo treatments. Six weeks of DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo conditions.


We find DHEA to be an effective treatment for midlife-onset major and minor depression.

Feel free to comment on your experience on using DHEA for your particular problems. Your feedback may help someone else.

2018;108:333-353. doi: 10.1016/bs.vh.2018.05.001. Epub 2018 Jul 13.

Dehydroepiandrosterone and Cardiovascular Disease.


The dehydroepiandrosterone and its metabolite, dehydroepiandrosterone sulfate, have been for a long while at the center of interest for endocrinologists and cardiologists. Consolidated data show that the dehydroepiandrosterone and the dehydroepiandrosterone sulfate present protective actions on the cardiovascular system. These actions are accomplished directly through target tissues such as endothelial cells, smooth muscle cells, and cardiomyocytes. At this level, they are able to activate a complex group of receptor, not completely identified, which modulate important functions such as vasodilation, antiinflammation, and antithrombosis. These data support the hypothesis that dehydroepiandrosterone could be used as drug for primary prevention of cardiovascular disease especially during aging and potentially also in addition of the common therapeutic strategy for the treatment and prevention of cardiovascular disease recurrence. In this publication, the effects of dehydroepiandrosterone and dehydroepiandrosterone sulfate on the cardiovascular system have been elucidated, starting with an analysis of the molecular action at target organ levels. In the second part, we evaluated the clinical effects of this administration, considering ultimately possible implications in introducing this hormone into clinical practice.

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