DHEA Supplementation in Men: What Do Studies Show?

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Nelson Vergel

Founder, ExcelMale.com
Dehydroepiandrosterone (DHEA)

DHEA is a steroid prohormone produced by the adrenal glands and transformed in target tissue through intracrine mechanisms to androgens or estrogens. Plasma DHEA levels decline with age. By the age of 70–80 years, levels may be as low as 10%–20% of those encountered in young individuals.

The importance of DHEA in steroid hormone production increases with age. Indeed, in postmenopausal women, production of estrogens by the ovaries declines dramatically, making the adrenals the only source of steroid hormones through DHEA. In men, although T secretion by the testicles continues late into life, T levels progressively decline, and DHEA's importance in steroid hormone production is also higher with increasing age. DHEA's effect is mostly through its hormone end products.

Nevertheless, in vitro studies have shown that DHEA may directly increase nitric oxide production from intact endothelial cells, probably through G protein-dependent activation of endothelial nitric oxide synthetase, thus supporting proper intrinsic physiological functions.

Effects of DHEA decline on the aging process and age-related diseases

DHEA decline with age is clinically relevant and has been related to a variety of age-related conditions. A positive relationship between DHEA levels and muscle mass, muscle strength, as well as mobility and a lower risk for falls, has been described in elderly individuals. Moreover, a positive effect of DHEA on BMD through transformation to estrogens (in vitro human osteoblasts present an aromatase activity),but also directly through mitogen-activated protein kinase signaling pathways, has been suggested. Indeed, DHEA levels have been positively related to BMD in women and men.

Concerning neuropsychiatric diseases, the relationship between DHEA and cognitive disorders has not been studied sufficiently in order to formally conclude on its effect on dementia onset and progression. On the other hand, the relationship between DHEA levels and mood disorders seems clearer. Low levels of DHEA have been related to depression symptoms.

The relationship between DHEA levels and cardiovascular disease risk factors such as cholesterol and glucose tolerance is inconsistent. Nevertheless, studies have shown that low DHEA levels are related to a higher risk for atherosclerosis,heart failure,cardiovascular complications, and overall mortality.

DHEA seems to play a rather important role in sexual function for both sexes. Low levels of DHEA were related to a higher risk for erectile dysfunction in men and low sexual responsiveness in women.

Efficiency and safety of DHEA supplementation

DHEA administration has had positive effects on muscle mass and strength, as well as physical performance parameters.Also, DHEA has had positive effects on BMD both in women and in men. Furthermore, DHEA supplementation has shown positive effects on mood as well as sexual function both for men and for women. However, no positive effects on erectile function were found when conditions such as diabetes or neurological disorders were present. Finally, DHEA supplementation has improved menopause symptoms in perimenopausal and early postmenopausal women. Also, intravaginal formulations have had a positive effect in reversing vaginal mucosa atrophy in postmenopausal women.

Most studies show a very satisfying safety profile for DHEA supplementation. Only minimal effects such as mild acne, seborrhea, facial hair growth, and ankle swelling have been reported in women. Otherwise, DHEA supplementation has had a rather positive effect on skin. No significant effect has been reported on hormone-dependent tumors such as breast and prostate cancer. On the contrary, animal studies showed that DHEA inhibits tumors of lymphatic tissue, lung, colon, breast, liver, and skin. Nevertheless, to our knowledge, the longest study durations for DHEA supplementation did not exceed 2 years. Consequently, no data exist on treatment safety regarding hormone-dependent tumors (breast, prostate, and endometrium), cardiovascular risk, or mortality for longer treatments.

Future perspectives of DHEA supplementation

DHEA has the status of a dietary supplement and is sold over the counter in the US. In Europe, in most countries it is either forbidden (France) or subject to medical prescription (Switzerland, Canada). DHEA is widely used in antiaging medicine and is considered as a “fountain of youth” hormone by some. As it is a prohormone, it is also used as a “hormone regulator”, permitting the body to reach a hormone equilibrium. DHEA is indeed a prohormone with positive effects on several age-related diseases. Supplementing a prohormone is also extremely interesting, as it would theoretically provide the organism with the possibility to use it and transform it according to local and general hormone needs. For the future, the role of DHEA supplementation in specific indications such as sarcopenia, falls and rehabilitation protocols, osteoporosis, mood and cognitive disorders, and also sexual well- being needs to be better studied in longer and larger studies. Finally, physicians prescribing DHEA should consider and inform their patients of the fact that long-term effects concerning efficiency, but also safety, are still uncertain.

Source: Off-label use of hormones as an antiaging strategy: a review. Nikolaos Samaras et al. Clinical Interventions in Aging 2014:9 1175-8211;1186

DHEA Erectile ED.jpg
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Defy Medical TRT clinic doctor


New Member
So, what is the verdict? Should those of us on TRT also supplement DHEA, or should we ask our providers to test levels first and then look into supplementation? I am speaking both from a perspective of the usual factors we address through TRT and as someone who is a "bodybuilder" of sorts.

Nelson Vergel

Founder, ExcelMale.com
It is always good to have your DHEA-S measured before supplementing it. Keep in mind that testosterone replacement will increase DHEA, so it is better to wait til you have been on TRT for at least 6 weeks to measure DHEA-S. Then you can make a decision with your physician if you should supplement.

Gene Devine

Super Moderator
It is always good to have your DHEA-S measured before supplementing it. Keep in mind that testosterone replacement will increase DHEA, so it is better to wait til you have been on TRT for at least 6 weeks to measure DHEA-S. Then you can make a decision with your physician if you should supplement.

Interesting, by what mechanism does DHEA serum levels increase via exogenous Testosterone?

DHEA is pro hormone and is far upstream of Testosterone.

I've done a lot research into DHEA and never heard of this happening and would like to know more.

Nelson Vergel

Founder, ExcelMale.com
I will look into the mechanism. After coaching men for several years and looking at their baseline numbers and then at week 6 and 12, I have seen increases in DHEA of at least 30 percent after they start TRT.

It is interesting that if you do a literature search all you find is study that tried to look at the effect of DHEA supplementation on testosterone blood levels but not vice-versa. These studies have found that DHEA increases T in women but not in men.

Gene Devine

Super Moderator
DHEA and Pregnenelone are not androgenic and therefore have little, if any, impact on body composition or other benefits of the such.

What's is important is that these prohormones are the two that sit at the top of all three metabolic pathways and are the building blocks for all other hormones in our bodies - man or women.

As we age, there is noted decline in the production of both which therefore compromise all three metabolic pathways.

If this is the case, than all three metabolic pathways will not perform to optimal levels and as result, just like low Testosterone levels, there are negative side effects that impact health and quality of life.

In my opinion, 50 mg daily of both are low to moderate doses and is just a good insurance policy for health as we age.

IF we are willing to supplement Testosterone and HGH we shouldn't be concerned about supplementing these important foundational hormones as well.

Just my $0.02 on the matter.


I had my DHEA levels checked in September. My levels were 177 on a scale of 77.6 - 375. 4. I just had recycled and after supplementing 20 mg pharmacy grade from Defy. My levels are now 577. I hbrg a haven't noticed any major changes but I do feel better it seemed when it was taken a bed time vs morning. Since starting Trt 1 year ago all changes have been positive but subtle improvements over time. Thanks gentlemen its been a great journey. Adding Citrulline and night was the most notably addition, placibo or not I'll take it.

Nelson Vergel

Founder, ExcelMale.com
hormone cascade.png

Dehydroepiandrosterone (DHEA) and its active metabolite DHEA sulfate (DHEAS), are steroid hormones synthesized and excreted primarily by the zona reticularis of the adrenal cortex in response to adrenocorticotropic hormone (ACTH). They exert weak androgenic effects and are therefore considered precursor hormones that need to be transformed to potent androgens or estrogens to exert their effects. The potential clinical roles of DHEA/DHEAS have been studied extensively, as previous epidemiologic and prospective studies associated the age-related decrease of DHEA/DHEAS levels with higher prevalence of degenerative disorders and increased frailty and mortality from all causes in the elderly, attributing to adrenal androgens anti-ageing properties. But do they really suggest that they are hormones related to longevity or just another pointless alchemy against ageing? This chapter summarizes the physiology and pathophysiology of adrenal androgen synthesis, secretion and action and provides current evidence regarding their efficacy in the management of aging-related disorders.

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Nelson Vergel

Founder, ExcelMale.com
Great article:
All About DHEA. Plus: In Practice - Supplementation Benefits & Dosages?[/b]
As you have heard DHEA is the most abundant steroid hormone in your body, it is produced in the mainly in the adrenal gland (~31mg in men and 18mg in women). In women specifically, DHEA is also the main precursor to androgens (testosterone, DHT & metabolites). For both men and women DHEA and DHEA-S the most abundant, sulfur-bound stable transport form of DHEA. It acts as a neurosteroid the age-induced decline of which has long been implicated as one, if not the main hormonal underpinnings of the cognitive decline we experience as we age.

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Nelson Vergel

Founder, ExcelMale.com
Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.
DOI: https://dx.doi.org/10.1210/jcem.78.6.7515387

Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

Nelson Vergel

Founder, ExcelMale.com
Biotransformation of Oral Dehydroepiandrosterone in Elderly Men: Significant Increase in Circulating Estrogens

The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 ± 5.1 yr; mean body mass index, 25.5 ± 1.5 kg/m[SUP]2[/SUP]) with serum DHEAS concentrations below 4.1 μmol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0–12 h (mean ± sd) for DHEA, 108 ± 22vs. 252 ± 45 vs. 349 ± 72 nmol/L·h; AUC 0–12 h for DHEAS, 33 ± 9 vs. 114 ±. 19 vs. 164± 36 μmol/L·h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17β-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men[ placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0–12 h for 17β-estradiol, 510 ± 198 vs. 635 ± 156 vs. 700 ± 209 pmol/L·h (P < 0.0001); AUC 0–12 h for estrone, 1443 ± 269 vs. 2537 ± 434 vs. 3254 ± 671 pmol/L·h (P< 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.
I've seen an absolute increase through testing, while using capsules sublingually and then a TD. I'm not sold on any feeling though, I know my levels are up and I believe that's what I need but I can't associate an improved feeling, of any kind, with DHEA.
Vince I have the same experience with DHEA (do not feel anything at all on them). However I can feel the effect on Pregnenolone but the feeling is not that exciting either only a bit calmer almost drowsy and sleepy.
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