Side Effects of DHEA
DHEA (dehydroepiandrosterone) is often presented as a "mild" and safe anti-aging remedy. However, it is not a vitamin but a precursor of sex hormones, and most of its undesirable effects follow directly from what it is converted into in tissues. The editorial team has compiled clinical trial data on which adverse reactions occur most often, what they depend on, and who is at the highest risk.
Where DHEA side effects come from
DHEA is produced mainly by the adrenal cortex and, to a lesser extent, by the gonads. In the blood it circulates mostly as a sulfate (DHEA-S), which serves as a kind of "reservoir." DHEA itself has almost no strong hormonal activity of its own: its biological action is realized when enzymes in peripheral tissues convert it into androstenedione, testosterone, dihydrotestosterone, or estrogens.
It is precisely this "intracrine" nature that explains why the response to the same amount of DHEA differs from person to person. In women, whose own testosterone is low, even a moderate rise in androgens becomes noticeable. In men, by contrast, DHEA's contribution to the overall testosterone pool is small, but part of the substance may go toward the synthesis of estradiol.
The second important factor is dose dependence. In studies of replacement use, 25–50 mg per day usually returns DHEA-S levels in older people roughly to the range of young adults. Higher amounts, which some manufacturers offer, easily push the readings beyond the physiological norm, and then the likelihood of undesirable effects increases.
Finally, DHEA is sold in many countries as a dietary supplement, while in the European Union and Ukraine its systemic forms are not an ordinary mass-market product. Because of this, the consumer often takes the product without monitoring test results and without understanding exactly how much active substance is in the capsule.
Androgenic reactions in women
The best-documented side effects of DHEA concern women. In a randomized study by Arlt and colleagues, women with adrenal insufficiency taking 50 mg per day raised androgen levels to the normal range and at the same time experienced oily skin, acne, and increased hair growth in some participants.
Similar reactions have been described in studies with postmenopausal women. A systematic review and meta-analysis by Elraiyah and colleagues, carried out on behalf of the Endocrine Society, showed that the risk of androgenic side effects, primarily acne and hirsutism, with DHEA use is higher than in the placebo group, while no convincing benefits for quality of life or sexual function were found.
Usually androgenic effects develop gradually, over several weeks or months, and after stopping use they mostly subside. However, hair growth on the face and body may persist longer, because hair follicles that have switched to the "terminal" type return to their original state slowly.
Rarer but potentially persistent changes are a lowering of the voice's pitch and male-pattern androgenic baldness. They are more characteristic of prolonged use of high amounts. This is precisely why the Endocrine Society's clinical guidelines on androgen therapy in women do not recommend routinely prescribing DHEA.
- oily skin and acne — the most common complaints;
- hirsutism (hair growth on the chin, above the lip, on the abdomen);
- hair loss on the crown;
- rarely — coarsening of the voice, irregular menstrual cycle.
Side effects in men
In men the picture is different. Since the testes produce the bulk of testosterone, additional DHEA changes its level little. A meta-analysis by Corona and colleagues on older men showed only modest changes in the hormonal profile and no significant benefits for body composition, mood, or sexual function.
Instead, part of the DHEA may be converted into estrogens. Some studies with young and older men recorded a rise in estradiol or estrone levels. Theoretically this may contribute to breast tissue sensitivity and gynecomastia, although in controlled studies of moderate amounts such cases are isolated.
In a study by Brown and colleagues, young men who trained with weights and took 100 mg of DHEA per day for 8 weeks gained neither a rise in testosterone nor an additional increase in strength compared with placebo. For an athlete this means risks without obvious benefit.
The state of the prostate gland deserves separate mention. DHEA is a substrate for the formation of dihydrotestosterone, so men with benign prostatic hyperplasia or suspected prostate cancer are not advised to take it on their own. Monitoring PSA before prolonged use is a sensible precaution mentioned in clinical reviews.
| Group of effects | Women | Men | What it depends on |
|---|---|---|---|
| Androgenic (acne, hair) | Often, especially at high amounts | Rarely | Baseline androgen level, dose |
| Estrogenic | Possible cycle changes | Rise in estradiol, breast sensitivity | Aromatase activity, adipose tissue |
| Lipid | Possible decrease in HDL | Data are contradictory | Dose, duration |
| Nervous system | Insomnia, irritability | Insomnia, irritability | Time of intake, individual sensitivity |
Lipids, heart, sleep, and mood
DHEA's effect on blood lipids is ambiguous. In a number of studies in women, a small decrease in high-density lipoprotein cholesterol (the "good" cholesterol) was observed, which is consistent with the known effect of androgens on lipid metabolism. In men the results are contradictory and mostly insignificant.
Large two-year studies, such as the work of Nair and colleagues in the New England Journal of Medicine, did not reveal serious cardiovascular events associated with 50 mg of DHEA per day, but also did not show any benefit. At the same time, such studies do not have sufficient power to assess rare or distant risks.
Among less specific complaints are insomnia, a feeling of agitation, irritability, headache, and palpitations. Some of them are linked to the stimulating effect of neurosteroids on the central nervous system, so taking it in the second half of the day may worsen sleep.
The medical literature contains reports of cases of manic or hypomanic states in people taking DHEA, particularly in those predisposed to bipolar disorder. These are isolated descriptions rather than the results of controlled studies, but they are grounds for particular caution in people with mental disorders.
Hormone-dependent tissues and supplement quality
The most serious theoretical concern is the effect on tissues sensitive to sex hormones: the mammary gland, endometrium, ovaries, prostate. Since DHEA can raise both androgens and estrogens, its use is contraindicated in people with a history of hormone-dependent tumors.
There are no long-term studies that would reliably assess oncological risk. The absence of a signal in two- or three-year studies does not equal proven safety, especially for middle-aged people who may take the supplement for decades.
A separate risk is related to product quality. An analysis of commercial DHEA supplements, published in JAMA in the late 1990s, showed that the actual content of the active substance in some products differed substantially from what was declared. This means that the real amount a person receives may be either less or more than what is written on the label.
For athletes there is another consequence: DHEA (prasterone) is included on the WADA Prohibited List as an endogenous anabolic androgenic steroid, so its use may lead to an anti-doping rule violation. For people without medical indications, the sum of the risks usually outweighs the dubious benefit.
Editorial conclusions
The side effects of DHEA are mostly a direct consequence of its conversion into androgens and estrogens. In women, acne, oily skin, and unwanted hair growth arise most often; in men, a possible rise in estrogens.
Serious reactions in controlled studies of moderate amounts are rare, but long-term safety has not been established, and benefit for healthy people and athletes has not been confirmed.
If you are considering DHEA, start with a DHEA-S test and a consultation with an endocrinologist, not with buying a jar online.
The editorial team also recommends reading our materials "Who Should Not Take DHEA," "Myths About DHEA," and "Pregnenolone: What It Is and How It Works."
References
- Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999;341(14):1013–1020.
- Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006;355(16):1647–1659.
- Elraiyah T, Sonbol MB, Wang Z, et al. The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3536–3542.
- Corona G, Rastrelli G, Giagulli VA, et al. Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. J Clin Endocrinol Metab. 2013;98(9):3615–3626.
- Brown GA, Vukovich MD, Sharp RL, et al. Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men. J Appl Physiol. 1999;87(6):2274–2283.
- Wierman ME, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(10):3489–3510.
- Parasrampuria J, Schwartz K, Petesch R. Quality control of dehydroepiandrosterone dietary supplement products. JAMA. 1998;280(18):1565.
- World Anti-Doping Agency. The World Anti-Doping Code: International Standard — Prohibited List. Montreal: WADA; чинна редакція.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
