Dehydroepiandrosterone, or DHEA, is one of the most abundant steroid hormones in the human body. It has been called the "hormone of youth" and sold as an anti-aging and muscle-building supplement. The editorial team explains what DHEA is from the standpoint of physiology, how it works, why its status in sport is special and what is actually known about the effects of taking it externally.
What DHEA is
DHEA is a steroid hormone synthesized mainly in the reticular zone of the adrenal cortex, and also in small amounts in the gonads and the brain. In the blood it circulates mostly in the form of a sulfate - DHEA-S, whose concentration is much higher than that of any other steroid.
DHEA itself has weak intrinsic hormonal activity. Its main role is to be a precursor: in peripheral tissues it is converted into androgens (androstenedione, testosterone, dihydrotestosterone) and estrogens. The Canadian endocrinologist Fernand Labrie described this phenomenon as "intracrinology" - the synthesis of active hormones directly in the cells where they act.
DHEA is of especially great importance for women: according to estimates by Labrie (2010), in postmenopausal women practically all estrogens and androgens are formed in peripheral tissues precisely from DHEA of adrenal origin. In men the main source of testosterone is the testes, so the contribution of DHEA is relatively smaller.
The pharmacological name of synthetic DHEA is prasterone. Under this name it is included in official registers of medicinal products and in the WADA Prohibited List.
The pathway of synthesis and conversion
Like all steroids, DHEA is formed from cholesterol. First cholesterol is converted into pregnenolone, then the enzyme CYP17A1 sequentially carries out 17-hydroxylation and cleavage of the side chain, resulting in the formation of DHEA. The sulfotransferase SULT2A1 adds a sulfate group, forming DHEA-S - a stable "reservoir" of the hormone in the blood.
In tissues, DHEA under the action of 3β-hydroxysteroid dehydrogenase is converted into androstenedione, from which testosterone can then be formed, and, with the participation of aromatase - estrogens. Which hormone will predominate depends on the set of enzymes in the particular tissue.
This explains why the effects of taking DHEA differ in men and women. In women, oral DHEA noticeably increases the level of testosterone in the blood, whereas in young men with normal testicular function the effect on testosterone in studies was minimal (Brown et al., 1999).
There are also data that DHEA can act as a neurosteroid, affecting receptors in the brain, however the clinical significance of these effects in humans is insufficiently studied.
- DHEA- the free form with a short lifespan in the blood.
- DHEA-S- the sulfated form, a stable circulating reserve.
- Conversion products- androstenedione, testosterone, DHT, estrone, estradiol.
Age-related dynamics
The DHEA-S level has a characteristic age-related curve. It is low in childhood, rises sharply during adrenarche - a few years before puberty - reaches a peak at approximately 20-30 years, and then gradually declines. In elderly people the concentration is only a small fraction of the peak.
It was this age-related decline that became the basis for the hypothesis that DHEA is the "hormone of youth", and that restoring it to a "youthful" level would slow aging. In the 1990s, on the wave of this idea, DHEA became one of the most popular supplements in the USA.
Large randomized studies, however, did not confirm the hypothesis. In the two-year study by Nair and colleagues (2006), published in the New England Journal of Medicine, taking DHEA by elderly people did not improve body composition, physical performance, insulin sensitivity or quality of life.
The French DHEAge study (Baulieu et al., 2000) found individual effects - for example, on bone density and skin condition in women over 70 - but not a "rejuvenation" of the body as a whole.
Medical use and legal status
The status of DHEA differs between countries. In the USA it is sold as a dietary supplement and is explicitly excluded from the list of anabolic steroids of federal law, whereas in many other countries, including the EU, it is a prescription drug or not registered at all for oral use.
The officially approved medical use of prasterone is limited. In 2016 the FDA approved vaginal inserts with prasterone for the treatment of dyspareunia (painful intercourse) in postmenopausal women caused by atrophy of the vulva and vagina.
| Context | Status / position | Source |
|---|---|---|
| Sport | Prohibited in and out of competition (class S1) | WADA Prohibited List |
| Women with low androgen levels | Routine prescription not recommended | Endocrine Society, Wierman et al., 2014 |
| Adrenal insufficiency in women | Studied, data ambiguous | Arlt et al., 1999 |
| Postmenopausal dyspareunia | Vaginal prasterone approved | FDA label (Intrarosa) |
| Anti-aging | Effect not confirmed in RCTs | Nair et al., 2006 |
The Endocrine Society clinical guidelines on androgen therapy in women (Wierman et al., 2014) do not recommend the routine use of DHEA because of the limited data on efficacy and safety.
In primary adrenal insufficiency, when DHEA synthesis is sharply reduced, the study by Arlt and colleagues (1999) showed an improvement in well-being and sexual function in women, however subsequent work gave contradictory results. The decision on such therapy is made only by an endocrinologist.
Risks and safety issues
Since DHEA is converted into sex hormones, its side effects reflect an excess of androgens or estrogens. In women this is primarily acne, oily skin, increased growth of facial and body hair; other androgenic effects have also been described in studies.
A theoretical but serious problem is the effect on hormone-dependent tissues. For people with a history of breast, ovarian, endometrial or prostate cancer, as well as with a suspicion of such diseases, DHEA is contraindicated without the decision of an oncologist and endocrinologist.
For athletes the main risk is a violation of anti-doping rules. DHEA is included in class S1 of the WADA Prohibited List, and a positive test threatens disqualification regardless of whether taking it provided any advantage.
An additional risk is quality: products sold as supplements may contain a dose different from the declared one, or other steroids. The editorial team considers taking the hormone on one's own, without tests and medical supervision, unjustified.
Editorial conclusions
DHEA is a natural adrenal steroid that serves as a precursor of androgens and estrogens; it is especially important for the hormonal balance of women.
The DHEA-S level decreases with age, but large randomized studies have not confirmed that taking DHEA slows aging or improves the physical fitness of elderly people.
Medical use is limited, in sport DHEA is banned by WADA, and the side effects are associated with an excess of sex hormones.
We also advise you to familiarize yourself with our materials "The benefits of DHEA for athletes: the evidence base", as well as with publications about tests for monitoring hormonal status and about the WADA Prohibited List.
References
- Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Res. 2010;182:97–148.
- 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.
- 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.
- Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA. 2000;97(8):4279–4284.
- 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.
- 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.
- World Anti-Doping Agency. The World Anti-Doping Code: International Standard — Prohibited List. Montreal: WADA; оновлюється щороку.
- U.S. Food and Drug Administration. Intrarosa (prasterone) vaginal inserts: prescribing information. Silver Spring (MD): FDA; 2016.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
