DHEA vs Pregnenolone: Which to Choose and for Whom

The question “which is better — DHEA or pregnenolone” usually comes from people who feel fatigue, a decline in libido or “age-related” changes and are looking for a simple hormonal way out. The editorial team answers honestly: for most people the right choice is neither of them without an examination. Below we explain in which situations doctors consider these substances, for whom they are contraindicated and where you should actually start.

Why this is not a choice between two vitamins

DHEA and pregnenolone are steroid hormones that are converted in the body into other active hormones: androgens, estrogens, progesterone, corticosteroids. Unlike vitamins, their excess is not simply excreted but changes the hormonal balance, and in each person in their own way.

In many countries, in particular in the EU, DHEA is not an ordinary dietary supplement, while in the US it is sold as a supplement. Such a difference in status does not mean a difference in biology: the substance is the same, only the rules of circulation change. For the consumer this is a signal that a “hormonal supplement” should be treated like a medicine.

Another nuance is unpredictability. Taking DHEA in women raises mostly androgens; in men it can affect estrogens more. Pregnenolone can be converted in several directions at once. Without tests it is impossible to predict in which direction the balance will shift specifically in you.

Therefore the correct way to pose the question is not “what to choose,” but “do I have indications for hormonal therapy and exactly what will a doctor prescribe.” In most cases the answer to the first part is no.

When DHEA is considered in medicine

The most justified medical use of DHEA is in women with adrenal insufficiency, in whom their own synthesis of DHEA is sharply reduced. In the study by Arlt and colleagues (1999) in this group, replacement DHEA at a dose of 50 mg per day improved wellbeing and sexual function. However, even here the decision is individual, and the Endocrine Society guidelines (Wierman et al., 2014) do not support routine prescription.

The second registered indication is intravaginal prasterone (DHEA) for the treatment of pain during sexual intercourse associated with menopausal atrophy. This is a local medicine with its own instructions, and it cannot be equated with oral capsules of supplements.

DHEA has also been studied in reproductive medicine in women with reduced ovarian reserve, but the data are contradictory, and such use is possible only within the framework of treatment by a reproductologist.

In contrast, for “general rejuvenation” of elderly people there is no evidence: in the two-year study by Nair and colleagues (2006), DHEA did not improve body composition, strength or metabolic indicators. For young men who want to raise testosterone, the result is also negative (Brown et al., 1999).

Pregnenolone: more questions than answers

Pregnenolone is often advertised as a “milder” alternative to DHEA that supposedly allows the body to “decide for itself” which hormones to synthesize from it. This idea sounds appealing, but has no confirmation: the enzyme that determines the direction of conversion is regulated by tissue needs, not by the presence of a precursor in a capsule.

Clinical studies of pregnenolone concern mostly psychiatry and neurology — for example, pilot works in schizophrenia (Marx et al., 2009). These studies were conducted under medical supervision, and their results cannot be transferred to healthy people or athletes.

Pregnenolone has no generally accepted medical indications, and there is no routine laboratory test in clinical practice that would help assess a “deficiency” of pregnenolone. So even justifying its intake is difficult.

The risks, meanwhile, are real: possible changes in mood, insomnia, acne, menstrual cycle disturbances, as well as an effect on hormone-dependent conditions. For a person without clear indications, the benefit-to-risk ratio is clearly unfavorable.

For athletes and people in the risk group

For athletes who undergo doping control, the answer is unambiguous. DHEA (prasterone) belongs to class S1 of the WADA Prohibited List and is prohibited at all times. Pregnenolone is not directly named in the List, but its effect on the steroid profile and the risk of supplement contamination make taking it an unjustified risk.

It should be emphasized separately: studies did not show that DHEA raises testosterone or improves the results of strength training in young men. That is, an athlete risks disqualification without any real benefit.

Groups for whom both substances are contraindicated or require special caution:

• people with a history of hormone-dependent tumors (breast, prostate, endometrial cancer);
• pregnant and breastfeeding women;
• patients with polycystic ovary syndrome and other conditions with an excess of androgens;
• people with liver diseases, disorders of lipid metabolism;
• young people with normal hormonal function.

If a person is already taking any of these substances and notices acne, increased hair growth, changes in mood or the menstrual cycle, it is worth stopping the intake and seeing an endocrinologist.

Where to start instead of self-prescription

Fatigue, reduced libido and worsening mood are nonspecific symptoms. They are often caused by chronic lack of sleep, a deficiency of iron or vitamin D, thyroid dysfunction, depression or overtraining. Therefore the first step is a doctor, not a hormonal capsule.

The basic examination most often prescribed in such a situation includes a complete blood count, ferritin, TSH, glucose, a lipid panel, and for men — morning total testosterone. Determination of DHEA-S is prescribed according to indications, for example when adrenal pathology is suspected.

For most people, the greatest contribution to hormonal health comes from the sleep regimen, sufficient caloric intake, body-weight control, strength training and recovery. These factors are safe and have a much broader evidence base than any steroid precursors.

If, however, the examination reveals endocrine pathology, the doctor will select a therapy with proven effectiveness and safety monitoring — and this will almost never be an over-the-counter “hormonal supplement.”

Editorial conclusions

Between DHEA and pregnenolone for self-administration, the editorial team does not recommend choosing either. DHEA has narrow medical indications, is prohibited in sport and does not raise testosterone in young men. Pregnenolone has no recognized indications at all and is studied even worse.

The correct sequence is symptoms, doctor, tests, the search for a cause. Hormonal therapy, if it is needed, should be prescribed and monitored by a specialist.

On the place of both substances in the steroid cascade, read the article “DHEA or Pregnenolone: What's the Difference.” We also recommend our materials on the tests for assessing the hormonal background and on the effect of sleep on testosterone levels.

References

1. 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.
2. 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.
3. 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.
4. 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.
5. Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology. 2009;34(8):1885–1903.
6. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
7. World Anti-Doping Agency. International Standard — Prohibited List. Montreal: WADA (чинна редакція).