DHEA, Boron and Pregnenolone: What the Add-Ons Actually Do
Our men's hormone tablet is enclomiphene plus three other things, and the honest way to describe them is separately. Enclomiphene carries the treatment: it is the component with controlled trials behind it, and the main page is about it. DHEA, boron and pregnenolone are adjuncts, each with a different — and smaller — weight of evidence, and a page that lumped them together as "supporting nutrients" would be doing what supplement marketing does.
So this page grades them one at a time.
DHEA — the best-studied of the three
Dehydroepiandrosterone is the adrenal gland's most abundant steroid and a precursor from which the body can make both testosterone and estrogen. It peaks in the mid-twenties and falls steadily thereafter, so that a man in his sixties has a fraction of the DHEA-S he had at thirty. That decline is measurable — the DHEA-S explainer covers the lab value — and it is the reason DHEA has been studied as a replacement for decades.
What the studies show is more modest than the decline implies. In older men with low DHEA-S, supplementation raises DHEA-S reliably, raises testosterone slightly or not at all, and has small, inconsistent effects on body composition, bone density and mood. The largest and longest trials — including a two-year study in elderly men and women — found no meaningful benefit on strength, physical performance or quality of life. Its most consistent effects are in women, where DHEA is a more significant source of androgens; in men, whose testes make most of their testosterone, it is a minor contributor.
Why include it, then? Because in a man whose DHEA-S is low on the panel, restoring it to the range of a younger man is physiologically reasonable, well tolerated at the amounts used, and inexpensive — and because enclomiphene acts on the testicular axis, not the adrenal one, so the two address different sources. We would not claim more than that. DHEA is not a testosterone therapy, and a man taking it for that purpose alone will be disappointed.
One firm caution. DHEA is a prohibited substance under the World Anti-Doping Code, in and out of competition. A man who is drug-tested in any sport should not take this product, and the still-competing page says so at length. We ask at assessment.
Boron — a small literature with a specific finding
Boron is a trace element, present in fruit, nuts and legumes, with no established deficiency disease in humans and therefore no recommended daily intake. Its relevance here is a handful of small studies — one in healthy men, a few in other populations — in which boron supplementation over about a week reduced sex-hormone-binding globulin and raised free testosterone, with a fall in inflammatory markers alongside.
That is a real finding and an interesting mechanism: less SHBG means more of the testosterone in circulation is unbound and active, which is what the free testosterone question is about. It is also a small finding, from small studies, without the long, controlled trials that would show whether the change in a lab value translates into a change a man can feel. Boron is included because the mechanism is plausible, the safety record at dietary-range amounts is clean, and the effect on SHBG is complementary to what enclomiphene does upstream. It is not included because we believe boron treats low testosterone. It does not.
Pregnenolone — the thinnest evidence
Pregnenolone is the first steroid the body makes from cholesterol — the precursor to DHEA, progesterone, cortisol and, downstream, every sex hormone. That position at the top of the pathway is the whole of the marketing argument for it ("the mother hormone"), and it is a poor argument, because the body regulates each step below pregnenolone tightly and does not simply push more product through a pathway because more raw material arrived.
The human evidence for pregnenolone supplementation is old, sparse and mostly about mood and cognition rather than hormones: small studies in the 1940s on fatigue and later ones in psychiatric populations, with modern interest in its brain-active metabolites rather than any effect on testosterone. There is no controlled evidence that pregnenolone raises testosterone in men. It is included in the formulation at a low amount as a precursor alongside DHEA; we consider it the least evidenced of the three, and we say so.
Why they are combined, and what we would not claim
The tablet is built around enclomiphene, which raises testosterone by restoring the pituitary's signal to the testes — a mechanism with trial evidence and the reason a man is prescribed it. The three adjuncts address the edges: the adrenal precursor pool (DHEA, pregnenolone) and the binding protein that governs how much testosterone is free (boron). Each is well tolerated, each has a plausible mechanism, and each has an evidence base that is small (boron), modest (DHEA) or thin (pregnenolone).
What we would not claim: that the adjuncts treat low testosterone on their own, that they add a measurable clinical benefit on top of enclomiphene (that has not been tested), or that "natural precursor" means anything about safety or effect. What we would claim is narrower — that they are reasonable, low-risk companions in a man whose panel shows room for them, and that the enclomiphene is what is doing the work.
If you take DHEA or pregnenolone already, or a supplement that contains them, tell us at assessment. They add up, and they affect the panel.
Frequently asked questions
Slightly or not at all, in most trials. It reliably raises DHEA-S, and is a more meaningful androgen source in women than in men. It is included to restore a low adrenal precursor, not as a testosterone therapy.
Small studies show boron reduces SHBG and raises free testosterone over about a week. The finding is real but the studies are small and short, and no trial has shown a benefit a man can feel.
It is the first steroid made from cholesterol and the precursor to the others. There is no controlled evidence that supplementing it raises testosterone; its evidence is thin and mostly about mood and cognition.
No. DHEA is prohibited by the World Anti-Doping Code in and out of competition. Tell us at assessment if you compete in a tested sport.
Enclomiphene is the treatment. The adjuncts address the adrenal precursor pool and SHBG, which enclomiphene does not. They are companions with a plausible rationale, not the reason for the prescription.
Yes — DHEA and pregnenolone are in many "testosterone support" products. They stack with the tablet and change what the panel shows.
Where this fits in your plan
The Enclomiphene ODT page covers the treatment; the baseline panel — including DHEA-S and SHBG — is what tells us whether the adjuncts have anything to do. The men's hormone page covers how the plan is built.
We measure first. Then we act.
References
- Nair KS et al. DHEA in elderly women and DHEA or testosterone in elderly men. New England Journal of Medicine 2006;355:1647–1659.
- Corona G et al. Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. Journal of Clinical Endocrinology & Metabolism 2013;98:3615–3626.
- Naghii MR et al. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology 2011;25:54–58.
- Pizzorno L. Nothing boring about boron. Integrative Medicine (Encinitas) 2015;14:35–48.
- Vallée M. Neurosteroids and potential therapeutics: focus on pregnenolone. Journal of Steroid Biochemistry and Molecular Biology 2016;160:78–87.
- World Anti-Doping Agency. The Prohibited List, current edition — S1 Anabolic Agents (DHEA, prasterone).
- Back toEnclomiphene / DHEA / Boron / Pregnenolone ODT
- Enclomiphene vs ClomidClomid is two molecules; enclomiphene is the one that does the work. What zuclomiphene adds, why it lingers, and why the FDA status of each is the reverse of what you'd expect.Read
- What DHEA-S meansDHEA-S falls steadily from your twenties onward, which makes an age-adjusted reading essential. What a high or low result means, and what it does not.Read
- Still competing? Anti-doping and treatmentIf you still compete in sanctioned events, some treatments are prohibited without an approved exemption — including ones we prescribe. What to check before you start.Read
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