Is Dehydroepiandrosterone (DHEA) recommended for use in Hormone Replacement Therapy (HRT) for men?

DHEA Use in HRT for Men

DHEA is not recommended as standard hormone replacement therapy for men, as current clinical guidelines do not support its routine use and evidence for benefit remains insufficient. 1

Guideline Position on DHEA for Men

Major clinical guidelines addressing male hormone replacement therapy do not recommend DHEA as a treatment option:

• The European Association of Urology (2025) guidelines on male hypogonadism make no mention of DHEA as a therapeutic option, focusing exclusively on testosterone formulations and gonadotropins for hormone replacement. 1

• The American College of Physicians (2020) guidelines on testosterone treatment in men with age-related low testosterone similarly do not include DHEA as a recommended therapy, concentrating solely on testosterone replacement formulations. 1

• The 2024 osteoporosis guidelines discuss testosterone replacement for bone health in hypogonadal men but do not recommend DHEA for this indication. 1

Why DHEA Is Not Recommended for Men

The absence of DHEA from clinical guidelines reflects several key issues:

• Testosterone is the primary and established hormone replacement for symptomatic hypogonadism in men, with proven efficacy for sexual function, bone density, and quality of life outcomes. 1

• Men continue to produce testicular androgens throughout life, unlike women who experience complete cessation of ovarian estrogen production at menopause. This makes the rationale for DHEA supplementation much weaker in men. 2

• The contribution of adrenal DHEA to total androgens in men is approximately 40% in elderly men, but this does not translate into a clear therapeutic indication for DHEA supplementation. 2

• Large-scale, randomized, placebo-controlled trials demonstrating clinical benefit of DHEA in men are lacking. 3

Limited Context Where DHEA Might Be Considered

The only clinical context where DHEA appears in recent guidelines is:

• Vaginal DHEA (prasterone) for postmenopausal women with dyspareunia and vaginal atrophy, where it has demonstrated efficacy. 1

• This indication is specific to women and not applicable to male hormone replacement therapy. 1

Clinical Algorithm for Male Hormone Replacement

When managing symptomatic hypogonadism in men, the evidence-based approach is:

1. Confirm biochemical hypogonadism with low serum total or free testosterone levels on at least two separate morning measurements. 1

2. Assess for reversible causes: obesity, metabolic disorders, medications that suppress the hypothalamic-pituitary axis. 1

3. Recommend lifestyle modifications first: weight loss through low-calorie diet and physical activity can increase testosterone by 1-2 nmol/L. 1

4. Initiate testosterone replacement therapy (not DHEA) if symptomatic hypogonadism persists, using formulations such as transdermal gels, intramuscular injections, or other approved testosterone preparations. 1

5. For men seeking fertility, use gonadotropin therapy (hCG and FSH) rather than testosterone, as testosterone suppresses spermatogenesis. 1

Important Caveats

• DHEA is classified as a dietary supplement in the United States but is considered a hormone requiring regulatory approval in many European countries, reflecting ongoing uncertainty about its therapeutic role. 4

• Despite widespread availability and use, no serious adverse events have been reported in the literature or FDA monitoring, suggesting a favorable safety profile. 2

• The lack of adverse events does not constitute evidence of efficacy, and safety alone is insufficient justification for clinical use without demonstrated benefit. 3

• Research suggesting DHEA benefits has primarily been in women (particularly postmenopausal women) and in animal models, with much less compelling evidence in men. 4, 2