DHEA — The Precursor Hormone
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenal glands. It serves as a precursor to both androgens and estrogens. DHEA levels peak in the mid-20s and decline ~80% by age 70, making it one of the most dramatic age-related hormonal changes.
Mechanism of Action
DHEA is converted peripherally to testosterone, estradiol, and other androgens/estrogens via tissue-specific enzymes (aromatase, 5α-reductase). It also has direct receptor-independent effects: activating PPAR-α, inhibiting NF-κB, and modulating insulin sensitivity. DHEA-S (the sulfated form) is the circulating reservoir.
Human Trial Evidence
The DHEA-HRT trial (Baulieu et al., PNAS 2000) showed 50 mg/day DHEA for 1 year improved bone mineral density, skin hydration, and libido in men and women aged 60–79. A 2006 NEJM trial showed DHEA improved sexual function in women with adrenal insufficiency. Multiple trials show improvements in mood, energy, and body composition.
Dosing Protocol
25–50 mg/day is the most studied range. Women typically use 10–25 mg/day (lower due to androgenic effects). Best taken in the morning with food. Monitor DHEA-S blood levels to avoid supraphysiological levels. Micronized or sublingual forms have better bioavailability.
Safety & Contraindications
Requires monitoring. Can cause acne, oily skin, and hair loss (androgenic effects) especially in women. May suppress endogenous DHEA production. Contraindicated in hormone-sensitive cancers (breast, prostate). Avoid in pregnancy. Requires physician supervision for long-term use.