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Dehydroepiandrosterone (DHEA), DHEA Sulfate, and Aging: Contribution of the DHEAge Study to a Sociobiomedical Issue

Baulieu EE, Thomas G, Legrain S, et al.

Proceedings of the National Academy of Sciences/2000/280 participants/12 months
Key Finding

DHEA 50 mg daily for 12 months significantly improved bone mineral density in women over 70 and enhanced skin hydration, sebum production, and self-reported well-being versus placebo in older adults.

Background

DHEA (dehydroepiandrosterone) is the most abundant circulating steroid hormone in humans, produced primarily by the adrenal glands. Plasma DHEA-S levels peak in the 20s and decline approximately 80% by age 75 — a phenomenon termed “adrenopause.” DHEA serves as a precursor to both androgens (testosterone) and estrogens.

The DHEAge study was the first large, placebo-controlled RCT to evaluate the effects of DHEA supplementation in healthy elderly men and women, addressing whether restoring youthful DHEA levels produces physiological benefits.

Methods

Randomized, double-blind, placebo-controlled trial at the Institut National de la Santé et de la Recherche Médicale (INSERM), France. Healthy older adults aged 60–79. DHEA 50 mg/day oral vs. placebo for 12 months.

Outcomes: bone mineral density (DXA), skin parameters (hydration, thickness, sebum), libido, cognitive function, insulin sensitivity, lipids.

Key Findings

OutcomeDHEA 50 mgPlaceboNotes
BMD (femoral neck, women >70)+2.4%−0.1%p=0.02
BMD (lumbar spine, women >70)ImprovedNo change
Skin hydrationIncreased (both sexes)No change
Sebum productionIncreased (both sexes)No change
Libido (self-report)Improved significantly (women)No change
Cognitive testsNo significant change
Insulin sensitivityNo significant change

Clinical Significance

DHEAge established DHEA’s most clinically meaningful benefit: bone protection in older women, a population at high risk for osteoporotic fracture. The skin improvements support its continued use in cosmetic and anti-aging contexts.

The lack of cognitive benefit was notable, as DHEA had been widely promoted as a “memory hormone” based on preclinical data — DHEAge helped calibrate expectations.

Limitations

  • 50 mg may not be optimal for all endpoints; dose-response not fully characterized
  • 12 months may be insufficient to detect cognitive or cardiovascular changes
  • Effects on libido were sex-specific (significant in women, not men) — unexpected finding
  • DHEA converts to sex steroids; long-term hormone exposure implications not fully assessed

Compounds Studied

Related Conditions