Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial

J Clin Endocrinol Metab. 2006 Aug;91(8):2986-93. doi: 10.1210/jc.2005-2484. Epub 2006 May 30.


Context: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) decrease with aging and are important androgen and estrogen precursors in older adults. Declines in DHEAS with aging may contribute to physiological changes that are sex hormone dependent.

Objective: The aim was to determine whether DHEA replacement increases bone mineral density (BMD) and fat-free mass.

Design, setting, and participants: A randomized, double-blinded, controlled trial was conducted at an academic research institution. Participants were 70 women and 70 men, aged 60-88 yr, with low serum DHEAS levels.

Intervention: The intervention was oral DHEA 50 mg/d or placebo for 12 months.

Measurements: BMD, fat mass, and fat-free mass were measured before and after intervention.

Results: Intent-to-treat analyses revealed trends for DHEA to increase BMD more than placebo at the total hip (1.0%, P = 0.05), trochanter (1.2%, P = 0.06), and shaft (1.2%, P = 0.05). In women only, DHEA increased lumbar spine BMD (2.2%, P = 0.04; sex-by-treatment interaction, P = 0.05). In secondary compliance analyses, BMD increases in hip regions were significant (1.2-1.6%; all P < 0.02) in the DHEA group. There were no significant effects of DHEA on fat or fat-free mass in intent-to-treat or compliance analyses.

Conclusions: DHEA replacement therapy for 1 yr improved hip BMD in older adults and spine BMD in older women. Because there have been few randomized, controlled trials of the effects of DHEA therapy, these findings support the need for further investigations of the benefits and risks of DHEA replacement and the mechanisms for its actions.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging*
  • Body Composition / drug effects
  • Bone Density / drug effects*
  • Calcium, Dietary / administration & dosage
  • Dehydroepiandrosterone / adverse effects
  • Dehydroepiandrosterone / deficiency
  • Dehydroepiandrosterone / therapeutic use*
  • Dehydroepiandrosterone Sulfate / blood
  • Diet
  • Double-Blind Method
  • Female
  • Femur
  • Hip
  • Hormone Replacement Therapy
  • Humans
  • Lumbar Vertebrae
  • Male
  • Middle Aged
  • Placebos
  • Sex Characteristics
  • Vitamin D / administration & dosage


  • Calcium, Dietary
  • Placebos
  • Vitamin D
  • Dehydroepiandrosterone
  • Dehydroepiandrosterone Sulfate