Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects.
Level 2 - randomized trial
Randomized incomplete block pharmacokinetic trial in humans
PubMed 10999810 · doi:10.1210/jcem.85.9.6805
What was done
Twenty-four healthy older men and women (mean age 67.8 ± 4.3 years) received daily oral DHEA (25 mg or 50 mg) or placebo for 8 days in a balanced incomplete block design. Blood was sampled nine times on day 1 and day 8 to evaluate the pharmacokinetics and concentrations of DHEA, DHEAS, testosterone, 5α-androstan-3α,17β-diol glucuronide, estradiol, and estrone.
What was found
Oral DHEA administration restored low baseline DHEA and DHEAS to youthful levels. Blood DHEA displayed an apparent terminal half-life of more than 20 hours, comparable to blood DHEAS, which the authors attributed to back-hydrolysis of formed DHEAS. Metabolic conversion of DHEAS to DHEA was significantly greater in women than in men. No accumulation of steroids was observed, and no concerning transformation to androgens or estrogens was recorded, with only a limited increase in estradiol observed in older women. The abstract did not report exact numerical pharmacokinetic values or confidence intervals.
Why it matters
This study demonstrates that oral DHEA provides sustained circulating steroid levels via back-hydrolysis of a DHEAS reservoir, supporting the feasibility and safety of a 50 mg daily dosing regimen for subsequent long-term clinical trials in elderly populations.
Limits
The study had a very small sample size (n = 24) and a very short treatment duration (8 days), precluding any assessment of long-term safety, sustained endocrine effects, or clinical efficacy outcomes. Specific numerical values (such as clearance, AUC, or exact hormone levels) were omitted from the abstract.
Cited by
- supports Studies investigating DHEA supplementation typically use doses between 25 and 50 milligrams.