DHEA in elderly women and DHEA or testosterone in elderly men.

The New England journal of medicine

Oct 2006

DOI: 10.1056/NEJMOA054629

Citations:543

Influential Citations:27

Interventional (Human) Studies

Enhanced Details

Methods

Two-year, placebo-controlled, randomized, double-blind trial in adults aged ≥60 with low sulfated DHEA; elderly men (N=87) had low bioavailable testosterone (<103 ng/dL) and low sulfated DHEA (<1.57 μg/mL); elderly women (N=57) had low sulfated DHEA (<0.95 μg/mL). Exclusions included clinically important coexisting illnesses; prostate screening (PSA and ultrasound) performed in men. Randomization allocated men to DHEA, testosterone, or placebo; women to DHEA or placebo. Outcomes included physical performance, body composition, bone mineral density, glucose tolerance, insulin sensitivity, and quality of life; conducted at Mayo Clinic; no industry sponsorship.

Intervention

Men receiving DHEA: DHEA 75 mg daily (oral) + transdermal placebo patch for 24 months. Men receiving testosterone: testosterone 5 mg per day via transdermal patch + placebo tablet for 24 months. Men receiving placebo: placebo tablet + placebo transdermal patch for 24 months. Women receiving DHEA: DHEA 50 mg daily (oral) for 24 months. Women receiving placebo: placebo tablet for 24 months.

Results

DHEA replacement and low-dose testosterone over 2 years did not yield clinically meaningful improvements in physical performance, insulin sensitivity, or quality of life. DHEA raised sulfated DHEA to high-normal young levels and increased estradiol (and total estradiol to some extent); in women, total testosterone rose; in men, bioavailable testosterone rose with testosterone therapy. DHEA did not change body composition; testosterone increased fat-free mass modestly but did not improve VO2 peak, muscle strength, or physical performance. Bone-mineral density changes were small and site-specific (DHEA: ultradistal radius in women; femoral neck in men; testosterone: femoral neck in men). Prostate measures (PSA and size) were not significantly altered; adverse events were similar across groups; long-term safety remains uncertain. Overall, no evidence supports DHEA or low-dose testosterone as antiaging therapies; higher-dose testosterone requires further study due to potential risks.

Limitations

Small subgroup sample sizes; some participants did not complete 24-month follow-up; 2-year duration may be insufficient for long-term safety, especially prostate outcomes; results may not generalize to broader elderly populations or different dosing regimens; only specific dosing regimens were tested; potential for undetected modest effects due to limited statistical power.

Abstract

BACKGROUND Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown. METHODS We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. RESULTS As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects. CONCLUSIONS Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].). show less