Although it has been speculated that supplemental dehydroepiandrosterone (DHEA) and testosterone may hold the key to a fountain of youth, a new study (N Engl J Med. 2006; 355:1647-1659) has largely debunked this idea.

This 2-year, placebo-controlled, randomized, double-blind study included 87 elderly men with low levels of the sulfated form of DHEA (<1.57 μg/mL) and of bioavailable testosterone (<103 ng/dL) and 57 elderly women with low levels of sulfated DHEA (<0.95 μg/mL). All participants were ≥60 years and had similar baseline characteristics. A group of 38 healthy young women and 37 healthy young men (ages 18-31) served as controls. Outcomes measured included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life.

The elderly men were randomized to 3 treatment groups: DHEA (75 mg/d), testosterone (5 mg/d), or placebo. The elderly women were randomized to receive DHEA (50 mg/d) or placebo.

At 24 months, the DHEA groups had significant increases in sulfated DHEA levels—a median of 3.4 μg/mL in men and 3.8 μg/mL in women—compared with the placebo groups.

Men in the testosterone group had a significant increase in bioavailable testosterone and total testosterone levels compared with the placebo group, as well as a slight increase in fat-free mass. Femoral neck BMD increased in men in both treatment groups, and BMD at the ultradistal radius increased in women in the DHEA group compared with the placebo groups.

Despite these increases in hormone levels, no significant changes were reported in physical performance or quality-of-life scores in either the DHEA or the testosterone groups. No group showed significant changes in fasting plasma glucose or in the insulin-sensitivity index. 

Of note, significant reductions occurred in high-density lipoprotein cholesterol levels in both men and women in the DHEA group (DHEA, P = .68 for women, .39 for men; testosterone, P = .39), but no other lipids were affected.

“Treatment with neither DHEA nor testosterone had any detectable effect on physical performance, insulin sensitivity, or the physical and mental component of the quality of life,” lead investigator K. Sreekumaran Nair, MD, PhD, and colleagues write. “The current data indicate that if short-term restoration of DHEA levels in elderly subjects has favorable biologic effects, they are not sustained.”