When older patients ask whether they should take dehydroepiandrosterone (DHEA) or testosterone, tell them not to bother. A two-year, double-blind, placebo-controlled study indicates that neither supplement confers any benefit.

A team of endocrinologists and other specialists at the Mayo Clinic in Rochester, Minn., studied 87 men (aged 62-72) who had low DHEA and testosterone levels and 57 women (aged 65-71) who had low DHEA levels. Twenty-nine men were randomized to receive DHEA 75 mg/day, 22 received testosterone 5 mg/day via a skin patch, and 31 men were given a placebo. Of the women, 27 were randomized to DHEA 50 mg/day and 30 to a placebo.

At the end of the two-year trial, the supplements had raised the subjects’ levels of DHEA to values that would be considered in the high-normal range for young people and significantly increased the levels of testosterone in men. No detectable beneficial effects were seen in any of the treatment groups regarding physical performance, insulin sensitivity, or physical and mental components of quality of life.

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Testosterone replacement increased fat-free mass but caused no significant improvement in muscle strength. DHEA had no effect on fat-free mass in either men or women. “The lack of a significant effect on thigh-muscle area, strength, or fitness largely discounts the relevance of the change in fat-free mass,” the investigators say. They also point out that testosterone supplements may be linked to prostate cancer and the worsening of benign prostatic hyperplasia.

Women in the DHEA group had a small but significant increase in bone mineral density (BMD) of the ultradistal radius. Men saw an increase in BMD in the femoral neck. No increases were seen at other sites. Since other pharmacologic agents result in a far greater increase in BMD, the value of DHEA for this purpose “is probably limited,” the researchers conclude (N Engl J Med. 2006;355:1647-1659).

In an accompanying editorial, a UK physician states, “The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA and testosterone through physiologic replacement regimens offers no answer.”