BETHESDA, MD (American College of Cardiology) -- Dehydroepiandrosterone (DHEA), a sex hormone precursor available over-the-counter in the United States and often promoted as an "anti-aging" supplement, may promote the formation of fatty plaques in arteries, according to a new laboratory study in the Dec. 3, 2003 issue of the Journal of the American College of Cardiology.

"Our lab study shows a surprising result that DHEA may promote coronary disease, rather than prevent it, and while it is a lab result, it does suggest that caution should be taken in the unsupervised self-administration of the hormone. It seems to suggest to us that any administration of DHEA in humans at the moment should probably be restricted to the context of research, rather than over-the-counter use," said Martin K. C. Ng, MBBS, FRACP from the Royal Prince Alfred Hospital and the University of New South Wales in Sydney, Australia.

DHEA is not available without a prescription in Australia.

In this laboratory study, the researchers exposed human macrophage cells to either DHEA and/or an androgen receptor antagonist. Other unexposed cells were used as a control. Exposure to DHEA produced a dose-dependent effect that appeared similar to an early stage in the formation of fatty plaques within the lining of coronary arteries. Specifically, the DHEA-exposed cells showed increases in the cholesterol ester content of male macrophage cells. Large amounts of cholesterol ester give the macrophage cells a foamy appearance, hence the term "foam" cell.

"It's the earliest and principal cell in early coronary disease," Dr. Ng said. "It's really the earliest hallmark of coronary disease that we know of."

The researchers saw no effect of DHEA on the adhesion of monocytes (precursors of macrophages) to human endothelial cells. Monocyte-endothelial adhesion is another early event in the formation of artery plaques.

Dr. Ng noted that although this study offered evidence of the direct effect of DHEA on human cells, it was not a human clinical trial.

"Someone taking DHEA does not experience an increase just in DHEA, they seem to have an increase in other circulating androgens, male sex hormones, as well; so the effects may be more complicated in a person," he said.

Dr. Ng said he and his colleagues reviewed other reports on DHEA and human health and noted that although DHEA levels decline later in life, while coronary disease increases, there is also evidence linking higher natural DHEA levels with higher rates of coronary disease. For instance, women in the United States and men in Japan both have lower rates of coronary disease -- and lower levels of DHEA -- than men in the United States. Therefore, he said there is evidence from observational studies that is consistent with the hypothesis that DHEA might promote coronary disease, rather than prevent it.

Sam Tsimikas, MD, from the University of California San Diego School of Medicine, who was not part of this research team, noted that the study was performed in laboratory cell cultures, not actual patients, so it does not address what may happen when the body converts DHEA into testosterone or estrogen. However, he urged that until further studies are done, "buyers beware."

"This adds to the growing evidence that anabolic steroids, or precursors thereof, such as DHEA, may have detrimental effects on cardiovascular health. With data showing that approximately one out of two Americans will eventually die of cardiovascular disease, this information has major health care implications, and more research will be needed to fully understand its effects on heart disease. With several highly publicized recent events where athletes have died in the setting of using performance enhancing supplements, it adds an imperative for potential users of such supplements to be cautious," Dr. Tsimikas said.

The American College of Cardiology, a 29,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.