DHEA: Boon or Bane?

David Williams, Ph.D.
Professor of Food Science and Technology
Affiliate Investigator, Linus Pauling Institut

David Williams

Dehydroepiandrosterone (DHEA) is now widely marketed and sold over the counter in many retail outlets--wonderful news for DHEA advocates who praise this compound as a fountain of youth to prevent or retard aging, cancer, AIDS, cardiovascular disease, lupus and diabetes. Additional benefits are reported to include mood elevation, increased energy and enhanced libido. But what is DHEA? Is it really a wonder drug with no harmful effects?

DHEA is a steroid hormone produced in the adrenal gland and present in high concentrations in human blood (of the steroids, second only to cholesterol), predominantly in the sulfated form (DHEAS). The physiological function of DHEA in the body is still somewhat of a mystery. Levels peak during an individual's twenties and then decline with age, an association that led many people to advocate DHEA replacement therapy as an effective anti-aging strategy.

DHEA is a precursor for the sex steroids, being converted in the body first into androgens (male sex steroids) and subsequently to estrogens (female sex steroids). This property of DHEA has led to a number of instances of unwanted masculinization phenomena, including the appearance of facial hair in women taking large doses. More importantly, one would expect that DHEA could contribute to a stimulation of hormone-dependent cancers in humans, including prostate cancer in men. While no long-term studies on DHEA have yet been done in humans, the estimated 75 million dollars in sales in the current year reflect a huge uncontrolled human clinical trial.

My laboratory, under the leadership of Dr. Gayle Orner, has demonstrated that DHEA is a potent liver tumor-promoting agent and a complete carcinogen in the trout tumor model. Scientists and clinicians have known for years that feeding high doses of DHEA over periods of a year or more to rodents results in liver cancers. The risk for humans, however, has been assumed to be negligible--the mechanism of carcinogenesis in rodents is thought to be through DHEA functioning as a peroxisome proliferating agent, and humans are known to be relatively insensitive to such agents. However, we have found that DHEA, when fed for only a few months, causes liver cancer in trout at 20-fold lower doses than in the rat. Furthermore, trout, like humans, are insensitive to peroxisome proliferators. We have recently obtained further evidence that the mechanism of DHEA liver carcinogenesis in trout relates to its conversion to androgens and estrogens, a mechanism relevant to humans.

What then is the risk of taking DHEA? If you are in your 60s, or older, and are taking small replacement doses (10-25 mg daily), the risk is probably minimal. However, significant doses of DHEA taken by young and middle-aged adults for a number of years may adversely affect liver function and enhance the risk of cancer. In any case, most responsible physicians and scientists who study DHEA agree that its availability over the counter is ill-advised. Administration of DHEA should be under a doctor's supervision to ensure that the potential benefits are not overshadowed by an unacceptable risk.

Last updated May, 1997

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