The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging.

With the passage of the U.S. Dietary Supplement Health and Education Act of 1994, dehydroepiandrosterone (DHEA, 5-androsten-3beta-ol-17-one) has become widely available, and a large and growing market has developed for this "fountain of youth." DHEA has been shown to have significant beneficial effects in animals, which may lead to clinical uses in man. Historically, the U.S. Food and Drug Administration removed DHEA from the over-the-counter market in 1985 because there was no support for the health claims that were made for this product. Almost all of the biological data was on animals and there was a lack of demonstrated efficacy in humans. Recently there have been a number of small clinical trials in humans but the results have not been as positive as in the animal tests. This review will be restricted to the effects of DHEA on carcinogenesis, obesity, the immune system, and aging. Four hypotheses have been proposed to explain the underlying biochemical mechanism(s) by which DHEA exerts its beneficial properties. The first is based on the inhibitory effect of DHEA on mammalian glucose-6-phosphate dehydrogenase. This mechanism can explain the antiinitiation and antipromotion steps in some cases of carcinogenesis. The second biochemical mechanism involves the induction of peroxisomes and peroxisome-associated enzymes. The third explanation is that DHEA works in a similar fashion to the known anticarcinogenic action of food restriction. An antiglucocorticoid mechanism has also been suggested. A hypothesis for the increase followed by the decrease in the levels of DHEA with age is proposed. A number of new synthetic DHEA analogs have been synthesized and tested. They offer the best hope for the development of a clinically useful drug based on the properties of DHEA.