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  •   Side Effects of DHEA Related to Increase in Testosterone Level

    Tuesday, February 24, 1998; Page Z15

    In advertisements on the Internet, DHEA is billed as "the Mother of Hormones" and "the amazing anti-aging pill." But many of the scientists whose work is cited as proof of DHEA's benefits have charged that such claims are exaggerated.

    "There is a lot less there than you would think, based on what the proponents say," said David Schardt, a nutritionist with the Center for Science in the Public Interest who reviewed the scientific studies often cited by those promoting the hormone.

    In animals, DHEA has been shown to prevent cancer, heart disease and diabetes. "These are exciting and dramatic effects, but unfortunately we have virtually no human data as to whether or not it works," said Arthur Schwartz, a professor of microbiology at Temple University's Fels Institute for Cancer Research and Molecular Biology and a leading DHEA researcher.

    That's because in animal studies, these effects require doses whose equivalent in humans would be between 1,000 and 2,000 milligrams a day -- too high to tolerate, Schwartz said. Such doses would cause a dramatic increase in the level of testosterone, a male sex hormone, with unpleasant and potentially dangerous consequences in both sexes. He said most of the studies that have been done so far in humans have used doses too low to produce clear-cut effects that could explore the hormone's potential as a treatment.

    DHEA stands for dehydroepiandrosterone. It's a steroid hormone, chemically related to the sex hormones testosterone and estrogen. In humans and other primates, it's manufactured in large quantities by the paired adrenal glands, which sit atop the kidneys. Levels of the hormone are highest in both sexes during young adulthood and decline steadily with age. Levels in young women are between 10 percent and 30 percent lower than in young men.

    A 1994 report by Samuel S.C. Yen of the University of California at San Diego sparked interest in DHEA as a possible anti-aging treatment. In the study, 13 men and 17 women who were between 40 and 70 years old were randomly assigned to receive either DHEA (50 milligrams a day) or a placebo for three months. Then the participants were switched to the alternative treatment and studied for another three months. Researchers measured levels of various other hormones, levels of circulating fats in the blood, and body fat content; they also asked about sex drive and general well-being.

    Yen and his team reported that DHEA treatment caused an increase in IGF-1, an important intermediary hormone that's responsible for the effects of growth hormone on the body's tissues. They also noted "a remarkable increase in perceived physical and psychological well-being" in people of both sexes who were treated with DHEA.

    However, a one-year follow-up study by UCSD researcher Arlene J. Morales, using 100 milligrams of DHEA, did not report an increase in well-being. It did find that recipients increased their lean body mass and that men (but not women) lost fat and improved their knee strength. Neither study noted any increase in sex drive. Other studies on mental function and mood have had mixed results, with some researchers reporting an antidepressant effect and others finding none.

    A decade ago, another UCSD researcher, Elizabeth Barrett-Connor, reported findings that suggested that men with naturally high levels of DHEA in the bloodstream might be protected against heart disease. Barrett-Connor measured DHEA levels in 2,000 men and women in the early 1970s, then observed how many developed heart disease. In a 1986 paper, she reported that men with the highest DHEA levels appeared to have a reduced risk, while women with high levels had an elevated risk. However, a follow-up analysis of the same group, published in 1995, found that the men who had had the highest DHEA levels 20 years earlier now had only slightly less heart disease than average. The 1995 report also found no correlation between the hormone and heart disease in women. (In rabbits, however, high-dose DHEA is effective in preventing the hardening of the arteries that causes heart disease, Schwartz said.)

    Research in humans on DHEA's effect on the immune system also has produced mixed results. A study last year by Yen noted improvements in the functioning of some white blood cells in elderly men given the hormone. However, other studies have found that DHEA does not improve the response of elderly people to vaccinations for tetanus or influenza.

    Schwartz said the most promising finding from human trials comes from a small 1995 study comparing DHEA to a placebo in women with systemic lupus, a serious illness in which the immune system attacks body tissues. A Stanford team reported that the hormone improved the women's condition.

    For women, DHEA can produce unwelcome and noticeable side effects, some of which may be permanent. Because the body converts some of the ingested hormone into testosterone, woman may grow facial or body hair, may develop acne and a deeper voice, and may stop menstruating. In men, researchers worry that the increase in testosterone could promote the growth of prostate cancer, although studies so far haven't documented higher cancer rates in hormone users. Similarly, since a smaller fraction of DHEA is also converted to estrogen, some experts are concerned about a possibly higher risk of breast cancer in women.

    Schwartz said he is working with a drug company and with the National Cancer Institute on tests of a DHEA-like substance that has been chemically modified to prevent its conversion by the body into testosterone and estrogen. In animals, this drug, fluasterone, is as effective as DHEA in preventing cancer and heart disease and appears to work as a treatment for diabetes and rheumatoid arthritis. Preliminary studies in people suggest that it's safe. Small trials are expected to begin this year in diabetics and people with rheumatoid arthritis. Schwartz said the NCI also plans to test fluasterone to prevent colon cancer in people with intestinal polyps.

    "In animals, [DHEA] is affecting these age-related diseases as much as anything I'm aware of," said Schwartz. But, he added, "to me, the only way to approach the problem of trying to utilize DHEA would be to try to change its structure" so that it's not converted into male sex hormones.

    © Copyright 1998 The Washington Post Company

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