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DHEA: Ignore the Hype

P.J. Skerret

News reports have called DHEA "the mother of all hormones." A new book calls it a "superhormone." On the Internet, it's billed as the "fountain of youth hormone."

In the court of media and public opinion, DHEA is king, a pill that can help us live longer, lose weight or gain it, prevent cancer, heart disease, and Alzheimer's, and combat AIDS and other infectious diseases. The crescendo of praise for this hormone has drowned out the serious cautions that top researchers in the field are raising:

"No one should take DHEA except under the supervision of a physician, who should routinely check steroid and cholesterol levels, glucose tolerance, and prostate health in men," says John Nestle, MD, professor of endocrinology and metabolism at Virginia Commonwealth University, who studies DHEA's effects on diabetes and blood clotting.

"DHEA is the snake oil of the '90s. It makes me very nervous that people are using a drug we don't know anything about. I won't recommend it," says Elizabeth Barrett-Connor, MD, professor and chair, department of family and preventive medicine at the University of California, San Diego. Her studies of natural DHEA levels in older people suggest that higher levels may protect men against heart disease.

"Selling potent steroid hormones in health food stores or by mail could be a disaster in the making. DHEA should be classified as an investigational drug and used only in clinical research until we figure out what it does and its side effects," says Peter Hornsby, PhD, associate professor of cell biology at Baylor College of Medicine. His team has just identified the body's DHEA-making cells.

Why such strong statements from researchers who think DHEA may someday have a medical use? To date, there's no solid proof that DHEA supplements have any real benefit for humans. There's also no proof that they are completely benign. "Unfortunately, we don't see the problems associated with hormone use until years later," says Peter Casson, MD, assistant professor of obstetrics and gynecology at Baylor College of Medicine. He cited as an example the higher of breast cancer in women who took diethylstilbestrol (DES) to prevent a miscarriage, which was discovered only after years of use.

What Is DHEA?

Dehydroepiandrosterone, or DHEA, is a steroid hormone, a chemical cousin of testosterone and estrogen. It is made from cholesterol by the adrenal glands, which sit atop each kidney. For the first few years of life, the adrenals make very little DHEA. Around age six or seven, they begin churning it out. Production peaks in the mid-20s, when DHEA is the most abundant hormone in circulation. From one's early '30s on, there's a steady decline in DHEA production, so the average 75-year-old has only 20% of the DHEA in circulation that he or she had 50 years earlier. At all ages, men tend to have higher DHEA levels than women.

By definition, hormones are chemical messengers made in a gland or tissue that start, stop, or otherwise orchestrate activity in some other issue. That makes DHEA a hormone in name only, since no one knows exactly what it does in the body. For years it was thought to be a kind of chemical trash left over from making other hormones. Today, "we still haven't been able to identify any mechanism of action," says Dr. Casson.

In fact, about the only thing that researchers can agree on is that DHEA is easily converted into other hormones, especially estrogen and testosterone.

The Food and Drug Administration isn't sure what to do with DHEA supplements. Ten years ago the agency told companies to stop selling DHEA, which was marketed at the time for weight loss, and classified it as an unapproved new drug, obtainable only by prescription. Then in 1994, DHEA was reclassified as a dietary supplement, allowing sales over the counter.

The Evidence

Much of DHEA's reputation as a wonder hormone comes from experiments in which mice or rats were fed daily doses. Such studies have shown that DHEA can prevent or delay the onset of cancer, "hardening" of the arteries, lethal viral infections, lowered immunity, obesity, and diabetes. But what works in rodents doesn't necessarily work in humans. That may be especially true in this case, because rats and mice produce only about 1/10,000 the DHEA we do.

An early human study that pointed to possible benefits for DHEA came from Dr. Barrett-Connor's group. They measured DHEA levels in blood samples taken from almost 2,000 men and women between 1972 and 1974 and looked at how many died from heart disease. In 1986, they reported that men with high DHEA levels were far less likely to have died of heart disease, while women with high DHEA levels were at greater risk. A more detailed analysis published late last year, however, showed that men with above-average DHEA levels back in the early 1970s were only 15% less likely to have died of heart disease, while there was no association between DHEA levels and heart disease in women.

The longest and perhaps most carefully conducted work in humans comes from Dr. Yen and his associates. In their latest study, published last year in a special issue of the Annals of the New York Academy of Sciences devoted to DHEA and aging, eight men and eight women aged 50 to 65 took either 100 milligrams of DHEA or an identical placebo pill each night for three months. For three months after that, they took the opposite pill.

Within two weeks of starting DHEA, circulating levels of the hormone were a bit higher than normally found in young adults. Lean body mass increased slightly in both sexes, as did muscle strength, which also improved with the placebo. Fat body mass decreased in men but increased a bit in women. There was also a rise in some chemical markers that suggested improvement in immune function, though the number of colds and other illnesses was not measured.

An earlier study from Dr. Yen's group showed that three months of daily 50-milligram doses of DHEA significantly improved the sense of "well-being," it did not improve sex drive, as advertisements for DHEA often claim..

Another study in which volunteers took DHEA suggests that this hormone may help treat the autoimmune disease lupus. Trials looking at DHEA's ability to boost the immune system and maintain mental function in older adults are in progress.

Experiments on a few dozen people over six months hardly constitute proof that a treatment works. "What we really need at this point are some long-term clinical trials to identify clear benefits and risks," says Dr. Nestler.

One reason why such trials are crucial is that DHEA has side effects, some of which may be irreversible. Since DHEA is converted into testosterone, some women who take it grow body or facial hair and, if they are under age 50 or so, can stop menstruating. DHEA has also been shown to decrease levels of HDL ("good") cholesterol in women, and could increase the risk of heart disease, the leading killer of older women. "We have no idea what DHEA might do to the risk of breast cancer," says Dr. Nestler.

In men, the increased levels of testosterone seen with daily DHEA pills could stimulate the growth of a tiny prostate tumor that would otherwise have remained dormant. Excess testosterone could also cause the prostate to enlarge, making urination difficult.

The Bottom Line

Much of the popular and scientific interest in DHEA stems from our culture's emphasis on youth. If levels of this hormone decline with age, the thinking goes, we could avoid the health problems that accompany aging -- or even extend our lifespan -- by keeping DHEA levels high. Many people are already taking DHEA just in case this turns out to be true. That wouldn't be a problem if this substance were as safe as vitamin C. But as a potent steroid hormone, DHEA has the potential for far-reaching side effects throughout the body. . . .

With DHEA and aging, there are no proven benefits and some potentially serious risks. Yet people are flocking to use this virtually unregulated substance, which troubles HealthNews associate editor Arthur Feinberg, MD.

"The potential for irreversible side effects is real," he says. "So given that there's no convincing evidence for any benefit of DHEA, I feel strongly that people should not take it."

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This article was reproduced with permission from the November 19, 1996, issue of HealthNews, a newsletter from the publishers of The New England Journal of Medicine.

Warning

Over the past two years, I have come across many cases of heart-rhythym disturbances associated with high-dose use of DHEA and pregnenolone. I reported one such case in a man taking 50 mg per day in the October 1998 issue of the Annals of Internal Medicine (volume 129, page 588). Other side effects include acne, unwanted hair growth, scalp hair loss, menstrual irregularities, irritability, and aggression. In my opinion, DHEA, androstenedione, or pregnenolone should not be sold over the counter in doses greater than 5 mg.

-- Ray Sahelian, M.D.
October 1998

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