DHEA

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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:

" The one thing you should tell your readers is that we know very

little about DHEA. The hype is out of control, and I can't stress

enough that it should be used with caution, if at all, until we know

more, " says Yen, MD, professor of reproductive medicine at the

University of California, San Diego. News reports and advertisements

widely cite his studies of people who took DHEA supplements for three

months as proof that the hormone " works. "

" 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 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 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 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

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 ls 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. "

_____________________

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 ls 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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This page was revised on January 27, 2004.