It's been more than 20 years since there's been a new drug to treat lupus. Now patients and doctors alike are cautiously optimistic that a steroid hormone, DHEA, may have a role in treating mild-to-moderate lupus, a disease in which an over-active immune system mistakenly attacks healthy cells and tissue.

DHEA (which is short for the tongue-twister dehydroepiandrosterone) is no stranger to the spotlight or the marketplace. A nutritional product that's widely available, DHEA has been promoted as a miracle drug that can supposedly stop the ravages of aging, prevent cancer and heart disease, improve dispositions, increase energy, melt fat, refresh memory and jump-start a lagging sex drive. While DHEA is modestly effective in some of these areas, the jury is still out on most of these extravagant claims.

But there is some evidence that DHEA may ease certain lupus symptoms and reduce the need for other medication among patients who have lupus that affects only their skin and joints.

Both lupus researchers and doctors are quick to caution, however, that despite this good news no one should rush to self-medicate with off-the-shelf DHEA supplements. "Unsupervised use of a steroid hormone is dangerous," says Robert Lahita, MD, PhD, a lupus expert and chief of rheumatology at St. Luke's Roosevelt Hospital in New York. "This is a drug that can have far-reaching effects."

Where DHEA Comes From

DHEA naturally occurs in all mammals; it's a mild androgen (or male hormone) produced by the adrenal glands, and used by the body to make other powerful hormones including the sex hormones testosterone and estrogen.

DHEA supplements are made from extracts taken from the barbasco root, or wild Mexican yam. The plant extracts have to be chemically altered before they can be converted to DHEA in the body: The "natural," or unprocessed, plant extracts in some supplements can't be used by the human body.

DHEA has been available over the counter for some 50 years, but not without controversy. In the 1980s, the FDA declared DHEA a drug and banned sales. (Drugs can only be sold after passing FDA review for safety and efficacy.) But it returned to store shelves after a 1994 change in the law allowed it to be sold as a nutritional supplement. Some other countries - such as Canada and the United Kingdom - have banned over-the-counter DHEA sales or taken it off the market altogether.

Hormone On Trial

Researchers have been investigating DHEA's effect on lupus since the 1980s. Studies in humans, so far, have focused on women, who make up 90 percent of those with lupus. The first human study was published by Stanford University researchers in 1994. In 1998, a multi-center trial was completed. That second trial was sponsored by Genelabs Technology Inc., of Redwood City, Calif., a pharmaceutical company that has been developing and testing a synthesized DHEA product called GL701.

The Genelabs study, conducted on 191 women with lupus at 27 medical centers, showed that women who were taking 200 milligram doses of DHEA could reduce their daily dosage of prednisone and still have equivalent relief of pain, inflammation and fatigue. The women also reported that they felt better.

Another Genelabs-sponsored one-year, multi-center trial of 370 women with lupus is nearing completion; it's looking at whether GL701 also improves or stabilizes disease activity, such as rashes and frequency of flares. The trial ends in March, and some researchers are optimistic that a prescription DHEA lupus drug may be approved for use in mild-to-moderate cases within two to three years. The GL701 form of DHEA is not available outside the study.

Researchers aren't sure of the mechanism by which DHEA affects lupus. But they do have clues. They know that DHEA levels are low in women with lupus, and that DHEA increases testosterone and estrogen levels, along with other hormones.

They also know that estrogens increase immune function while androgens suppress it, and that the estrogen-testosterone balance is off in women with lupus. And in both test tube and animal studies, they've seen that DHEA reduced the production of some cytokines, the molecular messengers that prompt release of inflammatory substances that can cause lupus symptoms.

Some Serious Questions

While researchers saw no significant side effects during the first major study, they emphasize that the full range of risks and benefits from DHEA isn't yet known. It's only now being tested on men, and research has raised some questions about the potential long-range effects, particularly its effect on some cancers.

Because DHEA has been shown to increase estrogen and testosterone levels, there's concern it could contribute to existing hormonally influenced cancers, such as breast, ovarian and uterine cancers in women and prostate cancer in men.

One doctor reported that a man's prostate cancer worsened after he took DHEA for fatigue symptoms. In the first multi-center study, researchers found some post-menopausal women on DHEA had estrogen levels equal to those on hormone replacement. That's troubling - taking estrogen without also taking progesterone is a known risk factor for endometrial (uterine) cancer, says Michelle Petri, MD, director of The Lupus Center at Johns Hopkins University School of Medicine and a principal investigator in the study.

DHEA also lowered the production of HDLs (the "good" cholesterol) in some women, which could raise total cholesterol levels, inviting associated problems such as heart attacks and strokes. In a different study, women taking very high doses of DHEA developed insulin resistance, which could mean problems for those with diabetes.

What Doctors Say

A few doctors prescribe prescription-grade DHEA to treat lupus patients who have difficulty tolerating standard drugs, carefully monitoring them for side effects.

Dr. Petri, however, suggests patients and doctors wait until more is known. "I can understand why patients want it now," she says, "but there is an ongoing study. We'd like to wait for those results, so patients can know the benefits and the risks."

Dr. Petri is particularly concerned about people self-treating. "DHEA is a drug," she says, "and no one should be taking a drug over-the-counter that requires physician monitoring. If something is strong enough to work, it's strong enough to harm."

Those who self-treat end up using DHEA that is sold over-the-counter as a "dietary supplement." These products are possibly ineffective - and potentially unsafe.

A Genelabs-sponsored study by SRI International, a research lab in Menlo Park, Calif., showed there's no way to ensure consistency in quality or dosage. The researchers there examined 16 randomly-chosen DHEA products: One provided no DHEA at all, two claimed 25 mg per dose yet actually had only .5 mg, and one contained doses half again as strong as the label claimed.

Also, nutritional supplements may contain harmful additives, or fillers such as alfalfa, which can stimulate the immune system and worsen lupus, according to lupus expert Daniel J. Wallace, MD, clinical professor of medicine at Cedars-Sinai Medical Center at the UCLA School of Medicine and one of the study's investigators.

Expert Advice

Experts advise a hands-off policy when it comes to over-the-counter DHEA. Still, they realize, some people will decide to try it despite the risks. If you are considering trying it, they advise the following:

• Tell your doctor. Ask if she's willing to find a reliable source of prescription-grade DHEA for you. If she can not - or will not - ask her to at least monitor your condition through frequent checkups.
• Stay on your physician-prescribed treatment plan, including taking prescribed medications.
• Monitor your cholesterol levels and blood pressure regularly, particularly if you already have or know that you may be predisposed to coronary artery disease.
• Be aware DHEA may cause greasy skin, acne, excessive sweating, plus facial hair and other masculinizing traits in women.
• Plan regular gynecological exams or prostate cancer tests. DHEA may increase the risks of hormonally influenced cancers.
• Don't take DHEA if you are pregnant or nursing without consulting your doctor.
• Be aware that there may be increased risks to taking DHEA if you have a type of cancer that may be hormonally influenced, or a family history or other risk factors for such cancer; if you are already taking hormone replacement therapy; or if you have diabetes.