Dehydroepiandrosterone (DHEA)

Daniel J. Wallace, M.D. Clinical Professor of Medicine, UCLA School of Medicine

Clinical Chief of Rheumatology at Cedars-Sinai Medical Center, UCLA School of Medicine.

The first new drug for mild to moderate lupus to be developed in some time is on the fast track. Dehydroepiandrosterone (DHEA) is an old drug with potentially important antilupus properties. A natural body substance made by the adrenal gland, DHEA has been available for more than 50 years and is not regulated by the Food and Drug Administration. DHEA is a hormone with male-like properties. Investigators have been interested in male hormones (androgens) because in animal studies they tend to decrease the immune response while female hormones (such as estrogen) tend to amplify it.

DHEA has additional effects that may have widespread implications. In animal models and human studies it has demonstrated potential to decrease obesity, reduce lipid levels, slow or halt osteoporosis, improve cognitive functioning, and increase levels of an important cytokine known as interleukin-2. Levels of DHEA decrease with age, and lupus patients at any age have less DHEA than one might expect.

Optimum doses of DHEA have not been determined. Amounts of the hormone available to compounding pharmacists and health or natural pharmacies were highly variable and used different delivery systems and preservatives. Several years ago, researchers at Stanford University, in cooperation with a biotechnology company known as Genelabs in Redwood City, California, successfully synthesized DHEA and studied the effects of this purified hormone on mice with lupuslike disease and subsequently humans.

Genelabs has applied for FDA approval for its synthetic hormone and has initiated well-controlled human trials. Several hundred lupus patients have been given the drug, and preliminary evidence suggests that it has anti-inflammatory effects in mild and moderate lupus and can steroid-sparing as well as being well tolerated with antimalarials. The major side effects encountered thus far include acne and facial hair growth. Some patients have reported headaches, irritability and fluid retention. The drug appears to be well tolerated and is currently being studied in a multicenter, double-blind study that our center has participated in. The therapeutic dose appears to be in the 50 mg to 200 mg range.

Even though it is premature to make any conclusive statements about DHEA, this hormone is a promising therapy that may be useful for lupus patients with non-organ threatening disease who do not have a complete response to nonsteroidal anti-inflammatory drugs, antimalarials or low dose steroids. I believe that it will be commercially available in a reliable form in 2-3 years.

From Lupus Letter Volume 1, No.1