DHEA For Lupus
DHEA For Lupus
Lead author: Kay Shaver, Pharm.D., Assistant Editor
Background
SLE is a chronic, autoimmune disease that affects various parts of the body, particularly the skin, joints, blood, and kidneys. The immune system is overactive and produces antibodies that react with the body's own tissues. This leads to the formation of immune complexes which build up in tissues and cause inflammation, pain, and tissue injury.1,2 Lupus can occur at any age and in either sex, although it is 10 to 15 times more common in women than in men. It is estimated that 0.5 to 1.5 million Americans have been diagnosed with lupus.1,3The Rationale For DHEA
DHEA is a hormone produced primarily by the adrenal glands.4 Most DHEA is converted to the sulfate ester (DHEA-S) in the adrenal glands and liver.5,6 Target organs convert DHEA-S back to DHEA where it is metabolized to androstenedione, the major precursor to androgens and estrogens.5-7 It is thought the primary role of DHEA is as a precursor to sex steroids.5,7 DHEA itself is thought to have mild androgenic activity, but this is hard to distinguish from the effects of its androgenic metabolites.5 Patients with SLE often have low levels of DHEA.4,7 In addition, administration of corticosteroids to treat the disease also decreases DHEA production.5 It is suggested that a high-estrogen, low-androgen state contributes to SLE, and that increasing the level of androgens would help patients with this disease.5 In high estrogen states, DHEA is thought to be primarily metabolized to androgens. It is also thought that DHEA has immunomodulatory effects and helps correct defective interleukin-2 production in T-lymphocytes in patients with SLE.5,7 Now, for the first time in decades, a new drug for the treatment of systemic lupus erythematosus (SLE) is on the verge of being approved. Following Phase III clinical trials, Genelabs Technologies filed a New Drug Application (NDA) for Aslera (prasterone) this past September. Prasterone is the pharmaceutical generic name for dehydroepiandrosterone (DHEA). The company is seeking an indication for Aslera to treat lupus in women with mild-to-moderate disease. The FDA has given Aslera a fast track designation. The FDA designates drugs as fast tract when they treat serious or life-threatening diseases that have no currently available adequate therapy.4,8Clinical Studies
Several small studies have been done on DHEA in patients with lupus. One double-blind, randomized trial included patients with severe and active SLE. Patients were given either 200 mg/day DHEA or placebo along with their regular therapy of steroids and/or immunosuppressants. After six months, patients taking DHEA had greater improvement in disease activity than patients taking placebo. Patients taking DHEA also maintained a stable spinal bone mineral density while this value decreased in patients taking placebo.9 Another double-blind, randomized trial included patients with mild to moderate SLE. Patients received 200 mg/day DHEA or placebo for three months. Patients taking DHEA had reductions in disease activity, flares, and prednisone doses compared to patients taking placebo.10 Similar results were also been seen in an open trial lasting 12 months. These patients also had mild to moderate SLE and were treated with 50 to 200 mg/day of DHEA.11 Larger, Phase III trials conducted on prasterone reinforce the above results. In one double-blind study, patients with mild to moderate SLE received 200 mg/day prasterone or placebo for 12 months. Overall, more patients responded to prasterone than placebo. This was especially true for patients with active disease, where 66% responded to treatment with prasterone, while 49% responded to placebo.12 In another large, double-blind study lasting one year, patients received prasterone 200 mg/day or placebo. In this study, patients taking prasterone experienced greater improvement in symptoms and fewer flares than patients taking placebo. This was still true in patients also receiving prednisone or immunosuppressants.13 This study, as well as another smaller study, also showed that prasterone can help patients on steroids maintain or improve bone mineral density.13,14The sparing effect on bone mineral density suggests a protective action of DHEA. Studies have shown improvements in both bone density and markers for bone resorption with the use of DHEA. The mechanism of this effect is thought to be stimulation of bone formation due to the androgenic properties of DHEA.9 However, the reduction in the dose of corticosteroids, or a combination of both mechanisms, may also be responsible for the bone-sparing effects of DHEA.
Commentary
Traditional treatments for SLE include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antimalarials (chloroquine or hydroxychloroquine), and immunomodulating drugs (azathioprine and cyclophosphamide). Effective treatment can minimize symptoms, reduce inflammation, and maintain normal bodily functions.15 But many patients still do not get relief.
With positive clinical trial results, patients may wonder if it's okay to take over-the-counter DHEA supplements. As with all dietary supplements, there are concerns about the purity and reliability of the content of DHEA supplements. There are also concerns about the appropriateness of patients with a serious chronic disease, such as lupus, self-treating with DHEA.5,16 There are reliable companies out there producing quality products, and the use of DHEA supplements might be worth a try. If patients use supplements, be sure they talk with their provider, in order to coordinate the therapy and get appropriate monitoring.
Some pharmacists are compounding DHEA capsules. One recipe for 100 capsules calls for 10 grams of DHEA combined with 9 grams of lactose. The #3 size capsules can be used. This gives 190 mg of the DHEA/lactose powder (100 mg DHEA and 90 mg of lactose) in each capsule. For patients that are lactose intolerant, starch can be used instead of lactose. Good sources for compounding chemicals and supplies are Spectrum Pharmacy Products at 1-800-791-3210 ext. 247, and Pharmasource at 1-800-222-2313. For more information on training in compounding, contact Professional Compounding Centers of America, Inc. (PCCA) at 1-800-331-2498, or Compounding Shops International at 1-303-858-8772.
DHEA has been used safely in studies for up to 12 months. There is some concern that long-term use, or use of DHEA in amounts that cause higher than normal physiological levels, might increase the risk of prostate cancer, breast cancer, or other hormone-sensitive cancers. In some cases, 50-100 mg daily can produce slightly higher than normal physiological DHEA levels. This could also have adverse effects during pregnancy or breast feeding.7 Major adverse effects seen more often than placebo in clinical trials include acne (33%) and hirsutism (facial hair growth) (16%).12 DHEA can also cause hair loss, voice deepening, insulin resistance, abdominal pain, hepatic dysfunction, hypertension, and minor menstrual changes.5,7 DHEA has been shown to decrease triglycerides, but it also decreases the beneficial high-density cholesterol.5,12DHEA-S, the active component of DHEA, has been shown to inhibit the cytochrome P450 3A metabolism of triazolam (Halcion), increasing blood levels of this drug. Because of the potential for DHEA to inhibit cytochrome P450 3A enzymes, DHEA could cause an increase in blood levels of other drugs. Drugs that can be affected include alprazolam (Xanax), amitriptyline (Elavil), amiodarone (Cordarone), buspirone (Buspar), cerivastatin (Baycol), citalopram (Celexa), felodipine (Plendil), fexofenadine (Allegra), itraconazole (Sporanox), ketoconazole (Nizoral), lansoprazole (Prevacid), losartan (Cozaar), lovastatin (Mevacor), ondansetron (Zofran), prednisone (Deltasone, Orasone), sertraline (Zoloft), sibutramine (Meridia), sildenafil (Viagra), simvastatin (Zocor), verapamil (Calan, Covera-HS, Isoptin), and others.7 The clinical significance of these interactions is not known.
Conclusion
The use of DHEA may provide SLE patients with several benefits. DHEA has the potential to provide relief from symptoms, a decreased need for systemic corticosteroids, a decrease in the frequency of disease flares, and possibly even a sparing effect on the bone.
References
December, 2000