One hundred-twenty women with active systemic lupus erythematosus (SLE) were randomly assigned to receive, in double-blind fashion, 200 mg/day of DHEA or placebo for 24 weeks. During the study, 18.3% of the patients in the DHEA group experienced a flare-up of their disease, compared with 33.9% of those in the placebo group. The incidence of disease flare-ups was 46% lower in the DHEA group than in the placebo group (p < 0.05). The mean change in the patients’ global assessment was significantly better in the DHEA group than in the placebo group (14.9% improvement vs. 16.1% worsening; p = 0.005). The mean improvement in the Systemic Lupus Activity Measure score was 25.3% in the DHEA group and 19.3% in the placebo group (difference not significant). No serious side effects were seen, but DHEA treatment increased testosterone levels and increased the incidence of acne.

Comment: These results confirm those of earlier studies indicating that high-dose DHEA is beneficial in the treatment of women with SLE. Although DHEA caused acne in this study, it was otherwise well tolerated, and should be considered as part of the overall treatment of this potentially serious disease.

The markedly higher prevalence of SLE among women, as compared with men, suggests that high concentrations of androgens may somehow protect against the development of this disease. DHEA is a weak androgen that has been shown to reduce disease severity in animal models of lupus. Plasma levels of DHEA-sulfate have been found to be lower in patients with untreated SLE than in healthy controls. Furthermore, treatment with glucocorticoids such as prednisone will further deplete DHEA by shutting down its main source of production, the adrenal glands. Whether physiological doses of DHEA (such as 5-15 mg/day for women or 10-30 mg/day for men), as part of a comprehensive program of dietary modification and nutritional supplementation, would be beneficial has not been investigated, although some clinicians have the impression that it is helpful in some cases.

Chang DM, et al. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus. A multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002;46:2924-2927.