Estrogen, progesterone, and testosterone: can they be used to treat autoimmune diseases?

Background: Sex hormones have marked immunomodulatory properties and may play important roles in the etiology of various autoimmune diseases.

Objective: To review the immunomodulatory effects of sex hormones, their roles in the etiology of autoimmune diseases, and their potential therapeutic applications.

Discussion: Progesterone and androgens suppress the immune system, prolactin stimulates it, and estrogens can do either. Rheumatoid arthritis tends to improve during pregnancy, during estrogen replacement therapy, and during treatment with estrogen-containing oral contraceptives. Systemic lupus erythematosus is aggravated by pregnancy and probably by estrogens. Therapy of rheumatoid arthritis with estrogens has not been promising, but testosterone replacement in men has shown modest benefits. In lupus, 19-nortestosterone has had little or no benefit, but danazol has been helpful in some patients, and encouraging preliminary results were obtained with dehydroepiandrosterone.

Conclusions: We strongly recommend estrogen replacement therapy to prevent postmenopausal osteoporosis in women with rheumatoid arthritis. Younger women with rheumatoid arthritis can undergo pregnancy or use estrogen-containing contraceptives. Estrogens can be used in lupus only with great caution. Recommendations regarding other hormones and other diseases are less firm, but research is continuing in this area.