Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases.

It is now documented that androgens and estrogens modulate susceptibility and progression to autoimmune rheumatic diseases. At any concentration, androgens seem to be primarily suppressive on cellular and humoral immunity, whereas at physiologic concentrations, estrogens seem to enhance humoral immunity. Further research should focus on the different and frequently opposite effects exerted by physiologic and pharmacologic doses of estrogens (dose-related effects). In addition to the influence of endogenous estrogen fluctuations (i.e., during pregnancy, postpartum, menstrual periods, menopause), estrogen replacement therapy, and the use of oral contraceptives, the susceptibility to autoimmunity might be increased by the environmental estrogens (xenobiotics). Further studies must be directed to the inflammatory mediators (i.e., cytokines) that seem to alter the peripheral metabolism of sex hormones and complicate the effects of sex hormones on susceptibility to autoimmunity. Finally, genetic factors might further interfere with the roles of androgens and estrogens in selected individuals.