Women are more frequently affected by autoimmune diseases (I), including both rheumatologic and nonrheumatologic disorders, than are men. Female: male ratios of> 5: 1 have been reported, for example, for scleroderma, systemic lupus erythematosus (SLE), Sjogren’s syndrome, Hashimoto’s thyroiditis, and primary biliary cirrhosis (2-6). Numerous studies have investigated sex hormones and autoimmunity, and effects of sex steroids on immune function have been demonstrated (7). Immunomodulatory effects of sex steroids have been particularly apparent in some animal models of autoimmune diseases (8). Perhaps as a result of these studies, the female predilection for autoimmune disease has sometimes been attributed to female/male differences in sex hormones. However, correlations between studies using animal models and human autoimmune diseases have frequently been lacking, and at least 3 additional observations argue against this assumption. These include the age-specific incidence patterns of different autoimmune diseases in women, contrasting effects of exogenous sex steroid administration, and contrasting effects of pregnancy.

If sex hormone levels explained the female predominance of autoimmunity, peak age-specific incidence would be expected to occur when sex hormone levels are highest. The peak incidence of SLE at 25-34 years in black females (3) is consistent with this expectation. However, this age-specific incidence pattern is not the rule. In women with rheumatoid arthritis (RA), the incidence of disease continues to rise with