The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males, and numerous investigations of this gender bias have been performed from several perspectives. Sex hormones, particularly estrogens, may be significant in causing the gender discrepancy. This article discusses the possible importance of estrogens in regulating the expression of and responsivity to autoantigens in SLE and in atopic disorders, which are associated with hyperreactivity to exogenous antigens. Estrogens seem to play an important role in the overexpression of endogenous autoantigens, such as human endogenous retroviruses (HERV), and this may be related to the existence of a gender bias in the incidence of SLE but not atopy.