Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease of unknown cause. Risk factors proposed as important in the pathogenesis of SLE include genetic, environmental, and hormonal factors (1). Strong evidence implicates sex steroid hormones in the pathogenesis of SLE and other autoimmune diseases in human beings. Female gender is considered the strongest risk factor for the development of SLE (2), which incidence is 8 times higher in females than in males during the reproductive years. This difference in the susceptibility for developing SLE strongly suggests the influence of sex hormones. We have shown a significantly increased risk to develop SLE among postmenopausal women under estrogen replacement therapy compared with postmenopausal women who did not take such hormones; this increased risk was directly related with the length of use of such therapy (3). Lupus flares have been reported during periods of major sex hormone changes such as puberty, menses, pregnancy and postpartum (4-7). Abnormal metabolism of estrogens yields an excess production of 16-alpha-hydroxyestrone in patients with SLE of both sexes (8), and low plasma androgens levels have been reported in women with active and quiescent disease (9,10). An association between SLE and Klinefelter's syndrome has been proposed (11). Estrogen receptors have been found on OKT8-positive lymphocytes (12).