The role of exogenous estrogen in the initiation and maintenance of human SLE remains very controversial. Although cohort studies suggest an increase in the incidence of SLE with both oral contraceptives and hormone replacement therapy, recent retrospective studies suggest that the risk of flare is not increased with hormone replacement therapy. However, exogenous estrogen does increase hypercoagulability, an issue in SLE patients with antiphospholipid antibodies. The prospective SELENA study will ultimately address whether exogenous estrogen increases severe flares in SLE.