Numerous epidemiological studies have found a strong relationship between estrogen and the development of SLE, and increased exogenous estrogen can lead to the development and exacerbation of SLE. For example, the incidence of SLE is significantly higher in all female populations on estrogenic contraceptives or replacement therapy. Likewise, SLE patients with postpartum menstruation have a significantly higher chance of relapse after the return of menstruation. Thus, there are significantly more female SLE patients than male patients, and first episodes of SLE are rare in prepubertal and postmenopausal women.