OBJECTIVE: Estrogen and prolactin may accelerate the progression of murine systemic lupus erythematosus (SLE). In humans, 85% of lupus patients are women, which also suggests the importance of hormonal factors in disease pathogenesis. The purpose of this study was to examine hormonal and reproductive risk factors for lupus among women. METHODS: This population-based, case-control study included 240 female SLE patients diagnosed between January 1, 1995 and July 31, 1999 who fulfilled the American College of Rheumatology classification criteria. Female controls (n = 321) were identified through driver's license records. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) as measures of association, adjusting for age, state, race, and education. Analyses were limited to exposures before diagnosis. RESULTS: Breast-feeding was associated with a decreased risk of developing SLE (OR 0.6, 95% CI 0.4-0.9), with a statistically significant trend for number of babies breast-fed and total weeks of breast-feeding. There were no associations with number of pregnancies or live births. Natural menopause occurred earlier in women with subsequent development of SLE compared with controls (P