BACKGROUND: Multiple reproductive factors are associated with stroke. Little is known about the cumulative effects of reproductive factors during a reproductive life course on stroke and its subtypes, especially among female Chinese. OBJECTIVE: To assess the associations of lifetime cumulative estrogen exposure due to reproductive factors with stroke and its etiological subtypes among postmenopausal Chinese . METHODS: From the China Kadoorie Biobank (CKB) study, postmenopausal females without prior stroke at baseline (2004-2008) were selected. Lifetime cumulative estrogen exposure due to reproductive factors was assessed using three composite indicators: reproductive lifespan (RLS), endogenous estrogen exposure (EEE), and total estrogen exposure (TEE). Stroke and its subtypes, ischemic stroke (IS), intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), were identified via linkage to a disease registry system and health insurance data during follow-up (2004-2015). Multivariable-adjusted Cox proportional hazards regression models were applied to estimate the adjusted hazard ratio (aHR) and 95% confidence intervals (CI) for the risk of stroke by quartiles of RLS, EEE, and TEE respectively. RESULTS: A total of 122,939 postmenopausal participants aged 40 to 79 years without prior stroke at baseline were included. During a median follow-up period of 8.9 years, 15,139 new-onset stroke cases were identified, including 12,853 IS, 2,580 ICH, and 269 SAH cases. Compared with the lowest quartile (Q1) of RLS, the highest quartile (Q4) had a lower risk of total stroke (aHR: 0.95, 95% CI: 0.92-0.98), IS (aHR: 0.95, 95% CI: 0.92-0.98), and ICH (aHR: 0.87, 95% CI: 0.81-0.94). Both EEE and TEE displayed a graded association with the subsequent descending risk of total stroke (aHR for Q4 vs Q1: EEE: 0.85, 95% CI: 0.82-0.89; TEE: 0.87, 95% CI: 0.84-0.90), IS (aHR for Q4 vs Q1: EEE: 0.86, 95% CI: 0.83-0.90; TEE: 0.86, 95% CI: 0.83-0.89), and ICH (EEE: 0.73, 95% CI: 0.65-0.81; TEE: 0.83,95% CI: 0.76-0.91), with a P-trend<0.001 for all of these associations. CONCLUSIONS: Patients' cumulative estrogen exposure due to reproductive factors could potentially be a valuable indicator for risk stratification of stroke events following menopause.
estrogen exposure, postmenopause, reproductive factors, reproductive lifespan, stroke