Association between duration of endogenous estrogen exposure and cardiovascular outcomes: A population – based cohort study

Aims: Duration of endogenous estrogen exposure is apparently associated with risk of cardiovascular disease, the longer durations being more cardiovascular disease protective in women. We aimed to investigate the association of cumulative duration of endogenous estrogen exposure over women's reproductive lifespans with cardiovascular disease outcomes. Main methods: For the purpose of the present study, of 10,192 female participants, after excluding those using HRT (n = 84), 3656 women, aged ≥30 years, who met eligibility criteria were selected and divided into three groups based on tertiles (T1, T2, T3) of exposure durations to endogenous estrogen. Cox proportional hazards regression model was used to estimate associations between exposure durations and cardiovascular disease outcomes. Key findings: Cardiovascular events occurred in 352 participants over a median follow-up of 14.2 (13.5, 14.6) years (7.7 per 1000 person years; 95% CI: 6.9–8.5). Incidence of outcome was 10.9 per 1000 person years (CI, 9.4–12.8) in T ₁ , 7.2 per 1000 person years (CI, 6.0–8.7) in T ₂ , and 5.1 per 1000 person years (CI, 4.1–6.4) in T ₃ . The hazard ratio of cardiovascular events in T ₁ was significantly higher than that inT ₃ , before and after adjustment for confounding variables. Before adjustment, women in T ₂ had a 40% higher risk of CVD, compared to T ₃ ; after adjustment however the risk was similar to that of women in T ₃ . Significance: Shorter durations of exposure to endogenous estrogen may increase the risk of cardiovascular diseases among these women later in life. Future studies should target women with short duration of exposure for timely screening and implementation of preventative interventions.