Reproductive history, hormonal exposure, and risk of heart failure in postmenopausal women: a Korean nationwide study

BACKGROUND AND AIMS: Evidence on the association between female-specific factors and heart failure (HF) remains limited. This study examined their associations with HF and subsequent mortality. METHODS: Using the Korean National Health Insurance Service database, 3 692 157 postmenopausal women without prior HF or structural heart disease and with intact ovaries and uterus were identified. Associations between reproductive factors, including parity, breastfeeding duration, oral contraceptive (OC) and menopausal hormone therapy (MHT) use, age at menarche, age at menopause, and total reproductive period, and HF risk were assessed using Fine-Gray competing risk models, with death treated as a competing event. Among women with HF hospitalization, associations between reproductive factors and mortality were evaluated using multivariable Cox regression. RESULTS: During a median follow-up of 120 months, 48 640 women were hospitalized for HF. OC (sub-distribution hazard ratios SHRs≥1y vs non-user: 0.942, 99.3% confidence interval CI 0.896-0.990) or MHT (SHR≥5y vs non-user: 0.782 99.3% CI 0.708-0.863) use was associated with a lower HF risk. Later menarche (SHRage≥17 vs 13-16y: 1.099 99.3% CI 1.071-1.128), earlier menopause (SHRage 40-44y vs 50-54y: 1.229 99.3% CI 1.173-1.288), and shorter reproductive period (SHRage <30y vs ≥40y: 1.284 99.3% CI 1.213-1.361) were linked to higher HF risk (all P for trend <.001). Among women with HF, OC, and MHT use were associated with lower mortality, while earlier menarche, earlier menopause, and shorter reproductive period were linked to increased mortality. CONCLUSIONS: Prolonged lifetime exposure to both endogenous and exogenous female sex hormones is associated with lower HF incidence and subsequent mortality.