Clinical impact of hormone replacement therapy on lone atrial fibrillation in postmenopausal women: a nationwide cohort study

Context: Individuals with atrial fibrillation (AF), especially women, have an increased risk of stroke and death. Although hormone replacement therapy (HRT) is widely used in postmenopausal women, the association between HRT use and AF risk has been scarcely explored. Objective: To investigate the association between various types of HRT and lone AF. Design: Population-based retrospective cohort study. Setting: The Korean National Health Insurance Service-National Sample Cohort (2004-2015). Patients: Participants were aged 45–60 years and were free from cardiovascular disease and AF at baseline. Main Outcomes: Incident AF. Results: In the overall population, 13,452 (64.03%) women never received HRT, 5,671 (26.99%) had received HRT previously, and 1,885 (8.98%) were currently receiving HRT. In multivariable analysis, the relative hazards for AF were significantly higher among HRT current users (HR:2.24; 95% CI:1.55-3.23; p<0.001) and lower among HRT past users (HR: 0.78; 95% CI: 0.60-1.02; p=0.069). For current users, significantly increased AF risk was observed for all HRT users except for estradiol-only HRT users. For past users, reduced AF risk was observed in estradiol plus progestin HRT after adjusting for covariates (HR: 0.57; 95% CI: 0.35-0.94; p=0.027), whereas it was not for other types of HRT. Conclusions: We observed that ongoing HRT posed an increased risk of AF. The degree of AF risk varied based on the specific type of estrogen and whether progestins were co-administered. These data support the assertion that HRT containing oral estradiol is more beneficial than HRT containing oral conjugated equine estrogen or tibolone, in terms of AF risk.