Hormone replacement therapy and the risk of achalasia in postmenopausal women: A nationwide cohort study.

Achalasia is an esophageal motility disorder characterized by progressive dysphagia, leading to a significant decline in the quality of life of affected individuals. This study aimed to investigate hormone replacement therapy (HRT) as a risk factor for achalasia in postmenopausal women. Postmenopausal women who underwent healthcare screening in 2009 through the Korean National Health Insurance Service were enrolled and followed up till December 31, 2022. The risk of achalasia in relation to history and duration of HRT (none, <2 years, 2-5 years, and over 5 years) was calculated using adjusted hazard ratios with 95% confidence intervals. Subgroup analyses were conducted based on age, income, history of autoimmune diseases, and female reproductive factors. The overall cumulative incidence of achalasia in the study cohort was 731 of 1,101,080 subjects. Across all adjusted models, the risk of developing achalasia was significantly higher in participants who received HRT than in those with no history of HRT. The risk increased in a dose-dependent manner with the HRT duration, reaching an adjusted hazard ratio of 1.47 (95% confidence interval: 1.25-1.73) in those with prolonged use of HRT for 5 years or longer. Such a trend remained consistent in the subgroup analyses. In this study, HRT use was associated with an increased risk of achalasia in a dose-dependent manner. These findings underscore the need for vigilant monitoring of esophageal symptoms in postmenopausal women with a prolonged history of HRT.