Hormone replacement therapy and the risk of asthma attacks: population-based cohort study.

Background: Women experience higher rates and greater severity of asthma after puberty, suggesting that sex hormones play a key role in airway disease. Hormone replacement therapy (HRT), which acutely alters circulating sex hormone levels, provides a useful model to examine their effects on asthma attacks. We sought to examine the association between HRT use and asthma attacks. Methods: We obtained a cohort of women with asthma, aged 45-60 years, using nationwide UK primary care health records linked to hospital and mortality data, 2004-2020, to compare HRT users to nonusers. We applied inverse-probability of treatment weighting and Cox proportional hazards, accounting for demographics, asthma severity and comorbidities; stratifying by potential modifiers, including body mass index (BMI), blood eosinophil count, smoking and HRT type (oestrogen-only, progesterone-only and combined). Results: 182 010 women were eligible for the study, of whom 9663 were incident HRT users and 172 347 were nonusers. The median age was 52 years (interquartile range 50-55 years). HRT users and nonusers were broadly similar in terms of BMI and smoking history, but nonusers had slightly higher proportions residing in more deprived areas, with more comorbidities, higher reliever use and asthma attacks in the year before study entry, but lower use of preventer inhalers. After applying weighting, there was no association found between HRT use and asthma attacks (weighted hazard ratio 0.97, 95% CI 0.90-1.04). There was no modification of that association by blood eosinophil level, BMI, smoking history or HRT type. Conclusion: HRT use is not associated with asthma attacks in women with established asthma aged 45-60 years.