Hormone replacement therapy and risk of severe asthma exacerbation in peri-menopausal and post-menopausal women: 17-year national cohort study

ABSTRACT Background The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. Objective To investigate the association between use of HRT and severe asthma exacerbation in peri-menopausal and post-menopausal women with asthma. Methods We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the UK, to construct a 17-year (1/1/2000–12/31/2016) cohort of peri-menopausal and post-menopausal (46-70 years, N=31,656) women. We defined use, subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. Results At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR] 1.24, 95%CI 1.22-1.26), combined (IRR 1.28, 95%CI 1.25-1.31), estrogen-only (IRR 1.18, 95%CI 1.14-1.21), and longer duration (1-2 years: IRR 1.16; 95%CI 1.13-1.19; 3-4 years: IRR 1.43; 95%CI 1.38-1.48; 5+ years: IRR 1.32; 95%CI 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared to non-use. The risk estimates were greater among lean women (BMI Conclusion Use of HRT and subtypes, particularly previous, but not current, use and use for more than two years, is associated with an increased risk of severe asthma exacerbation in peri-menopausal/post-menopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and non-smokers, respectively.