Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women: 17-Year National Cohort Study

Bright I. Nwaru, Syed A. Shah, Holly Tibble, Rebecca Pillinger, Susannah Mclean, Dermot Ryan, Hilary Critchley, Catherine M. Hawrylowicz, Colin R. Simpson, Ireneous N. Soyiri, Francis Appiagyei, David Price, Aziz Sheikh

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 perimenopausal and postmenopausal women with asthma. Methods: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women. We defined use of HRT, its 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% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (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 with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. Conclusion: Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.

Original languageEnglish
Pages (from-to)2751-2760.e1
JournalThe Journal of Allergy and Clinical Immunology: In Practice
Issue number7
Early online date1 Mar 2021
Publication statusPublished - Jul 2021

Keywords / Materials (for Non-textual outputs)

  • Asthma exacerbation
  • Cohort study
  • Combined hormone therapy
  • Estrogen-only therapy
  • Hormone replacement therapy
  • Menopause
  • Women


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