• 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, and Aziz Sheikh.
• Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Asthma UK Centre for Applied Research, Centre for Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh, United Kingdom. Electronic address: bright.nwaru@gu.se.
• J Allergy Clin Immunol Pract. 2021 Jul 1; 9 (7): 2751-2760.e1.

BackgroundThe impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain.ObjectiveTo investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma.MethodsWe 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.ResultsAt 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.ConclusionUse 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.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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