Bright I Nwaru1, Rebecca Pillinger2, Holly Tibble2, Syed A Shah2, Dermot Ryan3, Hilary Critchley4, David Price5, Catherine M Hawrylowicz6, Colin R Simpson7, Ireneous N Soyiri8, Francis Appiagyei9, Aziz Sheikh2. 1. 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, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom. Electronic address: bright.nwaru@gu.se. 2. Asthma UK Centre for Applied Research, Centre for Medical Informatics, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom. 3. Asthma UK Centre for Applied Research, Centre for Medical Informatics, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom; Optimum Patient Care, Cambridge, United Kingdom. 4. Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, United Kingdom. 5. Optimum Patient Care, Cambridge, United Kingdom; Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen; Observational and Pragmatic Research Institute, Singapore. 6. Asthma UK Centre in Allergic Mechanisms of Asthma, School of Immunology and Microbial Sciences, Guys Hospital, Kings College London, London, United Kingdom. 7. Asthma UK Centre for Applied Research, Centre for Medical Informatics, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom; School of Health, Faculty of Health, Victoria University of Wellington, Wellington, New Zealand. 8. Asthma UK Centre for Applied Research, Centre for Medical Informatics, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom; Hull York Medical School, Institute for Clinical and Applied Health Research (ICAHR), University of Hull, Hull, United Kingdom. 9. Optimum Patient Care, Cambridge, United Kingdom.
Abstract
BACKGROUND: Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma. OBJECTIVE: We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women. METHODS: Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data. RESULTS: At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows: any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years: HR, 0.83; 95% CI, 0.81-0.86; 3-4 years: HR, 0.64; 95% CI, 0.61-0.67; 5+ years: HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse. CONCLUSIONS: Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results.
BACKGROUND: Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma. OBJECTIVE: We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women. METHODS: Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data. RESULTS: At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows: any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years: HR, 0.83; 95% CI, 0.81-0.86; 3-4 years: HR, 0.64; 95% CI, 0.61-0.67; 5+ years: HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse. CONCLUSIONS: Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results.