Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study

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

doi:10.1136/thoraxjnl-2020-215540

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background:
Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.
Methods:
We used the Optimum Patient Care Research Database, a population-based longitudinal anonymised primary care database in the UK, to construct 17-year (1/1/2000–31/12/2016) retrospective cohort of reproductive-age
(16-45 years, N=83,084) women with asthma. Using READ codes, we defined use, subtypes, and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendation of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition.
Results:
The 17-year follow-up resulted in 456,803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen), and 9% progestogen-only contraceptives. Previous (incidence rate ratio [IRR] 0.94, 95%CI 0.92-0.97) and current (IRR 0.96, 95%CI 0.94-0.98) use of any, previous (IRR 0.92, 95%CI 0.87-0.97) and current use of combined (IRR 0.93, 95%CI 0.91-0.96), and longer duration of use (3-4 years: IRR 0.94; 95%CI 0.92-0.97; 5+ years: IRR 0.91; 95%CI 0.89-0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared to non-use.
Conclusion:
Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for influence of hormonal contraceptives on clinical
outcomes of asthma in women are required.

Original language	English
Pages (from-to)	109-115
Number of pages	7
Journal	Thorax
Volume	76
Early online date	23 Nov 2020
DOIs	https://doi.org/10.1136/thoraxjnl-2020-215540
Publication status	Published - 15 Jan 2021

Keywords

Asthma exacerbation
women
combined hormonal
oestrogen
progesterone
sex hormones
clinical epidemiology
asthma
asthma epidemiology
hormonal contraception
PROGESTERONE
LUNG-FUNCTION
REGULATORY T
CARE
WOMEN
UK
REPLACEMENT THERAPY
ESTROGEN
BODY-MASS INDEX
EPIDEMIOLOGY

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Nwaru_et_al_Thorax_DoesUseOfHormonal_AAM
This article has been accepted for publication in Thorax, 2020 following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/thoraxjnl-2020-215540.” © Authors (or their employer(s)) OR “© BMJ Publishing Group Ltd” ( for assignments of BMJ Case Reports) “ 2021". “Reuse of this manuscript version (excluding any databases, tables, diagrams, photographs and other images or illustrative material included where a another copyright owner is identified) is permitted strictly pursuant to the terms of the Creative Commons Attribution-Non Commercial 4.0 International (CC-BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/
Accepted author manuscript, 839 KBLicence: CC BY-NC

Cite this

@article{2b79fce5840048c5901512343d9c7fcb,

title = "Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study",

abstract = "Background:Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.Methods:We used the Optimum Patient Care Research Database, a population-based longitudinal anonymised primary care database in the UK, to construct 17-year (1/1/2000–31/12/2016) retrospective cohort of reproductive-age(16-45 years, N=83,084) women with asthma. Using READ codes, we defined use, subtypes, and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendation of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition.Results:The 17-year follow-up resulted in 456,803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen), and 9% progestogen-only contraceptives. Previous (incidence rate ratio [IRR] 0.94, 95%CI 0.92-0.97) and current (IRR 0.96, 95%CI 0.94-0.98) use of any, previous (IRR 0.92, 95%CI 0.87-0.97) and current use of combined (IRR 0.93, 95%CI 0.91-0.96), and longer duration of use (3-4 years: IRR 0.94; 95%CI 0.92-0.97; 5+ years: IRR 0.91; 95%CI 0.89-0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared to non-use.Conclusion:Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for influence of hormonal contraceptives on clinicaloutcomes of asthma in women are required.",

keywords = "Asthma exacerbation, women, combined hormonal, oestrogen, progesterone, sex hormones, clinical epidemiology, asthma, asthma epidemiology, hormonal contraception, PROGESTERONE, LUNG-FUNCTION, REGULATORY T, CARE, WOMEN, UK, REPLACEMENT THERAPY, ESTROGEN, BODY-MASS INDEX, EPIDEMIOLOGY",

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

note = "FUNDING: This work was supported by Asthma UK, grant number: AUK-IG-2016-346 and Health Data Research UK. We thank Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. BN acknowledges the support of Knut and Alice Wallenberg Foundation, the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden, and the VBG Group Herman Krefting Foundation on Asthma and Allergy. AS acknowledges support of Health Data Research UK (BREATHE). ACKNOWLEDGEMENTS: We would like to thank Dr Lynn Morrice for administrative assistance and members of the Patient and Public Involvement group of the Asthma UK Centre for Applied Research who helped shape this project during the grant application stage. We also thank Dr Susannah McLean who helped with selection of Read codes and design of strategy for determining start and end dates of pregnancies. We are grateful to Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. We also thank Derek Skinner of OPRI who contributed to the creation of the study data-cut, identification of READ codes and IMD Centiles.",

year = "2021",

month = jan,

day = "15",

doi = "10.1136/thoraxjnl-2020-215540",

language = "English",

volume = "76",

pages = "109--115",

journal = "Thorax",

issn = "0040-6376",

publisher = "BMJ Publishing Group Ltd",

}

TY - JOUR

T1 - Hormonal contraception and the risk of severe asthma exacerbation

T2 - 17-year population-based cohort study

AU - Nwaru, Bright I

AU - Tibble, Holly

AU - Shah, Syed A

AU - Pillinger, Rebecca

AU - Mclean, Susannah

AU - Ryan, Dermot

AU - Critchley, Hilary O D

AU - Price, David

AU - Hawrylowicz, Catherine M.

AU - Simpson, Colin R.

AU - Soyiri, Ireneous N.

AU - Appiagyei, Francis

AU - Sheikh, Aziz

N1 - FUNDING: This work was supported by Asthma UK, grant number: AUK-IG-2016-346 and Health Data Research UK. We thank Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. BN acknowledges the support of Knut and Alice Wallenberg Foundation, the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden, and the VBG Group Herman Krefting Foundation on Asthma and Allergy. AS acknowledges support of Health Data Research UK (BREATHE). ACKNOWLEDGEMENTS: We would like to thank Dr Lynn Morrice for administrative assistance and members of the Patient and Public Involvement group of the Asthma UK Centre for Applied Research who helped shape this project during the grant application stage. We also thank Dr Susannah McLean who helped with selection of Read codes and design of strategy for determining start and end dates of pregnancies. We are grateful to Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. We also thank Derek Skinner of OPRI who contributed to the creation of the study data-cut, identification of READ codes and IMD Centiles.

PY - 2021/1/15

Y1 - 2021/1/15

N2 - Background:Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.Methods:We used the Optimum Patient Care Research Database, a population-based longitudinal anonymised primary care database in the UK, to construct 17-year (1/1/2000–31/12/2016) retrospective cohort of reproductive-age(16-45 years, N=83,084) women with asthma. Using READ codes, we defined use, subtypes, and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendation of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition.Results:The 17-year follow-up resulted in 456,803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen), and 9% progestogen-only contraceptives. Previous (incidence rate ratio [IRR] 0.94, 95%CI 0.92-0.97) and current (IRR 0.96, 95%CI 0.94-0.98) use of any, previous (IRR 0.92, 95%CI 0.87-0.97) and current use of combined (IRR 0.93, 95%CI 0.91-0.96), and longer duration of use (3-4 years: IRR 0.94; 95%CI 0.92-0.97; 5+ years: IRR 0.91; 95%CI 0.89-0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared to non-use.Conclusion:Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for influence of hormonal contraceptives on clinicaloutcomes of asthma in women are required.

AB - Background:Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.Methods:We used the Optimum Patient Care Research Database, a population-based longitudinal anonymised primary care database in the UK, to construct 17-year (1/1/2000–31/12/2016) retrospective cohort of reproductive-age(16-45 years, N=83,084) women with asthma. Using READ codes, we defined use, subtypes, and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendation of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition.Results:The 17-year follow-up resulted in 456,803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen), and 9% progestogen-only contraceptives. Previous (incidence rate ratio [IRR] 0.94, 95%CI 0.92-0.97) and current (IRR 0.96, 95%CI 0.94-0.98) use of any, previous (IRR 0.92, 95%CI 0.87-0.97) and current use of combined (IRR 0.93, 95%CI 0.91-0.96), and longer duration of use (3-4 years: IRR 0.94; 95%CI 0.92-0.97; 5+ years: IRR 0.91; 95%CI 0.89-0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared to non-use.Conclusion:Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for influence of hormonal contraceptives on clinicaloutcomes of asthma in women are required.

KW - Asthma exacerbation

KW - women

KW - combined hormonal

KW - oestrogen

KW - progesterone

KW - sex hormones

KW - clinical epidemiology

KW - asthma

KW - asthma epidemiology

KW - hormonal contraception

KW - PROGESTERONE

KW - LUNG-FUNCTION

KW - REGULATORY T

KW - CARE

KW - WOMEN

KW - UK

KW - REPLACEMENT THERAPY

KW - ESTROGEN

KW - BODY-MASS INDEX

KW - EPIDEMIOLOGY

UR - http://www.scopus.com/inward/record.url?scp=85096794701&partnerID=8YFLogxK

U2 - 10.1136/thoraxjnl-2020-215540

DO - 10.1136/thoraxjnl-2020-215540

M3 - Article

C2 - 33234554

VL - 76

SP - 109

EP - 115

JO - Thorax

JF - Thorax

SN - 0040-6376

ER -

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study

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