Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study

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

doi:10.1016/j.jaci.2020.02.027

Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study

Bright I. Nwaru^* (Corresponding Author), Rebecca Pillinger, Holly Tibble, Syed A. Shah, Dermot Ryan, Hilary 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

9 Citations (Scopus)

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.

Original language	English
Pages (from-to)	438-446
Number of pages	9
Journal	Journal of Allergy and Clinical Immunology
Volume	146
Issue number	2
Early online date	15 Apr 2020
DOIs	https://doi.org/10.1016/j.jaci.2020.02.027
Publication status	Published - Aug 2020

Keywords

Asthma
cohort study
females
hormonal contraception
incidence
estrogen
progesterone
sex hormones

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Nwaru, B. I., Pillinger, R., Tibble, H., Shah, S. A., Ryan, D., Critchley, H., Price, D., Hawrylowicz, C. M., Simpson, C. R., Soyiri, I. N., Appiagyei, F., & Sheikh, A. (2020). Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study. Journal of Allergy and Clinical Immunology, 146(2), 438-446. https://doi.org/10.1016/j.jaci.2020.02.027

Nwaru, BI, Pillinger, R, Tibble, H, Shah, SA, Ryan, D, Critchley, H, Price, D, Hawrylowicz, CM, Simpson, CR, Soyiri, IN, Appiagyei, F & Sheikh, A 2020, 'Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study', Journal of Allergy and Clinical Immunology, vol. 146, no. 2, pp. 438-446. https://doi.org/10.1016/j.jaci.2020.02.027

@article{5ebc80e7381b451293b58eb8ff6aa1b5,

title = "Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study",

abstract = "BackgroundDespite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma.ObjectiveWe sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women.MethodsUsing 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.ResultsAt 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.ConclusionsHormonal 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.",

keywords = "Asthma, cohort study, females, hormonal contraception, incidence, estrogen, progesterone, sex hormones",

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

note = "Funding Information: This study was supported by Asthma UK (grant no. AUK-IG-2016-346) and Health Data Research UK. B.I.N. 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. The funders had no influence on the design of the study, interpretation of findings, or the decision to publish. Publisher Copyright: {\textcopyright} 2020 American Academy of Allergy, Asthma & Immunology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = aug,

doi = "10.1016/j.jaci.2020.02.027",

language = "English",

volume = "146",

pages = "438--446",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby/Elsevier,",

number = "2",

}

TY - JOUR

T1 - Hormonal contraceptives and onset of asthma in reproductive-age women

T2 - Population-based cohort study

AU - Nwaru, Bright I.

AU - Pillinger, Rebecca

AU - Tibble, Holly

AU - Shah, Syed A.

AU - Ryan, Dermot

AU - Critchley, Hilary

AU - Price, David

AU - Hawrylowicz, Catherine M.

AU - Simpson, Colin R.

AU - Soyiri, Ireneous N.

AU - Appiagyei, Francis

AU - Sheikh, Aziz

N1 - Funding Information: This study was supported by Asthma UK (grant no. AUK-IG-2016-346) and Health Data Research UK. B.I.N. 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. The funders had no influence on the design of the study, interpretation of findings, or the decision to publish. Publisher Copyright: © 2020 American Academy of Allergy, Asthma & Immunology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/8

Y1 - 2020/8

N2 - BackgroundDespite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma.ObjectiveWe sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women.MethodsUsing 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.ResultsAt 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.ConclusionsHormonal 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.

AB - BackgroundDespite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma.ObjectiveWe sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women.MethodsUsing 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.ResultsAt 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.ConclusionsHormonal 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.

KW - Asthma

KW - cohort study

KW - females

KW - hormonal contraception

KW - incidence

KW - estrogen

KW - progesterone

KW - sex hormones

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DO - 10.1016/j.jaci.2020.02.027

M3 - Article

C2 - 32305347

VL - 146

SP - 438

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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ER -

Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study

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