Hormone replacement therapy and asthma onset in menopausal women: National cohort study

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

doi:10.1016/j.jaci.2020.11.024

Hormone replacement therapy and asthma onset in menopausal women: National cohort study

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

^*Corresponding author for this work

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Abstract

BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma.

OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women.

METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs.

RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset.

CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.

Original language	English
Pages (from-to)	1662-1670
Number of pages	9
Journal	Journal of Allergy and Clinical Immunology
Volume	147
Issue number	5
Early online date	3 Dec 2020
DOIs	https://doi.org/10.1016/j.jaci.2020.11.024
Publication status	Published - 31 May 2021

Bibliographical note

We would like to thank Dr Lynn Morrice for administrative assistance and the 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 are grateful to Optimum Patient Care and the Observational and Pragmatic Research Institute Pte Ltd for making the Optimum Patient Care Research Database database (www.opcrd.co.uk) available free of charge. We also thank Derek Skinner of the Observational and Pragmatic Research Institute Pte Ltd, who contributed to creation of the study data cut, identification of Read codes, and IMD quintiles. B.N. acknowledges the support of the VBG Group Herman Krefting Foundation on Asthma and Allergy, Knut and Alice Wallenberg Foundation, and the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg.

Keywords

Asthma
estrogens
epidemiology
estradiol
progestogen

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10.1016/j.jaci.2020.11.024Licence: CC BY-NC-ND

Shah_etal_JACI_Hormone_Replacement_Therapy_VoR
2020 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Cite this

Shah, S. A., Tibble, H., Pillinger, R., McLean, S., Ryan, D., Critchley, H., Price, D., Hawrylowicz, C. M., Simpson, C. R., Soyiri, I. N., Appiagyei, F., Sheikh, A., & Nwaru, B. I. (2021). Hormone replacement therapy and asthma onset in menopausal women: National cohort study. Journal of Allergy and Clinical Immunology, 147(5), 1662-1670. https://doi.org/10.1016/j.jaci.2020.11.024

Shah, SA, Tibble, H, Pillinger, R, McLean, S, Ryan, D, Critchley, H, Price, D, Hawrylowicz, CM, Simpson, CR, Soyiri, IN, Appiagyei, F, Sheikh, A & Nwaru, BI 2021, 'Hormone replacement therapy and asthma onset in menopausal women: National cohort study', Journal of Allergy and Clinical Immunology, vol. 147, no. 5, pp. 1662-1670. https://doi.org/10.1016/j.jaci.2020.11.024

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title = "Hormone replacement therapy and asthma onset in menopausal women: National cohort study",

abstract = "BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma.OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women.METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs.RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset.CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.",

keywords = "Asthma, estrogens, epidemiology, estradiol, progestogen",

author = "Shah, {Syed A} and Holly Tibble and Rebecca Pillinger and Susannah McLean 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 and Nwaru, {Bright I}",

note = "We would like to thank Dr Lynn Morrice for administrative assistance and the 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 are grateful to Optimum Patient Care and the Observational and Pragmatic Research Institute Pte Ltd for making the Optimum Patient Care Research Database database (www.opcrd.co.uk) available free of charge. We also thank Derek Skinner of the Observational and Pragmatic Research Institute Pte Ltd, who contributed to creation of the study data cut, identification of Read codes, and IMD quintiles. B.N. acknowledges the support of the VBG Group Herman Krefting Foundation on Asthma and Allergy, Knut and Alice Wallenberg Foundation, and the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg.",

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doi = "10.1016/j.jaci.2020.11.024",

language = "English",

volume = "147",

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TY - JOUR

T1 - Hormone replacement therapy and asthma onset in menopausal women

T2 - National cohort study

AU - Shah, Syed A

AU - Tibble, Holly

AU - Pillinger, Rebecca

AU - McLean, Susannah

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

AU - Nwaru, Bright I

N1 - We would like to thank Dr Lynn Morrice for administrative assistance and the 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 are grateful to Optimum Patient Care and the Observational and Pragmatic Research Institute Pte Ltd for making the Optimum Patient Care Research Database database (www.opcrd.co.uk) available free of charge. We also thank Derek Skinner of the Observational and Pragmatic Research Institute Pte Ltd, who contributed to creation of the study data cut, identification of Read codes, and IMD quintiles. B.N. acknowledges the support of the VBG Group Herman Krefting Foundation on Asthma and Allergy, Knut and Alice Wallenberg Foundation, and the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg.

PY - 2021/5/31

Y1 - 2021/5/31

N2 - BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma.OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women.METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs.RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset.CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.

AB - BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma.OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women.METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs.RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset.CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.

KW - Asthma

KW - estrogens

KW - epidemiology

KW - estradiol

KW - progestogen

U2 - 10.1016/j.jaci.2020.11.024

DO - 10.1016/j.jaci.2020.11.024

M3 - Article

C2 - 33279576

SN - 0091-6749

VL - 147

SP - 1662

EP - 1670

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 5

ER -

Hormone replacement therapy and asthma onset in menopausal women: National cohort study

Abstract

Bibliographical note

Keywords

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