Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

Ricardo Costeira; Karla A. Lee; Benjamin Murray; Colette Christiansen; Juan Castillo-Fernandez; Mary Ni Lochlainn; Joan Capdevila Pujol; Heather Macfarlane; Louise C. Kenny; Iain Buchan; Jonathan Wolf; Janice Rymer; Sebastien Ourselin; Claire J. Steves; Timothy D. Spector; Louise R. Newson; Jordana T. Bell

doi:10.1371/journal.pone.0257051

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

Ricardo Costeira, Karla A. Lee, Benjamin Murray, Colette Christiansen, Juan Castillo-Fernandez, Mary Ni Lochlainn, Joan Capdevila Pujol, Heather Macfarlane, Louise C. Kenny, Iain Buchan, Jonathan Wolf, Janice Rymer, Sebastien Ourselin, Claire J. Steves, Timothy D. Spector, Louise R. Newson, Jordana T. Bell^*

^*Corresponding author for this work

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

68 Citations (Scopus)

Abstract

It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.

Original language	English
Article number	e0257051
Journal	PLoS ONE
Volume	16
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0257051
Publication status	Published - Sept 2021

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Costeira, R., Lee, K. A., Murray, B., Christiansen, C., Castillo-Fernandez, J., Lochlainn, M. N., Pujol, J. C., Macfarlane, H., Kenny, L. C., Buchan, I., Wolf, J., Rymer, J., Ourselin, S., Steves, C. J., Spector, T. D., Newson, L. R., & Bell, J. T. (2021). Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study. PLoS ONE, 16(9), Article e0257051. https://doi.org/10.1371/journal.pone.0257051

@article{ce43976d7a774a47978d70a68cf1bb79,

title = "Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study",

abstract = "It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.",

author = "Ricardo Costeira and Lee, {Karla A.} and Benjamin Murray and Colette Christiansen and Juan Castillo-Fernandez and Lochlainn, {Mary Ni} and Pujol, {Joan Capdevila} and Heather Macfarlane and Kenny, {Louise C.} and Iain Buchan and Jonathan Wolf and Janice Rymer and Sebastien Ourselin and Steves, {Claire J.} and Spector, {Timothy D.} and Newson, {Louise R.} and Bell, {Jordana T.}",

year = "2021",

month = sep,

doi = "10.1371/journal.pone.0257051",

language = "English",

volume = "16",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

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Costeira, R, Lee, KA, Murray, B, Christiansen, C, Castillo-Fernandez, J, Lochlainn, MN, Pujol, JC, Macfarlane, H, Kenny, LC, Buchan, I, Wolf, J, Rymer, J , Ourselin, S, Steves, CJ, Spector, TD, Newson, LR & Bell, JT 2021, 'Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study', PLoS ONE, vol. 16, no. 9, e0257051. https://doi.org/10.1371/journal.pone.0257051

TY - JOUR

T1 - Estrogen and COVID-19 symptoms

T2 - Associations in women from the COVID Symptom Study

AU - Costeira, Ricardo

AU - Lee, Karla A.

AU - Murray, Benjamin

AU - Christiansen, Colette

AU - Castillo-Fernandez, Juan

AU - Lochlainn, Mary Ni

AU - Pujol, Joan Capdevila

AU - Macfarlane, Heather

AU - Kenny, Louise C.

AU - Buchan, Iain

AU - Wolf, Jonathan

AU - Rymer, Janice

AU - Ourselin, Sebastien

AU - Steves, Claire J.

AU - Spector, Timothy D.

AU - Newson, Louise R.

AU - Bell, Jordana T.

PY - 2021/9

Y1 - 2021/9

N2 - It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.

AB - It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.

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U2 - 10.1371/journal.pone.0257051

DO - 10.1371/journal.pone.0257051

M3 - Article

AN - SCOPUS:85114821132

SN - 1932-6203

VL - 16

JO - PLoS ONE

JF - PLoS ONE

IS - 9

M1 - e0257051

ER -

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

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