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

  1. Ricardo Costeira
  2. Karla A. Lee
  3. Benjamin Murray
  4. Colette Christiansen
  5. Juan Castillo-Fernandez
  6. Mary Ni Lochlainn
  7. Joan Capdevila Pujol
  8. Heather Macfarlane
  9. Louise C. Kenny
  10. Iain Buchan
  11. Jonathon Wolf
  12. Janice Rymer
  13. Sebastien Ourselin
  14. Claire J. Steves
  15. Timothy D. Spector
  16. Louise R. Newson
  17. Jordana T. Bell
1 evaluations Published on
Read the full article Related papers
This article on Sciety

Abstract

Background

Men and older women have been shown to be at higher risk of adverse COVID-19 outcomes. Animal model studies of SARS-CoV and MERS suggest that the age and sex difference in COVID-19 symptom severity may be due to a protective effect of the female sex hormone estrogen. Females have shown an ability to mount a stronger immune response to a variety of viral infections because of more robust humoral and cellular immune responses.

Objectives

We sought to determine whether COVID-19 positivity increases in women entering menopause. We also aimed to identify whether premenopausal women taking exogenous hormones in the form of the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT) have lower predicted rates of COVID-19, using our published symptom-based model.

Design

The COVID Symptom Study developed by King’s College London and Zoe Global Limited was launched in the UK on 24thMarch 2020. It captured self-reported information related to COVID-19 symptoms. Data used for this study included records collected between 7thMay - 15thJune 2020.

Main outcome measures

We investigated links between COVID-19 rates and 1) menopausal status, 2) COCP use and 3) HRT use, using symptom-basedpredictedCOVID-19, tested COVID-19, and disease severity based on requirement for hospital attendance or respiratory support.

Participants

Female users of the COVID Symptom Tracker Application in the UK, including 152,637 women for menopause status, 295,689 for COCP use, and 151,193 for HRT use. Analyses were adjusted for age, smoking and BMI.

Results

Post-menopausal women aged 40-60 years had a higher rate ofpredictedCOVID (P=0.003) and a corresponding range of symptoms, with consistent, but not significant trends observed for tested COVID-19 and disease severity. Women aged 18-45 years taking COCP had a significantly lowerpredictedCOVID-19 (P=8.03E-05), with a reduction in hospital attendance (P=0.023). Post-menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates ofpredictedCOVID-19 (P=2.22E-05) for HRT users alone.

Conclusions

Our findings support a protective effect of estrogen on COVID-19, based on positive association betweenpredictedCOVID-19 and menopausal status, and a negative association with COCP use. HRT use was positively associated with COVID-19 symptoms; however, the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential comorbidities.

Trial registration

The App Ethics has been approved by KCL ethics Committee REMAS ID 18210, review reference LRs-19/20-18210

Related articles

Related articles are currently not available for this article.