Research published recently, led by King’s College London, has found that high levels of oestrogen may have a protective effect against the novel coronavirus. Using the COVID Symptom Study App, researchers examined the rate of predicted COVID-19 among post-menopausal women, pre-menopausal women using the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT), from more than 500,000 women in the UK, between 7 May and 15 June 2020.
The sex hormone oestrogen, which declines in women post-menopause, interacts with the immune system in various ways, including influencing how many immune cells are produced and how they respond to infection.
Researchers hypothesised that oestrogen could serve as a protectant against COVID-19. Previous studies on SARS-CoV and MERS suggest this might explain why men of all ages are at a higher risk of severe infection, including COVID-19.
The pre-print study, which has not been peer-reviewed, found post-menopausal women had a higher rate of predicted COVID-19 than other studied women. Women in the 45-50 age group were most likely to be at risk, and reported symptoms of anosmia, fever and a persistent cough, and the need for oxygen treatment in hospital were significant in this group.
Women using the COCP, between 18-45 years, had a lower rate of predicted COVID-19 and corresponding reduced frequency of symptoms, including persistent cough, delirium, anosmia, skipped meals, severe fatigue and pain. The rate of hospitalisation was also significantly lower.
HRT use, in post-menopausal women between 50-65 years, was associated with an increased rate of predicted COVID-19 but not with hospitalisation. The researchers advised HRT results should be considered with caution due to the lack of information about HRT type, route of administration and duration of treatment.
We hypothesised that pre-menopausal women with higher oestrogen levels would have less severe COVID-19 when compared to women of the same age and BMI who had been through the menopause, and our findings supported this. Additionally, when we compared a younger group of women on the combined oral contraceptive pill (COCP) with a similar group not taking the COCP we saw less severe COVID amongst those taking the COCP, suggesting hormones in the COCP may offer some protection against COVID-19. More research is certainly needed to further our knowledge: joint lead author Dr Karla Lee, from The School of Life Course Sciences
Joint lead author Dr Ricardo Costeira, from King’s College London, said: “Thanks to women of the COVID Symptom Study app we were able to show, with relatively large numbers, the significance of studying the sex hormone oestrogen in relation to COVID-19. We hope that results from our study can help inform ongoing biomedical research and clinical trials in the field.”
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 Kings College London and Zoe Global Limited was launched in the UK on 24th March 2020. It captured self-reported information related to COVID-19 symptoms. Data used for this study included records collected between 7th May – 15th June 2020.
Main outcome measures: We investigated links between COVID-19 rates and 1) menopausal status, 2) COCP use and 3) HRT use, using symptom-based predicted COVID-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 of predicted COVID (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 lower predicted COVID-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 of predicted COVID-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 between predicted COVID-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.
Authors
Ricardo Costeira, Karla A Lee, Benjamin Murray, Colette Christiansen, Juan Castillo-Fernandez, Mary Ni Lochlainn, Joan Capdevila Pujol, Iain Buchan, Louise C Kenny, Jonathan Wolf, Sebastien Ourselin, Claire Steves, Timothy Spector, Louise Newson,
Jordana Bell
[link url="https://www.kcl.ac.uk/news/post-menopausal-women-higher-risk-developing-severe-covid-19"]Kings College London material[/link]
[link url="https://www.medrxiv.org/content/10.1101/2020.07.30.20164921v2"]medRxiv abstract[/link]