What We Know About Oestrogen's 'Protective Effect' Against Covid-19

HuffPost UK reader Gill asked: “I heard research has shown reduced oestrogen makes you more vulnerable to bad Covid. Is this true?”
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Every Monday, we’ll answer your questions on Covid-19 and health in a feature published online. You can submit a question here.

This week, HuffPost UK reader Gill asked: “I heard that research has shown that reduced oestrogen makes you more vulnerable to bad Covid. Is this true?”

Early on in the pandemic, it became obvious that men – as well as older women – were more susceptible to negative outcomes from Covid-19. Men, especially, are more likely to be hospitalised by the virus and end up in intensive care. They are also twice more likely to die from the virus as women.

It led researchers to hypothesise that the female sex hormone oestrogen might have some kind of protective effect. The hormone – which is considered to be immunity-enhancing and can help the female body fight off viruses better – also decreases as a person ages, which could explain why older women are more susceptible to the virus than younger women.

Dr Louise Newson, a GP and menopause specialist, said during a webinar on the topic that women have “a stronger response to infections, but especially to viruses, compared to men” – and this is because women have different immune systems. She added that “frustratingly, so much research on immunity and in general is done in men and not in women”.

Earlier in the year, researchers from the Covid Symptom Study app set out to determine whether women entering menopause were more likely to test positive for Covid-19.

An analysis of data from 500,000 female members of the app suggested post-menopausal women aged 40-60 years old had a higher rate of *predicted* Covid. But the findings haven’t been peer-reviewed, and it’s important to note this was based on people having symptoms of Covid that were input into the app, rather than people testing positive. Hence the use of *predicted*.

The preprint also looked at whether women taking the combined oral contraceptive pill and post-menopausal women taking hormone replacement therapy (HRT) had lower predicted rates of Covid-19. It found women aged 18-45 years old who were taking the contraceptive pill had a lower rate of predicted Covid-19, with a reduction in hospital attendance too.

There was a bit of a spanner thrown in the works for the oestrogen theory, though, as post-menopausal women using HRT – which is basically an oestrogen top up – were found to have increased rates of predicted Covid-19. Researchers said these results should be considered with caution, though, “due to lack of data on HRT type, route of administration, duration of treatment, and potential co-morbidities”.

At the time, Dr Richard Quinton, a consultant and senior lecturer in endocrinology at the Royal Victoria Infirmary in Newcastle, pointed out that age increases a person’s risk of developing severe illness from Covid-19 – “so it might be an age effect, rather than a hormone effect”. A person’s age is the strongest predictor of their risk of dying from Covid-19, with the risk increasing from the age of 50 – around the same time a woman hits menopause.

Due to research in this area being limited, Haitham Hamoda, consultant gynaecologist and chair of the British Menopause Society, said people shouldn’t change what they’re doing with their prescriptions – and women should continue to use HRT and the contraceptive pill. “Overall, this is an interesting concept which requires further research,” he said.

There are other initial findings that suggest oestrogen could be a helpful player in the fight against Covid-19. A preprint study from China looked at Covid-19 patients hospitalised with the virus in January to March. Researchers looked at the correlation between menstruation status, sex hormones and prognosis of Covid-19.

It found women with low oestrogen levels were more likely to suffer severe Covid-19 symptoms than women with normal oestrogen levels. They concluded that the hormones E2 (a form of oestrogen) and AMH (anti-müllerian hormone) are “potential protective factors” for female Covid-19 patients.

When asked whether a decline in oestrogen makes a person more susceptible to Covid, Professor Sir Stephen O’Rahilly, director of the MRC Metabolic Diseases Unit at the University of Cambridge, told HuffPost UK “if there is a protective effect of oestrogen, it’s unlikely to be large”.

Sabra Klein, a scientist studying sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health, told the New York Times that if oestrogen was such a protective factor for women, then older women would fare as badly as elderly men – because women’s hormones plummet after the menopause – but this isn’t happening.

“Older men are still disproportionately affected, and that suggests to me it’s got to be something genetic, or something else, that’s not just hormonal,” she told the publication.

Other factors that could influence the gender gap – aside from sex hormones – include the number of ACE2 receptors (which basically welcomes Covid-19 in with open arms) in men’s bodies compared to women, as well as differences in lifestyle factors such as smoking and drinking.

Experts are still learning about Covid-19. The information in this story is what was known or available at the time of publication, but guidance could change as scientists discover more about the virus. To keep up to date with health advice and cases in your area, visit gov.uk/coronavirus and nhs.uk.