Postmenopausal women may be at higher risk of severe coronavirus, estrogen may have a protective effect: Study

The sex hormone estrogen which declines in women post-menopause interacts with immune system in many ways, including influencing how many immune cells are produced and how they respond to infection


                            Postmenopausal women may be at higher risk of severe coronavirus, estrogen may have a protective effect: Study
(Getty Images)

Postmenopausal women may be at higher risk of developing serious complications of Covid-19, according to researchers from King’s College London. They found that high levels of estrogen may have a protective effect against the novel coronavirus.

The sex hormone estrogen, 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, write the authors. They hypothesized that estrogen could serve as a protectant against Covid-19. Previous studies on severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) suggest this might explain why men of all ages are at a higher risk of severe infection, including Covid-19, says the team. Using the Covid symptom study app, researchers examined the rate of predicted Covid-19 among postmenopausal women, premenopausal women using the combined oral contraceptive pill (COCP), and postmenopausal women taking hormone replacement therapy (HRT), from more than 500,000 women in the UK, between May 7 and June 15. 

The analysis shows that postmenopausal women had a higher rate of predicted Covid-19 than other studied women. Postmenopausal women were 22% more likely to report symptoms of coronavirus than pre-menopausal women. “We hypothesized that pre-menopausal women with higher estrogen levels would have less severe Covid-19 when compared to women of the same age and body mass index (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-19 among 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,” writes joint lead author Dr Karla Lee, from The School of Life Course Sciences, in the pre-print study, which has not been peer-reviewed.

Women in the 45-50 age group were most likely to be at risk and reported symptoms of anosmia or loss of smell, fever and a persistent cough, and the need for oxygen treatment in the hospital was significant in this group, shows analysis. “Postmenopausal women had a higher rate of predicted Covid-19 (odds ratio 1.22) and a corresponding range of significant differences in symptoms including hoarse voice, skipped meals, muscle pains, and fever. Upon sub-group analysis by age, we observed that predicted Covid-19 results were most driven by the 45-50 age group (odds ratio 1.35), wherein anosmia, as well as fever and persistent cough, and the need for oxygen treatment in the hospital were also significant,” the findings state.

Using the Covid symptom study app, researchers examined the rate of predicted Covid-19 among postmenopausal women, premenopausal women using the combined oral contraceptive pill, and postmenopausal women taking hormone replacement therapy (Getty Images)

 

According to the research team, women using the COCP, between 18-45 years, had a lower rate of predicted Covid-19 and corresponding reduced frequency of symptoms, including a persistent cough, delirium, anosmia, skipped meals, severe fatigue and pain. The rate of hospitalization was also significantly lower, they add. HRT use in postmenopausal women between 50-65 years was associated with an increased rate of predicted Covid-19 but not with hospitalization. The authors have advised that HRT results should be considered with caution due to the lack of information about HRT type, route of administration and duration of treatment. “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 estrogen in relation to Covid-19. We hope that results from our study can help inform ongoing biomedical research and clinical trials in the field,” says joint lead author Dr Ricardo Costeira, King’s College London. 

A different study that was published in July had said that Covid-19 may increase the risk of blot clots in women who are pregnant or taking estrogen with birth control or hormone replacement therapy, 

According to experts, who were not part of the study, further research is needed to fully ascertain the impact of the different types of hormone replacement therapy and the combined oral contraceptive pill on the severity and experienced symptoms of Covid-19 among women. Commenting on the current study findings, Dr Melanie Davies, consultant gynecologist, University College London Hospitals, and a member of the Medical Advisory Council, British Menopause Society, says that as men are more likely than women to develop severe Covid-19 infection, there is an “interesting theory” that estrogen might be protecting women. However, no conclusions can be drawn about estrogen use and Covid-19 severity from this report, she emphasizes. “There are some important caveats. The data are collected on an app and are self-reported, which brings bias into the study as different groups of people may not use the app equally. This is a preprint of the study findings, so it has not undergone the process of peer-review and there may need to be changes,” says Dr Davies. 

Haitham Hamoda, consultant gynecologist and chair of the British Menopause Society, says that the study does not provide conclusive evidence that hormone replacement therapy and the combined oral contraceptive pill impact Covid-19 severity. “As research is limited in this area we feel that for those women currently using these preparations the benefits of HRT and COCP outweigh any possible impact that they may have on COVID-19. Overall, this is an interesting concept that requires further research,” says Hamoda.

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