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Published: 15 Feb, 2022

Female sex hormone may protect against death in COVID-19

NEWS The female sex hormone oestrogen may have some protective effect against becoming seriously ill and dying in COVID-19, according to a registry study conducted at Umeå University. If so, this could explain why men are more likely than women to die during the pandemic.

Text: Ola Nilsson

“The results are interesting enough to warrant further clinical studies. However, it is absolutely inappropriate to start experimenting with supplements yourself because oestrogen can also cause a number of more or less severe side effects and should only be taken in consultation with a doctor,” says Malin Sund, professor at Umeå University and first author of the study.

In the study, the researchers compared the death rates at the beginning of the pandemic for women with a COVID-19 diagnosis who were already being treated with drugs that raised and lowered estrogen levels.

Less than half

The study included a total of almost 15 000 women aged 50 to 80 who were diagnosed with COVID-19 between 4 February and 14 September 2020, including a group of 2 500 women who were taking oestrogen supplements to treat menopausal symptoms, a much smaller group of more than 200 women who were taking oestrogen-lowering drugs after cancer treatment, and a control group who were neither supplemented nor had their oestrogen levels lowered.

The researchers then found that the risk of death from COVID-19 in the group receiving oestrogen supplements was less than half, 2.1 percent, compared with the control group, where the mortality rate was 4.6 percent.

“This is a significant reduction in mortality that we show is associated with estrogen supplementation in particular. This is because we have adjusted for possible background factors,” says Anne-Marie Fors Connolly, researcher at Umeå University and senior author of the study.

The highest risk of death was in the group that received oestrogen replacement therapy. However, the causal link with oestrogen is not certain, as this group was both older and had undergone cancer treatment, which in itself increases the risk of severe disease and death in COVID-19. The study was carried out before there were vaccines against COVID-19, so it is not possible to say from this study how much oestrogen reduces the risk of severe disease and death among vaccinated women.

Don't stop medication

“For women who have undergone cancer treatment, it is important to continue taking their medication to reduce the risk of cancer recurrence. This study gives no reason to stop. However, they should of course be careful to get vaccinated and not expose themselves to unnecessary risk of infection,” says Malin Sund.

It is known that the risk of serious illness and death from COVID-19 is significantly higher for men than for women. One hypothesis has been that this is due to the male sex hormone testosterone. However, an earlier Swedish study of testosterone-lowering drugs failed to show any reduction in the risk of COVID-19 mortality among those who received the drug. Instead, a possible explanation for the difference in mortality between the sexes may be the female sex hormone oestrogen. However, randomised treatment trials are needed to confirm the findings of this registry study.

The study is published in the scientific journal BMJ Open.

About the study

Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden with death due to COVID-19 - a cohort study
Malin Sund, Osvaldo Fonseca-Rodríguez, Andreas Josefsson, Karin Welen, Anne-Marie Fors Connolly
doi 10.1136/ bmjopen-2021-053032

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Malin Sund
Visiting professor
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