A clue to why Covid is deadlier for men: Estrogen could play a protective role

It’s one of the lingering mysteries of the pandemic: Why have men died of Covid at higher rates than women?

The death rate from Covid among men was 1.7 times higher, on average, than the rate among women in 38 countries, according to a 2020 study. More recent research by scientists at Harvard University revealed that although men accounted for 49% of Covid cases in the United States, they accounted for 55% of Covid deaths from April 2020 to May 2021.

A study this week gave further support to a leading theory on the gap: estrogen may offer some protection against severe cases of Covid.

For the study, published in the journal Family Practice, UK, researchers compared women in England who had received hormone replacement therapy – which helps restore estrogen levels during menopause – within six months of a diagnosis of Covid to those who had not. The results showed that the first group had a 78% lower all-cause mortality rate than the second group.

In total, the study involved more than 5,400 women, most of whom were white and of menopausal age (about 59 years old, on average). The researchers controlled for socioeconomic status and pre-existing health conditions.

“This adds to the body of evidence as to why, especially at the start of the pandemic, we were seeing really different clinical outcomes for women compared to men,” said Anita Raj, professor of infectious diseases and health. public at the University of California. , San Diego, who did not participate in the research.

Although the study’s relative homogeneity is a limitation, she added, its conclusion “still seems to be aligned with the idea that it is specifically estrogen that produces the protective effect.”

Estrogen can help balance the immune response

Various other hypotheses have been made to explain the difference in Covid mortality between men and women over the past two years. In the Harvard study, the researchers suggested that the types of jobs women hold more often and their behavioral tendencies could have an effect on Covid outcomes. In the United States, for example, women are more likely to report wearing masks and social distancing, while men are more likely to participate in jobs that expose them to the virus.

But experts say it makes sense that estrogen could play a protective role against Covid, since the hormone is known to stimulate an immune response through the production of antibodies. At the same time, higher levels of estrogen can prevent the immune system from responding too aggressively to a viral infection, which can lead to life-threatening inflammation.

“We see in women, they have a faster and higher antibody response…to Covid infection, which probably means they can clear the infection faster than men,” said Dr Christopher Wilcox, co-author of the new study. and a University Clinical Fellow at the University of Southampton.

Wilcox added that “a number of studies have shown that higher estrogen levels appear to be associated with less severity of infectious disease in general.”

A 2016 lab study, for example, suggested that estrogen prevents the flu virus from replicating in cells. And other research has shown that estrogen can also prevent the replication of HIV, Ebola, and hepatitis.

The new research also aligns with a 2020 study that found hormone replacement therapy halved the risk of death from Covid in women over 50. This research, however, did not find a difference in pre-menopausal women.

For this and many other reasons, the experts said, it is unclear whether estrogen might be useful as part of a treatment regimen or preventative therapy for Covid. Hormone replacement therapy comes with its own risks, as long-term use can increase your risk of stroke, blood clots, or heart attack.

“There are risks associated with prescribing estrogen, but is it something that deserves further study? Yes, definitely,” Raj said.

At the very least, Wilcox said, her study suggests there is no need for women who contract Covid to discontinue hormone replacement therapy.

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