Estrogen May Protect Women From Dying of Covid-19

A New York ear, nose, and throat doctor on the prospect of hormone therapy

Image: chaofann/Getty Images

As an ear, nose, and throat (ENT) doctor in private practice in Manhattan, I’ve been considering — as have other doctors and researchers — a way to fight Covid-19 that may have been sitting under our noses all along.

Having felt the fear in the hundreds of Covid-19 patients I have treated, I started reading every study possible to try and make sense of this disease. I’ve noticed a common thread that is only beginning to get attention.

Though it’s true we don’t have a cure or a surefire way to prevent people from getting the virus, I wonder if there may be a way to save lives using tools we already have.

As it stands now, when people get infected, we tell them to stay home and tough it out on their own unless their symptoms become so severe that they require hospitalization.

At the hospital, there are only a handful of drugs providers can use for immediate treatment, none of which have been officially approved to treat Covid-19 (although some are showing good results).

Other than that, doctors can only provide supportive care, like IV fluids, oxygen, and most recently, pooled plasma from recovered patients. The most severely ill patients are being placed on ventilators, but ventilators do not guarantee survival. The odds of making it off the ventilator alive are only around 12%. Those are not great odds. Though we are chasing after this thing with everything we’ve got, a staggering number of people die from it every day.

But why are people dying?

A key distinction is that death is not caused by the virus itself. It is caused by the effect the virus has on the immune system of at-risk people. But who is most at risk? We have been told it is the elderly and those with certain medical conditions, such as diabetes, serious heart conditions, obesity, and chronic lung disease. But if you cross-reference demographics, you see an even more interesting picture.

As far as we know, men and women are both contracting the virus at the same rate, but men are dying at a higher rate. In the United States, as of May 6, 24,637 men and 19,378 women have died, according to the Centers for Disease Control and Prevention.

We see this same pattern around the world. According to Global Health 50/50, an independent initiative for gender health equality, to date, men account for 64% of deaths in China, 62% of deaths in Italy, 59% in France, and 58% of deaths in Spain and England. Medical experts have long known that women are less susceptible to death from viral infections.

As far as we know, men and women are both contracting the virus at the same rate, but men are dying at a higher rate… We see this same pattern around the world.

I think the difference may be due to estrogen.

First, let’s consider how Covid-19 affects the immune system. Like the SARS virus, it invades cells through ACE2 receptors, found in lung, heart, and nerve tissue. Once it gets into a cell, the cell creates an immune response aimed at making it hard for the virus to replicate. The most deadly immune response, the one that causes severe breathing issues and the need for a ventilator, is called a cytokine storm.

It is well known in the research literature that estrogen modulates cytokine storm. This was also demonstrated in studies involving two other coronaviruses, SARS and MERS, which are also twice as deadly in males. This finding was validated by studies in which male mice infected with SARS were twice as likely to die as infected female mice.

However, studies on SARS by Stanley Perlman, MD, PhD at the University of Iowa showed that female mice died at the same rate as males when their ovaries were removed or their estrogen was blocked. And yet another study from Johns Hopkins University showed that giving additional estriol (another form of estrogen) to female mice infected with the influenza A virus reduced pulmonary inflammation from cytokine storm. These studies suggest that estriol may have broad therapeutic uses in infectious and inflammatory diseases by decreasing tissue inflammation.

It is possible that having functioning estrogen makes women less likely to die from Covid-19. If this is true, then short-term hormone treatment with estrogen or estriol in women may be helpful.

This is not as wild of a medical suggestion as it may sound. Most oral contraceptives contain estrogen. And there is a potential option for men, too. Flutamide, an androgen blocker used to treat prostate cancer, has also been shown to reduce inflammation in the immune system through estrogen receptor-related pathways in mice.

So far, successful hormone-related treatments have only been demonstrated in mice, but if studied further, they could be a viable treatment option for those struggling with Covid-19 symptoms.

Now is the time to start looking into all possible treatments, not in three years when we are reflecting back on how we could have handled this pandemic better. When faced with few viable options, it is both efficient and ethical to consider established treatments in new ways while we wait for more long-term answers, like vaccines.

Otolaryngologist. Author of Tooth and Nail:The Making of a Female Fight Doctor & Suck It: Empowered Guide to Breastfeeding, http://dolcenter.net @drlindadahl

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