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May 21, 2020

COVID-19, Female Sex Hormones, and Immunity: What We Know (So Far)

COVID-19, Female Sex Hormones, and Immunity:  What We Know (So Far)

TL;DR Women are faring better with COVID-19 infections than men, and a few new studies are exploring whether this is related to female sex hormones. The results of these studies could have important implications for both men and postmenopausal women—as well as furthering our understanding of how hormones impact the immune system. 

Since the coronavirus pandemic began, it’s been clear that men are more likely to become severely ill and even die of the disease than women. At Cedars-Sinai Hospital, 75% of COVID-19 patients in intensive care and on ventilators have been men. In New York City, men have died at two times the rate of women from the illness. (More global statistics in the resources at the end of this post.)

In some ways, this reality is surprising, given that most lung-affecting diseases are more severe among women. COVID-19 clearly bucks the trend.

Scientists and doctors have postulated that this may be due to hormonal differences between the sexes. For this reason, some new studies are exploring whether estrogen and progesterone—also known as the female sex hormones—can be used to treat the disease in men and/or postmenopausal women.

Here’s what we know—and don’t know—at this point in time. 

Theories on Why Women Fare Better

What is the difference between men and women? It’s a question as old as time. For the purposes of scientific research, the clearest biological difference comes down to hormones. 

However, if this were the only difference, one would expect women in their postmenopausal years, who have far less estrogen and progesterone in their bodies naturally, to fare as poorly as men do. This has not been the case. 

This doesn’t necessarily rule out hormonal differences completely, but it points to a more complex picture. For example, heart disease, high blood pressure, and liver disease are more common in elderly men than elderly women, comorbidities that may explain why the differences between the sexes persist even beyond menopause.

There are also some behavioral differences between men and women, which vary from culture to culture that could impact outcomes. For example:

Cigarette smoking alone is unlikely to explain the outcomes, as the male vs. female outcome differences are similar even in countries where men and women smoke at about the same rates. 

Finally, it has been observed that women generally have higher, more robust immune responses. This can have negative consequences (higher incidence of autoimmune diseases, for example), but it may also explain why they have better outcomes with COVID-19. 

Clearly, there are a lot of factors at play, and we still don’t have enough data to draw definitive conclusions about why women are less likely to get very sick or die of COVID-19. 

But there are some compelling reasons to explore whether hormones play a role.

Given the seriousness of the pandemic, the short-term question has become: Can we use female sex hormones to develop therapeutics?

Two COVID-19 Hormone Therapy Studies in Progress

There are currently two studies in the early stages in the United States exploring whether female sex hormones and their impact on the immune system might help men and postmenopausal women better fight the disease. 

One trial at Stony Brook University in Long Island is testing estrogen patches to see if they improve immune response and COVID-19 outcomes among adult men and women over 55. You can read more on the study at ClinicalTrials.gov

Another trial at Cedars-Sinai Hospital in Los Angeles is treating patients with progesterone shots to see whether their status improves based on oxygen levels, ICU admission, and ventilator usage. You can read more on the study at ClinicalTrials.gov.

Do Postmenopausal Women Taking Hormone Replacement Therapy Have Increased COVID-19 Protection?

Of course, there are some postmenopausal women who already take hormone replacement therapy (HRT) to treat symptoms like hot flashes, mood changes, and decreasing bone density. It’s worthwhile to investigate whether these women generally have better outcomes when infected with COVID-19 vs. their peers who are not on HRT.

In the UK, the Covid Symptom Study, led by King’s College and the NHS England, is using a mobile app to collect information from more than three million people in the country, with the goal of developing a clearer picture of how the disease impacts different groups. 

They are exploring, among other things, whether HRT may help postmenopausal women better respond to COVID-19—and whether the treatment might be prescribed to help protect key workers.  

Dr. Louise Newson is an advisor to NHS England and menopause specialist. As she explains, “If there is some protection (from estrogen), it means that women who are menopausal who take HRT—which we know has more benefits than risks for the majority of women—might be able to have some protection."

Time Will Tell

It’s far too early to draw definitive conclusions about whether hormone treatments will work to reduce the negative impacts of COVID-19 among men and postmenopausal women; these studies are likely to go on for quite a while before any certain evidence can be gleaned. 

However, we find these studies promising and are glad to see doctors and researchers recognizing the benefits of hormone therapies in general.

To read our founder and Chief Medical Officer Dr. Leslie Meserve’s advice and recommendations for menopausal women in the age of COVID-19, check out this post:

Are Menopausal Women More Susceptible to COVID-19?

More Resources on This Topic

If you’d like to learn more about these topics, here are some resources we recommend:

 

Global Statistics: Differences Between Sexes

All Europe

  • 63% of COVID-19 related deaths in Europe have been among men (Source)
  • 71% of all ICU admissions have been among men (Source)

 

Italy

  • 82% of critically ill COVID-19 patients admitted to ICUs were men (Source)
  • 58% of all COVID-19 cases and 72% of all deaths occurred in men in Italy between Feb. 21 and Mar. 12 (Source)
  • Men were 75% more likely to die than women who contracted the disease in Italy (Source)

 

China

  • Men and women are equally likely to contract COVID-19 (Source)
  • 60% of those who became sick with COVID-19 in China from Dec. 2019 to Feb. 2020 were men (Source)
  • Men were 65% more likely to die than women who contracted the disease in China (Source)
  • The fatality rate for men in one study was 2.8% vs. 1.7% for women (Source)
  • 61% of children under age 16 treated for COVID-19 at Wuhan Children’s Hospital were male (Source)

 

South Korea

  • 62% of COVID-19 cases in South Korea occurred in men (Source)
  • Men were 89% more likely to die than women (Source)