Extra Estrogen Protects Against COVID

May 29, 2022

Extra Estrogen Protects Against COVID-19

Two observational studies have now shown the same thing. The first, published this April, looked at 198,822 adults living in Italy during the first wave of COVID who filled out an online questionnaire. Positive tests and severity of illness were asked about.   6,873 participants had a known result of a nasal swab and they made up the study. They were 47 years old (mean) and were 65% female. According to the multivariate statistical analysis, women were about 75% as likely as men to get an infection from COVID and only 46% chance of getting a severe infection. Then, for the 2, 153 women over age 60 who were getting hormone replacement, their risk of getting a positive test was 46% compared to their age-matched peers. So, there was a 25% advantage to being a woman over a man for infection risk and then a further 54% reduction for women over 60 on hormone replacement for even getting an infection. Sounds like a tilt in favor of estrogen, doesn't it?

Hence, a second study to see if Italians are just like Swedes. Turns out, they are. In this newly published study, 49,853 women who were diagnosed with a positive test for COVID constituted the study group. Of those, 16,693 were aged 50–80 years old. 2,535 were taking hormone replacement therapy and 227 were on estrogen-blocking drugs for breast cancer management. Extra estrogen versus no estrogen. After adjusting for all the confounding variables, they estimated that being on extra estrogen (HRT) reduced the risk of dying by some 53%. (Postmenopausal women will have a serum estradiol level of 6-10 naturally, but once on a blocker, a level of 0-1 pgm. On replacement, they will often be 30-50. Premenopausal women will be 100-200 pgm) Being on estrogen blockers and having no estrogen doubled the risk of dying from COVID, but ended up not reaching statistical significance. As in other studies, age was an additional confounding variable, increasing the chance of dying by 15% for every year over 60. Ditto with "medical conditions".

What on earth makes this remarkable advantage? Why is estrogen so good for the human immune response? The reasons aren't known but it may be as simple as estrogen increasing mucus in the nose where the virus gets trapped and disposed of. Another thread of evidence suggests that estrogen modulates the ACE2 receptor the virus attaches to. Women have dramatic differences in their innate immune system, hence a greater propensity to auto-immune diseases. In the case of viral infections, like COVID, that may be helpful. Stay tuned. But now is not a bad time to be on hormone replacement....and considering all the subvariants of COVID and the likelihood that this virus is here to stay for the foreseeable future, a good reason to stay on it.

www.What will Work for me. Being male puts me off this strategy. We are beginning to have a credible library of choices to make to fight this virus. The best is protection and vaccination. But we are vulnerable human beings who need community and love and human touch. A hug, a handshake, a smile are all parts of our lives that we can't do without forever with a deep sense of loss and isolation. I want every woman I care for to feel encouraged to stay on their hormones. In the complex formula of risk and benefit, this is chalk mark on the benefit side.

References: Maturitas, Medical News Today, BMJ Open, Hormones, Am Jr Phys Lung, Cell Immunology,

Pop Quiz

1. What effect does estrogen have on COVID risk as shown by these studies?                   Answer: Aha, trick question. These are observational studies, and as such, don't constitute "proof". Association does not mean causation. There could be confounding things we haven't considered. Firemen, at the scene of a fire, usually aren't the cause of the fire. But it opens the door for a legitimate question. It's hard to imagine a randomized trial to study it, so the question may never be answered.

2. Ok, if I take it as enough evidence, what is my added risk of having COVID if I am age 67.                  Answer: 15% for every extra year over 60.   7 times 15 =105% or doubled risk over age 60. And then 15% for every extra medical risk: diabetes, etc

3. What is the suggestion of reduced risk of being a woman over a man?                      Answer: around 25% less

4. And what is the suggestion of reduced risk for hormone replacement versus no hormones for women over age 60.                                  Answer: About in half

5. And what is the additional risk for women on estrogen blockers, aka, no estrogen?                     Answer: Another trick question. The trend line suggested doubled risk but this is not statistically valid so needs a double grain of salt. An association study with no statistical validity is really a weak argument. But the trend line is there.  As everything in science, it needs a bigger study.  More infected people.  Not happening.