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Long Covid and Estrogen


There are huge differences in morbidity (having COVID-19) and mortality (dying from COVID-19) between the sexes, with men at a higher risk of severe COVID-19 disease and death than women.

Early studies from China claim that estrogen or lack of it is the important factor. The scientists in Wuhan found that people with low estrogen admitted to hospital with Covid-19 were more likely to suffer severe symptoms.


What is Estrogen?


Estrogen is a hormone, or chemical messenger, that is primarily known for:

  • stimulating female characteristics at puberty and controlling a person's reproductive cycle

  • the development and release of an egg each month (ovulation) for implantation in the womb

  • the thickening of the lining of the womb to receive a fertilized egg


However estrogen also plays a significant role in the health, vitality, and function of your immune system, priming it to ward off infection and disease. Estrogen does this by:

  • working as an anti-viral for infections such as Hepatitis C, Ebola and HIV.

  • working to improve the number and lifespan of all immune cells including neutrophils, macrophages, dendritic cells and natural killer cells.

  • working in a protective way on the blood vessels (endothelium) and cardiovascular system.

  • blocking the production of interleukin-6, a contributor in the cytokine storm, which can lead to tissue damage, especially the lungs

  • inhibiting angiotensin-converting enzyme (ACE) which then has a protective effects on the heart, lung, kidneys, central nervous system and gut.


For those of you who have read my previous posts on how the SARS-CoV-2 virus behaves and why it is so damaging will understand that all the above points - the cytokine storm, ACE 2 receptors, the endothelial damage and the immune cells - may also have contributed to Long Covid. Therefore it seems adequate estrogen levels are vital both in the acute infection and possibly in the prevention of Long Covid.


So estrogen has a VERY important role in protecting your immune system. Estrogen deficiency reduces levels of B-cells and T-cells, powerful cells of the immune system. Estrogen deficiency also increases levels of pro-inflammatory cytokines, which interfere with healthy immune function.

As estrogen fluctuates and declines—during your monthly cycle, during and after pregnancy, or as part of perimenopause and menopause—your immune system can become vulnerable.

This may explain why many young people are also suffering with Long Covid as it may be due to the point in your cycle when you caught Covid-19 - when estrogen levels are naturally low; and why some pregnant women were very seriously unwell with acute Covid-19.


On average people reach menopause by the age of 51. However, some people begin the transition towards menopause, the perimenopause, from their mid-thirties. During this time your estrogen levels start to drop.

In the paper "Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study" Bell et al. they hypothesized that pre-menopausal women with higher estrogen levels would have less severe Covid-19 when compared to women of the same age, and BMI, who had been through the menopause. They investigated links between COVID-19 rates and:

  1. menopausal status

  2. COCP (the Pill) use

  3. HRT (Hormone Replacement Therapy) use


People with symptom-based COVID-19, positive tested COVID-19, and disease severity based on requirement for hospital attendance or respiratory support were included.

Users of the COVID Symptom Tracker App (ZOE app) in the UK, including 152,637 women for menopause status, 295,689 for COCP use, and 151,193 for HRT use were surveyed. Analyses were adjusted for age, smoking and BMI.

Their results were:

  1. Post-menopausal women aged 40-60 years had a higher rate of COVID-19 and a corresponding range of symptoms

  2. Women aged 18-45 years taking COCP had a significantly lower rate COVID-19 with a reduction in hospital attendance compared to those not taking COCP.

  3. Post-menopausal women using HRT or hormonal therapies showed a lower rate of Covid-19 symptoms however, the researchers felt that the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential comorbidities.


In essence the research found that higher levels of estrogen may have a protective effect against Covid-19, leaving people who have gone through menopause vulnerable.


Since this paper an analysis of electronic health records of nearly 70,000 patients who tested positive for COVID-19 from 17 countries has shown that women taking HRT were more than 50% less likely to die from COVID-19 compared to women not taking HRT.


Estrogen and Long Covid


It is still quoted that the largest group of patients with Long Covid appears to be women in their early 50s - we simply do not know if this is true currently as again the data comes from FB support groups and Covid-19 symptom tracker apps where women are more likely to engage.

However we do know that the average age of the menopause is 51 and the majority of women are perimenopausal in their 40s. Many of the symptoms of Long Covid do overlap with perimenopausal and menopausal symptoms. Symptoms such as:

  • fatigue

  • tinnitus

  • constipation

  • poor sleep

  • brain fog

  • anxiety

  • palpitations


As the SARS-CoV-2 virus can latch onto the specific ACE2 receptors found in say the lung and heart they can also latch onto those found in the ovaries and pituitary - organs that are fundamental estrogen, and testosterone, production.


An online survey of 1,294 women with Long Covid found that 73% of women reported that their periods have changed since having symptoms of COVID-19. Some who were perimenopausal have been tipped over into menopause. Furthermore, 72% of women reported that their symptoms of Long Covid changed in relation to their menstrual cycle with 77% of women reporting their symptoms being worse prior to or during their periods (when hormone levels are at their lowest). Many Long Haulers do report a relapse prior to our period. I am almost 12 months into Long Covid and this is still happening to me.

Dr Louise Newson, of the Newson Health Menopause Centre, a menopause specialist in the UK says:

"These symptoms are likely to be related to low estrogen and testosterone levels so consideration should be given as a priority to replacing these low hormone levels with the right dose and type of HRT".

She feels that all women who attend a Long Covid clinic need to be asked about the possibility of being perimenopausal or menopausal. Alongside maintaining the menstrual cycle, estrogen plays a key role in cognitive and bone health, the immune system, and the cardiovascular system. Again like Mast Cell Activation Syndrome I do not feel that the perimenopause totally explains Long Covid however for some people who feel their symptoms could be worsened by perimenopause or the menopause HRT could be an option. Benefits also include reducing the risk of cardiovascular disease, type 2 diabetes, obesity, osteoporosis, depressive symptoms and dementia.


There is also the option to run your OCP packs together having the break less often if you are not managing the pre period relapses.

Just as a side note I found a piece on the Mind Body Green blog -


"People with chronically low estrogen and women who enter perimenopause or menopause earlier in life are at greater risk for developing some autoimmune diseases than are women who begin menopause later in life. If you already suffer from one or more immune disorders, continued low estrogen might worsen your situation and exacerbated during menopause because of deficient estrogen.

Pregnancy, on the other hand, with its flood of estrogen, progesterone, and other hormones, frequently has a beneficial effect on autoimmune disease. Many women with autoimmune diseases experience an alleviation or cessation of symptoms while they are pregnant and see a return of or increase in symptoms after giving birth, which corresponds to falling levels of estrogen".


I find this interesting as Long Covid acts like an autoimmune disease and maybe those with low oestrogen pre period or throughout their cycle are feeling the effects more. As I say at the end of a majority of my blogs - more research needed!

Society is slowly waking up to the devastation the perimenopause and menopause can have on people both physically and mentally. If this is effecting you please find a wealth of supportive information at https://www.menopausedoctor.co.uk .



References

https://pubmed.ncbi.nlm.nih.gov/8190002/

https://www.medrxiv.org/content/10.1101/2020.03.26.20043943v1

https://www.medrxiv.org/content/10.1101/2020.07.30.20164921v3

https://www.forbes.com/sites/alicebroster/2020/10/23/what-are-the-signs-of-perimenopause/?sh=35e196397b96

https://www.newsonhealth.co.uk/media/files/Female-hormones-and-Covid.pdf

https://www.medrxiv.org/content/10.1101/2020.08.21.20179671v1

https://www.mindbodygreen.com/articles/can-estrogen-protect-your-immune-system-this-obgyn-thinks-so

https://pubmed.ncbi.nlm.nih.gov/26435006/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722767/

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