Long COVID and menopause - the connection explained

The relationship between menopause and Long Covid has been demonstrated

Long COVID affects women significantly more than men, with women between 40 and 60 years old at the highest risk for Long COVID. (1 and 2) In this age group there is an overlap with the (peri)menopause period.

The British doctor Louise Newson is specialized in hormones and advocates for improved menopause care. As founder of the Newson Clinic, Newson Education and the free Balance app, she is dedicated to raising awareness, providing education, and improving access to scientifically supported care and hormone treatments. She has researched the connection between Long COVID and hormones and treats women with these issues. (3 and 4) Dr. Newson has reviewed and approved this English version.

The most common Long COVID symptoms (which resemble perimenopause and menopause symptoms)

According to C-support, the Dutch foundation commissioned by the Ministry of Health, Welfare and Sport (VWS) for aftercare of COVID patients, the most common Long COVID symptoms are:

Exhausting fatigue
Concentration problems and forgetfulness
Brain fog
Sensitivity to light and sound
Shortness of breath
Headache
Depression and irritability
Sleep disorders
Muscle pain
Dizziness

In total, about 200 different symptoms have been reported. Many people have 10 to 15 symptoms simultaneously. (5)

The coronavirus affects the ovaries via the ACE2 receptor

The Dutch Long COVID Foundation (Stichting Long Covid) promotes research into causes and treatment of Long COVID. On their website you can find Dr. Newson's research (4): https://www.stichtinglongcovid.nl/hormonale-disbalans 

Dr. Newson has given an explanation of how Long COVID and hormones can be linked. The coronavirus attaches to ACE2 receptors (angiotensin-converting enzyme 2) to enter cells, working together with the TMPRSS2 enzyme (type II transmembrane serine protease).

The ovaries and other reproductive organs have many ACE2 receptors and TMPRSS2 enzymes – about 80% of the ovarian cells. This is comparable to the amount of receptors and enzymes in the lungs (Wu, 2021 (14). The reasoning is that the virus can easily infect cells in the ovaries due to the abundance of ACE2 receptors, which affects the functioning of the organs.
When the COVID infection takes hold in the ovaries, this can cause an hormone (progesterone, estradiol and testosterone) deficiency or exacerbate an existing one, thereby intensifying perimenopausal or menopausal symptoms. A hormonal deficiency can lead to an irregular menstrual cycle or to hormonal/menopausal symptoms.

Women with low hormones who are perimenopausal or menopausal can have a slower recovery from a COVID infection, potentially triggering Long COVID. However, women of any age can be affected Wu's research showed no difference in ACE2 or TMPRSS2 expression between older and younger women or the size of the egg reserve. (14); symptoms can therefore also occur in younger women and it is not possible to predict who will be affected. Women with existing hormonal complaints are more likely to be severely affected.

The protective role of estradiol on the ovaries 

Dr. Newson further explains that the hormone estradiol (one of the estrogens) has a protective effect preventing the virus from entering ovarian cells, where it would otherwise replicate. Estradiol also inhibits inflammation and supports the immune system.  Women with low estradiol levels allow easier viral replication, potentially worsening long COVID symptoms. 

One study has shown that women notice their Long COVID symptoms peak just before or during menstruation when estradiol levels are naturally lowest. (15) Many report menstrual changes after COVID infection: less regular cycles or lighter bleeding.

A chicken-and-egg story: Long COVID and (peri)menopause reinforce each other 

One could say this is a chicken-and-egg story:

Women in perimenopause might have a higher risk of getting Long COVID because they have less estradiol.
At the same time, estradiol levels that are low can make some women more ill from Covid and prolong recovery because they lack that natural protection from estradiol

Long COVID and perimenopausal symptoms overlap and can exacerbate each other.

A low testosterone level plays a role in Long COVID

Besides estradiol, many doctors worldwide now see in research that women with Long COVID have low testosterone levels. (4 and 6) Testosterone is not only a male hormone – women also need it in smaller amounts. Testosterone is the most biologically active hormone in women. Testosterone also reduces inflammation.

Women’s testosterone levels drop with increasing age. Women with Long COVID have lower levels of testosterone than those without.

Low testosterone can cause:

Fatigue and low energy
Concentration problems and forgetfulness
Depressed feelings
Joint pain and muscle weakness

These match the most common Long COVID symptoms. Dr. Newson and others report many women benefit from supplementation with body-identical testosterone. (4, 6, and 7)

Recommended treatment of Long COVID

Dr. Newson would advise doctors to first exclude perimenopause and testosterone deficiency before diagnosing Long COVID. On C-support’s site is also stated: “it is important that other medical causes or explanations be excluded before post-COVID [=Long COVID] diagnosis.” (8)  Dr. Newson and other doctors believe women with symptoms of both Long COVID and perimenopause / menopause should first be considered for treatment with hormone replacement therapy (HRT) to see if symptoms improve. (4)

This is also recommended by Dutch gynecologist and menopause specialist Dorenda van Dijken. On the PostCovidNL site, Dr. van Dijken advises trying HRT for 3 months if Long COVID and menopausal complaints coexist. (9)
(Please note, in the Netherlands, information about testosterone and its relationship with Long COVID is not yet widely known.)

Additional approaches based on low testosterone findings

Dr. Newson and other British doctors like Dr. Sarah Glynne go further, perscribing testosterone in some cases and recommending a 6-month trial to assess improvement.
Menopausal symptoms can start 5–10 years before menstruation stops. Doctors should therefore be asking about symptoms which could be related to low hormones, even in younger women with Long COVID, says Dr. Newson. 

The gut-brain connection: the microbiome and Long COVID

One interesting Long COVID symptom that deserves extra attention is the worsening of gastrointestinal complaints.
COVID can both damage the gut’s protective lining and disrupt the gut-brain axis. This can cause inflammation in the lining and/or bring about changes in the gut microbiome. The latter is called dysbiosis. (4, 5, and 6)

Besides digestive problems (such as bloating and constipation, among others), this has additional consequences. Neurotransmitters such as serotonin (the 'happiness hormone' that is also important for sleep processes) are largely produced in the gut. A disrupted gut function can therefore interfere with the production of neurotransmitters and thus negatively affect the functioning of serotonin. (6 and 10)

Lower estradiol in perimenopause often negatively affects gut health (many women experience bloating during perimenopause and menopause (11)) and neurotransmitter production is affected. Perimenopausal and menopausal women often also suffer from sleep disorders.

Women with both Long COVID and in perimenopause may therefore be doubly affected.

Post-vaccination syndrome

Finally, it is also interesting to note that similar symptoms to those of Long COVID are also reported after one or more COVID vaccinations.

Of the people who have reported this to C-Support since 2021, the largest group is women (over 60%) aged between 40 and 70 years. Their website states that the persistent symptoms after vaccination for which people mainly contact C-Support for support and advice are: "Fatigue, concentration and memory problems are most common. There is also a group of patients who report with one or a few very specific complaints. People with symptoms after vaccination experience an average of 10 different complaints."

This is sometimes called Post-vaccination syndrome and has been described by various researchers and doctors, but healthcare has not yet found a definitive answer. (12 and 13)

If post-vaccination syndrome is suspected, based on the above reasoning and advice, you could also consider trying HRT.

Summary

There are clear overlaps between Long COVID and perimenopausal symptoms. Women aged 40–60 can have symptoms that reinforce each other, leading to more severe and lasting effects. Hormone Replacement Therapy (HRT) using estradiol and progesterone, also with testosterone, may provide relief. Doctors should be alert to hormonal fluctuations linked to Long COVID and rule out hormonal deficiencies before diagnosing Long COVID. Since there is no test to pinpoint the exact cause, various doctors recommend trying HRT to these women. Some doctors also recommend testosterone.

Positive experience with HRT including testosterone:

After a COVID infection in 2020, Sandra Beers developed Long COVID, experiencing around 35 symptoms, with extreme fatigue and brain impact greatly affecting her life. She saw the following doctors and therapists over 5 years: 

1 occupational physician 
3 different general practitioners in 6 consultations 
1 neurologist and neurology assistant 
1 internist 
4 physiotherapists
 3 ergotherapists 
2 orthomolecular physicians
 2 rehabilitation doctors
 2 psychologists 
2 job coaches 
1 energetic therapist

Annual expenses exceeded €1500 for: biweekly float sessions in a magnesium bath, learning the Epiphora Method, many neurofeedback sessions, custom earplugs, a special pillow for body support, 2 prescription glasses and shoe insoles, various supplements and LDN (low dose naltrexone).

Some helped temporarily, some not at all.  In the past year, she saw only one doctor: a Belgian Lifestyle & Menopause Expert, who used her knowledge and care to “work wonders on her 35 symptoms!”. This doctor prescribed HRT including testosterone. Combining these 3 hormones made a real difference.  She can again engage in activities without suffering symptoms afterwards. She resumed muscle-building exercises and improves her overall fitness. Testosterone in particular has played a clearly positive role in this. Additionally, she is exploring the job market again. None of this was possible in recent years.

Dr. Louise Newson: hormone expert and best-selling author

Dr Louise Newson is a GP, hormone specialist and a leading voice in transforming menopause care worldwide. As the founder of the Newson Clinic and the not-for-profit Newson Education, she is dedicated to improving awareness, education and access to evidence-based care.

Through in-person events, a comprehensive library of freely available articles, and an education programme for healthcare professionals, she empowers both women and clinicians with the knowledge they need. A Sunday Times bestselling author and host of the UK's No.1 medical podcast, Dr Newson is passionate about driving positive change for women's future health.

A member of the UK Government’s Menopause Taskforce, Dr Newson has been described as the “medic who kickstarted the menopause revolution”. She is an award-winning educator, podcaster and author, committed to increasing awareness of hormone health including perimenopause and menopause. Her mission is to provide inclusive, accessible and evidence-based information in formats that suit all women, helping them make informed choices about their health. Through her work, she has empowered a generation to take control of their treatment, bodies and minds, ensuring menopause care is recognised as a vital part of women’s healthcare. Find the website here.