Everyone is talking about it, but what's the one thing they are missing?

Times are changing, and so is the conversation around menopause! Gone are the days when menopause was a hush-hush topic. Now, it's taking centre stage in scientific research, social media, TV and even in workplaces. This is a welcomed and long overdue shift. Women are now able to arm themselves with information about menopause, engage in open discussions and foster supportive and inclusive communities by sharing stories and advice through this transformative time. We are closer to finally breaking the stigma about a natural chapter of a woman's life.

I recently posted on my Instagram about the one thing missing in conversations about menopause. I followed this up with a post about inflammation and the menstrual cycle. For more reading, I have an older post on psychoneuroimmunology and menopause. Lots of you asked for a bit more detail than is possible in an Instagram post. I’ve tried to cover some of the pertinent stuff in this article. Before you dive in, I do need to caveat that this isn't meant to be and could never be a comprehensive article on the topic of the immune system and menopause for a few reasons. For one, this topic hasn't been fully explored in the medical literature. Secondly, it is crazy complex. We can take the reductionist approach to delineate the role of estrogen for example, but in any given person experiencing menopause will be a holistic mix of all the hormones as well as complex biopsychosocial determinants.

Let’s start with the basics

Let’s start with some basics. Every aspect of our physical and mental health is in the hands of our immune system. I know I am biased but I promise it’s true. This often tracks back to the immune system’s inflammatory response which has to tread a fine balance between being too weak (can’t fight off infections) and being overzealous (damaging our own delicate tissues). Inflammation can occur anywhere in the body, including our brain. Our nervous system is also very sensitive to inflammation. This means inflammation can damage both physical and mental health. Unwanted inflammation is a huge problem in modern diseases with >50% of deaths across the globe now considered inflammation-related. I’ll come back to the importance of inflammation in the context of sex hormones and menopause later.

What else do you need to know?

The second thing to know is that our immune cells express receptors for sex hormones. This holds profound significance in understanding how our hormones influence our immune system. These receptors act as communication channels allowing signals from the endocrine system (hormones) to influence immune cell behavior and functions. This crosstalk has far-reaching implications, including susceptibility to infections, the development of autoimmune diseases, and even responses to chronic inflammatory diseases.

This point relates to the fact that the immune response is what we call ‘sexually dimorphic’. Sexually dimorphic means that the immune system functions differently in males and females and ultimately influences our health and disease susceptibility. Some aspects of this sex dimorphism can be attributed to the differences in the hormones estrogen, progesterone and testosterone in males and females. This is why there is some truth in the old adage about man-flu being a real phenomenon. Generally speaking, females have higher levels of estrogen and progesterone, which can enhance immune responses and provide more robust protection from infections. Eostprgen is known to have a particularly profound impact on immune function (which I’ll elaborate more on further down).

Prior to menopause, females have approximately 5x more circulating estrogen than men. These levels fluctuate of course with menstrual cycling (and at some points in the month can be found at levels close to that found in men). This is why females can experience low-grade inflammation during the start of menstruation when estrogen levels are at their lowest. Estrogen levels tend to be at their highest during pregnancy, peaking during the 3rd trimester where they can be up to 60 times higher than when not pregnant.

Males have higher levels of testosterone, which has a more immune-suppressive effect. It can lead to a less aggressive immune response, which, in some cases, may lead to them suffering longer with infections. This is good news for infections in females but the flipside is that the more robust immune response in females results in them having a higher risk for autoimmune diseases. More than 80% of autoimmune diseases are in women which is a staggering figure. Recognising these differences is pivotal in designing better healthcare approaches but this has been largely overlooked and is only recently being explored in scientific research.

the immune system and menopause

If we dive into the immune system during the perimenopausal period and post-menopause. Menopause is marked by a significant drop in estrogen and progesterone levels, leading to a host of physical and emotional changes. But what often goes unnoticed is that this hormonal shift has a direct impact on the immune system. The low hormone situation post-menopause means that the female immune system behaves more like men. This means that women are at increased risk for infections than their pre-menopause self. This includes urinary tract infections, respiratory infections, gastrointestinal infections and skin infections. They can be more frequent, severe and/or prolonged with an increased risk of complications. Estrogen is particularly good at helping the early antiviral response (known as type 1 interferon response) get going, which nips the infection in the bud early before it can get a strong foothold. Because estrogen can rise during pregnancy to 60x higher than when not pregnant, this is, in part, why pregnancy is accompanied by an increased vulnerability to infection. This is also why those suffering from inflammatory conditions may experience a remission of symptoms during pregnancy.

Chronic inflammation is also an issue post-menopause. Estrogen, as I mentioned in the last paragraph, is helpful for getting the early anti-viral inflammatory response going. But it actually suppresses many proinflammatory mediators. For example, NK-kappaB is a master regulator of inflammation. It’s job is to turn on the proinflammatory genes giving inflammation the green light to get going. NF-kappaB is useful in the short term when responding to infection or injury but if turned on unnecessarily or not switched off properly when it’s no longer needed, it can precipitate chronic inflammation. This is one of the mechanisms that means menopause is now deemed an inflammatory event. Raised levels of inflammation over time will deregulate the immune response and ability to fight off infection. But this also causes micro damage to our tissues and impairs our ability to repair and recover. It also represents a risk factor for cardiovascular health and metabolic disease. Prolonged inflammation can promote the growth of cancer cells and increase the risk of cancer development. Inflammatory processes can damage DNA and support the survival and proliferation of cancerous cells. Chronic inflammation can impair the immune system's ability to recognize and eliminate abnormal or cancerous cells. This allows potentially cancerous cells to evade immunosurveillance which can further elevate risk for certain cancers.

It’s not just after menopause that we need to consider

The impact of menopause doesn't just start once a woman has had the absence of menstruation for 12 months. Perimenopause can vary in duration from person to person, but can last for up to 10 years and usually occurs between the ages of 45 and 55. The list of perimenopausal symptoms is long and includes both physical and mental manifestations. While we cannot attribute these symptoms solely to hormonal changes (perimenopause often falls at a time when life can be exhausting and stressful), immune-related changes are often not something people (or doctors) are aware of. This is why I feel passionate about advocating and supporting women to engage in open conversations with friends, family, colleagues and healthcare providers on immune health and inflammatory risks during menopause.

I realise this is all painting a bleak picture and I am conscious of this. This post isn’t meant to scare anyone. But by highlighting menopause as an inflammatory event that also increases the risk for infection we can support women in managing and reducing chronic inflammation through lifestyle changes and medical interventions (if needed).

some practical stuff

This brings me to the practical stuff. What can women do to mitigate some of these risks? The question of whether hormone replacement therapy (HRT) can ameliorate the impact of menopause on the immune system isn’t easy to tease out. It’s important to note that the issue of HRT is a personal one that should be discussed with your doctor. My aim is to paint an objective picture from available data but this should not overshadow your personal experience or personal feelings on HRT, nor any recommendations from your health care professional. It has been shown that HRT can partially limit the inflammatory menopausal state and somewhat reverse menopausal immune senescence (basically immune ageing - I didn’t even manage to get to that in this article. In short, another result of the menopausal transition is the senescence, or ageing, of the female immune system. Old things tend to not work as well so you get the picture). In human studies, it’s been found that women taking HRT have higher numbers of specific immune cells including lymphocytes (your adaptive immune system) and monocytes (your first line innate immune system) and a better ratio of CD4:CD8 T lymphocytes (i.e. better immune ageing) compared with post-menopausal women not receiving HRT. This difference is already obvious within the first month after treatment initiation. HRT is specifically through to counteract the effects of menopause on B cells - the antibody producers. We need to remember a study is just that, one study and the results may not be generalisable to a large heterogenous population of women. Studies differ with regard to regimen of HRT, dose, duration and when in the perimenopause journey treatment was started. This is likely the reason that various studies investigating the effect of HRT on inflammatory markers haven’t given a clear picture yet.

In terms of diet and lifestyle, I know everyone wants answers and simple answers that are both easy to employ in daily life and give immediate relief. There is a huge place for diet, lifestyle and supplementation in reducing unwanted inflammation, improving immune function and reducing some of the symptoms experienced during menopause. The challenge is that it usually requires a holistic approach and the science is in the compliance. Basically, lots of little things regularly can add up to have a big impact. When it comes to diet, think patterns not the reductionist approach to individual foods. Of course, certain foods should be held in high regard for their anti-inflammatory benefits, but ultimately it is the greater sum of all the foods eaten regularly, known as your dietary pattern, that will have the biggest effect. The Mediterranean diet is an example of an anti-inflammatory diet pattern and it is one of the most well-studied. Just be aware that there is no single definition of a Mediterranean diet, it is more an amalgamation of all the traditional, minimally processed diets eaten in the countries that border the Mediterranean Sea. This means a Mediterranean diet will vary in the types of foods and amounts of things like meat. Generally speaking, it is minimally processed, seasonal and full of plant fibre with olive oil being the key fat. Olive oil has its own unique anti-inflammatory benefits which I’ve covered more here so I’d encourage anyone concerned about inflammation to make this the key fat in their diet.

Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms. Found mainly in legumes, grains, nuts, and vegetables, with soybeans being the richest source, they have been used successfully for the treatment of menopausal symptoms and have also shown a favourable effect on the prevention and treatment of osteoporosis in postmenopausal women. Studies are now revealing a reduction in specific inflammatory molecules in blood after nutritional supplementation with isoflavones. Make it your mission to fill your plate with colourful antiinflammatory fruits and vegetables, but don’t forget flavanoid-rich legumes. These compounds are your allies not only for immune health but for maintaining a healthy weight, supporting bone health and protecting your heart.

I have so much more to write, we haven't covered the role of progesterone and testosterone nor the specifics of lifestyle change. But as this is getting rather long, I think I’ll follow up with a part two. I’d like to end by mentioning alcohol. When we zoom out, I often think alcohol is the one lever women approaching menopause don’t want to pull. Alcohol, even in small amounts can make lots of things more challenging. It’s a toxin, so your body has some work to do to remove it, there is some evidence that perimenopause makes it harder to metabolise alcohol too. It has a negative effect on your gut biome and gut barrier (which can add to the inflammatory load). Alcohol can also impact sleep, anxiety and many other long-term health issues. It might not be something you want to change, but just one to keep in mind.

Stay tuned to learn more. In the meantime, pick up a copy of my books:

In my second book, Your Blueprint for Strong Immunity, I discuss why habits are a cornerstone of improving your immune system.

In my first book The Science of Staying Well to discover my favourite ways to nourish healthy immune function.