Endometriosis is an inflammatory disease that is affected by hormones but is not cause through hormones. Instead, endometriosis is, at least in part, a disease of immune dysfunction.
In episode 4 of my podcast/YouTube video (released March 2022), I discuss some of the new research on endometriosis, including the link to genes that increase the risk of autoimmune disease, the role of a bacterial toxin called lipopolysaccharide or LPS, and new targets for natural immune-modulating treatments.
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Transcript
Endometriosis is an inflammatory disease that is affected by hormones but not caused by hormones. Instead, endometriosis is, at least in part, a disease of immune dysfunction.
Welcome to the podcast. I’m your host Lara Briden, a naturopathic doctor and author of books Weather Adjustment Manual and Handbook of Hormone Regulation. And this episode is about a disease I thought I knew a lot about. After all, I have treated endometriosis for 25 years and have written about it on my blog and in both books. And I already knew about the immune system link and something called the “bacterial contamination theory” of endometriosis, but this week I discovered how much more there is to learn.
Because in preparation for today and a practitioner-training session later this year, I’ve spent the last few days deep diving into all the recent scientific papers and an amazing new textbook called The Immunology of Endometriosis. Now, I will distill it all for you. And if you’re a visual person, you can also check out the YouTube version of this episode.
As you probably know, endometriosis is a disease in which tissue similar to endometrial tissue grows outside the uterus and can cause pain and other symptoms. Lesions can be laid before birth or get there through retrograde menstruation. And the pain can be improved with surgery, especially excision surgery, which is the approach of trying to excise or remove all the lesions.
The big question, however, is, “why is the immune system alarmed about the outside-of-uterus endometrial-like tissue in some women but not in others?” After all, retrograde menstruation occurs in most women, but in most women, the immune system just quietly clears it. What is the difference in women with endometriosis?
As it turns out, there are a lot of moving parts. Let’s examine some of the aspects of the disease. And then, I’ll outline what I think are the key elements in what I call the endometriosis roadmap and some targets for natural treatment.
The first prominent aspect is estrogen, which strongly stimulates endometriosis lesions and is even produced by endometriosis lesions. That’s why turning off estrogen has become the standard medical treatment, but unfortunately, that approach has trade-offs because estrogen is important for overall health.
On the hormonal side of things, there’s also the fact that endometriosis lesions are resistant to progesterone, which is bad because progesterone is supposed to be the hormone that slows the growth of lesions.
As an aside, both estrogen and progesterone also affect the immune system. For example, estrogen generally promotes inflammation while progesterone generally reduces inflammation, especially autoimmune type inflammation which we will discuss in a moment.
Next, there is the role of the nervous system and the fact that endometriosis lesions are
heavily innervated in a way that normal endometrial tissue is not. There is also a complex interaction between the nervous system and the immune system called neurogenic inflammation.
Next, there are research findings about high iron, probably from damaged cells, and hypoxia or low oxygen at the site of wounds. And actually, both of those things can activate a type of immune cell called a macrophage, which we’ll get to in a moment.
Next, there is strong evidence linking endometriosis to low androgen exposure in utero, possibly due to environmental toxins. And how that can cause epigenetic changes in hormone production, hormone-sensitive tissue, and the immune system—our topic today.
Of course, environmental toxins can cause other epigenetic changes, some of which may be transgenerational, meaning your endometriosis today may be the result of an environmental toxin, such as a dioxin, that your grandmother was exposed to. .
There are many research findings about genetics, including the presence of genes that also increase the risk of autoimmune diseases such as lupus, rheumatoid arthritis, celiac disease, autoimmune thyroid disease, and inflammatory bowel disease. That opens up a whole can of worms about whether endometriosis itself is an autoimmune disease— a question that, unfortunately, has become very controversial.
Let me just say that endometriosis looks and acts like an autoimmune disease. And later in the podcast, I’m going to offer some endo treatment strategies that are essentially the same strategies that work for autoimmune disease. But, I wouldn’t say that endo is an autoimmune disease because there really isn’t a need to put a definitive label on it.
And speaking of immune, there are over a thousand papers on the immune dysfunction of endometriosis. And, of course, the new textbook. The research looks at every aspect and nuance of the immune situation, including a lot about macrophages and the rather intriguing finding that women with endo are more likely to develop a nickel allergy, suggesting a common underlying mechanism.
And finally, there are research findings about the role of the microbiome and all the different ways our resident bacteria affect hormones, immune function, and endometriosis.
Which brings us to what I feel are the key elements of endometriosis, or what I call the road to endometriosis and what we can do about it.
First, let’s agree that there is a background vulnerability to disease, which is partly genetic and partly epigenetic.
Next, there is the presence of lesions or endometrial-like tissue that can be placed before birth and/or deposited by retrograde menstruation.
Next, there are normal estrogen levels that begin at puberty. Estrogen stimulates endometrial tissue and can become highly inflammatory, especially in the presence of a bacterial toxin called LPS.
Which brings us to the microbiome and the “bacterial contamination theory” of endometriosis, which states that the presence of a bacterial toxin called lipopolysaccharide or LPS in the pelvis may be an initiating factor in the immune dysfunction of endometriosis. In particular, LPS destroys macrophages, which then interact with all the other parts of the immune system and are big players in endometriosis. To the point that one paper called endometriosis “a disease of the macrophage.”
Interestingly, tissue hypoxia, which I briefly mentioned earlier, also activates macrophages relevant to hypoxia research.
But where does the bacterial toxin come from? According to some recent papers, LPS can come from either dysbiosis of the vaginal microbiome that moves up the uterine lining and out through retrograde menstruation and/or from the gut through intestinal permeability and something called the gut microbiota-derived extracellular vesicles.
wow That means that in women who are vulnerable due to genetics and epigenetics, exposure to LPS from the gut can flare up or cause endometriosis. And certainly, there is a strong correlation between endometriosis and bowel problems. In particular, women with endo are many times more likely to develop irritable bowel syndrome or SIBO, which is small intestinal bacterial overgrowth. And that link is thought to be a result of endo affecting the bowel. But it may be in the opposite direction, with intestinal permeability and LPS from SIBO driving endometriosis. In fact, one study found that women with endometriosis were more likely to have intestinal permeability.
And downstream from all of this is the deep inflammatory state of endometriosis and pain.
All right. That’s a zoomed-out view of a complex disease. But it provides several targets for natural treatment: autoimmune genotype, LPS toxin, and immune dysfunction.
First, the autoimmune genotype suggests that endometriosis can (and does) respond to the same dietary interventions that help autoimmune disease.
In particular, I am talking about the strict avoidance of gluten, drawing on the work of Dr Alessio Fasano, who was the first researcher to provide scientific evidence about the role of intestinal permeability and gluten in autoimmune disease.
In my clinical experience, the other protein that can drive endometriosis is A1 casein from normal dairy, which is quite similar to gluten. And sometimes eggs, but in about 1 in 3 women with endo.
The next target for natural treatment is the LPS toxin which can be reversed with an antimicrobial approach. For example, antibiotics have been found to reduce the size of endometriosis lesions. Antimicrobial supplements can also help, especially berberine, certain probiotics, and other supplements that work for SIBO. That’s the approach I take with my patients and discuss on my blog and in both books.
As I tell my patients, “The first step is to fix your digestion. Only then will we have any hope of improving your endo.
Finally, we can target the immune system with all the supportive anti-inflammatory nutrients and supplements that the immune system loves. Researched immune nutrients for endometriosis include zinc and pre-formed vitamin A or retinol, which are two nutrients best obtained from animal foods. Other researched immune nutrients include vitamin D, selenium, N-acetyl cysteine, curcumin, resveratrol, and more.
I also regularly prescribe high doses of iodine for endometriosis both for its anti-estrogen effects and its antimicrobial, immune-modulating effects. There are some safety issues around iodine, so please see my iodine blog post, which I’ll link to in the show notes.
As for the other references, they are too numerous to put in the show notes, so please ask me on my forum.
Hope this helps, and thanks so much for listening. Please share and leave a review.
And I’ll see you next time when I discuss body-identical or bioidentical hormone therapy.
