I still remember how confused I felt when I first started delving into the literature of endometriosis: people with endometriosis suffer from systemic inflammation and have a high incidence of food allergies, yet endo still isn’t considered an autoimmune disease in the conventional sense? What does that mean?!
Studies suggest that endometriosis often coexists with autoimmune diseases like celiac and lupus, but doctors have yet to classify it as an autoimmune disease in its own right. Admittedly, we have a limited understanding of the disease process of endometriosis, thanks to chronic underfunding from the National Institutes of Health. Still, the short answer is technically no: endometriosis is NOT considered an autoimmune disease…. right now.
I include the qualifier because there is mounting evidence that the immune system is involved in endometriosis. We don’t understand exactly how or to what extent, but the involvement is there. Still, as I started to read these things when I was first diagnosed with suspected endo, I only found myself getting more confused.
I was confused not just by what we don’t know about endo, but also by the clear disagreement within different communities of doctors about what endo really is. Some people swear it’s not an autoimmune disease, clinging to the old explanation of retrograde menstruation — while others insist that the possibility of autoimmunity should be explored further and demand more extensive research into the disease.
Now that I’ve talked to so many people with endo, and learned so much more about the disease, I thankfully have a better understanding of the issue of autoimmunity in endometriosis. So, I sat down to write this post for any newly diagnosed patients who might find themselves as confused as I once was.
Despite how much we don’t know, there’s a wealth of information about endometriosis — but it can be difficult to find and comprehend if you don’t know what you’re looking for. Thus, I’ve combed through all the research for you to write the post I wish I had when I was first diagnosed with suspected endo. So, without further ado, here’s everything we know, to date, on endometriosis and autoimmunity….
What Endometriosis Isn’t: Retrograde Menstruation Theory
Let’s start by debunking some important myths about endo. Endometriosis may or may not be an autoimmune disease, but we definitely know what it isn’t — and endo isn’t due to retrograde menstruation, as researchers once thought.
Sampson’s theory of retrograde menstruation is the scientific community’s lazy and outdated explanation for why endo exists. People who accept retrograde menstruation as gospel are, in my opinion, the reason why endometriosis research doesn’t receive enough funding or attention as-is. But what exactly does “retrograde menstruation” mean?
The short explanation is that retrograde menstruation refers to the backwards flow of menstrual blood during your period. Sampson believed that this menstrual blood carries uterine tissue up through the uterus, into the fallopian tubes, into the ovaries and the pelvic cavitiy. There, the tissue implants and begins to grow and bleed, leading to the development of endometriosis.
Logically, it makes sense — but here’s why it’s NOT the true cause of endometriosis: all people with periods have retrograde menstruation, but not all people with periods have endo. The body’s natural waste mechanisms take care of the fluid and tissue from retrograde menstruation, preventing it from causing symptoms. Many surgeons believe that if endo was caused by retrograde menstruation, it would not require excision surgery to remove — yet that is clearly not the case today.
Another reason why the retrograde menstruation theory doesn’t make sense has to do with the nature of the endometriosis implants themselves. The tissue found outside the uterus in women with endo is similar to the tissue that makes up the uterine lining, but it is not identical. In other words, this tissue can’t have come from period blood; if so, it would not have any discernable difference from the tissue of the uterine lining that we shed each month.
Furthermore, endometriosis implants appear to grow long before a biological female starts their first period. Research has discovered a number of cases of what is called “fetal endometriosis,” in which babies who are still in the womb appear to have endometrial implants suggestive of the disease. Obviously, fetuses do not menstruate — so if endometriosis was truly due to retrograde menstruation, it would not be possible for babies to have endo. Yet they do.
What Endometriosis Is: Endo and the Immune System
We’ve learned so much more about endometriosis since Sampson first developed his theory, with many facts contradicting the idea of retrograde menstruation. So, if endometriosis isn’t due to retrograde menstruation, what causes it? The problem is that, well, we don’t know.
I can’t tell you for certain what causes endometriosis (nor can anyone — so, be skeptical of anybody who claims to have all the answers!), but I can tell you what we know about it so far to help you put together your own thoughts and ideas about what endo really is. Here’s what we know:
Endo is an inflammatory disease.
If there’s anything I can tell you with confidence, it is that endometriosis leads to inflammation in the body. Any person with endo can attest to the role inflammation plays in their everyday lives. From crippling fatigue to chronic pain, the endometriosis experience clearly suggests that inflammation is at play.
But don’t just take my word for it: doctors agree with the observation that inflammation plays a role in the pathogenesis (read: the way a disease develops) of endometriosis. The body develops inflammation in response to endometrial implants in the pelvis. Our bodies know those implants aren’t supposed to be there, and inflammation is the immune system’s way of protecting itself.
Endometrial tissue also produces estrogen. Estrogen dominance is, therefore, probably not a cause of endometriosis, but, most likely, a result. Because these lesions produce so much estrogen, however, excess hormones in the pelvis trigger further inflammation. The role of hormones in mediating inflammation due to endometriosis explains why palliative treatments like oral contraceptives appear to soothe the symptoms of endo.
Patients with endo are more prone to autoimmune disease and allergies.
We don’t know for certain that endometriosis is an autoimmune disease, but we do know that people with endo tend to have more autoimmune diseases than the general population. People with endometriosis are at higher risk of autoimmune conditions like lupus, multiple sclerosis, inflammatory bowel disease, celiac disease, and more. They are also more likely to develop immune-mediated allergies to foods, medications, and the environment, as well as asthma.
This shouldn’t be read as clear evidence that endometriosis is due to autoimmunity. In fact, current studies fall short of proving that endometriosis is an autoimmune disease. However, researchers know that people with one autoimmune disease are more prone to developing another. In a condition known as polyimmunity or multiple autoimmune syndrome, one-fourth of people with autoimmune diseases will go on to be diagnosed with another autoimmune disorder.
The fact that people with endometriosis are more likely to have at least one autoimmune disease should be read as correlation, not causation. Still, this initial evidence is promising for those who believe endometriosis has links to autoimmunity. If people with autoimmune diseases are more likely to develop another, this could be the sign we have been waiting for that endometriosis is more than the backwards flow of period blood, after all.
Endo shares pathogenicity with autoimmune diseases.
What limited understanding we do have of the pathogenicity, or disease process, of endometriosis bears similarities to that of many autoimmune diseases. A novel 2018 study found that many cells with immune functions play a role in the development and progression of endometriosis. Examples include:
- T-cells, which kill infected host cells and regulate the immune response. An imbalance of the types of T-cells in the body appears to stimulate the production of inflammatory cytokines, which tell the body to target immune cells and produce a specific response.
- Neutrophils found in the peritonial lining of the pelvis, which are the most common type of white blood cell in the body. They appear to secrete biochemicals that allow endometrial growth and invasion.
- Macrophages, white blood cells that ingest foreign bodies, can be found in large amounts at sites of infection. Even so, they seem to be ineffective in eliminating endometrial tissue from the pelvic cavity, suggesting some dysregulation in the immune system.
The behavior of these cells mimics that found in many autoimmune diseases. For example, in rheumatoid arthritis, the function of T-cells is also severely impaired, leading to chronic inflammation.
What’s more unique is the behavior of white blood cells (WBCs) in endometriosis. In most autoimmune conditions, WBCs like neutrophils and macrophages mistake healthy cells for dangerous ones and attack them. In endometriosis, WBCs appear to be unable to attack endometrial implants, suggesting immune dysfunction but not autoimmunity.
There is an emerging link between bacteria and endometriosis.
Immune cells may behave uniquely in endometriosis, but that doesn’t mean we should dispose of the concept of autoimmunity entirely. Still, there appear to be other factors at play besides the immune system in the development of endometriosis.
In 2018, a study proposed a new theory, the “bacterial contamination hypothesis,” to explain why endometriosis develops. They cultured menstrual blood and uterine tissue from endo patients, only to find that the tissue was highly contaminated with E. coli bacteria. Many women were also suffering from endometritis, a bacterial infection of the uterine lining.
Normally, the female reproductive tract contains members of a bacterial family called Lactobacillus, which helps maintain a healthy pH in the vagina, among other roles it plays in the body. In humans, E. coli colonizes the gut, helping maintain a healthy digestive tract. We’ve long known that E. coli can cause infections when it spreads from the gut to other areas of the body. For example, it is a common culprit behind urinary tract infections (UTIs), as this bacteria can travel from the anus to the urethra when wiping at the toilet.
Some people think the reason why E. coli is found in the menstrual blood of patients with endometriosis has to do with gut permeability. An overgrowth of healthy bacteria in the gut, known as small intestinal bacterial overgrowth (SIBO), can lead to increased permeability of the intestines, meaning E. coli may be able to pass through the intestines into the pelvic organs. There’s limited evidence that SIBO and endometriosis are related, but it’s definitely an area begging further exploration.
One thing we do have substantial evidence for is that people who suffer from lower genital tract infections — UTIs, sexually transmitted infections (STIs), bacterial vaginosis, yeast infections, etc. — tend to get diagnosed with endometriosis at higher rates than those who haven’t had an infection. A study of nearly 80,000 patients found that lower genital tract infections were an independent risk factor for endometriosis, with a confidence level of 95 percent, even after controlling for comorbidities. I’m not a doctor, but I am an endo patient — and I can tell you that I myself have struggled with recurring vaginal infections for years.
Again, correlation should not be considered causation. One explanation for the overlap between endo and vaginal infections, for example, could be that pain from pelvic inflammatory disease (PID), which develops when an untreated vaginal infection spreads to the upper reproductive tract, is being mistaken for endometriosis in these patients. But the idea that bacteria could play a role in the development of endometriosis is a novel hypothesis that deserves more attention in the future.
Endometriosis is complicated. Most likely, it’s not any one event or process that causes it, but rather a combination of multiple complex factors. The way these factors — including immune dysfunction and possible bacterial contamination — interact appears to produce the chronic inflammation and systemic symptoms associated with endometriosis.
Until we start funding endometriosis research and taking this condition seriously, we may never know what truly causes endo to develop. But, hey: we know it’s not retrograde menstruation. At least that’s something.