Although there are many theories for the pathogenesis of endometriosis, none have been successively confirmed as a direct cause for disease development. Evidence suggests that endometriosis is caused by a combination of genetic, epigenetic, hormonal, inflammatory, stress and immunological (including autoimmune) factors. It’s thought that people who have endometriosis may have abnormal immune system responses. This could either stem from endometriosis, or the condition itself may be a result of the immune dysfunction. Endometriosis is an inflammatory disease, where endocrine-immunological interactions are believed to be involved in the development of the disease which also means the cause is likely multifactorial.
- Retrograde Menstruation
- Immune dysfunction
- Microbial dysfunction/IBS/SIBO/gram negative bacteria/nickel
- Hormone imbalance
The retrograde menstruation is one of the oldest theories, in which part of the menstrual blood each month flows into the interior of the abdomen rather than out of the body. The backward flow of menstrual blood into the pelvic cavity may displace endometrial-like cells outside of the uterus, causing similar cells to grow. However, this clearly doesn’t explain why there are some patients with cases of endometriosis on lungs or on the brain or how it has even been detected in a new-born baby’s umbilical cord? It also has another major flaw in that, nearly all women at some point experience retrograde menstruation and doesn’t explain why some women develop endometriosis and some do not. This theory also does not explain why endometriosis has developed in some women after hysterectomy, or why, in rare cases, endometriosis has been discovered in some men when they have been exposed to oestrogen through drug treatments.
It is believed that endometriosis has a genetic link because women with a mother or sister who suffer from endometriosis are 6 times more likely to have the condition themselves. Currently, no specific ‘endometriosis gene’ has been identified.
From a spiritual point of view, I also look at ancestral healing when looking at genetics.
Inflammation is an extremely significant part of endometriosis. It is so confusing in its pathway however, that it is difficult to know whether endometrioses causes inflammation or whether endometriosis is actually causing the inflammation. To me it seems like both. Inflammation is the body’s way of protecting itself from infection. In response to a virus or bacteria, the body makes white blood cells, which activate inflammatory cytokines that help protect the body from these foreign substances. Because endometriosis is not native to the body, the immune system is in constant defence mode. This reaction causes increased blood flow to the injury or area and can leak into the tissue causes swelling. This process also stimulates nerves and can cause pain.
The body’s immune response to having endometriosis in the pelvic cavity is inflammation. Peritoneal fluid (a liquid that is made in the abdominal cavity to lubricate the surface of the tissue that lines the abdominal wall, pelvic cavity and most organs in the abdomen) contains several types of cells from the immune system, including macrophages, NK cells, lymphocytes, monocytes, and mesothelial cells. In women diagnosed with endometriosis, the activation of macrophages is enhanced, they are shown to release more cytokines and prostaglandins. In endometriosis patients, an increased level of inflammatory cytokines and other inflammatory mediators are found in the peritoneal fluid.
These inflammatory mediators are also believed to promote the spreading of new blood vessels at the site of the lesions in the surrounding tissue. This local inflammation can also produce scar tissue, which then in turn can connect to other locally inflamed areas creating adhesions. Endometriosis can cause excessive free radical activity in the body leading to oxidative stress.
In endometriosis, the immune system may fail to recognise the endometrial tissue growing where it shouldn’t be in the body. It is believed endometrial lesions may even have some ability to block the immune response. This immune dysfunction is believed to be what prevents the immune system from clearing up endometrial lesions and instead, support the growth and spread of those lesions. Normally, when we experience internal bleeding, our immune system naturally tries to absorb it or breaks it down. This does not happen, however, with endometrial tissue.
Natural killer cells, seem to have reduced function in women diagnosed with endometriosis. This in turn, supports the survival of endometrial cells. As mentioned earlier, the peritoneal fluid of women with endometriosis has higher oxidative stress. Oxidative stress involves an imbalance between free radicals, which activate macrophages. Macrophages are extremely diverse cells present in all tissues of the body that perform functions vital for immunity, tissue homeostasis and repair if we are injured. They can modify their role depending on the signals they receive. In endometriosis, the macrophages seem to be confused about endometrial tissue, believing it to be a wound, they activate programs that help cell survival rather than hinder it. This basically means the macrophages aren’t doing their job of destroying the lesions but actually releasing a lot more inflammatory cytokines.
What is causing the immune dysfunction?
The Auto-immune Theory
This disease does share very similar characteristics with common autoimmune diseases such as rheumatoid arthritis (RA), Crohn’s disease, and psoriasis. Although endometriosis has not been classified as an autoimmune disease, it has been established that a connection might exist. It has been associated with very similar characteristics as other auto immune conditions such as; polyclonal B-cell activation which are cells that secrete anti-endometrial autoantibodies (which are antibodies to self) have been observed in women with endometriosis.
Women with endometriosis can often also have the same or similar autoimmune disorders like lupus, Rheumatoid arthritis(RA), inflammatory bowel disease(IBD) and coeliac disease (CLD). Researchers are trying to understand whether endometriosis and autoimmune diseases have a kind of “chicken and egg relationship” as in which comes first, which causes the other or whether they actually arise independently. The establishment of the possible connection could suggest that women with endometriosis should be checked for other autoimmune conditions, and women with pelvic pain that have been diagnosed with another autoimmune condition should be checked for endometriosis.
Microbial Dysbiosis / Leaky Gut / SIBO / Candida
See our detailed blog on Microbial Dysbiosis / Leaky Gut / SIBO / Candida.
Your gut microbiota (gut flora) is the name given to the huge microbe population living in your intestine. This microbiome, contains a variety of bacteria, viruses and yeast that live and are natural to your gut. The gut also houses the majority of your immune system – 70-80% of our immune cells are found here. Our immune system has co-evolved along with a diverse gut flora, not only to create defences against pathogens, but also to develop permeability for beneficial microbes.
If you suffer from Endometriosis, you likely also suffer with the bloating, other digestive symptoms and ‘endo belly.’ These digestive symptoms such as constipation and diarrhoea are common in women who have endometriosis. Many of the symptoms present the same in both endometriosis and IBS. Women are often diagnosed with IBS before they are diagnosed with Endometriosis. Another interesting thing to note is that endo-belly seems to occur regardless of the location of endometriosis. This means, that you could be experiencing gastrointestinal symptoms without endometriosis being located on the bowel.
Oestrogen dominance is when a woman’s levels of oestrogen and progesterone hormones, are out of balance. A type of oestrogen called estradiol regulates how your uterine tissue grows. High oestrogen production is a commonly observed feature of endometriosis (although it is important to note that not all women with high oestrogen experience endometriosis). Oestrogen is not believed to cause endometrial growth outside the uterus. It can, however, worsen the pain and inflammation already present with endometriosis.
Common to all theories, is that oestrogen is required for endometriotic lesions to grow and expand. It has more of a stimulating or triggering role. That is the common belief as to why endometriosis is hardly ever seen in young girls before they start menstruating and less lesions are seen in women who are post menopause. Exposure to environmental chemicals that mimic oestrogen’s- also known as xenoestrogens, which are found in things like plastics and personal care products are also believed to play a role.
Most women with endometriosis have symptoms of PMS including anxiety, mood swings, bloating, breast soreness, constipation, food cravings and headaches. These symptoms are believed to be associated with hormonal imbalance.
Progesterone response also seems to be impaired in women with endometriosis. Causes of this may include genetics, epigenetics and environmental toxins like dioxin. (which we get to below)
A very new study published in March 2021 in Evolution, Medicine, and Public Health and another published in the May 2021 issue of Evolutionary Applications called “Endometriosis and Polycystic Ovarian Syndrome (PCOS) Are Diametric Disorders.” Have been an interesting development in the potential role testosterone plays related to hormone exposure prenatal with too little testosterone (endometriosis) and too much testosterone (PCOS). In women, it is believed that testosterone decreases pain perception, while estradiol increases it.
Epigenetics are the study of how behaviours and environment can cause changes that may affect how our genes operate without actually altering our DNA sequence. If genes are the computer, epigenetics affect the program and how they behave. Researchers studying epigenetics have looked at how everything we do think, eat, breathe, stress about affects our genes. It’s the study of why some genes get turned on or off based on environmental factors leading to things like, endometriosis.
Environmental factors like dioxins can be important when looking at Endometriosis. Dioxin is an environmental pollutant. The term dioxin is also used when referring to “dioxin-like” polychlorinated biphenyls (PCBs), which have similar chemical and structural properties. These dioxins can disrupt the endocrine system, including affecting oestrogen.
Research studies have shown that when animals were exposed to high levels of dioxin they developed endometriosis. This theory has not yet been proven for humans. Dioxin is found in our food, especially in meat and dairy foods.
You can read about other endocrine disruptors in our blog article.
Stress might be looked at as both an aggravator and a consequence of Endometriosis. Stress produces cortisol which can affect your immune systems functioning. It also causes an inflammatory reaction in the body. On the other hand, the extreme pain and discomfort caused by the symptoms can affect every facet of your life including; ability to work, exercise, sex life, socialise and family and personal relationships. This anguish can create even more stress.
This is why managing the pain and soothing the nervous system is so important in holistic treatment.
There have also been recent studies that suggest an association between trauma, abuse and endometriosis. A very large study — published in Human Reproduction in 2018 — found that severe-chronic sexual and physical abuse of several types increased the risk of a formal endometriosis diagnosis by 79%. These studies however, did not conclude that all women with endometriosis experience abuse, it did however highlight the fact that both abuse and endometriosis are all too common.
For women suffering with endometriosis, negative body image can become a problem. In some cases, women with endometriosis might feel like their body has failed them or hates them. The painful and intense physical symptoms can negatively affect the way you might feel about your body. It can create a mistrust in the body due to its unpredictable, uncomfortable nature and potential effect on fertility. One of the first treatments I apply with my endometriosis clients is establishing how they feel about their bodies and cycle and gently provide information and tools that might help in changing the way they feel about themselves and more specifically their menstrual cycle.
New research is also strongly linking stress, and specifically childhood/sexual trauma although the studies might just be indicating the high cases of endometriosis and abuse worldwide.
Women with endometriosis and extensive adhesions are more likely to develop bowel problems, especially constipation, fertility challenges, and chronic bladder problems. Further, because of chronic pain, women are at risk of complications associated with the overuse of pain medications, from Panadol (liver toxicity) and ibuprofen (leaky gut, GI bleeding, heart attack), to becoming dependent on prescription pain medications.