physiological or
biological causes
Theories under investigation
There are many theories under investigation. What do they all have in common? They reiterate that endometriosis is a multifactorial disease - there are several factors involved in the disease - and that it creates vicious cycles in our system.
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A. Theory of retrograde menstruation
​When the uterus is unable to expel menstruation properly, menstruation with remnants of endometrium can rise and settle in the pelvis, causing endometriosis. However, this theory alone is not enough, since:
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There are men who have endometriosis [1]
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90% of women have had or have retrograde periods and only around 10-15% develop endometriosis [2]
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It does not explain how endometriosis can appear so far from the pelvis, such as in the eyes [3]
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Does not explain deep infiltrative endometriosis [4]
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However, it remains a very important theory and with great probability the first trigger of this multifactorial disease, which will then develop or not and to what extent, depending on many other factors.
In itself, the dysfunction of uterine contractions (“uterine dysperitalism”) also deserves an exhaustive analysis and is something that I incorporate in the elaboration of EndoYoga practices.
B. Surgeries
Another possibility for endometrial cells to end up outside the uterine cavity is through “contamination” during surgery in the abdominal area such as a cesarean section or hysterectomy. Imagine that endometrial cells “fall” out of the uterus during surgery and stay there. Like the previous theory, here too we need to explain what causes the body to not be able to “eliminate” these cells that are “aliens” outside the uterus.
C. Genetics
An article from February 2023 reveals that there are already 40 genetic risk factors mapped as important factors in the development of endometriosis and its extent. However, the dynamics between each of them require much more investigation. These are genes for hormonal regulation, cell adhesion and proliferation, particularly in stages 3 and 4 of the disease. We can say that a genetic risk profile for endometriosis for genes that cause mutations is beginning to emerge, something similar to carcinogens [2].
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Once again, it is important to emphasize that endometriosis is benign. However, some health professionals call it “benign cancer” precisely because of its genetic mutations and because it can appear in areas far from its origin. Consequently, the most serious cases of endometriosis can actually pose very serious dangers to a woman's health.
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Epigenetics is addressed in environmental and behavioral factors.
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D. Metaplasia theories (cell mutation or transformation)
There are several theories of metaplasia:
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Coelomic metaplasia: The development of female sexual organs in the embryo occurs from a pair of Müllerian ducts, which arise from coelomic epithelial cells of mesodermal origin. This theory assumes that the original coelomic membrane undergoes metaplasia and forms stroma and endometrial glands and is the most plausible theory for endometriosis in men, for example [5].
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Metaplasia of embryonic Müllerian duct cells: Similar to the previous one, but here the mutation occurs “at the second level”, at the level of the Müllerian duct cells themselves [4].
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Metaplasia of peritoneal cells: hormonal or immune system changes that can change the cells of the abdomen (peritoneal) into cells similar to those of the endometrium [4][5].
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Mutation of embryonic stem cells: Either the endometrium or the bone marrow. The latter explains the appearance (although rare) of endometriosis outside the pelvis, such as in the eyes [3].
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E. Sampson's theory of benign metastasis - Transport of cells via blood and/or lymphatic vessels
According to this theory, endometrial cells can reach sites as remote as the brain by transport via blood and/or lymphatic vessels [4].
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F. Hormonal imbalance and immune dysregulation
The imbalance in estrogen levels also leads to a deficiency and resistance to progesterone. Progesterone would be the hormone that helps regulate estrogen. It is a harmful cycle that feeds on itself and contributes to the fact that 50% of women with endo suffer or will suffer from anxiety and/or depression [4]. After all, we are talking about the hormones that are the leading figures in the women's mood show.
In turn, hormonal imbalance itself promotes conditions for inflammation. Menstrual cycles change and consequently the body's immune mechanisms fail due to unregulated levels of cells that would correct the situation. Not only menstruation is no longer expelled properly, but its remains are no longer properly eliminated as they would be under normal circumstances by the body, which leads to chronic inflammation.
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Other tumor-promoting and angiogenic factors support the progression of endometrial lesions and the inhibition of apoptosis (cells from unexpelled menstrual debris do not die as they should) promotes cell proliferation and lesion growth.
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In addition to the abnormal tissue growth promoted, there is the growth of nerve fibers, which can justify pain that can reach levels on the limit of the unbearable [4].
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G. Bacterial infections
This theory avenue focuses on the role of bacteria as the cause or progression of the disease. Chronic inflammation can also be explained by bacterial endotoxins and studies reveal that women with endo have deregulated microbiota (quantity and type of bacteria) in the intestine, vagina and uterus. They present higher levels of endotoxins in the menstrual and peritoneal flow. Namely, studies show that women with endo are more likely to have menstrual blood contaminated with the bacteria Escherichia coli. We also know that certain bacteria will inhibit and others will inhibit the progression of endo [2].
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A June 2023 study found the bacteria Fusobacterium to play a determining role in the formation of endometriosis in the ovaries. This bacteria was found in 64% of patients with endometriosis. The researchers infected mice with Fusobacterium and implanted endometrial cells. They then tested the use of antibiotics and the results are promising: to a large extent they found that the implantation of endometriosis was reduced, as well as the number and severity of the lesions. The eradication of this bacteria could be one of the ways to treat endometriosis in the future [6].
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References
[1] Endometriosis in men - Endometriosis news. (2018b, November 21). Endometriosis News. Retrieved December 11, 2024, from https://endometriosisnews.com/endometriosis-in-men/
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[2] Cousins, F. L., McKinnon, B. D., Mortlock, S., Fitzgerald, H. C., Zhang, C., Montgomery, G. W., & Gargett, C. E. (2023). New concepts on the etiology of endometriosis. Journal of Obstetrics and Gynaecology Research, 49(4), 1090–1105. https://doi.org/10.1111/jog.15549
[3] Eyes, menstruation and endometriosis - Facts, views & vision in ObGyn. (2023, 30 de Junho). Retrieved December 11, 2024, from https://fvvo.eu/archive/volume-15/number-2/reviews/eyes-menstruation-and-endometriosis/
[4] ​Lamceva, J., Uljanovs, R., & Strumfa, I. (2023). The main theories on the pathogenesis of endometriosis. International Journal of Molecular Sciences, 24(5), 4254. https://doi.org/10.3390/ijms24054254
[5] Endometriosis - Symptoms and causes. (n.d.). Mayo Clinic. Retrieved December 17, 2024, from https://www.mayoclinic.org/diseases-conditions/endometriosis/symptoms-causes/syc-20354656
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[6] Muraoka, A., Suzuki, M., Hamaguchi, T., Watanabe, S., Iijima, K., Murofushi, Y., Shinjo, K., Osuka, S., Hariyama, Y., Ito, M., Ohno, K., Kiyono, T., Kyo, S., Iwase, A., Kikkawa, F., Kajiyama, H., & Kondo, Y. (2023). Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts. Science Translational Medicine, 15(700). https://doi.org/10.1126/scitranslmed.add1531
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