There is no commonly accepted aetiology of the disease. Endometriosis is a complex, heterogeneous and multifactorial disease, in which are involved hormonal, genetic, environmental and immunologic factors. The most likely theories are:

1. Retrograde Menstruation¹: The most widely accepted theory, it was introduced in 1927.  Menstrual blood(containing endometrial cells) travels in a retrograde fashion, through the fallopian tubes and into the pelvic cavity, creating implants of endometriosis. It is not, however, clear why this process only causes the disease in certain (and not all) individuals. It may be secondary to events that take place during foetal and early neonatal life². Supporting this theory is the fact that the disease is more common in women with early menarche and late menopause. Moreover, endometriosis more commonly presents in the left side of the pelvis and the right diaphragm, possibly as a result of gravity.
2. Metaplasia: According to this theory, cells outside the uterus transform (metaplasia) in cells similar to the endometrium (the internal lining of the womb). These cells could be found in the mesothelial lining of the peritoneum (coelomic metaplasia) or elsewhere and could undergo metaplasia as a result of chemical or immunological stimuli³. This theory could potentially explain the rare cases of endometriosis in women before the menarche⁴.
3. Genetic/Epigenetic Theory: In women with genetic predisposition for the disease, the presence of epi-genetic changes (that happens through the activation and de-activation of certain genes, depending on the environment and for certain periods of time) leads to disease expression⁵.

What is more, the disease could be associated with the following:

1. Oxidative Stress and Inflammation: The increased oxidation of lipoproteins has been linked to inflammation, damage to the genetic material and the pathogenesis of the disease⁶. The increased concentration of free radicals goes hand in hand with the reduced levels of anti-oxidants⁶.
2. Immunological Dysfunction: The higher incidence of auto-immune diseases in women with endometriosis⁷, supports the opinion that a dysfunction of the immunological system may be associated with the pathogenesis of endometriosis. It has been shown that women with endometriosis have higher levels of macrophages and lower cellular immunity⁸. The presence of ectopic endometrium causes a localised inflammatory reaction⁹. It has also been shown that the peritoneal fluid of women with endometriosis has higher concentration of cytokines and angiogenic factors¹⁰.
3. Stem Cells: Those undifferentiated cells, that can transform in any cell type, may be associated with the development of endometriosis foci¹¹.

In conclusion, it is not very clear what causes endometriosis. It is likely to be a combination of the aforementioned theories. It is possible that certain women are ‘’born with endometriosis’’ and the clinical manifestation of the disease could be secondary to exposure to certain environmental factors¹².

References:

1. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination

of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;

14:422–69.

2. Vannuccini, S. et al. Potential influence of in utero and early neonatal exposures on the later development of endometriosis. Fertil. Steril. 105, 997–1002 (2016).

3. R. O. Burney and L. Giudice, “Pathogenesis and pathophysiology of endometriosis,” Fertility and Sterility, vol. 98, pp. 511–519, 2012.

4. P. G. M. Figueira, M. S. Abrão, G. Krikun, and H. Taylor, “Stem cells in endometrium and their role in the pathogenesis of endometriosis,” Annals of the New York Academy of Sciences, vol. 1221, no. 1, pp. 10–17, 2011.

5. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril. 2019 Feb;111(2):327-340. doi: 10.1016/j.fertnstert.2018.10.013. Epub 2018 Dec 7. PMID: 30527836.

6. A. A. Murphy, W. Palinski, S. Rankin, A. J. Morales, and S. Parthasarathy, “Evidence for oxidatively modified lipid-protein complexes in endometrium and endometriosis,” Fertility and Sterility, vol. 69, no. 6, pp. 1092–1094, 1998.

7. N. Sinaii, S. D. Cleary, M. L. Ballweg, L. K. Nieman, and P. Stratton, “High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis,” Human Reproduction, vol. 17, no. 10, pp. 2715–2724, 2002.

8. J. Sikora, A. Mielczarek-Palacz, and Z. Kondera-Anasz, “Role of Natural Killer cell activity in the pathogenesis of endometriosis,” Current Medicinal Chemistry, vol. 18, no. 2, pp. 200–208, 2011.

9. C. M. Kyama, A. Mihalyi, P. Simsa et al., “Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis,” Frontiers in Bioscience, vol. 1, pp. 444–454, 2009.

10. M. W. Laschke, C. Giebels, and M. D. Menger, “Vasculogenesis: a new piece of the endometriosis puzzle,” Human Reproduction Update, vol. 17, no. 5, pp. 628–636, 2011.

11. X. Santamaria, E. E. Massasa, and H. S. Taylor, “Migration of cells from experimental endometriosis to the uterine endometrium,” Endocrinology, vol. 153, pp. 5566–5574, 2012.

12. Bouquet de Jolinière J, Ayoubi JM, Lesec G, Validire P, Goguin A, Gianaroli L, Dubuisson JB, Feki A, Gogusev J. Identification of displaced endometrial glands and embryonic duct remnants in female fetal reproductive tract: possible pathogenetic role in endometriotic and pelvic neoplastic processes. Front Physiol. 2012 Dec 3;3:444.