Endometriosis is a disease that affects millions of women worldwide but often goes undetected and misdiagnosed. The condition is classically defined by tissue lining the uterus (endometrium) being found in abnormal areas of the body, i.e., outside the uterus. Endometriosis lesions are commonly found in the reproductive system, which includes the ovaries, fallopian tubes, and pelvic cavity. They cause abnormal periods characterized by dysmenorrhea (painful periods), menorrhagia (heavy menstrual flow), and dyspareunia (painful sex). However, more extensive cases can invade the bowels, bladder, and appendix.
This can lead to GI symptoms such as painful bowel movements, cramps, diarrhea, constipation, and nausea upon one’s period. Endometriosis can also lead to chronic pelvic pain, neuropathy, and even, in some cases, infertility. For these reasons, it is important to further our knowledge on the disease and continue funding research that works toward improving control and treatment measures from a medical standpoint. But before this can be done, it is key to first understand what exactly causes endometriosis.
Sadly, the answer to this question is not concrete. While there are a number of well-researched theories among the scientific community, there is no singular underlying cause of endometriosis. It would seem that, like many diseases, there is a combination of mechanisms that could lead to a greater risk of developing endometriosis. It is thus highly beneficial to discuss some of these proposed causes.1
1. Retrograde Menstruation
Retrograde menstruation is defined as the backward flow of menstrual debris. While this does occur in many women to a small extent, it is speculated that this mechanism can play a part in the development of endometriosis. Sampson’s theory on retrograde menstruation states that endometriosis arises from sloughed endometrial cells migrating via the fallopian tubes and dispersing into the pelvic cavity during menstruation. This is one of the oldest principles proposed for explaining the etiology of endometriosis.
Lesions caused by retrograde menstruation respond to the hormonal fluctuations that occur in women during menstruation. These lesions then grow, menstruate, and further spread along the normal lining of the uterus, through the fallopian tubes, and into the pelvic cavity. While this theory puts forth a hypothesis for how endometrial cells migrate, it does not fully explain how they are able to differentiate into endometriosis lesions and implant into ectopic regions.
2. Stem Cell Theory
One of the most currently discussed and controversial topics in the scientific community is stem cells. These undifferentiated cells are capable of transforming and giving rise to indefinitely more cells of the same type and form and of other differentiated cells. In other words, they can develop into all different types of cells in the human body. This is a hot topic of discussion as it presents a remarkable capacity for regenerative growth in various medical therapies. However, it also raises some ethical questions because to obtain embryonic stem cells, the early embryo must be destroyed. But for our interest, we are looking to how these pluripotent cells are believed to play a key role in the development of endometriosis.
As is commonly known, the uterine lining (endometrium) sheds in monthly cycles during a woman’s period. While this tissue is expelled, a new endometrial lining grows and differentiates. It is believed that pluripotent stem cells are responsible for this regeneration. Due to their potential for self-renewal and reconstitution, stem cells are hypothesized to play a role in developing endometrial tissue in areas outside of the uterus, causing endometriosis. This concept is thus known as the “stem cell hypothesis” of endometriosis.
While it explains how endometriosis lesions can latch onto ectopic regions, it does not identify how these cells migrate to the said areas. However, when paired with Sampson’s theory and mulleriosis (the development of tumors composed of ectopic tissue), the stem cell hypothesis serves as the missing link for a possible explanation as to how endometriosis arises.2
3. Genetics And Uterine Anomalies
Another discussion in the debate over the causes of endometriosis lies in the field of genetics. It has been noted that there is a connection between family members affected by endometriosis. Patients who have a family history of endometriosis are often more prone to be affected. In addition to genetics playing a role on the clinical level, they also can be seen on a more molecular level.
Upon further examination into the HOX gene, a group of related genes controlling the development of the body plan, certain regions are responsible for developing the uterus. However, mutations and alternate gene expression in the HOX gene can lead to uterine anomalies. These structural abnormalities of the uterus have been believed to make women more susceptible to developing endometriosis, as the composition of the endometrial tissue influences whether lesions will have the ability to interact with the peritoneum (lining of the abdominal cavity) and become functional. For example, the decreased expression of the HOXA10 gene in the ectopic endometrium is seen in animal models of endometriosis. All of this points to a possible epigenetic factor that could play a role in the development of endometriosis, secondary to other causes.3
4. Uterine Peristalsis
A similar but distinct theory from uterine structural abnormalities lies in the examination of uterine peristalsis (movement) and its effect on the spreading of the ectopic endometrial tissue. Experts have proposed that upon transvaginal ultrasound viewing of laparoscopically proven endometriosis patients, the myometrium (the smooth muscle of the uterus underlying the endometrium) can often be seen as enhanced.4
Similar findings have also been seen in fMRI studies. Because the myometrium and endometrium are responsible for uterine peristalsis, it is believed through transitive reasoning that abnormal uterine peristalsis could play a factor in the development of endometriosis. The combination of abnormal uterine movement and retrograde menstruation presents yet another causal possibility in the etiology of endometriosis.5
While the exact cause of endometriosis is yet to be determined, it can be seen that there are a number of well-documented theories, with the above just being some examples. Some of these hypotheses also seem to strengthen one another when combined. This is why many in the medical community believe that the underlying etiology of endometriosis does not lie in just one cause but many fine-tuned mechanisms that work with one another.
Ongoing research is needed to make any conclusions and this is why it is so crucial to continue supporting institutions that seek to gain further knowledge into this topic. It is with further discoveries that the scientific community will be able to determine the causes of endometriosis. This will ultimately help the world of medicine find new ways to improve upon how it currently diagnoses and treats endometriosis, a disease that puts millions of women in pain each and every day worldwide.
|↑1||Sourial, Samer, Nicola Tempest, and Dharani K. Hapangama. “Theories on the pathogenesis of endometriosis.” International journal of reproductive medicine 2014 (2014).|
|↑2||Batt, R. E., R. A. Smith, Louis GM Buck, D. C. Martin, C. Chapron, P. R. Koninckx, and J. Yeh. “Müllerianosis.” Histology and histopathology 22, no. 10 (2007): 1161-1166.|
|↑3||Zanatta, Alysson, André M. Rocha, Filomena M. Carvalho, Ricardo MA Pereira, Hugh S. Taylor, Eduardo LA Motta, Edmund C. Baracat, and Paulo C. Serafini. “The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review.” Journal of assisted reproduction and genetics 27, no. 12 (2010): 701-710. Harvard|
|↑4||Abramowicz, Jacques S., and David F. Archer. “Uterine endometrial peristalsis—a transvaginal ultrasound study.” Fertility and Sterility 54, no. 3 (1990): 451-454.|
|↑5||Kido, Aki, Kaori Togashi, Mizuki Nishino, Kanae Miyake, Takashi Koyama, Ryota Fujimoto, Kazuhiro Iwasaku, Shingo Fujii, and Katsumi Hayakawa. “Cine MR imaging of uterine peristalsis in patients with endometriosis.” European radiology 17, no. 7 (2007): 1813-1819.|