Introduction
Bulun et al. (2019) primarily define Endometriosis as the chronic inflammatory process emanating from the infiltration of endometrial tissues into other body sites. The classic definition of Endometriosis is the surgical detection of the endometrial cysts (endometriomas) outside the uterine cavity (Bulun et al., 2019). Pelvic pain is often the primary symptom of Endometriosis due to inflammation and activation of nerve cells specific body sites (Bulun et al., 2019). The inflammatory process is dependent on estrogen and may affect any part of the body. Again, women of the reproductive age are the at-risk population.
Risk Factors
The primary risk factor is the increased number of menstruation cycles. Early onset of menstruation at an early age usually increases the number of cycles a female would have in their lifetime (Bulun et al., 2019). In addition, the progressively decreasing number of pregnancies also contributes to ovulatory cycle disruptions, which in return contribute to Endometriosis. Most of the endometriomas originate from the ovarian follicles. The repeated ovulation cycles place females at a high risk of Endometriosis. As discussed above, the endometrioma from endometrial hemorrhage transitions easily to Endometriosis in individuals with exposed ovarian follicles.
Pathophysiology
Endometriosis is primarily the existence of the endometrial cells outside the uterine cavity. In pelvic Endometriosis, the endometrial often exists outside the uterine cavity, especially in the ovarian tissues. Sampson’s theory of retrograde menstruation is the most acceptable way to explain the etiology of Endometriosis. During endometrial hemorrhage, the cysts may find their way to the already open ovarian follicles and cause inflammation. Pelvic Endometriosis can occur through other mechanisms, including the metaplasia of the peritoneum, transverse vaginal septum, and vascular spread. The first etiology implies that Endometriosis is a product of organized differentiation of and transition of the peritoneum from the coelomic epithelium (Bulun et al., 2019). The peritoneum goes transformation into endometriotic lesions, which later generate inflammation. Likewise, the blood tissues from the bone marrow have also demonstrated such a pattern of transformation once they reach other body sites (Bulun et al., 2019). Another theory is that young women may have impenetrable hymen blocking the complete passage of the endometrial hemorrhage. As a result, the women may experience backflow of menstrual hemorrhage to the uterine cavity and thus find its way into the other tissues. A chronic pattern of blocked flow of endometrial hemorrhage deposits endometrioma on the ovarian tissues, thus leading to pelvic Endometriosis. Alternatively, Endometriosis can also develop due to blood circulation into the adjacent tissues and organs. When blood from the endometrium travels through the veins of the lymphatic vessels, the menstrual tissues can reach other organs. The deposited endometrial tissues in other organs may lead to the implantation of the same tissue in the organs. The vascular spread explains the existence of Endometriosis in the respiratory organs chest.
Sampson’s Theory of Retrograde Menstruation
The theory explains various mechanisms through which the endometrioma gets deposited into the adjacent tissues outside the uterine cavity. The concept of reflux menstruation implies the backflow of blood into the uterine cavity and the adjacent tissues. Reflux menstruation occurs in almost all women, but only ten percent develop the symptoms of Endometriosis. Eutopic endometrium is the term that covers the unwarranted deposition of the endometrial tissues on various tissue cavities. The deposition of the endometrial tissues in the ovary and peritoneum increases their implantation ability. Many women with eutopic Endometriosis possess high aromatase enzyme levels, which catalyzes the conversion of androgens to estrogen (Bulun et al., 2019). The observation shows the link between estrogen and Endometriosis. The human endometrial stem cells also play a critical role in onset Endometriosis. Estrogen often facilitates the growth and thickening of the endometrium’s basalis layer, which emanates from the stem cells. Besides, mesenchymal stem cells originating from the bone marrow also facilitate the implantation of the endometrial tissues. Defective cells from the bone marrow of healthy individuals are similar to those from diseased women (Bulun et al., 2019). In the peritoneum, implantation occurs because the peritoneum and the endometrium cells share commonalities in terms of embryonic origin. Bothe have the coelomic epithelium, which enables the adhesion of the tissues from the two organs.
Biological Processes involved in Endometriosis
The biological process in Endometriosis oscillates around the molecular abnormality of somatic cells of the endometrium. Endometrial stromal cells can resist progesterone, secret estradiol in excess, and produce prostaglandin and cytokines (Bulun et al., 2019). The abnormalities also result in somatic cell mutations and lead to benign cancerous cells developments in the somatic epithelial cells. Again some mechanisms necessitate the somatic cell mutations, such as disrupted apoptosis, incomplete differentiation of stromal cells, inflammation, proliferation, angiogenesis, and genome alterations. During apoptosis, cells undergo programmed death when an incorrigible alteration occurs in the cell. In stromal epithelial cell mutation, apoptosis does not occur and facilitates the spread of the mutation. Incomplete differentiation of the stromal epithelial cells, on the other hand, produce misprogrammed somatic cells. Progesterone resistance is a possible cause of incomplete differentiation. Inflammation is also a critical biological process in Endometriosis. The process often occurs due to the deposition of immune cells and cytokines on the surface of implantation. Individuals with vascular spread endometriosis often experience the inflammatory impacts of Endometriosis. The immune reaction and inflammation is the leading cause of pelvic pain in Endometriosis. The proliferation of the stromal epithelial cells also relates to the mutation of somatic cells. An increased number of epithelial cells in different body sites implies an increased mutation rate. Such proliferation may be linked to the influence of estrogen.
Genetic Linkage
Endometriosis can follow familial tendencies and spread in generations. The phenotypes for the condition pass in a polygenic manner among family members. According to Bulun et al. (2019), mothers and sisters of the women experiencing severe Endometriosis are at high risks of inheriting the condition (Rolla, 2019). There are also specific genes associated with the onset of Endometriosis. However, studies are inconclusive on the exact origins of the genes.
Diagnosis
Pelvic examination, laparoscopy, and imaging of endometriomas are some of the promising methods. The examination majorly assesses pain in the pelvic region. A painful palpation may indicate the presence of Endometriosis (Rolla, 2019). Laparoscopy helps visualize the endometriomas and their walls. Imaging can also help detect the presence of endometriomas. Ultrasound is also a promising diagnostic approach that helps observe endometriomas. Transvaginal ultrasound can help detect hypoechogenic linear thickening of the endometrial lesions.
Treatment
The treatment goal in Endometriosis is to alleviate pain. Pain is often a result of nerve activation and inflammation in the body sites of implantation. As a result, estrogen and ovulation suppression are the main approaches to alleviating pain in Endometriosis. Physicians often prescribe oral contraceptives and GnRH antagonists in specific (Bulun et al., 2019). In essence, clinical treatments often rely on hormonal approaches. In severe cases, laparoscopic surgery is often effective in destroying or removing the endometrioma.
Novel Treatment Approaches
The novel treatment approaches focus on replacing the abnormal stromal cells with the normal cells, which is the potential approach for Endometriosis. Since the endometrial stromal epithelial cells can travel from the endometrium, deposit in other body sites, and mutate, there is a need to develop treatments that target its replacement. As a result, there are ongoing studies on the possibilities of cell-based treatment approaches to develop cells with molecular similarity to stromal. One promising approach is that the iPS cells derived from the bone marrow are a potential treatment approach that would effectively help (Bulun et al., 2019).
References
Bulun, S. E., Yilmaz, B. D., Sison, C., Miyazaki, K., Bernardi, L., Liu, S., Kohlmeier, A., Yin, P., Milad, M., & Wei, J. (2019). Endometriosis. Endocrine Reviews, 40(4), 1048–1079. https://doi.org/10.1210/er.2018-00242
Rolla E. (2019). Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Research, 8, F1000 Faculty Rev-529. https://doi.org/10.12688/f1000research.14817.1
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