{"paper_id":"108a3dfe-1ba3-4b09-938c-86bcaaf57b4e","body_text":"Copyright@ Shawky ZA Badawy | Biomed J Sci & Tech Res| BJSTR. MS.ID.003299.\n14315\nMini Review\nISSN: 2574 -1241\nEndometriosis Pathogenesis and Management\nShawky ZA Badawy*\nDepartment of Obstetrics and Gynecology, Reproductive Endocrinology, Pathology, Upstate Medical University Syracuse, USA\n*Corresponding author: Shawky ZA Badawy, Department of Obstetrics and Gynecology, Reproductive Endocrinology,  \nPathology, Upstate Medical University Syracuse, New York, USA\n      DOI: 10.26717/BJSTR.2019.19.003299\nReceived: \n   June 28, 2019\nPublished: \n   July 05, 2019\nARTICLE INFO Abstract\nCitation: Shawky ZA Badawy. Endometriosis Pathogenesis and Management. Biomed J \nSci & Tech Res 19(3)-2019. BJSTR. MS.ID.003299.\nIntroduction\nEndometriosis has been described over 300 years ago [1-3]. It is \na major cause of pain and infertility in 35-50% of women and chronic \npelvic pain in 6-10% of women. It is a major cause of hospitalization \nand hysterectomy, with annual cost of 1.8 billion dollars in 2009 \nin Alberta and Quebec, Canada [4], 1.5 billion dollars in Germany, \nand 20 billion dollars in the United States [5]. Endometriosis is an \nestrogen dependent condition. On the other hand, this disease leads \nto defective response of Eutopic endometrium to progesterone and \ntherefore implantation is difficult to occur thus leading to infertility \nor pregnancy loss. In addition, nerve fibers have been demonstrated \nin Eutopic endometrium of patients with endometriosis [6].\nInfertility due to pelvic endometriosis may be caused by \nseveral factors. Ovulatory dysfunction may result from the high \nconcentrations of prostoglandins and cytokines in the peritoneal \nfluid in these patients [7]. Prostaglandins also may lead to tubal \ndysfunction that will interfere with the pickup of the oocyte from \nthe ovary, and also the motion of the sperm towards the oocyte with \nthe result of failure of fertilization to take place. Furthermore, the \nendometrium of these patients has been shown to have aromatase \nthat leads to high estradiol concentration and that might lead to \ndefective response to progesterone, and the end result will be \nfailure of implantation [8].\nHistorical Aspects of Endometriosis\nThe first reference to endometriosis associated symptoms are \nfound in the Ebers Papyrus (Tebas, Egypt, 500 BC) in which treatment \nfor painful disorder of menstruation is described. In the 18th \nCentury, scientists from England, Germany, Holland, and Scotland \ndescribed endometriosis in autopsy studies [9]. Rokitansky (mid \npart of 19th Century-1885), suggested the presence of endometrial  \nglands and stroma in ovarian and uterine neoplasia [10]. Cullen  \n \n(1919) [11]: Was the first scientist to demonstrate histologically \nendometrial structures in the peritoneum of patients and called this \nprocess as adenomyoma of the peritoneum or adenomysis externa. \nRussel [12]: Published a report in 1899 of an ovaries containing \nuterine mucosa. Sampson (1927) [13]: The first to describe the \nmenstrual reflux theory for the development of endometriosis. He \nalso described the various types of the disease including chocolate \ncysts, and deep infiltrating disease in the pelvis.\nPathogenesis of Endometriosis - Criteria of Eutopic \nEndometrium as Precursor for Endometriosis [14-17]\na) Macrophages are increased with increased interleukins \nand prostaglandins.\nb) Apoptosis of endometrial cells is reduced.\nc) Increased integrins that leads to proliferation of \nendometrial cells.\nd) Increased various growth factors leading to increase \nangiogenesis.\ne) Aromatase in these cells increases estrogen production \nwhich leads to increased proliferation of these cells.\nf) Increase metalloproteinases promotes invasion of \nendometrial cells and development of endometriosis.\ng) Increase in Estrogen Receptor B in endometriosis is \nimportant in establishment and progression of the disease.\nTheories for development of Endometriosis\nA. Retrograde menstrual fluid through Fallopian tubes\nB. Stem cells from basal endometrium, or bone marrow\n\nCopyright@ Shawky ZA Badawy | Biomed J Sci & Tech Res | BJSTR. MS.ID.003299.\nVolume 19- Issue 3\nDOI: 10.26717/BJSTR.2019.19.003299\n14316\nC. Displaced embryonic epithelial remnants along the \nunderdeveloped Mullerian system, can lead to endometriosis \nas reported in patients with Mullerian Agenesis (MRKH)\nD. Coelomic Metaplasia Theory\nE. Genetic predisposition\nF. Ovarian chocolate cyst\nInversion of ovarian cortex with the endometriosis implant.\ni. or- Secondary involvement of functional ovarian cyst.\nii. or – Metaplasia of Coelomic epithelium on the ovary.\nDiagnosis of Endometriosis\nUsually patients present with history of severe dysmenorrhea, \npelvic pain, and dysparunia. If there is a bowel involvement, \npatient then will have constipation, diarrhea, and rectal bleeding. \nIf there is bladder involvement, the patient will have hematuria. \nThe pelvic examination will demonstrate pelvic pain, thickened \nand indurated utero sacral ligaments, and enlarged ovaries if there \nare endometriomas. Pelvic sonogram will aid in the diagnosis \ndemonstrating masses or cysts. MRI of abdomen and pelvis may be \nordered to evaluate abdominal or intestinal masses.\nUltrasound Based Endometriosis Staging (UBESS)\na) Assessment of uterus and adnexa\nb) Tenderness guided assessment\nc) Assessment of pouch of Douglas status, ovarian and organ \nmobility\nd) Assessment of none bowel deep endometriosis of anterior, \nlateral, and posterior pelvic compartments\ne) Assessment of anterior wall of rectum and sigmoid. \nThis system has been used in Australia and New Zealand [18].\nThe next step in the diagnosis is laparoscopy [19]. This helps \nto define the disease and its location according to its morphologic \ncriteria which includes vesicular forms, dark pigmented areas, or \nchocolate cysts in the ovaries. The vesicular form and pigmented \nareas can be treated with laser or using electro cautery to ablate the \ndisease. In cases of chocolate cysts, the endometrioma is surgically \nexcised followed by reconstruction of the ovary.\nMedical Treatment of Endometriosis\nMedical treatment of endometriosis is applied to early stages of \nthe disease or recurrence after surgical medical treatment. Usually \nthe treatment is for a period of six months. Various medications are \nused including birth control pills, Danazol, Medroxyprogesterone \nand GnRH agonist or antagonist [20].\nBirth Control Pills\nUse of steroidal oral contraceptives in patients with \nendometriosis alleviates severe dysmenorrhea in these patients. \nThere are no data to support any effect on the reduction of the size \nof the lesions.\nDanazol\nThis is a synthetic steroid derivative of 17 alpha-ethinyl \ntestosterone. It inhibits the secretion of FSH and LH, and leads to \ninhibition of ovarian function. The end result is pseudomenopause, \nand hypoestrogen status. This leads to suppression of endometriosis \nand its regression in about 80% of the patients. Following \ndiscontinuation of the treatment, the pregnancy rate is about 70%. \nThe recurrence rate after 24 months follow up was reported to be \n29%.\nGonadotropin Releasing Hormone Agonist\nIts administration leads to suppression of gonadotropins \nthrough inhibition of GnRH receptors in pituitary. This will \nlead to hypoestrogenism and the end result is suppression of \nendometriosis. This also leads to reduction in dysmenorrhea. \nThe use of gonadotropin releasing hormone antagonist\nAll the studies show that the use of GnRH antagonist for pain \nrelated to endometriosis, have shown marked improvement. \nThe medication is well tolerated. It is also an oral medication. \nLaproscopic studies showed regression of endometriosis.\nAntiangiogenic Factors\nIn a study to evaluate cabergoline effect on endometrioma, \nas compared to control groups given GnRH agonist 3.75mg \nsubsequently one time. Patients were evaluated by base line \nsonogram and 3 months after the treatment. The results showed \nsignificant decrease in size of endometrioma with the use \nof Cabergoline [21]. The use of Quinagolide for treatment of \nendometriosis induced in a rat model. The results showed significant \ndecrease in interleukin 6 and vascular endothetrial growth factor in \nperitoneal fluid samples after Quinagolide treatment as compared \nto levels before treatment. In addition, tissue samples showed \nsignificant reduction of glandular and stromal tissue after the \ntreatment. The use of Lovostatin added to endometrial in vitro \nculture, showed inhibition of cell proliferation and angeogensis. All \nthese agents are still being under evaluation and certainly will add \nnew lines of medical treatment for endometriosis.\nSurgical Management\nThis is usually done by laparoscopy and or laparotomy. The \nlesions are either excised, or fulgrated using bipolar cautery; \nor vaporized using laser [22]. Recently a study in experimental \nanimals showed the beneficial effect of platelet rich plasma, and \n\nCopyright@ Shawky ZA Badawy | Biomed J Sci & Tech Res| BJSTR. MS.ID.003299.\nVolume 19- Issue 3\nDOI: 10.26717/BJSTR.2019.19.003299\n14317\nfibrin sealant on bowel wound healing after shaving endometriosis \nlesions experimentally induced. The results showed that these \nagents are safe and associated with improved tissue healing after \nshaving endometriosis from colon wall.\nExtrapelvic Types of Endometriosis\nThoracic Endometriosis [23,24]\nThis includes these categories\na. Catamenial Pneumothorax\nb. Catamenial Hemothorax\nc. Catamenial hemoptysis\nThese result from the presence of endometrial glands and \nstroma in the lungs and pleura. Endometrial tissue may have \nmigrated from the abdomen, through defects in the diaphragm and \nresided in the chest. Another possibility is hematogeneous and/or \nlymphatic spread. The diagnosis to confirm the disease is facilitated \nby biopsies from pleura in cases of catamenial pleural effusion or \ncatamenial hemothroax. In cases of catamenial hemoptysis, the \nuse of bronchoscopy and lung biopsy will help to establish the \ndiagnosis. In addition to the surgical treatment, the use of medical \ntreatment may be helpful. This is accomplished with the use of GnRH \nagonist, or Danozol. If fertility is not an issue, then the patient will \nbenefit from total abdominal hysterectomy and bilateral salpingo \noophorectomy.\nIntestinal Endometriosis\nThis is the most common extrapelvic location of endometriosis. \nIt commonly affects the rectosigmoid part of the bowel. It could be \nsuperficial disease, but sometimes it affects the whole thickness of \nthe bowel wall. The symptoms will vary according to the degree \nof bowel involvement. The patient will complain of pelvic pain, \nor abdominal pain. In addition, the symptoms may be diarrhea, \nconstipation, and/or rectal bleeding. Radiological studies including \nCT scan, MRI of the abdomen will show the location of the lesion. \nIn addition, Barium enema and Colonoscopy will be confirmatory. \nSmall intestines may be affected with endometriosis, but it is \nusually less common. The treatment of bowel endometriosis is \nsurgical excision, and bowel anastomosis. The incidence of bowel \nendometriosis is 12% in women with endometriosis.\nReferences\n1. Knapp VJ (1999) How old is endometriosis? Late 17 th and 18th Century \nEuropean descriptions of the disease. Fertil Steril 72(1): 10-14.\n2. Liselotte Mettler, Dietmar Schmidt, Pter Maher (2016) The impact of \nendometriosis on health of women 2016. 2016: 1747280.\n3. Levy AR, Osenekokm, Lozano Ortega G, Sambrook R, Jeddi M, et al. \n(2011) Economic burden of surgically confirmed endometriosis in \nCanada. J Obstetrical Gynecology 33 (8): 830- 837.\n4. Bansari G Patel, Martin Rudnicki, Jie Yu, Yimin Schu, Robert N (2017) \nTaylor: Acta Obstetrics et Gynocologica Scandinavica 96: 623-632.\n5. Badawy SZ, Cuenca V, Marshall L (1987) Peritoneal fluid prostaglandins \nin patients with endometriosis. Contrib Gynecological Obstetrics 16: 60-\n65.\n6. Luis S Noble, Evan R Simpson, Alan Johns, Serdar E Bulun (1996) \nAromatase expression in Endometriosis. J Clin Endocrinology Metab \n81(1): 174-179.\n7. Benagiano G, Brosens I (1991) The history of endometriosis: Identifying \nthe disease. Hum Reprod 6(7): 963-968.\n8. Benagiano G, Brosens I (2009) Who identified endometriosis? Fertil \nSteril 92: 1536-1543.\n9. Cullen T (1896) Adenomyoma of the round ligament. Johns Hopkins \nHospital Bull 7: 112-113.\n10. Russell W (1899) Aberrant portions of the Mullerian duct found in an \novary. Ovarian cysts of Mullerian origin. Bull John Hopkins Hosp 10(8).\n11. Sampson JA (1925) Heterotopic or misplaced endometrial tissue. \nJournal of Obstetrics and Gynecology 10: 449-664.\n12. Bruner-Tran KL, Eisenberg E, Yeaman GR, Anderson TA, McBean J, et \nal. (2002) Steroid and cytokine regulation of matrix metalloproteinase \nexpression in Endometriosis and the establishment of experimental \nendometriosis in nude mice. J Clin Endocrinol Metab 87: 4782-4791.\n13. Shifren JL, Tseng JF, Zalondek CJ, Ryan IP , Meng YG, et al. (1996) Ovarian \nsteroid regulation of vascular endothelial growth factor in the human \nendemetrium: Implications for angiogenesis during the menstrual cycle \nand in the pathogenesis of endometriosis. J Clin Endocrinol Metab 81: \n312-318.\n14. McLaren J, Prentice A, Charnock-Jones DS, Smith SK (1996) Vascualr \nEndothelial growth factor (VEGF) Concentrations are elevated in \nperitoneal fluid of women with endometriosis. Hum Reprod 11: 220-\n223.\n15. Tompsett J, Leonardi M, Gerges B, Lu C, Reid S, et al. (2019) Ultrasound \nbased endometriosis staging system: validation study to predict \ncomplexity of laparoscopic surgery. J Minim Invasive Gynecol 26(3): \n477-483.\n16. Erica Schipper, Camran Nezhat (2012) Video assisted laparoscopy for \nthe detection and diagnosis of endometriosis: Safety, reliability, and \ninvasiveness. Int J Women’s Health 4: 383-393.\n17. (2010) Practice Bulletin No. 114: Management of endometriosis. Obstet \nGynecol 116(1): 223-236.\n18. Ferrero S, Ragni N, Remorgida V (2006) Antiangiogenic therapies in \nEndometriosis. Br J Pharmacol 149(2): 133-135.\n19. Visouli AN, Zarogoulidis K, Kougioumtzi I, Huang H, Li Q, et al. (2014) \nCatamenial Pneumothorax. J Thorac Dis 6: 5448-5460.\n20. Foster DC, Stern JL, Buscema J, Rock JA, Woodruff JD (1981) Pleural and \nparynchemal pulmonary endometriosis. Obstet Gynecol 58: 552-556.\n21. Wood DJ, Krishnan K, Ward MJ (1993) Catramenial hemogstysis a rare \ncause. Thorax 48: 1048-1049.\n22. Remorgida V, Ferrero S, Fulchori E, Ragni N, Martin DC (2007) Bowel \nendometriosis: presentation, diagnosis, and treatment. Obstet Gyncolol \nSurg 62(7): 461-470.\n23. Gustofson RL, Kim N, Liu S, Stratton P (2006) Endometriosis and the \nappendix: A case series and comprehensive review of the literature. \nFertil Steril 86(2): 298-303.\n24. Faccioli N, Foti G, Manfredi R, Mainardi P , Spoto E, et al. (2010) Evaluation \nof colonic involvement in endometriosis: Double- contract barium \nenema vs. magnetic resonance imaging. Abdom Imaging 35(4): 414-421.\n\nCopyright@ Shawky ZA Badawy | Biomed J Sci & Tech Res | BJSTR. MS.ID.003299.\nVolume 19- Issue 3\nDOI: 10.26717/BJSTR.2019.19.003299\n14318\nSubmission Link: https://biomedres.us/submit-manuscript.php\nAssets of Publishing with us\n• Global archiving of articles\n• Immediate, unrestricted online access\n• Rigorous Peer Review Process\n• Authors Retain Copyrights\n• Unique DOI for all articles\nhttps://biomedres.us/\nThis work is licensed under Creative\nCommons Attribution 4.0 License\nISSN: 2574-1241\nDOI: 10.26717/BJSTR.2019.19.003299\nShawky ZA Badawy. Biomed J Sci & Tech Res","source_license":"CC0","license_restricted":false}