{"paper_id":"a696fb8f-4c64-48e7-b1b3-973ef9a22874","body_text":"Remedy Publications LLC., | http://clinicsinoncology.com/\nClinics in Oncology\n2020 | Volume 5 | Article 17101\nEndometriosis: Current Trends in Management\nOPEN ACCESS\n *Correspondence:\nManu Goyal, Department of Obstetrics \n& Gynecology, All India Institute of \nMedical Sciences, Jodhpur, India, Tel: \n91-9971833603; \nE-mail: drmanu_8@yahoo.co.in\nReceived Date: 09 May 2020\nAccepted Date: 02 Jun 2020\nPublished Date: 05 Jun 2020\nCitation: \nGoyal M, Sharma JB, Singh P, Agarwal \nN. Endometriosis: Current Trends in \nManagement. Clin Oncol. 2020; 5: \n1710.\nCopyright © 2020 Manu Goyal. This is \nan open access article distributed under \nthe Creative Commons Attribution \nLicense, which permits unrestricted \nuse, distribution, and reproduction in \nany medium, provided the original work \nis properly cited.\nReview Article\nPublished: 05 Jun, 2020\nAbstract\nEndometriosis is most common cause of chronic pelvic pain in women. It affects women \nboth physically and psychologically. Important clinical symptoms of endometriosis include \ndysmenorrhea, dyspareunia and subfertility. Till date there is no definitive cure for it. Treatment of \nit is based to relieve its clinical symptoms and to reduce the disease load. Medical management is \nbroadly anti-inflammatory and estrogen suppression therapy. Surgery is gold standard for diagnosis \nand treatment. Its treatment and loss in work productive days is economic burden for society. A \nmultidisciplinary research is needed for timely diagnosis and appropriate treatment of such disease.\nKeywords: Endometriosis; Chronic pelvic pain; Dysmenorrhoea; USG\nManu Goyal*, Jai Bhagwan Sharma, Pratibha Singh and Neha Agarwal\nDepartment of Obstetrics & Gynecology, All India Institute of Medical Sciences, India\nIntroduction\nEndometriosis is defined as presence of endometrial glands and stroma outside the uterine \ncavity, first described by Rokitansky in 1860 [1]. It affects about 7% to 12% of women in reproductive \nage group. The incidence is high in patients suffering from infertility about 25% to 35% [1]. It is also \nhigh in patients with chronic pelvic pain (30% to 55%). There are varied symptoms of the disease. \nThe classical triad for endometriosis is dysmenorrhoea, dyspareunia and sub-fertility [1]. Other \nsymptoms are heavy menstrual bleeding, dysuria, dyschezia, abdominal pain, chronic pelvic pain. \nIt may involve bladder, rectum, and gastrointestinal tract leading to hematuria, hematochezia and \nconstipation.\nThe most common site of involvement is ovary, utero-sacral ligaments, and pouch of Douglas, \npelvic peritoneum, tubes, recto-vaginal septum, and posterior surface of uterus. The rare sites of \ninvolvement are pulmonary, sub-diaphragmatic area, paracolic gutters, and scar site of episiotomy, \nhysterotomy, and cesarean section.\nThere are various theories for etiology of endometriosis [2]:\n1. Sampson’s theory of retrograde menstruation\n2. Coelomic metaplasia theory\n3. Stem cell theory\n4. Lymphatic and vascular spread theory\n5. Genetic theory\n6. Immunological theory\n7. Hormonal and inflammation theory\nDiagnosis\nDiagnosis is mainly by strong clinical suspicion based on symptoms as there is typical history \nof progressive dysmenorrhoea where the pain increases in duration, severity gradually becoming \nchronic pelvic pain [2]. Physical examination has poor sensitivity, specificity, and predictive value in \nthe diagnosis of endometriosis [3]. Clinical examination may reveal tenderness in fornices, adnexal \nmass in presence of chocolate cyst, restricted mobility of uterus and thickening of recto-vaginal \nseptum, nodularity in the posterior vaginal fornix, and visible vaginal endometriotic lesions. Imaging \nmodalities include ultrasound, in which mainly transvaginal scan is helpful. Transrectal USG also \nis useful when transvaginal cannot be performed and to detect recto-vaginal endometriosis. USG \nwill detect ovarian endometrioma, hematosalpinx, where it will show the homogenous ground-glass \nappearance of the endometrioma [3]. Hydronephrosis secondary to ureteric endometriosis may be \ndetected by transabdominal USG. Minimal and mild endometriosis is difficult to be diagnosed on \nultrasound. MRI is said to be better for diagnosis of moderate to severe and deep endometriosis. \n\nManu Goyal, et al., Clinics in Oncology - Obstetrics & Gynecology\nRemedy Publications LLC., | http://clinicsinoncology.com/\n 2019 | Volume 4 | Article 17102\nIt should not be ordered as primary investigation for diagnosis of \nendometriosis.\nRole of serum bio-marker CA-125 is controversial. It may be high \n(>35 mIU/ml) suggesting the presence of endometriosis, its rupture \nbut normal value of CA-125 does not exclude endometriosis [4].\nManagement\nLaparoscopy is the gold standard in diagnosis and management \nof endometriosis [5]. It is both diagnostic and therapeutic. Visual \ninspection of endometriotic spots on laparoscopy is also not \nconfirmatory. It has to be proven histologically by presence of glands \nand stroma both but negative biopsy does not rule out endometriosis. \nThe endometriotic patches may appear as red, pink, bluish-purple, \nvelvety lesions or white powder burnt patches [6]. One should be \naware of different appearances of endometriotic spots so as to identify \nthem all and properly treat them in the same sitting of surgery. DIE \n(Deep Infiltrating Endometriosis) may be missed even at laparoscopy \nand if diagnosed, it requires expertise to remove it [7].\nWhen endometriosis is diagnosed, the gynecologist should \ndocument a detailed description of the appearance and site of \nendometriosis. The staging should be done as per ASRM/ESHRE \nor revised AFS classification given in 1997 [1]. Recent classification \nis ENZIAN which takes into consideration DIE and Endometriosis \nFertility Index (EFI).\nEndometriosis causes infertility due to immunological, ovulatory \ndysfunction, alteration in endometrial receptivity and tubal factors \nin severe cases. Endometriosis causes ovulatory infertility by altering \nfolliculogenesis and ovulation due to inflammation associated with \nendometriosis. Endometriosis causes immunological infertility \ndue to increased production of ROS by macrophages and poly \nmorphonuclear cells associated with endometriosis which causes \nincreased oxidative stress. Decreased expression of integrins and \nincreased production of cytokines are noted. Endometriosis causes \ndecreased sperm quality and function due to inflammatory toxic \neffects of the peritoneal fluid and activated macrophages upon the \nsperms. Endometriosis affects endometrial receptivity by causing \nprogesterone resistance, dysregulation of progesterone receptors and \nby increased Estrogen production secondary to elevated aromatase \nenzymes.\nEndometriosis is a chronic, recurrent, progressive disorder \nwhich affects the quality of life rather than decreasing the survival \n[7]. Management options are both medical and surgical. It is \nbased mainly on symptoms, patient’s age and desire for fertility. \nMedical management is mainly for patients suffering from pain, \ndysmenorrhoea, and dysuria. It is also used for prevention and \ntreatment of recurrence and if patient refuses surgery. But if the \npatient has main complain of infertility, then one has to go for \nsurgical management.\nMedical management\nThere are many groups of drugs being used for medical \nmanagement of endometriosis. These are described below:\na) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): The pain \npathogenesis is through prostaglandin pathway so COX 1 and COX \n2 inhibitors are first line therapy in endometriosis associated pelvic \npain and dysmenorrhoea. Mefenamic acid and ibuprofen are most \ncommonly used and they are effective in almost 50 % to 60% cases \nwhen given thrice daily [6].\nb) Combined oral contraceptive pills: These are mainly used in \nwomen who are not trying for conception. They suppress endogenous \nrelease of gonadotropins, reduce menstrual flow and progesterone \ncomponent decidualized endometriotic implants. They can be used \nas continuous or cyclic regimen. Continuous regimen for 6 months is \nmore effective in controlling pain and dysmenorrhoea in about 40% \nto 50% [5].\nc) Progestins: They cause atrophy of the endometriotic \nimplants and pseudo-pregnancy state. It can be given for 3 to 6 \nmonths continuously and leads to 60% reduction in pain. Various \npreparations are used such as medroxyprogesterone acetate in \n20 mg to 80 mg daily dose, norethisterone 10 mg to 20 mg daily, \nInjection Depot medroxyprogesterone acetate 150 mg every 3 \nmonths for 6 to 9 months, dienogest 2 mg daily for 6 to 9 months \n[5,6]. Dienogest is fourth generation synthetic progesterone which \nhas recently been proposed as treatment of choice for this condition. \nLong term progesterone delivery system in the form of LNG-IUS \n(Levonorgestrel Intrauterine System) is also beneficial in these \npatients as amenorrhoea is achieved in 88%-92% of patients after 9 \nto 12 months. It delivers 20 mcg of progesterone daily for five years. \nIt has less systemic side effects and more effective in causing local \natrophy of endometrium.\nd) GnRH agonists: They cause pituitary desensitization and \nthereby leading to inhibition of ovarian steroidogenesis. They lead to \npseudomenopause and also called medical oophorectomy. Common \npreparations available are leuprolide acetate 3.75 mg, triptorelin 3.75 \nmg, goserelin 3.6 mg [4-6]. They are given as monthly injections for 6 \nmonths. If one has to give it for longer duration than 6 months then \nadd-back therapy is used to prevent hypoestrogenic side effects and \ndecrease in bone mineral density.\nAdd-back therapy includes conjugated equine estrogen (0.3 mg \nto 0.625 mg) combined with norethisterone acetate (2.5 mg to 5 mg) \n[3].\ne) GnRH antagonist: Cetrorelix in dose of 0.25 mg daily or weekly \ndose of 3 mg for 3 months can also be used [7].\nf) Aromatase inhibitors: These agents lead to hypoestrogenism \nwhich is responsible for suppression of endometriotic implants. \nAnastrozole (2 mg) or letrozole (2.5 mg) is use for 6 months \ncontinuously [6].\ng) Selective Progesterone Receptor Modulator (SPRM): They \nbind to progesterone receptors and exert varying effects on different \ntissues. Ulipristal acetate and mifepristone are used for this condition \nfor 3 to 6 months [6].\nh) Gestrinone: It is 19-nortestosterone derivative having anti-\nestrogenic and anti-progestin activity. It is used in the dose of 2.5 mg \ntwice weekly for 6 months. Danazol was also used for endometriosis \nin dose of 400 mg to 800 mg daily doses but it is not used as it has got \nmany androgenic side effects and has gone into disrepute [3].\ni) Others: TNF-alpha inhibitors, MMP (Matrix Metalloproteinase)-\ninhibitors, pentoxifylline, raloxifene etc are experimental [7].\nSurgical management\nLaparoscopic ablation or excision and adhesiolysis improve \npregnancy rate in stage I and II endometriosis when compared to \ndiagnostic laparoscopy alone. Operative laparoscopy in stage III \nand IV endometriosis has shown to improve pregnancy rates as \n\nManu Goyal, et al., Clinics in Oncology - Obstetrics & Gynecology\nRemedy Publications LLC., | http://clinicsinoncology.com/\n 2019 | Volume 4 | Article 17103\ncompared to expectant management [6]. It restores the anatomy \nof tubes and ovaries and also decreases the inflammatory milieu \nwithin the peritoneum and uterus for better implantation rates. \nWhen endometrioma or chocolate cyst is present, then cystectomy is \npreferred to drainage and fulguration as it improves pregnancy rate \nand also associated with reduced recurrence rates. Cyst wall should \nbe removed completely and cautery should be done to the base of \nthe cyst.\nSurgery can also be done by laparotomy as well as laparoscopically. \nIf the patient’s age is advanced and she has completed her family with \nno desire to retain uterus, then hysterectomy with bilateral salpingo-\noophorectomy can be offered to woman. Laparoscopic Uterine Nerve \nAblation (LUNA) is also an option for endometriosis-associated pain \nbut it has very low efficacy (30% to 40% only) [4]. In DIE, one has \nto go for radical surgical excision of all deep seated endometriotic \nlesions with extensive bowel and ureteric dissection [7]. Pre-sacral \nneurectomy can also be done for transection of presacral nerves but it \nis obsolete in current practice.\nTreatment of Infertility associated with endometriosis: \nLaparoscopy with treatment of the endometriotic lesions is must. This \nis followed by ovulation induction and intrauterine insemination in \nstage I and II diseases. While stage III and stage IV disease patients \nshould undergo ART (Assisted Reproductive Technique) with IVF-\nET (In Vitro Fertilization-Embryo Transfer) or ICSI (Intracytoplasmic \nSperm Injection) [4].\nRecurrence: Endometriosis is one disease which is known for \nhigh rates of recurrence. The disease recurs in almost 20% of patients \nin 2 years and 40% recurrence is seen after 5 years [1]. There is high \nmorbidity and surgical complications are also more in recurrent \ncases. Resistant and repeated cases ultimately require hysterectomy \nand bilateral salpingo-oophorectomy [6].\nReferences\n1. Revised American society for reproductive medicine classification of \nendometriosis. Fertility Sterility. 1997;67(5):817-21.\n2. American Society for Reproductive Medicine. Treatment of pelvic pain \nassociated with endometriosis: A committee opinion. Fertility Sterility. \n2014;101(4):927-35.\n3. European society of Human Reproduction (ESHRE) Endometriosis \nGuideline Group 2013.\n4. Dunselman GAJ, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe \nT, De Bie B, et al. ESHRE guidelines: Management of women with \nendometriosis. Hum Reprod. 2014;29(3):400-12.\n5. The investigation and management of endometriosis. RCOG Guidelines. \n2006 Green top guidelines No. 24.\n6. Endometriosis: Diagnosis and management. NICE guideline September \n2017.\n7. Dysmenorrhoea and endometriosis in Adolescent. Practice Bulletin \nACOG 2018 November.","source_license":"CC0","license_restricted":false}