Pain Management in Endometriosis

Pain, Endometriosis, Endometrioma, Pain Management Dear Editor, Endometriosis, characterized by the presence of en- dometrial implants outside the endometrial cavity , is a chronic and incurable disease in many women of repro- ductive age that requires lifelong management. Pain as- sociated with endometriosis includes dysmenorrhea, dys- pareunia, dyschezia, dysuria, and nonmenstrual pelvic pain. Extensive studies have been done in this field, but optimal management is still unclear. This article describes the available medical and surgical treatment options for pain caused by endometriosis. The choice of treatment is individualized and clinical symptoms, the severity of symptoms, age of the patient, extent, and location of the disease, tendency to fertility , drug side effects, surgical complications, and cost are considered. Medical Treatment Options Analgesics: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat primary dysmenor- rhea and pelvic pain, although there is very low quality evidence to support their use in treating endometriosis pain (1). Patients planning for pregnancy can use NSAIDs, although, according to some studies, selective COX-2 in- hibitors (celecoxib, rofecoxib, and valdecoxib) can delay or prevent ovulation (2). Besides, NSAIDs can be used alone or combined with continuous hormonal contraceptives. Neuromodulators: Neuromodulators (eg, anti- depressants, selective serotonin uptake inhibitors, or anticonvulsants) are mainly used to treat chronic and permanent pain. They affect the central nervous system’s modulation of pain. There is hope for their use in treating endometriosis-related pain. However, randomized clinical trials of chronic pelvic pain management have not shown their significance for treating chronic pelvic pain com- pared to placebo, especially considering their possible severe side effects (3, 4). Hormone Treatments Hormone treatments include combined oral contraceptives, progestogens, anti-progestogens, gonadotrophin-releasing hormone (GnRH) agonists, GnRH antagonists, the levonorgestrel intrauterine sys- tem (LNG-IUS), and danazol and aromatase inhibitors (eg, letrozole). All of them significantly reduce the pain associated with endometriosis compared with placebo (5). The side effects and efficacy of hormone treatments are individual-dependent. Estrogen-progestin Contraceptives: Several system- atic reviews have concluded that combined estrogen- progestin contraceptives, including combined oral contra- ceptive pills (OCP), vaginal rings, and transdermal patches, significantly reduce endometriosis-related pain (6). They can be used as the first-line treatment for most patients due to the possibility of long-term use and reasonable price, availability , and contraceptive effects. They also re- duce the risk of ovarian and endometrial cancer. Both continuous and standard cyclic OCP have been effective, although some studies have found that the continuous

is more effective (7). Progestogens and Antiprogestogens: Progestin- only therapy is used in contraindicated patients with combined estrogen-progestin contraceptives or those who prefer not to use them. The 19-nortestosterone deriva- tives norethindrone acetate (5 mg dose), dienogest, and medroxyprogesterone acetate are the most common pro- gestins used to treat endometriosis-related pain. Etono- gestrel implant (ENG) and levonorgestrel-releasing in- trauterine system also significantly reduce endometriosis- related pain. Danazol: Danazol is not recommended anymore un- less no other medical therapy is available because of its se- vere androgenic side effects. Gonadotropin-releasing Hormone Ago- nists/Antagonists: GnRH agonists and antagonists Copyright © 2022, Interventional Pain Medicine and Neuromodulation. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Sarbazi F et al. effectively reduce the pain associated with endometrio- sis, but due to their side effects, they are recommended as second-line treatment in cases where hormonal con- traceptives or progestogens are not effective. There is limited evidence regarding the dosage and duration of treatment. It is recommended to use add-back treatment with GnRH agonist therapy to prevent osteoporosis and hypoestrogenic symptoms (8). Aromatase Inhibitors: Due to severe side effects, aro- matase inhibitors are used only in cases where the pain associated with endometriosis is resistant to other medi- cal treatments or surgical treatment. Aromatase inhibitors may be combined with oral estrogen-progestin contracep- tives, progestogens, and GnRH agonists or antagonists. Surgical Treatment Due to the risks of surgery , its high cost, the lengthy re- covery period, and the possibility of recurrence, medical treatments have priority , and surgical treatment is consid- ered when the patient is resistant to medical treatments or cannot use them for any reason. Disadvantages of surgical procedures are related to the usual surgical risks, includ- ing the risk of injury , especially to the bowel and bladder, and the possibility of reduced ovarian reserve and adhe- sions. Conservative Surgery: In conservative surgery , all en- dometriosis lesions are removed, and adhesions are re- leased while the uterus and ovaries are preserved. This sur- gical procedure is considered the first-line treatment for most women planning for surgical treatment because it preserves hormone production and fertility and is less in- vasive and morbid than definitive surgery . However, recur- rence is more likely with this method than with definitive surgery . Definitive Surgery: Definitive surgery includes hys- terectomy (total hysterectomy is preferred) with or with- out oophorectomy . Definitive surgery is recommended for patients with debilitating pain or completed childbearing or when other medical and surgical treatments have failed. Laparoscopy is preferred to laparotomy due to better sur- gical visualization, shorter hospital stay , less pain, shorter recovery period, and better cosmetic results. Footnotes Authors’ Contribution: All authors contributed equally to this article. Conflict of Interests: There are no personal/financial in- terests. Funding/Support: The authors did not declare it.

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