Abstract
Purpose of Review
The purpose of this review is to summarize the up-to-date pain management options and recommendations for the challenging disease, endometriosis.
Recent Findings
The mainstays of endometriosis advances of both surgical and medical management continue to evolve. Experimental pharmaceuticals include Gestirone, and aromatase inhibitors have shown promise but are still under scrutiny. Surgical techniques include laparoscopic uterosacral nerve ablation/resection and presacral neurectomy.
Summary
No studies have directly compared medical versus surgical management, and as such, no one treatment modality can be recommend as superior to the other. Patients may initially be given a medical diagnosis and treated with nonsteroidal anti-inflammatory drugs, neurolepitcs, OCP, GNRH agonists/antagonists, and Danazol. Assessing the success of these regimens has proved difficult. Surgical management relies on various methods including excision/ablation of the lesions, nerve ablation, neurectomy, hysterectomy, and oophorectomy.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9.
Parasar P, Ozcan P, Terry KL. Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep. 2017;6(1):34–41.
Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–99.
Balasch J, Creus M, Fabregues F, Carmona F, Ordi J, Martinez-Roman S, et al. Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study. Hum Reprod. 1996;11(2):387–91.
Rawson JM. Prevalence of endometriosis in asymptomatic women. J Reprod Med. 1991;36(7):513–5.
Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982;38(6):667–72.
Carter JE. Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain. J Am Assoc Gynecol Laparosc. 1994;2(1):43–7.
Koninckx PR, Meuleman C, Demeyere S, Lesaffre E, Cornillie FJ. Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril. 1991;55(4):759–65.
Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet Gynecol. 1999;93(1):51–8.
•• Peritoneal Endometriosis, Due to the menstrual dissemination of endometrial tissue into the peritoneal cavity: Dr. John A. Sampson, Albany, N. Y., read a paper on. (For original article see October, 1927, issue, page 422.). Am J Obstet Gynecol. 1928;15(1):101-110. Landmark paper describing the initial concept of endometriosis pathogenesis.
Garrido N, Navarro J, Garcia-Velasco J, Remoh J, Pellice A, Simon C. The endometrium versus embryonic quality in endometriosis-related infertility. Hum Reprod Update. 2002;8(1):95–103.
Meresman GF, Vighi S, Buquet RA, Contreras-Ortiz O, Tesone M, Rumi LS. Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis. Fertil Steril. 2000;74(4):760–6.
Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–79.
Guo SW. Epigenetics of endometriosis. Mol Hum Reprod. 2009;15(10):587–607.
Murphy AA, Palinski W, Rankin S, Morales AJ, Parthasarathy S. Evidence for oxidatively modified lipid-protein complexes in endometrium and endometriosis. Fertil Steril. 1998;69(6):1092–4.
Matorras R, Rodriguez F, Pijoan JI, et al. Are there any clinical signs and symptoms that are related to endometriosis in infertile women? Am J Obstet Gynecol. 1996;174(2):620–3.
Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77(6):1148–55.
•• ACOG Practice bulletin. Medical management of endometriosis. Number 11, December 1999 (replaces Technical Bulletin Number 184, September 1993). Clinical management guidelines for obstetrician-gynecologists. Int J Gynaecol Obstet. 2000;71(2):183-196. ACOG recommendations on medical management of endometriosis.
Mounsey AL, Wilgus A, Slawson DC. Diagnosis and management of endometriosis. Am Fam Physician. 2006;74(4):594–600.
Chiantera V, Abesadze E, Mechsner S. How to understand the complexity of Endometriosis-related pain. J Endometr Pelvic Pain Disord. 2017;9(1):30–8.
Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ. Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci. 2001;21(14):5027–35.
Bedaiwy MA, Falcone T, Goldberg JM, Sharma RK, Nelson DR, Agarwal A. Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients. Hum Reprod. 2006;21(3):788–91.
Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002;17(2):426–31.
Buyalos RP, Funari VA, Azziz R, Watson JM, Martinez-Maza O. Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology. Fertil Steril. 1992;58(2):302–6.
Nirgianakis K, Bersinger NA, McKinnon B, Kostov P, Imboden S, Mueller MD. Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment. Eur J Obstet Gynecol Reprod Biol. 2013;170(2):550–4.
Anaf V, Simon P, El Nakadi I, et al. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod. 2002;17(7):1895–900.
McKinnon BD, Bertschi D, Bersinger NA, Mueller MD. Inflammation and nerve fiber interaction in endometriotic pain. Trends Endocrinol Metab. 2015;26(1):1–10.
As-Sanie S, Harris RE, Napadow V, Kim J, Neshewat G, Kairys A, et al. Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain. 2012;153(5):1006–14.
Anaf V, Simon P, El Nakadi I, et al. Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod. 2000;15(8):1744–50.
Berkley KJ, Rapkin AJ, Papka RE. The pains of endometriosis. Science. 2005;308(5728):1587–9.
•• Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927–935. Expert guidelines on treatment of endometriosis.
• Chaichian S, Kabir A, Mehdizadehkashi A, Rahmani K, Moghimi M, Moazzami B. Comparing the efficacy of surgery and medical therapy for pain Management in Endometriosis: a systematic review and meta-analysis. Pain Physician. 2017;20(3):185–95. Meta-analysis on surgical vs medical management of endometriosis.
Mettler L, Ruprai R, Alkatout I. Impact of medical and surgical treatment of endometriosis on the cure of endometriosis and pain. Biomed Res Int. 2014;2014:264653.
Berlanda N, Vercellini P, Fedele L. The outcomes of repeat surgery for recurrent symptomatic endometriosis. Curr Opin Obstet Gynecol. 2010;22(4):320–5.
Shakiba K, Bena JF, McGill KM, Minger J, Falcone T. Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol. 2008;111(6):1285–92.
Murphy AA, Green WR, Bobbie D, dela Cruz ZC, Rock JA. Unsuspected endometriosis documented by scanning electron microscopy in visually normal peritoneum. Fertil Steril. 1986;46(3):522–4.
Vercellini P, Vendola N, Bocciolone L, Colombo A, Rognoni MT, Bolis G. Laparoscopic aspiration of ovarian endometriomas. Effect with postoperative gonadotropin releasing hormone agonist treatment. J Reprod Med. 1992;37(7):577–80.
Donnez J, Nisolle M, Gillerot S, Anaf V, Clerckx-Braun F, Casanas-Roux F. Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage. Fertil Steril. 1994;62(1):63–6.
Marana R, Caruana P, Muzii L, Catalano GF, Mancuso S. Operative laparoscopy for ovarian cysts. Excision vs aspiration. J Reprod Med. 1996;41(6):435–8.
Vercellini P, Aimi G, Busacca M, Apolone G, Uglietti A, Crosignani PG. Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial. Fertil Steril. 2003;80(2):310–9.
Proctor ML, Latthe PM, Farquhar CM, Khan KS, Johnson NP. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev. 2005;4:CD001896.
Davis GD. Uterine prolapse after laparoscopic uterosacral transection in nulliparous airborne trainees. A report of three cases. J Reprod Med. 1996;41(4):279–82.
Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steril. 1994;62(4):696–700.
Vercellini P, De Giorgi O, Pisacreta A, Pesole AP, Vicentini S, Crosignani PG. Surgical management of endometriosis. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(3):501–23.
Carter JE. Surgical treatment for chronic pelvic pain. JSLS. 1998;2(2):129–39.
Candiani GB, Fedele L, Vercellini P, Bianchi S, Di Nola G. Presacral neurectomy for the treatment of pelvic pain associated with endometriosis: a controlled study. Am J Obstet Gynecol. 1992;167(1):100–3.
Zullo F, Palomba S, Zupi E, Russo T, Morelli M, Cappiello F, et al. Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial. Am J Obstet Gynecol. 2003;189(1):5–10.
Rizk B, Fischer AS, Lotfy HA, Turki R, Zahed HA, Malik R, et al. Recurrence of endometriosis after hysterectomy. Facts Views Vis Obgyn. 2014;6(4):219–27.
•• Gambone JC, Mittman BS, Munro MG, Scialli AR, Winkel CA. Consensus statement for the management of chronic pelvic pain and endometriosis: proceedings of an expert-panel consensus process. Fertil Steril. 2002;78(5):961–72. Consensus statement on treatment of pain associated with endometriosis from ASRM.
Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev. 2015;7:CD001751.
Allen C, Hopewell S, Prentice A. Non-steroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev. 2005;4:CD004753.
Kauppila A, Puolakka J, Ylikorkala O. Prostaglandin biosynthesis inhibitors and endometriosis. Prostaglandins. 1979;18(4):655–61.
Kauppila A, Ronnberg L. Naproxen sodium in dysmenorrhea secondary to endometriosis. Obstet Gynecol. 1985;65(3):379–83.
Benzon HT, Raja SN, Liu SS, et al. Dedication. In: Benzon HT, Raja SN, Liu SS, Fishman SM, Cohen SP, eds. Essentials of Pain Medicine (Fourth Edition). Elsevier; 2018:v.
• Kremer M, Salvat E, Muller A, Yalcin I, Barrot M. Antidepressants and gabapentinoids in neuropathic pain: mechanistic insights. Neuroscience. 2016;338:183–206. Gabapentin and antidepressants for treatment of neuropathic pain.
Sator-Katzenschlager SM, Scharbert G, Kress HG, Frickey N, Ellend A, Gleiss A, et al. Chronic pelvic pain treated with gabapentin and amitriptyline: a randomized controlled pilot study. Wien Klin Wochenschr. 2005;117(21–22):761–8.
Zito G, Luppi S, Giolo E, et al. Medical treatments for endometriosis-associated pelvic pain. Biomed Res Int. 2014;2014:191967.
Olive DL. Medical therapy of endometriosis. Semin Reprod Med. 2003;21(2):209–22.
Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril. 2008;90(5):1583–8.
Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril. 1993;60(1):75–9.
Laschke MW, Menger MD. Anti-angiogenic treatment strategies for the therapy of endometriosis. Hum Reprod Update. 2012;18(6):682–702.
Vercellini P, Cortesi I, Crosignani PG. Progestins for symptomatic endometriosis: a critical analysis of the evidence. Fertil Steril. 1997;68(3):393–401.
McCormack PL. Dienogest: a review of its use in the treatment of endometriosis. Drugs. 2010;70(16):2073–88.
Vercellini P, Frontino G, De Giorgi O, Aimi G, Zaina B, Crosignani PG. Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Fertil Steril. 2003;80(2):305–9.
Fedele L, Bianchi S, Zanconato G, Portuese A, Raffaelli R. Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis. Fertil Steril. 2001;75(3):485–8.
• Lockhat FB, Emembolu JO, Konje JC. The evaluation of the effectiveness of an intrauterine-administered progestogen (levonorgestrel) in the symptomatic treatment of endometriosis and in the staging of the disease. Hum Reprod. 2004;19(1):179–84. IUD progesterone use for medical managment.
Sagsveen M, Farmer JE, Prentice A, Breeze A. Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density. Cochrane Database Syst Rev. 2003;4:CD001297.
Brown J, Pan A, Hart RJ. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010;12:CD008475.
Barbieri RL. Endometriosis and the estrogen threshold theory. Relation to surgical and medical treatment. J Reprod Med. 1998;43(3 Suppl):287–92.
• Bedaiwy MA, Alfaraj S, Yong P, Casper R. New developments in the medical treatment of endometriosis. Fertil Steril. 2017;107(3):555–65. Review of novel medical treatments.
Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, et al. Treatment of endometriosis-associated pain with Elagolix, an Oral GnRH antagonist. N Engl J Med. 2017;377(1):28–40.
Surrey E, Taylor HS, Giudice L, Lessey BA, Abrao MS, Archer DF, et al. Long-term outcomes of Elagolix in women with endometriosis: results from two extension studies. Obstet Gynecol. 2018;132(1):147–60.
Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007;4:CD000068.
Ferrero S, Tramalloni D, Venturini PL, Remorgida V. Vaginal danazol for women with rectovaginal endometriosis and pain symptoms persisting after insertion of a levonorgestrel-releasing intrauterine device. Int J Gynaecol Obstet. 2011;113(2):116–9.
Mizutani T, Nishiyama S, Amakawa I, Watanabe A, Nakamuro K, Terada N. Danazol concentrations in ovary, uterus, and serum and their effect on the hypothalamic-pituitary-ovarian axis during vaginal administration of a danazol suppository. Fertil Steril. 1995;63(6):1184–9.
Igarashi M, Iizuka M, Abe Y, Ibuki Y. Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis. Hum Reprod. 1998;13(7):1952–6.
Cobellis L, Razzi S, Fava A, Severi FM, Igarashi M, Petraglia F. A danazol-loaded intrauterine device decreases dysmenorrhea, pelvic pain, and dyspareunia associated with endometriosis. Fertil Steril. 2004;82(1):239–40.
Pavone ME, Bulun SE. Aromatase inhibitors for the treatment of endometriosis. Fertil Steril. 2012;98(6):1370–9.
• Nawathe A, Patwardhan S, Yates D, Harrison GR, Khan KS. Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG. 2008;115(7):818–22. Review of aromatase inhibitors.
Bulun SE, Fang Z, Imir G, Gurates B, Tamura M, Yilmaz B, et al. Aromatase and endometriosis. Semin Reprod Med. 2004;22(1):45–50.
Soysal S, Soysal ME, Ozer S, Gul N, Gezgin T. The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod. 2004;19(1):160–7.
• Wayne PM, Kerr CE, Schnyer RN, et al. Japanese-style acupuncture for endometriosis-related pelvic pain in adolescents and young women: results of a randomized sham-controlled trial. J Pediatr Adolesc Gynecol. 2008;21(5):247–57. Evidence for acupuncture for endometriosis.
Rubi-Klein K, Kucera-Sliutz E, Nissel H, Bijak M, Stockenhuber D, Fink M, et al. Is acupuncture in addition to conventional medicine effective as pain treatment for endometriosis? A randomised controlled cross-over trial. Eur J Obstet Gynecol Reprod Biol. 2010;153(1):90–3.
Flower A, Liu JP, Chen S, Lewith G, Little P. Chinese herbal medicine for endometriosis. Cochrane Database Syst Rev. 2009;3:CD006568.
Montenegro ML, Vasconcelos EC, Candido Dos Reis FJ, Nogueira AA, Poli-Neto OB. Physical therapy in the management of women with chronic pelvic pain. Int J Clin Pract. 2008;62(2):263–9.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Daniel Carlyle, and Tarek Khader, David Lam, Nalini Vadivelu, Devina Shiwlochan, and Cho Yonghee declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Other Pain
Rights and permissions
About this article
Cite this article
Carlyle, D., Khader, T., Lam, D. et al. Endometriosis Pain Management: a Review. Curr Pain Headache Rep 24, 49 (2020). https://doi.org/10.1007/s11916-020-00884-6
Published:
DOI: https://doi.org/10.1007/s11916-020-00884-6