Citation Information :
Dubrovina SO, Berlim YD, Bezhenar VF, Gimbut VS, Baranov II. Pharmacological Management of Endometriosis-related Pain: The Expert Opinion. J South Asian Feder Obs Gynae 2020; 12 (6):415-420.
Aim: The aim of this review article was to analyze and summarize the current treatment options of endometriosis-associated pain to provide additional information about treatment personalization for clinicians. Background: Despite numerous studies being published, endometriosis is still one of the main challenges in gynecology. The etiology of endometriosis is unclear while its mechanism is believed to be connected to the peritoneal endometriotic lesions via retrograde menstruation, immunity abnormalities, and genetic, environmental, and lifestyle factors. Patients with endometriosis generally have to cope with chronic pelvic pain which definitely affects the quality of life. The disease is often characterized by a persistent recurrent course; therefore, when choosing a treatment, special attention should be paid not only to its efficacy, but also to long-term safety, tolerability, and compliance. Review results: Actual and relevant publications in PubMed and eLibrary databases were studied. The authors highlight the pathogenic mechanisms of endometriosis and the current state of pharmacological management options. The available evidence on the use of combined oral contraceptives (COCs) for pelvic pain is critically assessed and the authors propose their opinion on the alternative treatment options with progestogens which seem to be an effective alternative to COCs with a more favorable safety profile. Conclusion: Progestogens are an effective alternative to COCs in the treatment of endometriosis-associated pain; however, further well-conducted trials are needed in both types of therapy. Clinical significance: The results of this literature review provide additional information to enable clinicians to personalize the treatment of endometriosis-associated pain.
Ouchi N, Akira S, Mine K, et al. Recurrence of ovarian endometrioma after laparoscopic excision: risk factors and prevention. J Obstet Gynaecol Res 2014;40(1):230–236. DOI: 10.1111/jog.12164.
Franke HR, Van De Weijer PHM, Pennings TMM, et al. Gonadotropin-releasing hormone agonist plus “add-back” hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial. Fertil Steril 2000;74(3):534–539. DOI: 10.1016/s0015-0282(00)00690-7.
Maruyama T, Yoshimura Y. Stem cell theory for the pathogenesis of endometriosis. Front Biosci—Elit 2012;4 E:2754–2763. DOI: 10.2741/e589.
Moggio A, Pittatore G, Cassoni P, et al. Sorafenib inhibits growth, migration, and angiogenic potential of ectopic endometrial mesenchymal stem cells derived from patients with endometriosis. Fertil Steril 2012;98(6):1521–30.e2. DOI: 10.1016/j.fertnstert.2012.08.003.
Albertsen HM, Ward K. Genes linked to endometriosis by GWAS are integral to cytoskeleton regulation and suggests that mesothelial barrier homeostasis is a factor in the pathogenesis of endometriosis. Reprod Sci 2017;24(6):803–811. DOI: 10.1177/1933719116660847.
Vercellini P, Buggio L, Frattaruolo MP, et al. Medical treatment of endometriosis-related pain. Best Pract Res Clin Obstet Gynaecol 2018;51:68–91. DOI: 10.1016/j.bpobgyn.2018.01.015.
Vercellini P, Barbara G, Somigliana E, et al. Comparison of contraceptive ring and patch for the treatment of symptomatic endometriosis. Fertil Steril 2010;93(7):2150–2161. DOI: 10.1016/j.fertnstert.2009.01.071.
Vercellini P, Fedele L, Arcaini L, et al. Laparoscopy in the diagnosis of chronic pelvic pain in adolescent women. J Reprod Med 1989;34(10):827–830. PMID: 2529373.
Vercellini P, Somigliana E, Vigano P, et al. ‘Blood On The Tracks’ from corpora lutea to endometriomas. BJOG An Int J Obstet Gynaecol 2009;116(3):366–371. DOI: 10.1111/j.1471-0528.2008.02055.x.
Vercellini P, Somigliana E, Daguati R, et al. Postoperative oral contraceptive exposure and risk of endometrioma recurrence. Am J Obstet Gynecol 2008;198(5):504.e1–504.e5. DOI: 10.1016/j.ajog.2007.11.010.
Jensen JT, Schlaff W, Gordon K. Use of combined hormonal contraceptives for the treatment of endometriosis-related pain: a systematic review of the evidence. Fertil Steril 2018;110(1):137–152.e1. DOI: 10.1016/j.fertnstert.2018.03.012.
Flores VA, Vanhie A, Dang T, et al. Progesterone receptor status as a predictor of response to progestins in endometriosis. Fertil Steril 2018;110(4):e383. DOI: 10.1016/j.fertnstert.2018.07.1072.
de Sanctis V, Matalliotakis M, Soliman AT, et al. A focus on the distinctions and current evidence of endometriosis in adolescents. Best Pract Res Clin Obstet Gynaecol 2018;51:138–150. DOI: 10.1016/j.bpobgyn.2018.01.023.
Brion F, Le Page Y, Piccini B, et al. Screening estrogenic activities of chemicals or mixtures in vivo using transgenic (cyp19a1b-GFP) zebrafish embryos. PLoS One 2012;7(5):e36069. DOI: 10.1371/journal.pone.0036069.
Casper RF. Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills. Fertil Steril 2017;107(3):533–536. DOI: 10.1016/j.fertnstert.2017.01.003.
Dunselman GAJ, Vermeulen N, Becker C, et al. ESHRE guideline: Management of women with endometriosis. Hum Reprod 2014;29(3):400–412. DOI: 10.1093/humrep/det457.
Grandi G, Barra F, Ferrero S, et al. Hormonal contraception in women with endometriosis: a systematic review. Eur J Contracept Reprod Heal Care 2019;24(1):61–70. DOI: 10.1080/13625187.2018.1550576.
Vercellini P, Ottolini F, Frattaruolo MP, et al. Shifting from oral contraceptives to norethisterone acetate, or vice versa, because of drug intolerance: does the change benefit women with endometriosis? Gynecol Obstet Invest 2018;83(3):275–284. DOI: 10.1159/000486335.
Miller JA, Missmer SA, Vitonis AF, et al. Prevalence of migraines in adolescents with endometriosis. Fertil Steril 2018;109(4):685–690. DOI: 10.1016/j.fertnstert.2017.12.016.
Harada T, Kosaka S, Elliesen J, et al. Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial. Fertil Steril 2017;108(5):798–805. DOI: 10.1016/j.fertnstert.2017.07.1165.
Brown J, Crawford TJ, Datta S, et al. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev 2018 May 22;5(5):CD001019. DOI: 10.1002/14651858.CD001019.pub3.
Yong PJ, Alsowayan N, Noga H, et al. CHC for pelvic pain in women with endometriosis: ineffectiveness or discontinuation due to side-effects. Hum Reprod Open 2020;2020(2):1–9. DOI: 10.1093/hropen/hoz040.
Chapron C, Souza C, Borghese B, et al. Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis. Hum Reprod 2011;26(8):2028–2035. DOI: 10.1093/humrep/der156.
Dubrovina DSO, Berlim BYD. Progestogens in the therapy of endometriosis. Akush Ginekol (Sofiia). 2018;5_2018:150–155. DOI: 10.18565/aig.2018.5.150-155.
Kitawaki J, Kusuki I, Yamanaka K, et al. Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Eur J Obstet Gynecol Reprod Biol 2011;157:212–216. DOI: 10.1016/j.ejogrb.2011.03.012.
Di Francesco A, Pizzigallo D. Use of micronized palmitoylethanolamide and trans-polydatin in chronic pelvic pain associated with endometriosis. An open-label study. G Ital di Ostet e Ginecol 2014;36(2):353–358. DOI: 10.11138/giog/2014.36.2.353.
Vercellini P, De Giorgi O, Mosconi P, et al. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril 2002;77(1):52–61. DOI: 10.1016/s0015-0282(01)02951-x.
Zupi E, Marconi D, Sbracia M, et al. Add-back therapy in the treatment of endometriosis-associated pain. Fertil Steril 2004;82(5):1303–1308. DOI: 10.1016/j.fertnstert.2004.03.062.
Dubrovina SO, Berlim YuD, Areshyan KA. Comparative characteristics of eutopic and ectopic endometrium with ovarian endometric cysts and normal endometrium. Problemy Reproduktsii 2018;24(6):108–112 [In Russ.]. DOI: 10.17116/repro201824061108.
Mönckedieck V, Sannecke C, Husen B, et al. Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model. Mol Hum Reprod 2009;15(10):633–643. DOI: 10.1093/molehr/gap063.
Liang B, Wu L, Xu H, et al. Efficacy, safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis: a comparison study in mice. Reprod Biol Endocrinol 2018;16(1):32. DOI: 10.1186/s12958-018-0347-9.
Chwalisz K, Surrey E, Stanczyk FZ. The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis. Reprod Sci; 2012;19(6):563–571. DOI: 10.1177/1933719112438061.
Schindler AE, Campagnoli C, Druckmann R, et al. Classification and pharmacology of progestins. Maturitas 2008;61(1-2):171–180. DOI: 10.1016/j.maturitas.2008.11.013.
Africander D, Verhoog N, Hapgood JP. Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 2011;76(7):636–652. DOI: 10.1016/j.steroids.2011.03.001.
Ebert AD, Dong L, Merz M, et al. Dienogest 2 mg daily in the treatment of adolescents with clinically suspected endometriosis: the VISanne study to assess safety in ADOlescents. J Pediatr Adolesc Gynecol 2017;30(5):560–567. DOI: 10.1016/j.jpag.2017.01.014.
Momoeda M, Harada T, Terakawa N, et al. Long-term use of dienogest for the treatment of endometriosis. J Obstet Gynaecol Res 2009;35(6):1069–1076. DOI: 10.1111/j.1447-0756.2009.01076.x.
Petraglia F, Hornung D, Seitz C, et al. Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment. Arch Gynecol Obstet 2012;285(1):167–173. DOI: 10.1007/s00404-011-1941-7.
Kim SA, Um MJ, Kim HK, et al. Study of dienogest for dysmenorrhea and pelvic pain associated with endometriosis. Obstet Gynecol Sci 2016;59(6):506–511. DOI: 10.5468/ogs.2016.59.6.506.
Jeong SH, Lee D, Kim SK, et al. Symptom-alleviating effect and adverse effect of dienogest in Korean women with endometriosis. Gynecol Endocrinol 2018;34(11):970–974. DOI: 10.1080/09513590.2018. 1469610.
Köhler G, Faustmann TA, Gerlinger C, et al. A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis. Int J Gynecol Obstet 2010;108(1):21–25. DOI: 10.1016/j.ijgo.2009.08.020.
Strowitzki T, Marr J, Gerlinger C, et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: A 24-week, randomized, multicentre, open-label trial. Hum Reprod 2010;25:633–641. DOI: 10.1093/humrep/dep469.
Bulun SE, Cheng YH, Pavone ME, et al. 17-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis. Semin Reprod Med 2010;28(1):44–50. DOI: 10.1055/s-0029-1242992.
Vercellini P, Buggio L, Berlanda N, et al. Estrogen-progestins and progestins for the management of endometriosis. Fertil Steril 2016;106(7):1552–1571.e2. DOI: 10.1016/j.fertnstert.2016.10.022.
SukhikhGT, AdamyanLV, SerovVN, et al. Advisory Board Resolution on the subject: “Possibilities of personalized hormone-based therapies for endometriosis using dydrogesterone/Approval of the protocol of an Observational Open-Label Multicenter Study of Real Clinical Practice to Evaluate the Effects of Hormonal therapy with Oral Dydrogesterone for Treatment of Confirmed Endometriosis (the ORCHIDEA study)”. Russ J Hum Reprod 2018;24(5):41–44 [In Russ.]. DOI: 10.17116/repro20182405141.
Ohlenroth G, Hatzmann W. Treatment of juvenile dysmenorrhea with 6-dehydro-retro-progesterone. Med Welt 1982;33:645–646. PMID: 7098828.
Trivedi P, Selvaraj K, Mahapatra P Das, et al. Effective post-laparoscopic treatment of endometriosis with dydrogesterone. Gynecol Endocrinol 2007;23(Suppl. 1):73–76. DOI: 10.1080/09513590701669583.
Brown J, Kives S, Akhtar M. Progestogens and anti-progestogens for pain associated with endometriosis. Cochrane Database Syst Rev 2012;2012(3):CD002122. DOI: 10.1002/14651858.CD002122.pub2.