{"paper_id":"b4d35ff9-6c7c-49a0-99af-e5e2bb1feb4e","body_text":"Mini Review\nVolume 2 Issue 3 - Seprember 2017\nDOI: 10.19080/GJORM.2017.02.555586\nGlob J Reprod Med\nCopyright © All rights are reserved by Kazushige Adachi\nDienogest in the Treatment of Endometriosis\nKazushige Adachi*, Akiko Otake and Yoshimitsu Yamamoto\nDepartment of Obstetrics and Gynecology, Minoh City Hospital, Japan\nSubmission: September 6, 2017; Published: September 11, 2017\n*Corresponding author:  Kazushige Adachi, Department of Obstetrics and Gynecology, Minoh City Hospital, 5-7-1 Kayano, Japan,  \nTel: , FAX: , Email: \nIntroduction\nEndometriosis is a common disease in up to 10% of \nwomen of reproductive age. It often causes symptoms such as \ndysmenorrhea, chronic pelvic pain, dyspareunia and dyschezia \n[1]. It is also associated with ovarian endometrioma which \nrequires surgery for both diagnosis and treatment. However, \nrecurrence rates are approximately 30-50% within 5 years after \nsurgery [2]. Dienogest is a new synthetic oral progestin that was \napproved for the treatment of endometriosis [3]. \nIt works by preventing the growth of the endometrium \nand suppressing estrogen production [4]. Additionally, it is \nallowed for long-term administration unlike gonadotropin \nreleasing hormone agonist (GnRHa) [5]. Long-term dienogest \nshowed a favorable safety and tolerability profile, including \na low incidence of hypoestrogenic effects and minimal change \nin bone mineral density [6]. The aim of this study is to review \nliterature and assess the efficacy of dienogest in the treatment \nof endometriosis.\nPain Relief\nIn a 12-week randomized placebo-controlled study involving \n198 women, dienogest 2 mg/day was more effective than placebo \nfor reducing endometriosis-associated pelvic pain [7]. A study \nof one year-treatment demonstrated that dienogest showed \npelvic pain reduction through the treatment period [5] and  \n \nthe decrease of pelvic pain persisted for at least 24 weeks after \ntreatment cessation [8]. Dienogest 2mg/day for 24 weeks was \nequivalently effective to subcutaneous leuprolide acetate 3.75 \nmg every 4 weeks [9] or intranasal buserelin acetate 900mg/day \n[10] in relieving the painful symptoms of endometriosis. \nPostoperative administration of dienogest showed a \nsignificant higher pelvic pain reduction than the expectant \nmanagement group until 24 months of follow-up in a multi-\ncenter study [11]. Dienogest prevented pelvic pain recurrence as \neffectively as GnRHa after laparoscopic surgery for endometriosis \n[12]. Dienogest plus estradiol valerate is significantly more \neffective than levonorgestrel-releasing intrauterine device in \nreducing pelvic pain after surgery for endometriosis [13]. \nOvarian Endometrioma\nTreatment of dienogest over 12 months decreased the size of \nendometrioma to approximately 30% of the initial sizes [14] and \nthe similar effect was also observed in the patients of recurrent \nendometrioma [15]. \nThere has been reported the efficacy of postoperative \ndienogest on endometrioma recurrence. A postoperative \ndienogest treatment versus a control group showed a significant \ndifference in recurrence at 12 (0% vs.16.5%) or 24 months (0% \nvs. 24.0%) [11]. Although recurrence was not seen in patients \nGlob J Reprod Med 2(3): GJORM.MS.ID.555586 (2017)  0041\nAbstract\nEndometriosis is a prevalent chronic disease in up to 10% of women of reproductive age and often causes pain symptoms. In some \npatients, these symptoms negatively affect quality of life for a long time. Dienogest is an oral progestin that was recently approved for the \ntreatment of endometriosis. It is allowed for long-term administration with a favorable safety and tolerability profile. Dienogest 2mg/day \nwas superior to placebo in relieving pain symptoms in patients with endometriosis, equivalently effective to gonadotropin releasing hormone \nagonist (GnRHa). The size of endometriomas was reduced by use of dienogest. Postoperative administration of dienogest showed the efficacy \nin relieving pain and suppressing recurrence of endometrioma in patients with endometriosis. Dienogest was also effective in relieving \nsymptoms in women with deep infiltrating endometriosis (DIE) or extragenital endometriosis. Dienogest is an alternative for the treatment of \nendometriosis because of its efficacy, safety and tolerability.\nKeywords: Dienogest; Endometriosis\nAbbreviations: GnRHa: Gonadotropin Releasing Hormone Agonist; DIE: Deep Infiltrating Endometriosis;\n\n\nHow to cite this article: Kazushige A, Akiko O, Yoshimitsu Y. Dienogest in the Treatment of Endometriosis. Glob J Reprod Med. 2017; 2(3): 555586. DOI: \n10.19080/GJORM.2017.02.5555860042\nGlobal Journal of Reproductive Medicine\nwith dienogest, no medication group showed recurrence up \nto 50% at 5 years after surgery [16]. No significant difference \nwas observed in the postoperative recurrence rate between the \ndienogest and goserelin (subcutaneous 1.8 mg every 4 weeks) \ngroup [17]. \nDeep Infiltrating Endometriosis (DIE)\nDIE can affect the bowel and the urinary tract and causes \nsevere pain. Dienogest is as effective as surgical treatment \nin relieving pain in more than 90% of women with DIE at one \nyear follow-up [18]. Postoperative administration of dienogest \nsignificantly reduced the endometriosis-related pain in the DIE \npatients [19]. A prospective cohort study demonstrated that \ndienogest for 12 months was effective to control pain related to \nDIE, even without reducing the volume of DIE nodules [20].\nExtragenital Endometriosis\nThere are a few pilot studies describing the efficacy of \ndienogest on extragenital endometriosis. Four cases with \ncolon endometriosis, treated with dienogest for over 6 months, \nexhibited their size reduction and pain relief related with the \nlegions [21]. By treatment of dienogest for 12 months, symptoms \nwere improved and the nodules reduced in size in 6 cases of \nbladder endometriosis [22].\nConclusion\nThe above studies suggested that dienogest is an alternative \nas first-line therapy for relieving pain and suppressing \nrecurrence in patients with endometriosis. However, there is \nstill a need to establish the effect of long-term treatment with \ndienogest and the recurrence after its discontinuation. Moreover, \nthere were no studies comparing the efficacy and safety between \ndienogest and combined oral contraceptives which are also \neffective in the treatment of endometriosis. Further randomized \ninvestigations are necessary to elucidate strategies of dienogest \nfor the treatment of endometriosis. \nReferences\n1. Giudice LC, Kao LC (2004) Endometriosis. Lancet 364 (9447): 1789-\n1799.\n2. Vercellini P , Somigliana E, Daguati R, Vigano P , Meroni F, et al. (2008) \nPostoperative oral contraceptive exposure and risk of endometrioma \nrecurrence. Am J Obstet Gynecol 198(5): 504.e1-5.\n3. Sasagawa S, Shimizu Y, Kami H, Takeuchi T , Mita S, et al. (2008) \nDienogest is a selective progesterone receptor agonist in transactivation \nanalysis with potent oral endometrial activity due to its efficient \npharmacokinetics profile. Steroids 73(2): 222-231.\n4. Klipping C, Duijkers I, Remmers A, Faustmann T , Zulth C, et al. (2012) \nOvulation-inhibiting effects of dienogest in a randomized, dose-\ncontrolled pharmacodynamics trail of healthy women. J Clin Pharmacol \n52(11): 1704-1713.\n5. Seitz C, Gerlinger C, Faustmann T , Strowitzki T (2009) Safety of \ndienogest in the long-term treatment of endometriosis: a one-year, \nopen-label, follow-up study. Fertil Steril 92 (23): S107.\n6. Strowitzki T , Faustmann T , Gerlinger C, Schumacher U, Ahlers C, et al. \n(2015) Safety and tolerability of dienogest in endometriosis: pooled \nanalysis from the European clinical study program. Int J Women Health \n7: 393-401.\n7. Strowitzki T , Faustmann T , Gerlinger C, Seitz C (2010) Dienogest in \nthe treatment of endometriosis-associated pelvic pain: a 12 week, \nrandomized, double-blind, placebo-controlled study. Eur J Obstet \nGynecol Reprod Biol 151(2): 193-198.\n8. Petraglia F, Hornung D, Seitz C, Faustmann T , Gerlinger C, et al. (2012) \nReduced pelvic pain in women with endometriosis: efficacy of long-\nterm dienogest treatment. Acta Gynecol Obstet 285(1): 167-173.\n9. Strowitziki T , Marr J, Gerlinger C, Faustmann T , Seitz C (2010) Dienogest \nis as effective as leuprolide acetate in treating the painful symptoms of \nendometriosis: a 24-week, randomized, multicenter, open-label trial. \nHuman Reprod 25(3): 633-641. \n10. Harada T , Momoeda M, Taketani Y, Aso T , Fukunaga M, et al. (2009) \nDienogest is as effective as intranasal buserelin acetate for the relief of \npain symptoms associated with endometriosis: a randomized, double-\nblind, multicenter, controlled trial. Fertil Steril 91(3): 675-681.\n11. Adachi K, Takahashi K, Nakamura K, Otake A, Sasamoto N, et al. [2016] \nPost -operative administration of dienogest for suppressing recurrence \nof disease and relieving pain in subjects with ovarian endometriomas. \nGynecol Endcriol 32(8): 646-649.\n12. Lee DY, Lee JY,  Seo JW, Yoon BK,  Choi D (2016)  Gonadotropin-releasing \nhormone agonist with add-back treatment is as effective and tolerable \nas dienogest in preventing pain recurrence after laparoscopic surgery \nfor endometriosis. Arch Gynecol Obstet 294 (6): 1257-1263.\n13.  Morelli M, Sacchinelli A, Venturella R, Mocciaro R, Zullo F (2013) \nPostoperative administration of dienogest plus estradiol velerate \nversus levonorgestrel-releasing intrauterine device for prevention of \npain relapse and disease recurrence in endometriosis patients. J Obstet \nGynecol Res 39(5): 985-990. \n14. Sugimoto K, Nagata C, Hayashi H, Yanagida S, Okamoto A (2015) Use of \ndienogest over 53 weeks for the treatment of endometriosis. J Obstet \nGynecol Res 41(12): 1921-1926. \n15.  Park SY, Kim SH, Chae HD, Kim CH, Kang BM (2016) Efficacy and \nsafety of dienogest in patinets with endometriosis: A single-center \nobservation study over 12 months. Clin Exp Reprod Med 43 (4): 215-\n220.\n16. Ouchi N, Akira S, Mine K. Ichikawa M, Takeshita T (2014) Recurrence \nof ovarian endometrioma after laparoscopic excision: Risk factors and \nprevention. J Obstet Gynecol Res 40(1): 230-236.\n17. Takaesu Y, Nishi H, Kojima J, Sasaki T , Nagamatsu Y, et al. (2016) \nDienogest compared with gonadotropin-releasing hormone agonist \nafter conservative surgery for endometriosis. J Obstet Gynecol Res \n42(9): 1152-1158.\n18. Berlanda N, Somigliana E, Frattaruolo MP , Buggio L, Dridi D, et al. \n(2017) Surgery versus hormonal therapy for deep endometriosis: is it \na choice of the physician? Eur J Obstet Gynecol Reprod Biol 209: 67-71.\n19. Yamanaka A, Hada T , Matsumoto T , Kanno K, Shirane A, et al. (2017) \nEffect of dienogest on pain and ovarian endometrioma occurrence after \nlaparoscopic resection of uterosacral ligaments with deep infiltrating \nendometriosis. Eur J Obstet Gynecol Reprod Biol 216: 51-55.\n20. Leonardo-Pinto JP , Benetti-Pinto CL, Cursino K, Yela DA (2017) \nDienogest and deep infiltrating endometriosis: The remission of \nsymptoms is not relate to endometriosis nodule remission. Eur J Obstet \nGynecol Reprod Biol 211: 108-111.\n21. Harada M, Osuga Y, Izumi G, Takamura M, Takemura Y, et al. (2011) \nDienogest, a new conservative strategy for extragenital endometriosis: \na pilot study. Gynecol Endocrinol 27(9): 717-720.\n22. Angioni S, Nappi L, Pontis A, Sedda F, Luisi S, et al. (2015) Dienogest. A \npossible conservative approach in bladder endometriosis. Results of a \npilot study. Gynecol Endocrinol 31(5): 406-408.\n\nHow to cite this article: Kazushige A, Akiko O, Yoshimitsu Y. Dienogest in the Treatment of Endometriosis. Glob J Reprod Med. 2017; 2(3): 555586. DOI: \n10.19080/GJORM.2017.02.5555860043\nGlobal Journal of Reproductive Medicine\nYour next submission with Juniper Publishers    \n      will reach you the below assets\n• Quality Editorial service\n• Swift Peer Review\n• Reprints availability\n• E-prints Service\n• Manuscript Podcast for convenient understanding\n• Global attainment for your research\n• Manuscript accessibility in different formats \n         ( Pdf, E-pub, Full Text, Audio) \n• Unceasing customer service\n                       Track the below URL for one-step submission \n               https://juniperpublishers.com/online-submission.php\nThis work is licensed under Creative\nCommons Attribution 4.0 Licens\nDOI: 10.19080/GJORM.2017.02.555586","source_license":"CC0","license_restricted":false}