{"paper_id":"5b5c6e1f-b6a9-4f33-a741-2e1d07d433a9","body_text":"Abstract\nAdenomyosis is a common gynaecological condition that can cause pelvic pain, heavy menstrual bleeding and adverse reproductive outcomes in reproductive-aged women. Hysterectomy remains the definitive treatment for adenomyosis. However, given the young age of patients at presentation, there is growing interest in fertility-preserving medical treatments. Medical management mainly involves the levonorgestrel-releasing intrauterine system (LNG-IUS), dienogest, oral contraceptives and gonadotropin-releasing hormone (GnRH) agonists. Progestins (LNG-IUS and dienogest) and GnRH agonists can be considered as first- and second- line therapies, respectively, to manage symptoms. Treatments with novel targets are being explored for adenomyosis, but these need further investigation.\nSimilar content being viewed by others\nReferences\nDason ES, Maxim M, Sanders A, et al. Guideline no. 437: diagnosis and management of adenomyosis. J Obstet Gynaecol Can. 2023;45(6):417–29.\nMoldassarina RS. Modern view on the diagnostics and treatment of adenomyosis. Arch Gynecol Obstet. 2023;308(1):171–81.\nSharara FI, Kheil MH, Feki A, et al. Current and prospective treatment of adenomyosis. J Clin Med. 2021;10(15):3410.\nUpson K, Missmer SA. Epidemiology of adenomyosis. Semin Reprod Med. 2020;38(2–03):89–107.\nEtrusco A, Barra F, Chiantera V, et al. Current medical therapy for adenomyosis: from bench to bedside. Drugs. 2023;83(17):1595–611.\nBulun SE, Yildiz S, Adli M, et al. Adenomyosis pathogenesis: insights from next-generation sequencing. Hum Reprod Update. 2021;27(6):1086–97.\nNational Institute for Health and Care Excellence. Heavy menstrual bleeding: assessment and management [NG88]. 2021. https://www.nice.org.uk/. Accessed 16 Jul 2024.\nSheng J, Zhang WY, Zhang JP, et al. The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Contraception. 2009;79(3):189–93.\nOsuga Y, Watanabe M, Hagino A. Long-term use of dienogest in the treatment of painful symptoms in adenomyosis. J Obstet Gynaecol Res. 2017;43(9):1441–8.\nNeriishi K, Hirata T, Fukuda S, et al. Long-term dienogest administration in patients with symptomatic adenomyosis. J Obstet Gynaecol Res. 2018;44(8):1439–44.\nNagata C, Yanagida S, Okamoto A, et al. Risk factors of treatment discontinuation due to uterine bleeding in adenomyosis patients treated with dienogest. J Obstet Gynaecol Res. 2012;38(4):639–44.\nOzdegirmenci O, Kayikcioglu F, Akgul MA, et al. Comparison of levonorgestrel intrauterine system versus hysterectomy on efficacy and quality of life in patients with adenomyosis. Fertil Steril. 2011;95(2):497–502.\nZheng J, Xia E, Li TC, et al. Comparison of combined transcervical resection of the endometrium and levonorgestrel-containing intrauterine system treatment versus levonorgestrel-containing intrauterine system treatment alone in women with adenomyosis: a prospective clinical trial. J Reprod Med. 2013;58(7–8):285–90.\nShaaban OM, Ali MK, Sabra AM, et al. Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial. Contraception. 2015;92(4):301–7.\nMcCormack PL. Dienogest: a review of its use in the treatment of endometriosis. Drugs. 2010;70(16):2073–88.\nOta I, Taniguchi F, Ota Y, et al. A controlled clinical trial comparing potent progestins, LNG-IUS and dienogest, for the treatment of women with adenomyosis. Reprod Med Biol. 2021;20(4):427–34.\nFawzy M, Mesbah Y. Comparison of dienogest versus triptorelin acetate in premenopausal women with adenomyosis: a prospective clinical trial. Arch Gynecol Obstet. 2015;292(6):1267–71.\nBeaumont H, Augood C, Duckitt K, et al. Danazol for heavy menstrual bleeding. Cochrane Database Syst Rev. 2002;2: CD001017.\nIgarashi M. A new therapy for pelvic endometriosis and uterine adenomyosis: local effect of vaginal and intrauterine danazol application. Asia Oceania J Obstet Gynaecol. 1990;16(1):1–12.\nIgarashi M, Abe Y, Fukuda M, et al. Novel conservative medical therapy for uterine adenomyosis with a danazol-loaded intrauterine device. Fertil Steril. 2000;74(2):412–3.\nLuisi S, Razzi S, Lazzeri L, et al. Efficacy of vaginal danazol treatment in women with menorrhagia during fertile age. Fertil Steril. 2009;92(4):1351–4.\nTakebayashi T, Fujino Y, Umesaki N, et al. Danazol suspension injected into the uterine cervix of patients with adenomyosis and myoma: preliminary study. Gynecol Obstet Invest. 1995;39(3):207–11.\nHassanin AI, Youssef AA, Yousef AM, et al. Comparison of dienogest versus combined oral contraceptive pills in the treatment of women with adenomyosis: a randomized clinical trial. Int J Gynaecol Obstet. 2021;154(2):263–9.\nDella Corte L, Barra F, Mercorio A, et al. Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis. Expert Opin Drug Metab Toxicol. 2020;16(9):759–68.\nBadawy AM, Elnashar AM, Mosbah AA. Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial. Acta Obstet Gynecol Scand. 2012;91(4):489–95.\nMarjoribanks J, Ayeleke RO, Farquhar C, et al. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev. 2015;2015(7):CD001751.\nBofill Rodriguez M, Lethaby A, Farquhar C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;9(9):CD000400.\nAkira S, Mine K, Kuwabara Y, et al. Efficacy of long-term, low-dose gonadotropin-releasing hormone agonist therapy (draw-back therapy) for adenomyosis. Med Sci Monit. 2009;15(1):CR1–4.\nWagenfeld A, Saunders PT, Whitaker L, et al. Selective progesterone receptor modulators (SPRMs): progesterone receptor action, mode of action on the endometrium and treatment options in gynecological therapies. Expert Opin Ther Targets. 2016;20(9):1045–54.\nHong YH, Han SJ, Lee D, et al. Adverse symptoms during short-term use of ulipristal acetate in women with uterine myomas and/or adenomyosis. J Obstet Gynaecol Res. 2019;45(4):865–70.\nFerrero S, Racca A, Tafi E, et al. Changes in the sonographic characteristics of adenomyosis after treatment with ulipristal acetate [abstract no. OP30.04]. Ultrasound Obstetr Gynecol. 2016;48(S1):151.\nYanase T, Kikuchi A, Sasagawa M, et al. Two cases of endometrial cancer arising from adenomyosis during aromatase inhibitors therapy after mastectomy. J Obstet Gynaecol. 2017;37(7):952–4.\nDonnez J, Donnez O, Brethous M, et al. Treatment of symptomatic uterine adenomyosis with linzagolix, an oral gonadotrophin-releasing hormone antagonist: a pilot study. Reprod Biomed Online. 2022;44(1):200–3.\nCapmas P, Brun JL, Legendre G, et al. Ulipristal acetate use in adenomyosis: a randomized controlled trial. J Gynecol Obstet Hum Reprod. 2021;50(1):101978.\nFerrero S, Remorgida V, Maganza C, et al. Aromatase and endometriosis: estrogens play a role. Ann N Y Acad Sci. 2014;1317(1):17–23.\nMori T, Kawashima S, Nagasawa H. Induction of uterine adenomyosis by pituitary grafting and retardation of its development by bromocriptine-mesilate (CB-154) in BALB/c mice. In Vivo. 1991;5(2):107–9.\nAndersson JK, Khan Z, Weaver AL, et al. Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: a pilot study. Acta Obstet Gynecol Scand. 2019;98(10):1341–50.\nAndersson JK, Pozzi Mucelli R, Epstein E, et al. Vaginal bromocriptine for treatment of adenomyosis: impact on magnetic resonance imaging and transvaginal ultrasound. Eur J Obstet Gynecol Reprod Biol. 2020;254:38–43.\nLiu X, Nie J, Guo SW. Elevated immunoreactivity against class I histone deacetylases in adenomyosis. Gynecol Obstet Invest. 2012;74(1):50–5.\nLiu X, Guo SW. A pilot study on the off-label use of valproic acid to treat adenomyosis. Fertil Steril. 2008;89(1):246–50.\nXishi L, Lei Y, Guo SW. Valproic acid as a therapy for adenomyosis: a comparative case series. Reprod Sci. 2010;17(10):904–12.\nLiang Z, Yin M, Ma M, et al. Effect of pretreatment with a levonorgestrel-releasing intrauterine system on IVF and vitrified-warmed embryo transfer outcomes in women with adenomyosis. Reprod Biomed Online. 2019;39(1):111–8.\nRocha TP, Andres MP, Borrelli GM, et al. Fertility-sparing treatment of adenomyosis in patients with infertility: a systematic review of current options. Reprod Sci. 2018;25(4):480–6.\nCozzolino M, Pellicer N, Galliano D, et al. Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis. Reprod Biomed Online. 2023;46(1):150–5.\nHenshaw J, Tremellen K. Intralipid infusion therapy as an adjunct treatment in women experiencing adenomyosis-related infertility. Ther Adv Reprod Health. 2023;17:26334941231181256.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nFunding\nThe preparation of this review was not supported by any external funding.\nAuthorship and conflict of interest\nE. S. Kim, a contracted employee of Adis International Ltd/Springer Nature, and T. Nie, a salaried employee of Adis International Ltd/Springer Nature, declare no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.\nEthics approval, Consent to participate, Consent for publication, Availability of data and material, Code availability\nNot applicable.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nKim, E.S., Nie, T. Consider fertility-preserving medications when treating adenomyosis. Drugs Ther Perspect 40, 357–362 (2024). https://doi.org/10.1007/s40267-024-01099-0\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s40267-024-01099-0","source_license":"CC0","license_restricted":false}