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Evaluation of pharmacological interventions in the management of adenomyosis: a systematic review

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Medical management of adenomyosis largely revolves around symptom management, with very few drugs having received regulatory approval for the disease. However, the level of evidence supporting the use of pharmacological interventions is low, making it difficult to establish their efficacy in the treatment of adenomyosis. Hence, the aim of our systematic review is to identify the strength of evidence currently available and evaluate the effectiveness of different medical interventions in the management of adenomyosis.


The search was performed in MEDLINE, Embase, Cochrane Library, CENTRAL and Articles published between 1 January 2010 and 30 November 2020 were considered. Randomized controlled trials and observational studies that assessed the efficacy of medical interventions in patients with adenomyosis were included. The quality of the data was analyzed using RevMan 5.3 software.


LNG-IUS (levonorgestrel intrauterine system), dienogest and gonadotropin-releasing hormone (GnRH) analogues were effective in reducing pain, uterine volume and menstrual bleeding. However, these data were largely obtained in the non-trial setting and were fraught with issues that included patient selection, short duration of therapy, small sample size, and limited long-term safety and effectiveness data.


Although LNG-IUS, dienogest and GnRH analogues have better evidence for effectiveness in adenomyosis, the need of the hour is to thoroughly evaluate other novel molecules for adenomyosis using well-designed randomized controlled trials.

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  1. Vannuccini S, Petraglia F (2019) Recent advances in understanding and managing adenomyosis. F1000Research vol. 8 F1000 Faculty Rev-283.

  2. Taran FA, Stewart EA, Brucker S (2013) Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy. Geburtshilfe Frauenheilkd 73(9):924–931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dessouky R, Gamil SA, Nada MG, Mousa R, Libda Y (2019) Management of uterine adenomyosis: current trends and uterine artery embolization as a potential alternative to hysterectomy. Insights Imaging. 10(1):48. Published 2019 Apr 27.

  4. Vannuccini S, Tosti C, Carmona F et al (2017) Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online 35(5):592–601.

    Article  CAS  PubMed  Google Scholar 

  5. Zhai J, Vannuccini S, Petraglia F, Giudice LC (2020) Adenomyosis: Mechanisms and Pathogenesis. Semin Reprod Med 38(2–03):129–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vannuccini S, Luisi S, Tosti C, Sorbi F, Petraglia F (2018) Role of medical therapy in the management of uterine adenomyosis. Fertil Steril 109(3):398–405.

    Article  PubMed  Google Scholar 

  7. Kuan-HaoTsui W-L, Chen C-Y, Sheu B-C, Yen M-S, Chang T-C, Wang P-H (2014) Medical treatment for adenomyosis and/or adenomyoma. Taiwan J Obstet Gynecol 53(4):459–465.

    Article  Google Scholar 

  8. Badawy AM, Elnashar AM, Mosbah AA (2012) Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial. Acta Obstet Gynecol Scand 91(4):489–495.

    Article  CAS  PubMed  Google Scholar 

  9. Capmas P, Brun JL, Legendre G, Koskas M, Merviel P, Fernandez H (2021) Ulipristal acetate use in adenomyosis: A randomized controlled trial. J Gynecol Obstet Hum Reprod 50(1):101978.

    Article  PubMed  Google Scholar 

  10. Osuga Y, Fujimoto-Okabe H, Hagino A (2017) Evaluation of the efficacy and safety of dienogest in the treatment of painful symptoms in patients with adenomyosis: a randomized, double-blind, multicenter, placebo-controlled study. Fertil Steril 108(4):673–678.

    Article  CAS  PubMed  Google Scholar 

  11. Rukhliada NN, Krylov KY, Matukhin VI (2020) The quality of life of women and morphological changes in the glands of adenomyosis under the influence of dienogest-containing preparations. Journal of Endometriosis and Pelvic Pain Disorders 12(3–4):128–133.

    Article  Google Scholar 

  12. Shaaban OM, Ali MK, Sabra AM, Abd El Aal DE (2015) Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial. Contraception 92(4):301–7.

  13. Osuga Y, Watanabe M, Hagino A (2017) Long-term use of dienogest in the treatment of painful symptoms in adenomyosis. J Obstet Gynaecol Res 43(9):1441–1448.

    Article  CAS  PubMed  Google Scholar 

  14. Yang X, Zhang X, Lin B, Feng X, Aili A (2019) Combined therapeutic effects of HIFU, GnRH-a and LNG-IUS for the treatment of severe adenomyosis. Int J Hyperthermia 36(1):486–492.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang P, Song K, Li L, Yukuwa K, Kong B (2013) Efficacy of combined levonorgestrel-releasing intrauterine system with gonadotropin-releasing hormone analog for the treatment of adenomyosis. Med Princ Pract 22(5):480–483.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Andersson JK, Khan Z, Weaver AL, Vaughan LE, Gemzell-Danielsson K, Stewart EA (2019) Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: A pilot study. Acta Obstet Gynecol Scand 98(10):1341–1350.

    Article  CAS  PubMed  Google Scholar 

  17. Ekin M, Cengiz H, Ayağ ME, Kaya C, Yasar L, Savan K (2013) Effects of the levonorgestrel-releasing intrauterine system on urinary symptoms in patients with adenomyosis. Eur J Obstet Gynecol Reprod Biol 170(2):517–520.

    Article  CAS  PubMed  Google Scholar 

  18. Kelekci S, Kelekci KH, Yilmaz B (2012) Effects of levonorgestrel-releasing intrauterine system and T380A intrauterine copper device on dysmenorrhea and days of bleeding in women with and without adenomyosis. Contraception 86(5):458–463.

    Article  CAS  PubMed  Google Scholar 

  19. Andreeva E, Absatarova Y (2020) Triptorelin for the treatment of adenomyosis: A multicenter observational study of 465 women in Russia. Int J Gynaecol Obstet 151(3):347–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fawzy M, Mesbah Y (2015) Comparison of dienogest versus triptorelin acetate in premenopausal women with adenomyosis: a prospective clinical trial. Arch Gynecol Obstet 292(6):1267–1271.

    Article  CAS  PubMed  Google Scholar 

  21. Li L, Leng J, Jia S, Lang J (2019) Treatment of symptomatic adenomyosis with the levonorgestrel-releasing intrauterine system. Int J Gynaecol Obstet 146(3):357–363.

    Article  CAS  PubMed  Google Scholar 

  22. Li Q, Ding Y, Zhang XY, Feng WW, Hua KQ (2018) Drug therapy for adenomyosis: a prospective, nonrandomized, parallel-controlled study. J Int Med Res 46(5):1855–1865.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wu J, Huang Y, Chen L, Hu J, Zou Y (2018) Treatment of Adenomyosis with Subcutaneous Etonogestrel Implants: A Clinical Observational Study in 17 Patients. Med Sci Monit 1(24):6085–6092.

    Article  Google Scholar 

  24. Xie M, Yu H, Zhang X, Wang W, Ren Y (2019) Elasticity of adenomyosis is increased after GnRHa therapy and is associated with spontaneous pregnancy in infertile patents. J Gynecol Obstetr Hum Reprod 48(10):849–853.

    Article  PubMed  Google Scholar 

  25. Chen S, Wang J, Sun W, Zhu L, He J, Zhang X (2020) Efficacy of the levonorgestrel-releasing intrauterine device is associated with different subtypes of adenomyosis: a retrospective study. Ann Transl Med 8(21):1356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Muneyyirci-Delale O, Chandrareddy A, Mankame S, Osei-Tutu N, Gizycki HV (2012) Norethindrone acetate in the medical management of adenomyosis. Pharmaceuticals (Basel). 5(10):1120–1127. Published 2012 Oct 22.

  27. Hirata T, Izumi G, Takamura M, Saito A, Nakazawa A, Harada M, Hirota Y, Koga K, Fujii T, Osuga Y (2014) Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study. Gynecol Endocrinol 30(10):726–729.

    Article  CAS  PubMed  Google Scholar 

  28. Matsushima T, Akira S, Fukami T, Yoneyama K, Takeshita T (2018) Efficacy of Hormonal Therapies for Decreasing Uterine Volume in Patients with Adenomyosis. Gynecol Minim Invasive Ther. 7(3):119–123. Epub 2018 Aug 23

  29. Neriishi K, Hirata T, Fukuda S, Izumi G, Nakazawa A, Yamamoto N, Harada M, Hirota Y, Koga K, Wada-Hiraike O, Fujii T, Osuga Y (2018) Long-term dienogest administration in patients with symptomatic adenomyosis. J Obstet Gynaecol Res 44(8):1439–1444.

    Article  CAS  PubMed  Google Scholar 

  30. Park DS, Kim ML, Song T, Yun BS, Kim MK, Jun HS, Seong SJ (2015) Clinical experiences of the levonorgestrel-releasing intrauterine system in patients with large symptomatic adenomyosis. Taiwan J Obstet Gynecol 54(4):412–415.

    Article  PubMed  Google Scholar 

  31. Radzinsky VE, Khamoshina MB, Nosenko EN, Dukhin AO, Sojunov MA, Orazmuradov AA, Lebedeva MG, Orazov MR (2016) Treatment strategies for pelvic pain associated with adenomyosis. Gynecol Endocrinol 32(sup2):19–22.

    Article  CAS  PubMed  Google Scholar 

  32. Song SY, Lee SY, Kim HY, Park DB, Kim DE, Lee KH, Lee S, Yang JB, Yoo HJ (2020) Long-term efficacy and feasibility of levonorgestrel-releasing intrauterine device use in patients with adenomyosis. Medicine (Baltimore) 99(22):e20421.

    Article  Google Scholar 

  33. Tosti C, Vannuccini S, Troìa L et al (2017) Long-Term Vaginal Danazol Treatment in Fertile Age Women with Adenomyosis. Journal of Endometriosis and Pelvic Pain Disorders 9(1):39–43.

    Article  Google Scholar 

  34. Uysal A, Taner CE, Mun S, Uysal F, Celimli FH (2013) Use of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated heavy menstrual bleeding. J Pak Med Assoc 63(11):1349–1352

    PubMed  Google Scholar 

  35. Harada T, Taniguchi F (2010) Dienogest: A New Therapeutic Agent for the Treatment of Endometriosis. Women’s Health. 27–35.

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We would like to thank SRM Institute of Science & Technology for administrative support.

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The study was conceptualized and designed by MG, KKR and JJA. The literature search and title and abstract review were performed by JJA, KKR, SAS and HPS. MG and MS conducted the data analysis. MG, MS and AP carried out the process of abstracting and quality assessment of the included studies. All authors contributed to the writing and revision of the final manuscript. The final manuscript was read and approved by all authors.

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Rathinam, K.K., Abraham, J.J., S, H.P. et al. Evaluation of pharmacological interventions in the management of adenomyosis: a systematic review. Eur J Clin Pharmacol 78, 531–545 (2022).

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