CC BY 4.0 · Rev Bras Ginecol Obstet 2019; 41(09): 564-574
DOI: 10.1055/s-0039-1695737
Review Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Pharmacological Treatment for Symptomatic Adenomyosis: A Systematic Review

Tratamento farmacológico para adenomiose sintomática: revisão sistemática
1   Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil
Ticiana Aparecida Alves de Mira
1   Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil
Daniela Angerame Yela
1   Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil
Cassia Raquel Teatin-Juliato
1   Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil
Luiz Gustavo Oliveira Brito
1   Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil
› Author Affiliations
Further Information

Publication History

12 March 2019

24 June 2019

Publication Date:
23 September 2019 (online)


Objective To assess the efficacy of non-surgical treatment for adenomyosis.

Data Sources A search was performed by two authors in the Pubmed, Scopus, and Scielo databases and in the grey literature from inception to March 2018, with no language restriction.

Selection of Studies We have included prospective randomized studies for treating symptomatic women with adenomyosis (abnormal uterine bleeding and/or pelvic pain) diagnosed by ultrasound or magnetic resonance imaging.

Data Collection Studies were primarily selected by title and abstract. The articles that were eligible for inclusion were evaluated in their entirety, and their data was extracted for further processing and analysis.

Data Synthesis From 567 retrieved records only 5 remained for analysis. The intervention groups were: levonorgestrel intrauterine system (LNG-IUS)(n = 2), dienogest (n = 2), and letrozole (n = 1). Levonorgestrel intrauterine system was effective to control bleeding when compared to hysterectomy or combined oral contraceptives (COCs). One study assessed chronic pelvic pain and reported that LNG-IUS was superior to COC to reduce symptoms. Regarding dienogest, it was efficient to reduce pelvic pain when compared to placebo or goserelin, but less effective to control bleeding than gonadotropin-releasing hormone (GnRH) analog. Letrozole was as efficient as GnRH analog to relieve dysmenorrhea and dyspareunia, but not for chronic pelvic pain. Reduction of uterine volume was seen with aromatase inhibitors, GnRH analog, and LGN-IUD.

Conclusion Levonorgestrel intrauterine system and dienogest have significantly improved the control of bleeding and pelvic pain, respectively, in women with adenomyosis. However, there is insufficient data from the retrieved studies to endorse each medication for this disease. Further randomized control tests (RCTs) are needed to address pharmacological treatment of adenomyosis.


Objetivo: Avaliar a eficácia de tratamento não cirúrgico para adenomiose.

Fontes de dados: Uma pesquisa foi realizada por dois autores nas bases de dados Pubmed, Scopus, Scielo e na literatura cinzenta desde o início de cada base de dados até março de 2018, sem restrição de idioma.

Seleção de estudos: Incluímos estudos prospectivos randomizados para tratamento de mulheres sintomáticas com adenomiose (sangramento uterino anormal e/ou dor pélvica) diagnosticadas por ultrassonografia ou ressonância magnética.

Coleta de dados: Os estudos foram selecionados principalmente por título e resumo. Os artigos que preencheram os critérios de inclusão foram avaliados na íntegra, e seus dados foram extraídos para posterior processamento e análise.

Síntese dos dados: De 567 registros recuperados, somente 5 permaneceram para análise. Os grupos de intervenção foram: sistema intrauterino de levonorgestrel (SIU-LNG) (n = 2), dienogest (n = 2), e letrozol (n = 1). O SIU-LNG foi efetivo no controle do sangramento quando comparado à histerectomia ou aos contraceptivos orais combinados (COCs). Um estudo avaliou a dor pélvica crônica e relatou que o SIU-LNG foi superior ao COC para reduzir os sintomas. Em relação ao dienogest, este foi eficiente em reduzir a dor pélvica quando comparado ao placebo ou à goserelina, mas foi menos eficaz no controle do sangramento do que o análogo do hormônio liberador de gonadotropina (GnRH). O letrozol foi tão eficiente quanto o análogo do GnRH para aliviar a dismenorreia e a dispareunia, mas não para a dor pélvica crônica. Redução do volume uterino foi observada com inibidores de aromatase, análogo de GnRH, e SIU-LNG.

Conclusão: O SIU-LNG e dienogest apresentaram bons resultados para o controle de sangramento e dor pélvica, respectivamente, em mulheres com adenomiose. No entanto, não há dados suficientes para endossar cada medicação para tratar essa doença. Futuros estudos randomizados são necessários para avaliar o tratamento farmacológico da adenomiose.


All the authors participated actively in the study, as follows: Yela D. A., Benetti-Pinto C. L., and Brito L. G. O. were responsible for writing the protocol and the final manuscript. Teatin-Juliato C. R. and Mira T. A. A. collected the data and conducted a review of the literature.

  • References

  • 1 Levy G, Dehaene A, Laurent N. , et al. An update on adenomyosis. Diagn Interv Imaging 2013; 94 (01) 3-25 . Doi: 10.1016/j.diii.2012.10.012
  • 2 Bazot M, Daraï E. Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis. Fertil Steril 2018; 109 (03) 389-397 . Doi: 10.1016/j.fertnstert.2018.01.024
  • 3 Azziz R. Adenomyosis: current perspectives. Obstet Gynecol Clin North Am 1989; 16 (01) 221-235
  • 4 Brosens JJ, Barker FG, de Souza NM. Myometrial zonal differentiation and uterine junctional zone hyperplasia in the non-pregnant uterus. Hum Reprod Update 1998; 4 (05) 496-502 . Doi: 10.1093/humupd/4.5.496
  • 5 Leyendecker G, Herbertz M, Kunz G, Mall G. Endometriosis results from the dislocation of basal endometrium. Hum Reprod 2002; 17 (10) 2725-2736 . Doi: 10.1093/humrep/17.10.2725
  • 6 Peric H, Fraser IS. The symptomatology of adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20 (04) 547-555 . Doi: 10.1016/j.bpobgyn.2006.01.006
  • 7 Exacoustos C, Manganaro L, Zupi E. Imaging for the evaluation of endometriosis and adenomyosis. Best Pract Res Clin Obstet Gynaecol 2014; 28 (05) 655-681 . Doi: 10.1016/j.bpobgyn.2014.04.010
  • 8 Dueholm M, Lundorf E. Transvaginal ultrasound or MRI for diagnosis of adenomyosis. Curr Opin Obstet Gynecol 2007; 19 (06) 505-512 . Doi: 10.1097/GCO.0b013e3282f1bf00
  • 9 Bergeron C, Amant F, Ferenczy A. Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20 (04) 511-521 . Doi: 10.1016/j.bpobgyn.2006.01.016
  • 10 Valentini AL, Speca S, Gui B, Soglia G, Miccò M, Bonomo L. Adenomyosis: from the sign to the diagnosis. Imaging, diagnostic pitfalls and differential diagnosis: a pictorial review. Radiol Med (Torino) 2011; 116 (08) 1267-1287 . Doi: 10.1007/s11547-011-0714-5
  • 11 Andres MP, Borrelli GM, Ribeiro J, Baracat EC, Abrão MS, Kho RM. Transvaginal ultrasound for the diagnosis of adenomyosis: systematic review and meta-analysis. J Minim Invasive Gynecol 2018; 25 (02) 257-264 . Doi: 10.1016/j.jmig.2017.08.653
  • 12 Younes G, Tulandi T. Conservative surgery for adenomyosis and results: a systematic review. J Minim Invasive Gynecol 2018; 25 (02) 265-276 . Doi: 10.1016/j.jmig.2017.07.014
  • 13 Rocha TP, Andres MP, Borrelli GM, Abrão MS. Fertility-sparing treatment of adenomyosis in patients with infertility: a systematic review of current options. Reprod Sci 2018; 25 (04) 480-486 . Doi: 10.1177/1933719118756754
  • 14 de Bruijn AM, Smink M, Lohle PNM. , et al. Uterine artery embolization for the treatment of adenomyosis: a systematic review and meta-analysis. J Vasc Interv Radiol 2017; 28 (12) 1629-1642.e1 . Doi: 10.1016/j.jvir.2017.07.034
  • 15 Pontis A, D'Alterio MN, Pirarba S, de Angelis C, Tinelli R, Angioni S. Adenomyosis: a systematic review of medical treatment. Gynecol Endocrinol 2016; 32 (09) 696-700 . Doi: 10.1080/09513590.2016.1197200
  • 16 National Institute for Health Research. Prospero: International Prospective Register of Systematic Reviews. 2013. . Accessed September 20, 2018.
  • 17 Moher D, Liberati A, Tetzlaff J, Altman DG. ; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535 . Doi: 10.1136/bmj.b2535
  • 18 Preston DW, Dietz ER. The Art of Experimental Physics. New York, NY: John Wiley & Sons; 1991
  • 19 Higgins JPT, Altman DG. Assessing risk of bias in included studies. In: Higgins JPT, Green S. , eds. Cochrane Handbook for Systematic Reviews of Interventions. New York, NY: John Wiley & Sons; 2008: 187-241
  • 20 Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations. Hamilton: The GRADE Working Group; 2013. . Accessed September 20, 2018.
  • 21 Ozdegirmenci 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 (02) 497-502 . Doi: 10.1016/j.fertnstert.2010.10.009
  • 22 Badawy 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 (04) 489-495 . Doi: 10.1111/j.1600-0412.2012.01350.x
  • 23 Shaaban OM, Ali MK, Sabra AM, Abd El Aal DE. Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial. Contraception 2015; 92 (04) 301-307 . Doi: 10.1016/j.contraception.2015.05.015
  • 24 Fawzy M, Mesbah Y. Comparison of dienogest versus triptorelin acetate in premenopausal women with adenomyosis: a prospective clinical trial. Arch Gynecol Obstet 2015; 292 (06) 1267-1271 . Doi: 10.1007/s00404-015-3755-5
  • 25 Osuga Y, Fujimoto-Okabe H, Hagino A. 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 2017; 108 (04) 673-678 . Doi: 10.1016/j.fertnstert.2017.07.021
  • 26 Elwyn G, O'Connor A, Stacey D. , et al; International Patient Decision Aids Standards (IPDAS) Collaboration. Developing a quality criteria framework for patient decision aids: online international Delphi consensus process. BMJ 2006; 333 (7565): 417 . Doi: 10.1136/bmj.38926.629329.AE
  • 27 Frank L, Basch E, Selby JV. ; Patient-Centered Outcomes Research Institute. The PCORI perspective on patient-centered outcomes research. JAMA 2014; 312 (15) 1513-1514 . Doi: 10.1001/jama.2014.11100
  • 28 Gordts S, Grimbizis G, Campo R. Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis. Fertil Steril 2018; 109 (03) 380-388.e1 . Doi: 10.1016/j.fertnstert.2018.01.006
  • 29 Van den Bosch T, Dueholm M, Leone FP. , et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol 2015; 46 (03) 284-298 . Doi: 10.1002/uog.14806