Recent Therapies for Endometriosis: A Systematic Review
DOI:
https://doi.org/10.19166/med.v13i1.10779Keywords:
endometriosis, systematic review, therapy, hormonal treatment, surgeryAbstract
Background:
Endometriosis is a chronic gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity. It commonly affects women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. The disease significantly impacts productivity, social functioning, and sexual health, making it one of the leading causes of disability and reduced quality of life among women.
Methods:
This review was conducted through a literature search using databases such as PubMed, ScienceDirect, Google Scholar, and ResearchGate. Articles published between 2016 and 2025 were selected using the keywords endometriosis, hormonal therapy, and non-hormonal therapy. Relevant studies were analyzed, cross-referenced, and evaluated to identify current therapeutic strategies for endometriosis management.
Result:
The management of endometriosis currently includes both hormonal and non-hormonal therapies. Hormonal treatments involve the use of aromatase inhibitors, gonadotropin-releasing hormone (GnRH) analogues, selective estrogen receptor modulators (SERMs), selective progesterone receptor modulators (SPRMs), and dienogest, all aimed at suppressing estrogen production and endometrial growth. Non-hormonal therapies, on the other hand, utilize anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms to target the inflammatory cascade that contributes to the pathogenesis of endometriosis. These therapies aim to reduce chronic inflammation, cell proliferation, and pain without interfering with ovulation or fertility.
Conclusions:
Both hormonal and non-hormonal therapies play a crucial role in managing endometriosis. While hormonal therapy remains the mainstay of treatment, non-hormonal approaches show promising results with fewer side effects and greater patient tolerability. However, further clinical studies are required to evaluate their long-term efficacy and safety before they can be widely implemented in clinical settings.
References
1. Tsamantioti ES, Mahdy H. Endometriosis. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Oct 27]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK567777/.
2. Cano-Herrera G, Salmun Nehmad S, Ruiz De Chávez Gascón J, Méndez Vionet A, Van Tienhoven XA, Osorio Martínez MF, Muleiro Alvarez M, Vasco Rivero MX, López Torres MF, Barroso Valverde MJ, et al. Endometriosis: A Comprehensive Analysis of the Pathophysiology, Treatment, and Nutritional Aspects, and Its Repercussions on the Quality of Life of Patients. Biomedicines. 2024;12:1476. doi: 10.3390/biomedicines12071476.
3. Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;e070750. doi: 10.1136/bmj-2022-070750.
4. Pašalić E, Tambuwala MM, Hromić-Jahjefendić A. Endometriosis: Classification, pathophysiology, and treatment options. Pathology - Research and Practice. 2023;251:154847. doi: 10.1016/j.prp.2023.154847.
5. Gheorghisan-Galateanu AA, Gheorghiu ML. HORMONAL THERAPY IN WOMEN OF REPRODUCTIVE AGE WITH ENDOMETRIOSIS: AN UPDATE. Acta Endocrinol (Buchar). 2019;15:276–281. doi: 10.4183/aeb.2019.276. Cited: in: : PMID: 31508191.
6. Vannuccini S, Clemenza S, Rossi M, Petraglia F. Hormonal treatments for endometriosis: The endocrine background. Rev Endocr Metab Disord. 2022;23:333–355. doi: 10.1007/s11154-021-09666-w. Cited: in: : PMID: 34405378.
7. Sanamiri K, Mahdian S, Moini A, Shahhoseini M. Non-Hormonal Therapy for Endometriosis Based on Angiogenesis, Oxidative Stress and Inflammation. Int J Fertil Steril. 2024;18:305–313. doi: 10.22074/ijfs.2024.2012554.1547. Cited: in: : PMID: 39564820.
8. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;n71. doi: 10.1136/bmj.n71.
9. Sadłocha M, Toczek J, Major K, Staniczek J, Stojko R. Endometriosis: Molecular Pathophysiology and Recent Treatment Strategies—Comprehensive Literature Review. Pharmaceuticals. 2024;17:827. doi: 10.3390/ph17070827.
10. Petraglia F, Vannuccini S, Donati C, Jeljeli M, Bourdon M, Chapron C. Endometriosis and comorbidities: molecular mechanisms and clinical implications. Trends in Molecular Medicine. 2025;S1471491425002114. doi: 10.1016/j.molmed.2025.09.002.
11. Mercorio A, Giampaolino P, Romano A, Dällenbach P, Pluchino N. Is intracrinology of endometriosis relevant in clinical practice? A systematic review on estrogen metabolism. Front Endocrinol (Lausanne). 2022;13:950866. doi: 10.3389/fendo.2022.950866. Cited: in: : PMID: 36204107.
12. Chantalat E, Valera M-C, Vaysse C, Noirrit E, Rusidze M, Weyl A, Vergriete K, Buscail E, Lluel P, Fontaine C, et al. Estrogen Receptors and Endometriosis. IJMS. 2020;21:2815. doi: 10.3390/ijms21082815.
13. Tang H, Lin T, Wu M, Tsai S. Progesterone resistance in endometriosis: A pathophysiological perspective and potential treatment alternatives. Reprod Medicine & Biology. 2024;23:e12588. doi: 10.1002/rmb2.12588.
14. Tosti C, Biscione A, Morgante G, Bifulco G, Luisi S, Petraglia F. Hormonal therapy for endometriosis: from molecular research to bedside. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2017;209:61–66. doi: 10.1016/j.ejogrb.2016.05.032.
15. Wong RSY. Role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Cancer Prevention and Cancer Promotion. Advances in Pharmacological Sciences. 2019;2019:1–10. doi: 10.1155/2019/3418975.
16. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging Dis. 2018;9:143–150. doi: 10.14336/AD.2017.0306. Cited: in: : PMID: 29392089.
17. Khan S, Huda B, Bhurka F, Patnaik R, Banerjee Y. Molecular and Immunomodulatory Mechanisms of Statins in Inflammation and Cancer Therapeutics with Emphasis on the NF-κB, NLRP3 Inflammasome, and Cytokine Regulatory Axes. IJMS. 2025;26:8429. doi: 10.3390/ijms26178429.
18. Farhangnia P, Noormohammadi M, Delbandi A-A. Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis. Reprod Health. 2024;21:61. doi: 10.1186/s12978-024-01797-y. Cited: in: : PMID: 38698459.
19. Barrea L, Verde L, Annunziata G, Chedraui P, Petraglia F, Cucalón G, Camajani E, Caprio M, Gorini S, Iorio GG, et al. Effectiveness of Medical Nutrition Therapy in the Management of Patients with Obesity and Endometriosis: from the Mediterranean Diet To the Ketogenic Diet, Through Supplementation. The Role of the Nutritionist in Clinical Management. Curr Obes Rep. 2025;14:68. doi: 10.1007/s13679-025-00662-8. Cited: in: : PMID: 40920291.
20. Zhang X, Duan H. Effect of high-intensity focused ultrasound ablation on endometriosis of the abdominal wall. Int J Clin Exp Pathol. 2018;11:2118–2124. Cited: in: : PMID: 31938321.
21. Wu S, Liu J, Liu X, Han Y. High-intensity focused ultrasound for endometrial ablation in adenomyosis: a clinical study. Front Med (Lausanne). 2024;11:1332080. doi: 10.3389/fmed.2024.1332080. Cited: in: : PMID: 38576714.
22. Maiorana A, Maranto M, Restivo V, Gerfo DL, Minneci G, Mercurio A, Incandela D. Evaluation of long-term efficacy and safety of dienogest in patients with chronic cyclic pelvic pain associated with endometriosis. Arch Gynecol Obstet. 2024;309:589–597. doi: 10.1007/s00404-023-07271-7. Cited: in: : PMID: 38019280.
23. Muzii L, Di Tucci C, Galati G, Carbone F, Palaia I, Bogani G, Perniola G, Tomao F, Kontopantelis E, Di Donato V. The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis. Reprod Sci. 2023;30:3135–3143. doi: 10.1007/s43032-023-01266-0.
24. Ali M, Raslan M, Ciebiera M, Zaręba K, Al-Hendy A. Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids. Expert Opin Drug Saf. 2022;21:477–486. doi: 10.1080/14740338.2022.1989409. Cited: in: : PMID: 34612122.
25. Surrey ES. GnRH agonists in the treatment of symptomatic endometriosis: a review. F S Rep. 2023;4:40–45. doi: 10.1016/j.xfre.2022.11.009. Cited: in: : PMID: 37223763.
26. Carballo-Casla A, García-Esquinas E, Banegas JR, Rodríguez-Artalejo F, Ortolá R. Fish consumption, omega-3 fatty acid intake, and risk of pain: the Seniors-ENRICA-1 cohort. Clinical Nutrition. 2022;41:2587–2595. doi: 10.1016/j.clnu.2022.09.007.
27. Jerab D, Blangero F, Da Costa PCT, De Brito Alves JL, Kefi R, Jamoussi H, Morio B, Eljaafari A. Beneficial Effects of Omega-3 Fatty Acids on Obesity and Related Metabolic and Chronic Inflammatory Diseases. Nutrients. 2025;17:1253. doi: 10.3390/nu17071253.
28. Xu B, Liang D, Chen G. Evaluation of the Clinical Outcomes Associated With the Use of Fatty Acids and Vitamin D in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis. Food Sci Nutr. 2025;13:e70473. doi: 10.1002/fsn3.70473. Cited: in: : PMID: 40692609.
29. Chen F-Y, Wang X, Tang R-Y, Guo Z-X, Deng Y-Z-J, Yu Q. New therapeutic approaches for endometriosis besides hormonal therapy. Chin Med J (Engl). 2019;132:2984–2993. doi: 10.1097/CM9.0000000000000569. Cited: in: : PMID: 31809322.
30. Ramos-Nino ME. Non-Hormonal Strategies in Endometriosis: Targets with Future Clinical Potential. JCM. 2025;14:5091. doi: 10.3390/jcm14145091.
31. Atlihan U, Yavuz O, Ata C, Avsar HA, Erkilinc S. Effects of dienogest treatment on endometrioma-related clinical symptoms and endometrioma size: retrospective cohort study. Front Med. 2025;12:1581661. doi: 10.3389/fmed.2025.1581661.
32. Lee SR, Yi KW, Song JY, Seo SK, Lee D-Y, Cho S, Kim SH. Efficacy and Safety of Long-Term Use of Dienogest in Women With Ovarian Endometrioma. Reprod Sci. 2018;25:341–346. doi: 10.1177/1933719117725820. Cited: in: : PMID: 29161960.
33. Wu W, Tang F, Wang Y, Yang W, Zhao Z, Gao Y, Dong H. Cost-effectiveness analysis of combination therapies involving novel agents for first/second-relapse patients with multiple myeloma: a Markov model approach with calibration techniques. Health Econ Rev. 2025;15:21. doi: 10.1186/s13561-025-00611-0. Cited: in: : PMID: 40088315.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Ananda Putra, Raymond Malvin Winata, El-Varel Baby Berlianzsa, Angelica Isabella Monica Chandra, Charles Pauris Manubulu, Tiara Namora Tarigan, Devanti Octavia Ellyamurti, Najmarani Devi Firdaus, Dilla Alfinda Risdiana
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (CC-BY-SA 4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website). The final published PDF should be used and bibliographic details that credit the publication in this journal should be included.
