Effectiveness of GnRH agonist (leuprolide acetate) after surgical treatment of endometriosis: A systematic review
DOI:
https://doi.org/10.35335/midwifery.v14i4.2470Keywords:
Endometriosis, Gonadotropin-releasing, hormone agonists, Leuprolide acetate, Recurrence, InfertilityAbstract
Endometriosis may recur after surgery despite removal of visible lesions. Postoperative hormonal suppression is therefore used to control residual disease and symptoms. Gonadotropin-releasing hormone (GnRH) agonists, including leuprolide acetate, provide ovarian suppression, but their benefits after surgery remain uncertain. This study aimed to evaluate the effectiveness of postoperative GnRH agonist therapy, particularly leuprolide acetate, in reducing pain and recurrence and improving reproductive outcomes after endometriosis surgery. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 framework and searched PubMed, Scopus, Cochrane Library, and ScienceDirect for studies published from 2020 to 2026. Among 312 identified records, 54 duplicates were removed and 258 records were screened. Forty-four full-text articles were assessed, of which 41 were excluded, leaving 3 publications for qualitative synthesis. These comprised one randomized controlled trial (n=20), one comparative clinical study (n=158), and one review of 10 randomized controlled trials. In the randomized trial, pelvic pain decreased in the leuprolide group from 4.6 ± 0.84 at baseline to 0.2 ± 0.42 at week 12 (p=0.003), with no significant difference compared with dienogest (p=1.000). The comparative study reported lower recurrence and higher pregnancy rates with leuprorelin than the comparator (both p<0.05), although effect estimates and 95% confidence intervals were not reported. Adverse reactions did not differ significantly between groups (10.13% vs. 6.33%, p>0.05). Overall, evidence for pain was more supportive, whereas evidence for recurrence and reproductive outcomes remained limited and heterogeneous. Further randomized controlled trials are needed
Downloads
References
AL-Jefout, M., Awar, S. Al, Yaghi, S., & Dabas, O. (2025). Extended GnRH Agonist and NETA Add-Back: An Effective and Safe Option for Refractory Endometriosis/Adenomyosis Pain. Biomedical and Pharmacology Journal, 18(3), 1938–1946. https://doi.org/10.13005/BPJ/3226
Amirudin, A., & Tjandra, S. (2025). Leuprorelin acetate hormone therapy in the management of ovarian endometriosis: A case report. Malahayati International Journal of Nursing and Health Science, 8(5), 638–643. https://doi.org/10.33024/MINH.V8I5.852
Becker, C. M., Bokor, A., Heikinheimo, O., Horne, A., Jansen, F., Kiesel, L., King, K., Kvaskoff, M., Nap, A., Petersen, K., Saridogan, E., Tomassetti, C., Van Hanegem, N., Vulliemoz, N., Vermeulen, N., Altmäe, S., Ata, B., Ball, E., Barra, F., … Yazbeck, C. (2022). ESHRE guideline: endometriosis. Human Reproduction Open, 2022(2). https://doi.org/10.1093/HROPEN/HOAC009
Burney, R. O., & Giudice, L. C. (2012). Pathogenesis and pathophysiology of endometriosis. Fertility and Sterility, 98(3), 511–519. https://doi.org/10.1016/j.fertnstert.2012.06.029
Chapron, C., Marcellin, L., Borghese, B., & Santulli, P. (2019). Rethinking mechanisms, diagnosis and management of endometriosis. Nature Reviews. Endocrinology, 15(11), 666–682. https://doi.org/10.1038/S41574-019-0245-Z
Chiu, C. C., Hsu, T. F., Jiang, L. Y., Chan, I. S., Shih, Y. C., Chang, Y. H., Wang, P. H., & Chen, Y. J. (2022). Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery – A Systematic Review and Network Meta-analysis. Journal of Minimally Invasive Gynecology, 29(5), 602–612. https://doi.org/10.1016/j.jmig.2021.11.024
D’Alessandro, G., Barra, F., & Ferrero, S. (2020). Use of GnRH analogue in the endometriosis recurrence after surgery. Gynecology and Pelvic Medicine, 3(0), 21–21. https://doi.org/10.21037/GPM-20-31
Dick, A., Matok, I., Gutman-Ido, E., Lessans, N., & Dior, U. P. (2025). GnRH analogues and dienogest for second line treatment of endometriosis-associated pain: a systematic review, meta-analysis, and network meta-analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 312. https://doi.org/10.1016/J.EJOGRB.2025.114093
Filindris, T., Papakonstantinou, E., Keramida, M., Panteris, E., Kalogeropoulos, S., Georgopoulos, N., Taniguchi, F., Adonakis, G., Harada, T., & Kaponis, A. (2024). The effect of GnRH-a on the angiogenesis of endometriosis. Hormones (Athens, Greece), 23(3), 509. https://doi.org/10.1007/S42000-024-00559-6
Patel, M. (2024). Recent Trends in Medical Management of Endometriosis. Journal of Obstetrics and Gynaecology of India, 74(6), 479. https://doi.org/10.1007/S13224-024-02097-Y
Pinto da Costa Viana, D., Jacobsen, L., Padovesi, I., Comin, A., Correia, E. L. de S., Fernandes, D. D. M., & Dias, A. C. P. (2025). Tolerability and Shared Decision-Making in the Hormonal Management of Endometriosis-Associated Pain. Biomedicines, 13(9), 2294. https://doi.org/10.3390/BIOMEDICINES13092294
Purwanto, J. P., Effendi, Y., Manan, H., & Theodorus. (2020). Effectiveness, Safety and Obedience of Dienogest and Leuprolide Acetate in Postlaparoscopic Endometriosis Patients: Efektivitas, Keamanan dan Kepatuhan terhadap Dienoges dan Leuprolide Asetat pada Pasien Endometriosis Pascalaparoskopi. Indonesian Journal of Obstetrics and Gynecology, 8(1), 44–51. https://doi.org/10.32771/INAJOG.V8I1.1110
Qing, X., He, L., Ma, Y., Zhang, Y., & Zheng, W. (2024). Systematic review and meta-analysis on the effect of adjuvant gonadotropin-releasing hormone agonist (GnRH-a) on pregnancy outcomes in women with endometriosis following conservative surgery. BMC Pregnancy and Childbirth, 24(1), 237. https://doi.org/10.1186/S12884-024-06430-1
Richard, E., Morin, J., Murji, A., Lemyre, M., Laberge, P. Y., & Maheux-Lacroix, S. (2022). Effect of Postoperative Hormonal Suppression on Fertility in Patients With Endometriosis After Conservative Surgery: A Systematic Review and Meta-analysis. Obstetrics and Gynecology, 139(6), 1169–1179. https://doi.org/10.1097/AOG.0000000000004811
Roman, H., Chanavaz-Lacheray, I., Hennetier, C., Tuech, J. J., Dennis, T., Verspyck, E., & Merlot, B. (2023). Long-term risk of repeated surgeries in women managed for endometriosis: a 1,092 patient-series. Fertility and Sterility, 120(4), 870–879. https://doi.org/10.1016/j.fertnstert.2023.05.156
Rzewuska, A. M., Żybowska, M., Sajkiewicz, I., Spiechowicz, I., Żak, K., Abramiuk, M., Kułak, K., & Tarkowski, R. (2023). Gonadotropin-Releasing Hormone Antagonists—A New Hope in Endometriosis Treatment? Journal of Clinical Medicine, 12(3), 1008. https://doi.org/10.3390/JCM12031008/S1
Surrey, E. S. (2022). GnRH agonists in the treatment of symptomatic endometriosis: a review. F&S Reports, 4(2 Suppl), 40. https://doi.org/10.1016/J.XFRE.2022.11.009
Taylor, H. S., Kotlyar, A. M., & Flores, V. A. (2021). Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet, 397(10276), 839–852. https://doi.org/10.1016/S0140-6736(21)00389-5
Vercellini, P., Buggio, L., Frattaruolo, M. P., Borghi, A., Dridi, D., & Somigliana, E. (2018). Medical treatment of endometriosis-related pain. Best Practice and Research: Clinical Obstetrics and Gynaecology, 51, 68–91. https://doi.org/10.1016/j.bpobgyn.2018.01.015
Veth, V. B., Keukens, A., Reijs, A., Bongers, M. Y., Mijatovic, V., Coppus, S. F. P. J., & Maas, J. W. M. (2024). Recurrence after surgery for endometrioma: a systematic review and meta-analyses. Fertility and Sterility, 122(6), 1079–1093. https://doi.org/10.1016/j.fertnstert.2024.07.033
Veth, V. B., van de Kar, M. M. A., Duffy, J. M. N., van Wely, M., Mijatovic, V., & Maas, J. W. M. (2023). Gonadotropin-releasing hormone analogues for endometriosis. The Cochrane Database of Systematic Reviews, 6(6). https://doi.org/10.1002/14651858.CD014788.PUB2
Wang, J. Y., Zhang, Y., & Ding, J. (2025). Oral Gonadotropin-Releasing Hormone Antagonists in the Treatment of Endometriosis: Advances in Research. Journal of Clinical Medicine Research, 17(6), 299. https://doi.org/10.14740/JOCMR6236
Yu, L., Sun, Y., & Fang, Q. (2022). Efficacy of Laparoscopic Surgery Combined With Leuprorelin in the Treatment of Endometriosis Associated With Infertility and Analysis of Influencing Factors for Recurrence. Frontiers in Surgery, 9, 873698. https://doi.org/10.3389/FSURG.2022.873698
Zakhari, A., Delpero, E., McKeown, S., Tomlinson, G., Bougie, O., & Murji, A. (2020). Endometriosis recurrence following post-operative hormonal suppression: a systematic review and meta-analysis. Human Reproduction Update, 27(1), 96. https://doi.org/10.1093/HUMUPD/DMAA033
Zondervan, K. T., Becker, C. M., & Missmer, S. A. (2020). Endometriosis. New England Journal of Medicine, 382(13), 1244–1256. https://doi.org/10.1056/NEJMRA1810764
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Ath Thaariq Prasetiyo, Fatimah Usman, Faiza Khairunnisa, Zhafirah Afilia Putri, Nadhirah Sofhi Amanda, Muhammad Fadhil, Annisa Salsabillah, M. Irvan Ramadhan Putra, Arkan Abdullah Nashif
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
