Comparative effectiveness of hormonal therapies for preventing recurrence in endometriosis: a real-world retrospective cohort study with risk factor analysis

Chen Z, Zhuo Chen, Yingying Zheng, Zheng Y
BMC women's health · 2026 · vol. 26(1) · doi:10.1186/s12905-026-04636-3 · PMID:42380844 · PMC13587277 · W7166676450
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Sequential GnRH-a plus dienogest demonstrated a lower 3-year recurrence rate compared to LNG-IUS, with severe dysmenorrhea, pelvic surgery history, and r-AFS stage IV identified as recurrence risk factors.

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This retrospective cohort study evaluated the comparative effectiveness of dienogest, combined oral contraceptives, and the levonorgestrel-releasing intrauterine system for preventing postoperative recurrence of ovarian endometriomas in 167 patients. The results indicated that sequential gonadotropin-releasing hormone agonist maintenance with dienogest yielded a significantly lower three-year cumulative recurrence rate compared to the intrauterine system group, while showing a non-significant trend toward superiority over combined oral contraceptives. Multivariate analysis identified severe dysmenorrhea, prior pelvic procedures, and advanced disease stage as independent risk factors for recurrence, whereas older surgical age was protective. This paper is centrally about endometriosis — specifically assessing hormonal therapies to prevent recurrence after laparoscopic cystectomy for ovarian endometriomas.

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Abstract

BACKGROUND: Endometriosis is a common chronic disease in women of reproductive age, and long-term postoperative medical management is a key strategy for preventing recurrence. Currently used clinical medications include dienogest (DNG), GnRH agonists (GnRH-a), combined oral contraceptives (COC), and the levonorgestrel-releasing intrauterine system (LNG-IUS). However, comparative effectiveness of different hormonal therapies for preventing recurrence in real-world clinical practice and the basis for individualised patient selection remain insufficient. OBJECTIVE: To systematically evaluate the efficacy and safety of DNG, GnRH-a, COC, and LNG-IUS in preventing postoperative recurrence of ovarian endometriomas; to analyse independent risk factors for postoperative recurrence, providing evidence-based support for individualised clinical treatment decisions. METHODS: A retrospective cohort study design was adopted. A total of 167 patients who underwent laparoscopic cystectomy at our hospital between January 2020 and January 2022, had a postoperative pathological diagnosis, and received sequential GnRH-a maintenance therapy were enrolled. According to the sequential maintenance regimen, patients were divided into three groups: GnRH-a + DNG group (n = 61), GnRH-a + COC group (n = 64), and GnRH-a + LNG-IUS group (n = 42). The primary outcome was the recurrence rate within 3 years after surgery. Secondary outcomes included menstrual bleeding profiles, recurrent cyst diameter, and adverse drug reactions. Cumulative recurrence rates were calculated using the Kaplan‑Meier method, and intergroup comparisons were performed using the log‑rank test. Multivariate logistic regression analysis was used to identify independent risk factors for postoperative recurrence. RESULTS: There were no statistically significant differences in baseline data among the three groups (P > 0.05), indicating comparability. The 3‑year cumulative recurrence rate in the GnRH-a + DNG group was 19.67% (12/61), significantly lower than that in the GnRH-a + LNG-IUS group (45.24%, 19/42; P = 0.003). The recurrence rate in the GnRH-a + DNG group was also lower than that in the GnRH-a + COC group (34.38%, 22/64), although this difference did not reach statistical significance (P = 0.053). No significant differences were observed among the three groups in mean daily menstrual blood loss, incidence of dysmenorrhoea, or menstrual cycle length (P > 0.05). However, the incidence of spotting in the LNG-IUS group (52.38%) was significantly higher than that in the DNG group (24.59%) and the COC group (12.50%, P  0.05). Multivariate logistic regression analysis suggested that higher dysmenorrhea VAS score (OR = 1.376), history of pelvic procedures (OR = 1.483), and r-AFS stage IV (OR = 2.676) were independent risk factors for postoperative recurrence (all P < 0.05), while older age at surgery was a protective factor (OR = 0.891) (P < 0.05). CONCLUSION: Among sequential GnRH-a maintenance regimens, DNG was associated with a lower recurrence rate than LNG-IUS in preventing 3‑year recurrence after laparoscopic cystectomy in this cohort. Although the recurrence rate in the DNG group was lower than that in the COC group, the difference did not reach statistical significance, indicating only a trend toward superiority. All three regimens have a favourable overall safety profile, but the LNG-IUS group has a higher incidence of spotting. Severe dysmenorrhoea, previous pelvic operation history, and r-AFS stage IV are independent risk factors for postoperative recurrence, whereas older age at surgery has a protective effect.
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Abstract

Background Endometriosis is a common chronic disease in women of reproductive age, and long-term postoperative medical management is a key strategy for preventing recurrence. Currently used clinical medications include dienogest (DNG), GnRH agonists (GnRH-a), combined oral contraceptives (COC), and the levonorgestrel-releasing intrauterine system (LNG-IUS). However, comparative effectiveness of different hormonal therapies for preventing recurrence in real-world clinical practice and the basis for individualised patient selection remain insufficient.

Objective

To systematically evaluate the efficacy and safety of DNG, GnRH-a, COC, and LNG-IUS in preventing postoperative recurrence of ovarian endometriomas; to analyse independent risk factors for postoperative recurrence, providing evidence-based support for individualised clinical treatment decisions.

Methods

A retrospective cohort study design was adopted. A total of 167 patients who underwent laparoscopic cystectomy at our hospital between January 2020 and January 2022, had a postoperative pathological diagnosis, and received sequential GnRH-a maintenance therapy were enrolled. According to the sequential maintenance regimen, patients were divided into three groups: GnRH-a + DNG group (n = 61), GnRH-a + COC group (n = 64), and GnRH-a + LNG-IUS group (n = 42). The primary outcome was the recurrence rate within 3 years after surgery. Secondary outcomes included menstrual bleeding profiles, recurrent cyst diameter, and adverse drug reactions. Cumulative recurrence rates were calculated using the Kaplan‑Meier method, and intergroup comparisons were performed using the log‑rank test. Multivariate logistic regression analysis was used to identify independent risk factors for postoperative recurrence.

Results

There were no statistically significant differences in baseline data among the three groups (P > 0.05), indicating comparability. The 3‑year cumulative recurrence rate in the GnRH-a + DNG group was 19.67% (12/61), significantly lower than that in the GnRH-a + LNG-IUS group (45.24%, 19/42; P = 0.003). The recurrence rate in the GnRH-a + DNG group was also lower than that in the GnRH-a + COC group (34.38%, 22/64), although this difference did not reach statistical significance (P = 0.053). No significant differences were observed among the three groups in mean daily menstrual blood loss, incidence of dysmenorrhoea, or menstrual cycle length (P > 0.05). However, the incidence of spotting in the LNG-IUS group (52.38%) was significantly higher than that in the DNG group (24.59%) and the COC group (12.50%, P 0.05). Multivariate logistic regression analysis suggested that higher dysmenorrhea VAS score (OR = 1.376), history of pelvic procedures (OR = 1.483), and r-AFS stage IV (OR = 2.676) were independent risk factors for postoperative recurrence (all P < 0.05), while older age at surgery was a protective factor (OR = 0.891) (P < 0.05).

Conclusion

Among sequential GnRH-a maintenance regimens, DNG was associated with a lower recurrence rate than LNG-IUS in preventing 3‑year recurrence after laparoscopic cystectomy in this cohort. Although the recurrence rate in the DNG group was lower than that in the COC group, the difference did not reach statistical significance, indicating only a trend toward superiority. All three regimens have a favourable overall safety profile, but the LNG-IUS group has a higher incidence of spotting. Severe dysmenorrhoea, previous pelvic operation history, and r-AFS stage IV are independent risk factors for postoperative recurrence, whereas older age at surgery has a protective effect. Similar content being viewed by others Abbreviations - DNG: - Dienogest - GnRH-a: - Gonadotropin-releasing hormone agonist - COC: - Combined oral contraceptives - LNG-IUS: - Levonorgestrel-releasing intrauterine system - r-AFS: - revised American Fertility Society - VAS: - Visual Analog Scale - CA125: - Cancer antigen 125 - CA199: - Cancer antigen 199 - FIB: - Fibrinogen - D-D: - D-dimer - PT: - Prothrombin time - BMI: - Body mass index - OR: - Odds ratio - CI: - Confidence interval - HADS: - Hospital Anxiety and Depression Scale - DXA: - Dual-energy X-ray absorptiometry

Acknowledgements

None. Funding None. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate The study protocol was reviewed and approved by the Ethics Committee of Jinhua Municipal Central Hospital (Approval No.: (2026) Ethics approval No.(295)), and the requirement for patient informed consent was waived by the same ethics committee. Consent for publication Not Applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Chen, Z., Zheng, Y. Comparative effectiveness of hormonal therapies for preventing recurrence in endometriosis: a real-world retrospective cohort study with risk factor analysis. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04636-3 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12905-026-04636-3

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MeSH descriptors

Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Contraceptives, Oral, Combined Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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References (42)

SciLite annotations

organisms 1
noordeloos 2009062
chemicals 2
dienogest levonorgestrel

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