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

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 < 0.001). There were no statistically significant differences in the total incidence of adverse drug reactions (13.11%, 14.06%, 11.90%) or recurrent cyst diameter among the groups (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.