Efficacy and related factors of levonorgestrel‐releasing intrauterine system combined with metformin in fertility‐preserving treatment for atypical endometrial hyperplasia and early endometrial cancer: A retrospective cohort study

OBJECTIVE: To compare the efficacy of the levonorgestrel-releasing intrauterine system combined with metformin versus oral progestin combined with metformin in fertility-preserving treatment for patients with atypical endometrial hyperplasia and early endometrial cancer, and to analyze related factors affecting efficacy. METHODS: From January 2015 to December 2023, clinical data of patients with atypical endometrial hyperplasia or early endometrial cancer were retrospectively analyzed. Patients were divided into a study group and a control group based on treatment method. Complete remission rate, remission time, recurrence rate, pregnancy outcomes, and adverse reactions were compared between groups. Multivariate logistic regression was used to identify factors associated with complete remission, recurrence, and pregnancy. RESULTS: Post-treatment endometrial thickness decreased in both groups compared with pre-treatment levels, with a greater reduction in the study group than the control group. Compared with the control group, the study group demonstrated a higher complete remission rate at 3, 6, 9, and 12 months, shorter time to onset and time to complete remission, lower recurrence rate, higher pregnancy and live birth rates, and lower incidence of adverse reactions. Multivariate logistic regression analysis identified age 35 years or older, body mass index (BMI) of 28 or greater, polycystic ovary syndrome, and pathologic type of endometrial cancer as risk factors for complete remission. BMI of 28 or greater and pathologic type of endometrial cancer were risk factors for recurrence. Age 35 years or older and BMI 28 or greater were risk factors for pregnancy. BMI stratification analysis demonstrated that patients with lower BMI achieved better treatment outcomes. CONCLUSIONS: This retrospective study preliminarily suggests that the levonorgestrel-releasing intrauterine system combined with metformin shows a trend toward better treatment response in fertility-preserving treatment, manifested by higher complete remission rates, shorter time to remission, lower recurrence rates, and favorable pregnancy outcomes. In addition, obesity, age of 35 years or older, polycystic ovary syndrome, and pathologic type of endometrial cancer were identified as factors influencing treatment response.