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Objective To explore the efficacy of Hongjin Xiaojie Concentrated Pills combined with mifepristone on patients following laparoscopic resection of multiple uterine leiomyomas, as well as their effects on serum sex hormone levels, transforming growth factor-β1 (TGF-β1), and insulin-like growth factor binding protein-3 (IGFBP-3). Methods A total of 124 patients with multiple uterine leiomyomas who were treated in our hospital from June 2020 to June 2022 were selected for this study. The patients were randomly divided into two groups of 62 each. All patients underwent laparoscopic myomectomy (LM). The observation group received combined treatment with Hongjin Xiaojie Concentrated Pills and mifepristone postoperatively, while the control group received only mifepristone. After three months of continuous treatment, clinical efficacy was compared between the two groups. Serum sex hormone levels (estradiol [E2], follicle-stimulating hormone [FSH], luteinizing hormone [LH]), as well as TGF-β1 and IGFBP-3 levels, were measured before and after treatment. The incidence of adverse reactions was recorded, and all patients were followed up for at least 12 months to compare recurrence rates at 6 and 12 months postoperatively. Results The total effective rate in the observation group was 98.39% (61/62), significantly higher than the 87.10% (54/62) in the control group (P＜0.05). After treatment, serum levels of E2, FSH, LH, and TGF-β1 significantly decreased in both groups (P＜0.05), while IGFBP-3 levels significantly increased (P＜0.05). Post-treatment, the observation group had significantly lower serum levels of E2, FSH, LH, and TGF-β1, and significantly higher IGFBP-3 levels compared to the control group (P＜0.05). The recurrence rates at 6 and 12 months post-surgery in the observation group were 1.61% and 4.84%, respectively, compared to 6.45% and 16.13% in the control group; the observation group had a significantly lower recurrence rate at 12 months (P＜0.05). The incidence of adverse reactions in the observation group was 6.45%, while it was 14.52% in the control group, with no significant difference between the two groups (P＞0.05). Conclusion The combination of Hongjin Xiaojie Concentrated Pills and mifepristone after laparoscopic myomectomy for multiple uterine leiomyomas effectively regulates serum sex hormones and levels of TGF-β1 and IGFBP-3, enhances clinical efficacy, and reduces postoperative recurrence. [ABSTRACT FROM AUTHOR]