Preliminary Evaluation of Leuprorelin Acetate Microspheres Plus Levonorgestrel‐Releasing Intrauterine System in Endometriosis: An Exploratory Study Focusing on  BNIP3 and EPAC1 Expression

Aim This exploratory pilot study aimed to assess the preliminary clinical effects of leuprorelin acetate microspheres for injection [gonadotropin‐releasing hormone agonist (GnRH‐a)] combined with levonorgestrel‐releasing intrauterine system (LNG‐IUS) in treating endometriosis (EMs), and to examine associated changes in Bcl‐2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and exchange protein directly activated by cAMP 1 (EPAC1) messenger RNA (mRNA) expression. Methods A total of 120 EMs patients undergoing laparoscopic surgery between June 2020 and December 2023 were enrolled. Participants were allocated to a control group ( n = 60, postoperative treatment with GnRH‐a) or a combined group ( n = 60, postoperative treatment with GnRH‐a + LNG‐IUS) using a simple alternation method as part of an exploratory allocation strategy. Results The combined group demonstrated a higher overall response rate and greater improvements in Visual Analog Scale and Kupperman scores compared with the control group ( p < 0.05). After 6 months, patients receiving combined therapy exhibited lower follicle‐stimulating hormone, estradiol, and progesterone levels and higher luteinizing hormone levels relative to controls ( p < 0.05). Additionally, treatment was associated with decreased mRNA expression and increased BNIP3 mRNA expression in the combined group ( p < 0.05). Conclusions This exploratory pilot study suggests that postoperative GnRH‐a combined with may offer enhanced symptom relief and hormonal regulation in patients with EMs, accompanied by preliminary changes in serum BNIP3 and EPAC1 mRNA expression. However, the findings are hypothesis‐generating and require confirmation in future randomized controlled trials.