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

Junying Liu, Ming Li, M-Q Li, Jun Zhang
Journal of Obstetrics and Gynaecology Research · 2026 · vol. 52(5) , pp. e70304 · doi:10.1111/jog.70304 · PMID:42120175 · W7160893316
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

This pilot study found that combining leuprorelin acetate microspheres with a levonorgestrel-releasing intrauterine system enhanced symptom relief and hormonal regulation in endometriosis patients, with associated changes in BNIP3 and EPAC1 mRNA expression.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

This exploratory pilot study enrolled 120 endometriosis patients undergoing laparoscopic surgery (June 2020–December 2023) and allocated them to postoperative GnRH-a alone versus GnRH-a plus a levonorgestrel-releasing intrauterine system, with outcomes including symptom scores and serum reproductive hormones and measurements of BNIP3 and EPAC1 mRNA expression. The combined therapy group showed a higher overall response rate and greater improvements in Visual Analog Scale and Kupperman scores than the GnRH-a control group (p < 0.05). After 6 months, combined therapy was associated with lower FSH, estradiol, and progesterone and higher LH compared with control (p < 0.05), alongside decreased EPAC1 mRNA expression and increased BNIP3 mRNA expression (p < 0.05). The authors emphasize that these results are hypothesis-generating and require confirmation in randomized controlled trials, and state that data cannot be shared due to institutional ethical requirements. This paper is centrally about endometriosis—evaluating combined leuprorelin (GnRH-a) plus LNG-IUS effects and linked BNIP3/EPAC1 mRNA changes.

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Abstract

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.
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Abstract

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. Disclosure The article was not presented in abstract form at a conference or as part of a presentation. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement We are unable to share data because of the ethical requirement of our institution to prevent harm and promote fairness that benefited the enrolled subjects.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (21)

SciLite annotations

chemicals 7
medroxyprogesterone acetate levonorgestrel goserelin acetate levonorgestrel estradiol progesterone

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