Extracellular matrix deficiency contributes to irregular uterine bleeding following progestin therapy for adenomyosis

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ID: 320294
2026
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Abstract
Abstract Adenomyosis is a common gynecological disorder that causes heavy menstrual bleeding and chronic pelvic pain. Progestin-based therapy is widely used for long-term management, but irregular uterine bleeding frequently occurs and severely affects patient quality of life. The mechanisms underlying this side effect remain unclear. In this study, we performed proteomic sequencing on endometrial tissues from adenomyosis patients before progestin treatment. We found that patients who later developed irregular bleeding exhibited significantly reduced extracellular matrix and collagen levels. Cell experiments showed that matrix metalloproteinase inhibition increased collagen expression in patient-derived endometrial stromal cells. In a mouse model of progestin-induced uterine bleeding, both matrix metalloproteinase inhibition and intrauterine collagen supplementation effectively reduced bleeding. These findings indicate that insufficient extracellular matrix predisposes patients to bleeding during progestin therapy and provide potential strategies to prevent progestin-related irregular bleeding.
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openalex_W7167812862 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Xiaoye Ye, Ou Jin, Aolin Zheng, Nengyuan Lv, Jialu Guo, Jingjing Xiang, Hao Chen, Fengjuan Liu, Yuan Liu, Chunyu Jin, Yongfeng Wu, Jinyi Tong
Journal biology of reproduction
Year 2026
DOI
10.1093/biolre/ioag141
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