How does the extent of fibrosis in adenomyosis lesions contribute to heavy menstrual bleeding?

PURPOSE: To investigate how the extent of fibrosis in adenomyosis lesions contributes to heavy menstrual bleeding (HMB). METHODS: We recruited 57 women with histologically confirmed adenomyosis, 29 of whom reported moderate/heavy bleeding (MHB) (menstrual blood loss (MBL) ≥20 but <100 mL) and the remaining 28, excessive MBL (EXB; ≥100 mL). Lesional stiffness was measured by transvaginal elastosonography. Full‐thickness uterine tissue columns containing the lesion and its neighboring endometrial‐myometrial interface (EMI) and endometrial tissues were evaluated for tissue fibrosis and immunohistochemical analysis of HIF‐1α, COX‐2, EP2, and EP4. RESULTS: The lesional stiffness in the EXB group was significantly higher than that of MHB, and consistently, the extent of lesional fibrosis and the extent of tissue fibrosis in both EMI and eutopic endometrium were also significantly higher. In adenomyotic lesions and their neighboring EMI and eutopic endometrial tissues, the immunostaining of HIF‐1α, COX‐2, EP2, and EP4 was significantly reduced. The extent of fibrosis and the immunostaining levels of HIF‐1α, COX‐2, EP2, and EP4 were negatively correlated in all tissues. CONCLUSIONS: Lesional fibrosis begets stiffening matrix, propagating fibrosis to neighboring EMI and eutopic endometrium, resulting in reduced PGE(2) and HIF‐1α signaling, and thus likely reduced hypoxia necessary for endometrial repair, leading to HMB.