Endometriosis and Adenomyosis: Mechanotransduction, Microenvironment, and Mechanisms Beyond Lesions

Endometriosis and adenomyosis are characterized by the presence of endometrial-like tissue outside its normal anatomical location and are associated with pain, infertility, and other clinical manifestations. Although they share pathogenic features, including inflammation, hormonal responses, immune dysregulation, and fibrosis, their clinical and histopathological phenotypes are highly heterogeneous. This review integrates tissue mechanics and mechanobiology with inflammation, hormonal signaling, oxidative stress, angiogenesis, and neurogenesis to propose a microenvironment-dependent framework for understanding lesion formation, maintenance, and progression. Direct measurements of tissue stiffness, including elastography, have been reported, but standardized comparisons among lesion types remain limited. Existing evidence suggests that tissue stiffening may affect cellular proliferation, invasion, fibrosis, and tissue remodeling through mechanotransduction pathways such as integrin signaling. However, much of this evidence derives from in vitro studies, experimental models, or other fibrotic diseases, and direct causal relationships in human endometriosis and adenomyosis remain insufficiently established. Conversely, chronic inflammation, recurrent bleeding, and ECM accumulation may contribute to both tissue stiffening and fibrosis, indicating reciprocal interactions between mechanical and biological processes. Thus, lesion phenotypes may reflect interactions among lesion origin, cell-intrinsic properties, and the local microenvironment. Mechanobiology may complement established inflammatory, hormonal, immune, and fibrotic concepts and provide hypotheses for understanding lesion heterogeneity and progression. Longitudinal, lesion-level studies integrating mechanical and biological parameters are needed to test these hypotheses.