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This review synthesises current molecular evidence to propose a unified mechanistic framework initiated by tissue injury and repair (TIAR), aberrant stem cell activation, or de novo metaplasia, all of which converge to disrupt the endometrial\u2013myometrial interface disruption (EMID). Following this structural breach, a self\u2010perpetuating \u2018vicious cycle\u2019 is triggered, driven by four interconnected axes: (1) Hormonal Dysregulation, characterised by local hyper\u2010estrogenism, progesterone resistance, and a specific paracrine prolactin loop that drives reactive myometrial hypertrophy; (2) Immune\u2010Hemostatic Crosstalk, where activated platelets and M2\u2010polarised macrophages establish a pro\u2010fibrotic niche via TGF\u2010\u03b21 signalling; (3) Hypoxia and Neuroangiogenesis, where HIF\u20101\u03b1 stabilisation orchestrates metabolic reprogramming (Warburg effect) and the pathological sprouting of sensory nerves, underpinning chronic pain; and (4) Epigenetic Fibrosis, driven by the oestrogen\u2013slug\u2013VEGF axis and HDAC\u2010mediated chromatin remodelling leading to epithelial\u2013mesenchymal transition (EMT). Furthermore, we clarify the genetic distinction between adenomyosis and uterine leiomyomas, highlighting their divergent responses to androgen receptor signalling. By elucidating these molecular targets, we discuss emerging non\u2010hormonal therapeutics\u2014including anti\u2010platelet agents and dopamine agonists\u2014offering mechanism\u2010based strategies for fertility preservation.<\/jats:p>","DOI":"10.1111\/jcmm.71129","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T03:35:36Z","timestamp":1776051336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pathogenesis of Adenomyosis: An Integrated Review of Cellular Origins, Molecular Mechanisms, and Intersecting Diseases"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1248-4009","authenticated-orcid":false,"given":"Jiang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Gynecology Maternal and Child Health Hospital of Hubei Province  Wuhan 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