Chronic Aseptic Myometritis: A Mechanistic Framework Linking Sterile Myometrial Inflammation to Uterine Fibroid Initiation and a Roadmap for Primary Prevention.

Uterine fibroids, the most common tumors in reproductive-age women, remain without a defined precursor tissue state. Unlike cervical dysplasia preceding cervical cancer, or colonic polyps preceding colorectal malignancy, no equivalent "at-risk" tissue marker exists for fibroids, and diagnosis relies on radiological imaging only after tumors are already well-established and often symptomatic including excessive menstrual bleeding, pelvic pain, infertility and obstetric complications. In this narrative review, we propose that a subset of women with unexplained AUB may harbor a chronic, non-infectious inflammatory condition of the myometrium, which we term Chronic Aseptic Myometritis (CAM). We synthesize mechanistic and human tissue evidence suggesting that sterile inflammation driven by damage-associated molecular patterns, NLRP3 inflammasome activation, oxidative DNA damage, and TGF-β-mediated extracellular-matrix remodeling may underlie the transition from normal myometrium (MyoN) to a pre-fibroid, inflamed and stiffened state (MyoF), and may contribute both to abnormal uterine bleeding (AUB) and to fibroid initiation. We propose a preliminary framework for future CAM research, including the identification of candidate biomarker categories and imaging correlates. We also discuss whether early mechanism-based interventions, such as vitamin D and epigallocatechin gallate (EGCG), may offer a potential pathway toward primary prevention. Because the components of this model derive largely from experimental and cross-sectional human studies, CAM is presented as a hypothesis-generating, myometrium-centered framework rather than a validated clinical entity, and prospective validation is required.