MicroRNAs as Biomarkers for Adenomyosis: A Systematic Review

Background/Objectives: Adenomyosis is a chronic gynecological disorder characterized by the presence of endometrial tissue within the myometrium, causing pelvic pain, abnormal uterine bleeding, and infertility. Despite its high prevalence, the molecular mechanisms underlying disease initiation and progression remain incompletely understood. Current evidence implicates disruption of the endometrial-myometrial interface, epithelial-mesenchymal transition, and progesterone resistance in driving tissue invasion and remodeling. Diagnosis relies mainly on imaging modalities, while reliable non-invasive biomarkers are lacking. MicroRNAs, as stable post-transcriptional regulators of gene expression, have emerged as key modulators of proliferation, inflammation, and hormonal signaling, and represent promising candidates for novel diagnostic strategies. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD42025637752). A comprehensive search of the Medline, Embase, Scopus, and Cochrane databases was performed in April 2025. Studies investigating miRNA expression in patients with adenomyosis compared with controls were included. The quality of the studies and the risk of bias were assessed using the Newcastle-Ottawa scale. Two reviewers independently performed study selection, data extraction, and quality assessment. Results: Twenty-seven studies published between 2015 and 2025 met the inclusion criteria. Thirty-nine distinct miRNAs were reported as significantly dysregulated in adenomyosis. Recurrently altered miRNAs included let-7a, miR-145, miR-10b, miR-30c-5p, miR-141-3p, miR-143, and miR-191. Functional analyses have consistently implicated miRNAs in key pathogenic pathways, including Hippo-YAP, PI3K/AKT, MAPK/ERK, JAK/STAT, and Wnt/β-catenin signaling. These alterations were associated with enhanced epithelial-mesenchymal transition, increased cellular proliferation and migration, progesterone resistance, chronic inflammation, and immune modulation. Emerging evidence highlights exosomal and circulating miRNAs as promising non-invasive biomarkers, with a few studies already demonstrating diagnostic potential using serum, plasma, or urine samples. However, substantial heterogeneity in tissue types, sampling timing, and analytical methods precluded meta-analysis. Conclusions: MiRNAs play a central role in the molecular pathogenesis of adenomyosis and show strong potential as non-invasive diagnostic biomarkers. However, large-scale validation studies and standardized methodologies are required before clinical implementation.