Metabolic reprogramming in adenomyosis: a systematic review of metabolomics studies

Stefano Di Michele, Di Michele S, Camoglio C, Chiara Camoglio, Luigi Nappi, Nappi L, Raffaele Tinelli, Tinelli R, Angelos Daniilidis, Daniilidis A, Grimbizis G, Grigoris Grimbizis, Stefano Angioni, Angioni S
European journal of obstetrics, gynecology, and reproductive biology · 2026 · vol. 327 , pp. 115465 · doi:10.1016/j.ejogrb.2026.115465 · PMID:42815247 · W7214668525
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This systematic review synthesizes evidence from eleven studies to demonstrate that adenomyosis involves widespread metabolic reprogramming, particularly in lipid and energy pathways, which may clarify disease pathophysiology and support biomarker research.

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Abstract

PURPOSE: To synthesize current evidence on metabolomic alterations in women with adenomyosis and identify recurrent metabolic patterns that may clarify disease pathophysiology and support biomarker research. METHODS: PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched from inception to December 22, 2025. Eligible studies were peer-reviewed observational studies reporting targeted or untargeted metabolomics analyses, including lipidomics, in adult women with adenomyosis diagnosed by imaging or histopathology. Proteomics-only studies, animal studies, and in vitro studies were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale or, where appropriate, the Joanna Briggs Institute Critical Appraisal Checklist. Metabolomics-specific analytical and reporting features were evaluated using a complementary predefined checklist, in which analytical robustness was classified as high, moderate, or low according to key criteria specific to targeted and untargeted metabolomics studies; the complete scoring rules and thresholds are reported in Online Resource 2. Owing to heterogeneity in biological matrices, analytical platforms, and reporting, findings were synthesized qualitatively by biochemical category. RESULTS: Eleven studies comprising a total of 846 participants were included, most conducted in China and using mass spectrometry across different biological samples. Overall, findings indicate widespread metabolic alterations, particularly in lipid pathways, including glycerophospholipids, lysophospholipids, acylcarnitines, and sphingolipids. Alterations were also observed in amino acid metabolism, nucleotide-related compounds, and central energy pathways such as glycolysis and the tricarboxylic acid cycle. These patterns suggest enhanced lipid signaling, altered mitochondrial function and energy metabolism, inflammation, oxidative stress, and increased cellular proliferation. Several studies proposed discriminative metabolite panels, but none underwent external validation. CONCLUSION: Adenomyosis is associated with broad metabolic reprogramming involving lipid, amino acid, nucleotide, and energy metabolism. These patterns may improve understanding of disease mechanisms and support future research on diagnostic biomarkers and therapeutic targets. PROSPERO REGISTRATION: Registration date: January 8, 2026 Registration number: CRD420251271258 URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251271258.

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