Menstrual Blood as a Diagnostic Tool for Endometriosis: Systematic Review

Ruth Niedermeier, Noemi Castelletti, Andreas Bender, Michael Hoelscher, Olena Ivanova, Kathrin Held
In: F&S Reviews · 2026 · vol. 7(3) , pp. 100116 · doi:10.1016/j.xfnr.2026.100116 · W7172497316
Systematic review / meta-analysis OA: hybrid CC0
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This systematic review analyzes existing research to evaluate the potential of menstrual blood as a non-invasive diagnostic tool for endometriosis.

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Abstract

Importance: To diagnose endometriosis remains challenging because confirmation still largely relies on invasive laparoscopy. Menstrual blood (MB) offers a promising, noninvasive source of diagnostic biomarkers that reflect the local uterine environment. Objective: This systematic review aimed to critically evaluate the current landscape of molecular, cellular, and biochemical MB-derived potential biomarkers for endometriosis and to appraise their clinical usefulness and translational readiness by distinguishing promising biomarker candidates from exploratory biomarker candidates. Evidence review: A systematic search of PubMed, Embase, and Web of Science identified 32 eligible studies investigating MB biomarkers in endometriosis. Data extraction followed PRISMA guidelines. Study quality was assessed using the Newcastle-Ottawa scale and a specifically designed "Early-stage biomarker quality assessment scale" (EBQAS) addressing validation strategy, methodological transparency, and reporting quality. Biomarker candidates were classified according to diagnostic accuracy, sample size, methodological quality, and clinical feasibility. Due to heterogeneity, a narrative synthesis was performed. Findings: Most identified markers remained exploratory because of small sample sizes, limited diagnostic validation, and heterogeneous methodologies. A few markers were deemed promising biomarker candidates based on their performance and detection method. Specifically, these were P450 aromatase (sensitivity 94.6%, specificity 90.9%) measured by immunocytochemistry (ICC), transforming growth factor-ß1 (TGF-β1) (AUC 97.3%), and insulin-like growth factor binding protein-1 (IGFBP1) (AUC 92%) measured by enzyme-linked immunosorbent assay (ELISA), and progesterone receptor B (PR-B) messenger ribonucleic acid (mRNA) expression (sensitivity 90.5%, specificity 85.7%), aromatase (AUC 97.7%), steroidogenic factor-1 (SF-1) (86.2%), and 17b-hydroxysteroid dehydrogenase-2 (HSD17B2) (80.7%), all measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). These markers were identified using clinically translatable analytical methods, including ELISA, RT-qPCR, and ICC. Conclusion and Relevance: Menstrual blood is a clinically attractive substrate for noninvasive endometriosis diagnostics, but evidence remains limited to a few promising biomarker candidates within a largely exploratory field. Future research should prioritize multicenter validation and development of standardized, clinically feasible assays for routine diagnostics or point-of-care testing.

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