Endometriosis is a chronic, estrogen-dependent inflammatory disorder affecting approximately 10% of reproductive-age women, often leading to pelvic pain, infertility, and reduced quality of life. Diagnosis is typically delayed by several years due to reliance on invasive laparoscopy rather than reliable non-invasive biomarkers. CA-125 remains the cornerstone biomarker, particularly effective in advanced and ovarian endometriosis, but its limited specificity necessitates combination with other markers. Integrative multi-biomarker strategies combining CA-125 with Annexin A5 (ANXA5), HE4, CA72-4, and inflammatory indices like the platelet-to-lymphocyte ratio (PLR) significantly enhance diagnostic accuracy. Urinary biomarkers such as vitamin D-binding protein (VDBP) and alpha-1 antitrypsin (A1AT) further improve non-invasive detection, achieving high sensitivity (up to 90.9%) and specificity (76.5%). Incorporating clinical parameters, including cyst morphology, dysmenorrhea, and BMI, refines diagnostic precision and staging. Dynamic-phase CA-125 measurement across menstrual cycles also increases accuracy in deep infiltrative endometriosis. Overall, multi-marker, integrative approaches combining serum, urinary, and clinical data hold promise for earlier, more accurate, and less invasive diagnosis of endometriosis. Future research should focus on validating standardized biomarker panels and defining optimal cut-off values to reduce diagnostic delays and improve patient outcomes globally.

Endometriosis, CA-125, multi-biomarker panel, Annexin A5 (ANXA5)

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