Serum biomarkers associated with disease stage and pain severity among women with endometriosis in Indonesia

Endometriosis is a chronic estrogen-dependent disease characterized by the presence of endometrial-like tissue outside the uterine cavity, resulting in chronic inflammation, recurrent pain, and infertility, and affecting approximately 190 million women worldwide. Chronic inflammation in endometriosis may stimulate overexpression of cyclooxygenase-2 (COX-2), which catalyzes prostaglandin E2 production, whereas cancer antigen 125 (CA-125) is a glycoprotein biomarker released by endometrial and mesothelial cells in response to inflammatory processes. The aim of this study was to analyze the correlations between serum COX-2 and CA-125 levels and the degree of endometriosis, based on the revised American Society for Reproductive Medicine classification, and between these levels and pain severity, based on the Numeric Rating Scale. A cross-sectional study was conducted among patients with endometriosis at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia. The levels of COX-2 and CA-125 were measured using enzyme-linked immunosorbent assay and chemiluminescence immunoassay, respectively. Spearman correlation and ordinal logistic regression were used for statistical analysis. The median age of the participants was 36 years (range: 19-51 years), and most patients had Stage IV endometriosis (78.6%). COX-2 showed a significant positive correlation with both the degree of endometriosis (r=0.526; p<0.001) and pain severity score (r=0.769; p<0.001). CA-125 also showed a significant positive correlation with the degree of endometriosis (r=0.433; p=0.004), but not with pain severity (r=0.256; p=0.102). Receiver operating characteristic curve analysis showed that COX-2 had good discriminative ability for severe endometriosis (AUC=0.865) and for severe pain (AUC=0.864). In the multivariable model, COX-2 and CA-125 were also significantly associated with pain severity. These findings suggest that COX-2 was more strongly associated with pain severity, whereas CA-125 was more closely related to the degree of endometriosis. Further studies with larger sample sizes and prospective designs are needed to validate these findings and clarify the clinical utility of these biomarkers in endometriosis management.