Evaluation of Serum Growth Differentiation Factor-15 (Gdf-15) as a Non-Invasive Biomarker for Disease Severity and Pain Intensity in Endometriosis: a Hospital Based Case-Control Study

<b>Background:</b> Endometriosis is a chronic, oestrogen-dependent inflammatory gynaecological disorder affecting 10 to 15 percent of women of reproductive age. The condition is characterised by pelvic pain and infertility, and diagnosis is frequently delayed by 7 to 10 years due to reliance on invasive laparoscopy and the absence of validated non-invasive biomarkers. Growth Differentiation Factor-15 (GDF-15), a stress-responsive cytokine implicated in inflammatory and nociceptive pathways, has emerged as a candidate biomarker in multiple pain-related disorders; however, its clinical utility in endometriosis has not been adequately defined.<br /> <b>Objective:</b> The primary objective of this study was to evaluate serum GDF-15 as a diagnostic biomarker capable of differentiating women with confirmed endometriosis from healthy controls. The secondary objective was to assess its potential as a disease severity marker by examining the association between GDF-15 levels and r-AFS staging, and its exploratory relationship with pain intensity scores.<br /> <b>Methods:</b> This was a hospital-based case-control study conducted over 24 months at a tertiary teaching hospital. The study enrolled 100 women with laparoscopically and histopathologically confirmed endometriosis (cases) and 100 age-matched healthy controls. Serum GDF-15 concentration was quantified using enzyme-linked immunosorbent assay (ELISA). Disease severity was graded using the revised American Fertility Society (r-AFS) staging system. Pain intensity was assessed using the Visual Analogue Scale (VAS) and the Numerical Rating Scale (NRS). Statistical analysis included independent samples t-test, one-way analysis of variance (ANOVA), Pearson correlation coefficient, binary logistic regression, and receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p less than 0.05.<br /> <b>Results:</b> Serum GDF-15 was significantly elevated in cases compared to controls (961.7 ± 195.2 pg/mL vs. 508.0 ± 99.6 pg/mL; <i>p</i> less than 0.001; Cohen's d = 2.93). ROC curve analysis demonstrated excellent diagnostic discriminatory performance (AUC = 0.942; 95% CI: 0.907 to 0.977; sensitivity 89.0%; specificity 88.0% at an optimal cut-off of 720.5 pg/mL). A numerical increasing trend in GDF-15 was observed across r-AFS stages (Stage I: 906.3 ± 234.3 pg/mL to Stage IV: 987.5 ± 192.7 pg/mL); however, this difference did not reach statistical significance (one-way ANOVA, <i>p</i> = 0.265) and should be interpreted as exploratory. Pearson correlation between GDF-15 and pain scores was weak and did not achieve statistical significance (VAS: r = 0.174, <i>p</i> = 0.084; NRS: r = 0.191, <i>p</i> = 0.058). Binary logistic regression confirmed GDF-15 as an independent predictor of endometriosis diagnosis after adjustment for age and BMI (adjusted OR = 3.84; 95% CI: 2.61 to 5.65; <i>p</i> less than 0.001).<br /> <b>Conclusion:</b> Serum GDF-15 is significantly elevated in women with endometriosis and demonstrates excellent diagnostic discriminatory performance, supporting its role as a non-invasive diagnostic biomarker. The non-significant numerical trend across r-AFS stages and the weak, non-significant correlations with pain scores do not permit conclusions regarding GDF-15 as a severity or pain prediction marker on the basis of the current data. External validation in larger multicentre prospective cohorts is required before clinical translation.