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

Background: 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.

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.

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.

Serum GDF-15 was significantly elevated in cases compared to controls (961.7 ± 195.2 pg/mL vs. 508.0 ± 99.6 pg/mL; p 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, p = 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, p = 0.084; NRS: r = 0.191, p = 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; p less than 0.001).

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. CITATION Jaishankar T, Madhan P, Datchanamurthi S, Vairavan Pillai Subbammal K, Madhan R. 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. J CLIN MED KAZ. 2026;23(2):31-8. https://doi.org/10.23950/jcmk/18292

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