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

Thirunavukkarasu Jaishankar 1 * , Preetha Madhan 2 * , Sarguru Datchanamurthi 3, Kalaiselvi Vairavan Pillai Subbammal 4, Rhona Madhan 5
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1 Department of Biochemistry, Karpagam Faculty of Medical Science & Research, Coimbatore, Tamil Nadu, India
2 Department of Obstetrics and Gynecology, PSP Medical College Hospital and Research Institute, Chennai - Tamil Nadu, India
3 Department of Biochemistry, Sri Lalithambigai Medical College, Dr. MGR Educational & Research Institute, Maduravoyal, Chennai, Tamil Nadu, India
4 Department of Biochemistry, Sree Balaji Medical College & Hospital, Bharath Institute of Higher Education & Research, Chennai, Tamil Nadu, India
5 Department of Obstetrics and Gynecology, SRM Medical College Hospital and Research Centre, SRMIST, Chennai - Tamil Nadu, India
* Corresponding Author
J CLIN MED KAZ, Volume 23, Issue 2, pp. 31-38. https://doi.org/10.23950/jcmk/18292
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Author Contributions: Conceptualization, P.M and T.J; Methodology, R.M and P.M; Formal Analysis, T.J; Investigation, R.M, and S.D.; Resources, S.D.; Data Curation, S.D.; Writing – Original Draft Preparation, T.J and K.V.S; Writing – Review and Editing, K.V.S., T.J., and R.M.; Supervision, S.D; Project Administration, P.M. All authors have read and agreed to the published version of the manuscript.

Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Artificial Intelligence (AI) Disclosure Statement: The authors declare no AI Tools used for preparation of this work.

ABSTRACT

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.
Objective: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
Keywords: Endometriosis, Growth Differentiation Factor-15, Biomarker, Pelvic pain, Disease severity, r-AFS staging

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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