Correlation of PGP9.5 and TGF-β1 Levels in Menstrual Blood with Dysmenorrhea Severity in Adenomyosis Patients: A Cross-Sectional Study

Yohanes Iddo Adventa, Anita Rachmawati, Dian Tjahyadi, Hartanto Bayuaji, Hanom Husni Syam, Mulyanusa Amarullah Ritonga, Ida Bagus Putra AdnyanaDepartment of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital, Bandung, West Java, IndonesiaCorrespondence: Yohanes Iddo Adventa, Email [email protected]: Adenomyosis is a common gynecological disorder characterized by invasion of endometrial tissue into the myometrium, often presenting with severe dysmenorrhea. The pathophysiology involves neurogenesis and inflammation, with protein gene product 9.5 (PGP9.5) as a nerve fiber marker and transforming growth factor-beta 1 (TGF-β 1) as an inflammatory mediator. Menstrual blood represents an easily obtainable, non-invasive alternative to conventional tissue-based biomarker assessment.Objective: To analyze the association between PGP9.5 and TGF-β 1 levels in menstrual blood with dysmenorrhea severity in adenomyosis patients, and to evaluate their diagnostic performance.Methods: This cross-sectional study included 72 women aged 20– 45 years (36 with adenomyosis confirmed by histopathology and 36 controls) at Dr. Hasan Sadikin Hospital and Bandung Kiwari Hospital, Indonesia, from September 2025 to January 2026. Menstrual blood samples were collected using menstrual cups on the second or third day of menstruation. PGP9.5 and TGF-β 1 levels were measured using ELISA. Dysmenorrhea severity was assessed using the Visual Analog Scale (VAS). Statistical analyses included Mann–Whitney test, Spearman correlation, and ROC curve analysis.Results: PGP9.5 levels were significantly higher in adenomyosis patients compared to controls (median 335,77 vs 223,77 ng/L, p< 0.001), as were TGF-β 1 levels (median 608,92 vs 379,43 ng/mL, p< 0.001). VAS scores were also significantly higher in the adenomyosis group (median 9.00 vs 0.50, p< 0.001). Significant positive correlations across the overall study population were observed between PGP9.5 and VAS (r = 0.562, p < 0.001), TGF-β 1 and VAS (r = 0.581, p < 0.001), and between PGP9.5 and TGF-β 1 (r = 0.878, p < 0.001). ROC analysis demonstrated excellent diagnostic performance for PGP9.5 and TGF-β 1 with AUC of 0.943 and 0.942, with optimal cut-offs of 260.43 ng/L for PGP9.5 and 482.95 ng/mL for TGF-β 1, yielding sensitivity and specificity of 91.7% for both markers.Conclusion: PGP9.5 and TGF-β 1 levels in menstrual blood are significantly elevated in adenomyosis patients and positively correlate with dysmenorrhea severity. These findings provide proof of concept that menstrual blood PGP9.5 and TGF-β 1 may serve as non-invasive biomarkers for adenomyosis.Keywords: adenomyosis, dysmenorrhea, PGP9.5, TGF-β 1, menstrual blood, biomarkers, neurogenesis, fibrogenesis