Urinary Urocortin as a Potential Non-Invasive Biomarker in Endometriosis: Exploratory Study with Histone H4

Background and Objectives: Endometriosis, a complex and often underdiagnosed gynecological condition, frequently manifests with ovarian involvement, posing significant clinical challenges. Current diagnostic protocols primarily rely on invasive techniques, thus highlighting the critical need for reliable, non-invasive biomarkers. This study aimed to evaluate the diagnostic performance and clinical relevance of Urocortin and Histone H4, assessed in both serum and urine, as potential biomarkers for ovarian endometriosis. Materials and Methods: We implemented an exploratory study design to investigate potential biomarkers for ovarian endometriosis. The study cohort consisted of 40 women, divided into three groups: Those with histologically confirmed ovarian endometriosis are 30, those with parietal endometriosis are 5, and 5 healthy controls. Standardized ELISA protocols were employed for the quantification of Urocortin and Histone H4 in both serum and urine samples. To ensure consistency, all participants were assessed during the proliferative phase of their menstrual cycle. Finally, comparative and multivariate statistical analyses were conducted to evaluate biomarker variability in the context of relevant clinical parameters. Results: Serum Urocortin levels were comparable across the three groups (mean ± SD: 3.63 ± 0.41 µg/mL in ovarian endometriosis vs. 3.59 ± 0.31 µg/mL in parietal endometriosis and 3.70 ± 0.38 µg/mL in controls; p > 0.05). In contrast, urinary Urocortin levels were significantly elevated in patients with ovarian endometriosis (2.51 ± 1.36 µg/mL), compared to both parietal endometriosis (0.13 ± 0.04 µg/mL) and controls (0.33 ± 0.18 µg/mL; p = 0.001). Multivariate linear regression revealed that age, age at menarche, and disease duration accounted for 28.3% of the variance in urinary Urocortin levels (adjusted R2 = 0.283; p = 0.002). Serum Histone H4 concentrations were modestly elevated in the ovarian endometriosis group (0.49 ± 0.18 ng/mL), although no statistically significant intergroup differences were observed. Urinary Histone H4 levels showed subtle variation but lacked discriminatory value. Conclusions: Urinary Urocortin showed a preliminary diagnostic signal in this small exploratory cohort, whereas Histone H4 did not perform significantly. Our findings require replication in larger, multicenter, and rigorously controlled studies with validated urine normalization methods. Nonetheless, our study opens further perspectives for complementing the biomarker panel with potential non-invasive diagnostic value with new candidates.