Serum trefoil factor 3 levels in women with polycystic ovary syndrome: a cross-sectional study

Abstract

Polycystic ovary syndrome (PCOS) is associated with chronic anovulation and prolonged unopposed estrogen exposure, which may contribute to endometrial dysfunction. Trefoil factor 3 (TFF3) is an estrogen-responsive peptide involved in epithelial repair and mucosal integrity. However, data on circulating TFF3 levels in women with PCOS are limited. This exploratory cross-sectional study included 41 women with PCOS and 34 age-matched women without PCOS. Serum TFF3 levels were measured and compared between groups. The association between TFF3 levels and menstrual cycle patterns was also evaluated. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory performance of TFF3 for PCOS. Serum TFF3 levels were significantly higher in women with PCOS compared with controls (1742 ± 582 vs. 1185 ± 704 pg/mL, p < 0.001). TFF3 levels were not associated with menstrual cycle pattern or oligomenorrhea. ROC analysis showed that TFF3 had a moderate ability to discriminate PCOS (AUC: 0.728), with a sensitivity of 80.5% and a specificity of 61.8% at the optimal cut-off value. No independent associations were identified in multivariate regression analysis. Serum TFF3 levels were higher in women with PCOS than in women without PCOS, but this association was not independent of BMI and other clinical/hormonal factors in multivariate analysis, and no endometrial tissue data were available; therefore, any link between TFF3 and PCOS-related endometrial changes remains speculative. Given the lack of association with menstrual patterns, the moderate diagnostic performance, and the absence of independent association after adjustment, TFF3 alone is unlikely to serve as a reliable biomarker. Further prospective studies incorporating endometrial tissue evaluation and metabolic assessment are needed to clarify its biological and clinical significance.