Objective: To evaluate the association between endometrial thickness (ET) and histopathologically confirmed endometrial cancer or atypical hyperplasia in postmenopausal women presenting with vaginal bleeding, stratified by menopausal hormone therapy (HT) status, and to assess diagnostic performance across therapy groups. Methods: Retrospective cohort study of postmenopausal women referred to an urgent cancer pathway between September 2022 and August 2023 at a United Kingdom district hospital. ET was measured by transvaginal ultrasonography as double-layer thickness. Histopathologic diagnosis from endometrial biopsy or hysteroscopy-directed sampling served as the standard. Diagnostic discrimination was evaluated using receiver operating characteristic curves and area under the curve (AUC) with 95% confidence intervals; sensitivity and specificity were calculated at prespecified thresholds. Multivariable logistic regression assessed predictors including age, ET, recurrent bleeding, and HT status. Results: Among 1,082 women with histopathologic outcomes, 32 had clinically significant endometrial pathology. ET demonstrated excellent discrimination in women not using HT (AUC: 0.925) but markedly reduced discrimination in women using continuous combined HT (AUC: 0.597). At a 4 mm threshold, negative predictive value exceeded 99% in both groups, while positive predictive value remained low in HT users. Age and ET were independent predictors in adjusted models. Conclusions: ET performs well as a triage test in women not using HT, but is less informative as a standalone measure in women using continuous combined HT; HT status should inform interpretation and referral decisions.
