Objective To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB).Design Retrospective cohort study.Setting One-stop PMB clinic in a Hong Kong teaching hospital. Main outcome measures Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve.Results Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%).Conclusions Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

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Background Growth differentiation factor 15 (GDF15) is a key regulator of body weight in animals by regulating food intake. Its receptor, glial cell-derived neurotrophic factor receptor alpha-like (GFRAL), was identified recently. Pre-clinical studies showed that it is a promising therapeutic target for cardiometabolic diseases and anorexia/cachexia. Although many pharmaceutical companies are developing drugs targeting GFRAL, whether the findings from animal studies can be extrapolated to man is unknown. Mendelian randomization (MR) is useful in investigating the relationship between risk factors and disease outcomes. We aimed to use a two-sample MR approach to evaluate the clinical usefulness of targeting GDF15 for cardiometabolic diseases. Methods Genetic instruments and summary statistics for MR analyses were obtained from a large genome-wide association study (GWAS) of GDF15 and cardiometabolic outcomes ( n = 27,394 to 644,875), including body mass index, waist-hip ratio, waist circumference, whole-body lean mass, fat percentage, Type 2 Diabetes, fasting glucose, glycated haemoglobin, fasting insulin, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglycerides, coronary artery disease, and estimated BMD (eBMD). Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of GDF-15 with different outcomes; weighted median and MR-egger were used for sensitivity analyses. Findings There was null association between GDF15 levels and anthropometric outcomes. One SD increase in genetically-determined GDF15 was significantly associated with reduced HDL-C (beta: -0.048SD; SE: 0.014; P = .001) but the result was not significant in sensitivity analyses. A consistent significant causal association was observed between GDF15 and eBMD in IVW (beta: 0.026 SD; SE: 0.005; P < .001) and subsequent sensitivity analyses. Interpretation This study sheds lights on the potential of drugs targeting the GDF15/GFRAL axis. It suggested that the effect of targeting GDF15/GFRAL axis for weight control in human may be different from the effects observed in animal studies. GDF15 treatment may improve BMD in humans. Fund No specific funding was received for this study.