Obesity is an independent risk factor for endometrial adenocarcinoma (EC), yet it is unknown which attributes of obesity contribute to EC pathogenesis. We hypothesize that heterogeneity in metabolic health distinguishes which obese women are at risk for EC. We previously found that more premenopausal women with pre-malignant hyperplasia had type 2 diabetes and dyslipidemia than women with benign hyperplasia (BH), despite similar BMI. BH is the ideal control condition since presenting symptoms are similar, yet malignant transformation is negligible. Thus, we sought to compare metabolic abnormalities in postmenopausal women with EC and BH. We reviewed medical records of 284 women who received a biopsy/hysterectomy at our center over 3 years. We examined non-Hispanic white women age 50-65 years with BMI 25-50 kg/m2, to limit variability in factors known to affect metabolism. 122 women had histologically confirmed EC (n=74) or BH (n=48), and 60% had lab data. Variables were analyzed by chi-squared or Student’s T test. Women with EC were older (58 ± 0.5 vs. 53 ± 0.4 years, p<0.0001) and had higher BMI (37 ± 1 vs. 32 ± 1 kg/m2, p<0.0001) than women with BH. BMI distribution was markedly different between groups, with a higher frequency and greater severity of obesity among women with EC (p<0.0001). More women with EC than BH had type 2 diabetes (19% vs. 4%, p<0.05) and hypertension (54% vs. 25%, p<0.01). Women with EC had higher triglycerides (140 ± 12 vs. 110 ± 13 mg/dL, p<0.05) and lower HDL (55 ± 2 vs. 60 ± 4 mg/dL, p=NS). However, these differences can be explained by the skewed BMI distribution. LDL and total cholesterol as well as statin use (20% vs. 25%) were similar between groups (p=NS). The striking differences in BMI among postmenopausal women with EC and BH highlights the role of obesity in EC pathogenesis. Since BMI affects metabolism, a prospective study of BMI-matched women is necessary to determine whether metabolic dysregulation independently influences cancer development.


K.M. Cooke: None. E. Dun: None. A.K. Anam: None. C. Flannery: None.

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