Detecting Endometrial Hyperplasia and Cancer in Women <45 Years Old: Who Warrants an Endometrial Biopsy?

Objectives: Endometrial cancer incidence is rising, particularly in premenopausal women. While endometrial sampling guidelines are clear for older women with abnormal uterine bleeding, there is minimal data to guide decision making in women <45 years old. We aimed to determine the prevalence of endometrial hyperplasia or cancer (EH/EC) diagnosed from endometrial sampling procedures performed in this population, and identify factors associated with EH/EC diagnosis. Methods: A retrospective cohort study was performed using procedural claims codes to identify all endometrial sampling procedures (i.e., endometrial biopsies and non-obstetrical dilation and curettage) performed in a single hospital enterprise system from 07/2016 to 10/2019 in women ages 18-44 years. Clinico-demographic characteristics were extracted using diagnosis codes. Pathology reports were reviewed and classified as benign, EH, or EC. We estimated the prevalence of EH/EC by body mass index (BMI) and examined differences further stratified by race. Multivariable logistic regression was used to identify factors independently associated with EH/EC on endometrial sampling. Results: A total of 3,504 women were included; the median age was 38 (Interquartile range (IQR): 34-42); 44 % were White, 39% were BlackBlack, and 17% were of other race. Median BMI was 29kg/m2 (IQR 23.87-36.51) and 15% had a BMI above 40.A total of 3.8% were diagnosed with EH (n=101) and EC (n=32). The prevalence of EH/EC increased in a dose-response fashion with increasing BMI: from the lowest at 1.9% in those with BMI <25, to 4.4% in those with BMI 30-39.9, to 7.4% in those with BMI 40-49.9, and as high as 15.9% in those with BMI ≥50 (P-trend< 0.01). While this dose-response trend was consistent across race, the prevalence estimates were qualitatively lower in all BMI categories in Black women compared to White or other race (Table). After controlling for age, BMI, race, smoking status, diabetes, hypertension, family history, and polycystic ovarian syndrome (PCOS), increasing BMI remained strongly associated with EH/EC prevalence. In women with BMI ≥50, the odds of diagnosing EH/EC was 12 times higher than women with BMI <25 (odds ratio (OR):12.2; 95% CI: 5.7-26.1). In addition, women with PCOS were more likely to be diagnosed with EH/EC (OR=4.1; 95% CI: 2.5,6.8), as well as women of other race (OR=1.6; 95% CI:1,2.6). Black women were less likely (OR= 0.56, 95% CI: 0.2,0.5) to be diagnosed with EH/EC compared to White women. Conclusions: In women <45 years old undergoing endometrial sampling, higher levels of obesity significantly increased the odds of diagnosing EH/EC - up to 12 times higher in women with the highest BMI. This suggests that endometrial sampling should be considered as early diagnostic intervention in this population. Given our differential findings and the known differences in EC risk type by race, additional investigation into premenopausal EH/EC risk by race warrants further consideration. Graphical Abstract View Large Image Figure Viewer Download Hi-res image Endometrial cancer incidence is rising, particularly in premenopausal women. While endometrial sampling guidelines are clear for older women with abnormal uterine bleeding, there is minimal data to guide decision making in women <45 years old. We aimed to determine the prevalence of endometrial hyperplasia or cancer (EH/EC) diagnosed from endometrial sampling procedures performed in this population, and identify factors associated with EH/EC diagnosis. A retrospective cohort study was performed using procedural claims codes to identify all endometrial sampling procedures (i.e., endometrial biopsies and non-obstetrical dilation and curettage) performed in a single hospital enterprise system from 07/2016 to 10/2019 in women ages 18-44 years. Clinico-demographic characteristics were extracted using diagnosis codes. Pathology reports were reviewed and classified as benign, EH, or EC. We estimated the prevalence of EH/EC by body mass index (BMI) and examined differences further stratified by race. Multivariable logistic regression was used to identify factors independently associated with EH/EC on endometrial sampling. A total of 3,504 women were included; the median age was 38 (Interquartile range (IQR): 34-42); 44 % were White, 39% were BlackBlack, and 17% were of other race. Median BMI was 29kg/m2 (IQR 23.87-36.51) and 15% had a BMI above 40.A total of 3.8% were diagnosed with EH (n=101) and EC (n=32). The prevalence of EH/EC increased in a dose-response fashion with increasing BMI: from the lowest at 1.9% in those with BMI <25, to 4.4% in those with BMI 30-39.9, to 7.4% in those with BMI 40-49.9, and as high as 15.9% in those with BMI ≥50 (P-trend< 0.01). While this dose-response trend was consistent across race, the prevalence estimates were qualitatively lower in all BMI categories in Black women compared to White or other race (Table). After controlling for age, BMI, race, smoking status, diabetes, hypertension, family history, and polycystic ovarian syndrome (PCOS), increasing BMI remained strongly associated with EH/EC prevalence. In women with BMI ≥50, the odds of diagnosing EH/EC was 12 times higher than women with BMI <25 (odds ratio (OR):12.2; 95% CI: 5.7-26.1). In addition, women with PCOS were more likely to be diagnosed with EH/EC (OR=4.1; 95% CI: 2.5,6.8), as well as women of other race (OR=1.6; 95% CI:1,2.6). Black women were less likely (OR= 0.56, 95% CI: 0.2,0.5) to be diagnosed with EH/EC compared to White women. In women <45 years old undergoing endometrial sampling, higher levels of obesity significantly increased the odds of diagnosing EH/EC - up to 12 times higher in women with the highest BMI. This suggests that endometrial sampling should be considered as early diagnostic intervention in this population. Given our differential findings and the known differences in EC risk type by race, additional investigation into premenopausal EH/EC risk by race warrants further consideration.