ASPO Abstracts
Endometrial changes in premenopausal obese women, an at-risk cohort
Category: Early Detection & Risk Prediction
Conference Year: 2020
Abstract Body:
Background: Obesity is a well-known risk factor for endometrial cancer, yet mechanisms of obesity-related
carcinogenesis are not well-defined, particularly for premenopausal women. Research has generally focused on
obesity-mediated increased cancer risk via imbalance of estrogen/progesterone leading to endometrial
proliferation. Despite the substantial increased risk at the population level, most obese women do not develop
endometrial cancer. The molecular determinants for development of cancer are unknown for this high-risk cohort.
Purpose: The prevalence of endometrial precancers (hyperplasia) was determined in obese premenopausal
women. We also sought to evaluate whether obesity mediates changes in endometrial markers associated with
altered estrogen/progesterone balance in premenopausal women.
Methods: Premenopausal women with BMI ≥30 kg/m2 (n=97) or BMI ≤25 kg/m2 (n=33) were prospectively
enrolled in a cross-sectional study, including assessment of serum metabolic markers and timed endometrial
biopsy for pathology evaluation and hormone-regulated biomarker analysis. Medical and gynecologic history was
obtained. Endometrial biomarkers were also compared by BMI groups in a previous cohort of premenopausal
women with inherited cancer risk (Lynch syndrome).
Results: Of 97 obese premenopausal women enrolled, one case of complex atypical hyperplasia was identified. In
addition to known systemic metabolic changes, normal endometrium from obese women showed decreased
expression of estrogen-induced genes (RALDH2, IGF-1, and survivin) compared to non-obese women. In
contrast, obese women with Lynch syndrome had increased IGF-1. Obese women with insulin resistance had
increased survivin expression.
Conclusions: Endometrial markers in obese premenopausal women without inherited risk reflect a progesterone-
dominant profile (decreased cancer risk). In describing premenopausal endometrial cancer risk, it may be
insufficient to describe obesity alone as a high-risk state and additional risk factors (such as insulin resistance)
may be required. However, in Lynch syndrome, endometrial biomarkers suggest that obesity further increases risk.
Additional studies are needed to translate population-based observations to individualized risk assessment and
prevention strategies.
Keywords: Obesity, endometrial cancer, premenopausal, Lynch syndrome