Obesity and Endometrial Cancer Precursors

Abstract

The menstrual cycle is composed of two phases - proliferative and secretory. During the proliferative phase, estrogen stimulates the endometrium leading to growth of both the stromal and epithelial compartments. During this period of abundant mitotic activity, mutations inevitably arise within the epithelial compartment. It is typically the rise of progesterone during the secretory cycle that selects against further proliferation of these mutant cells. However, in patients with excess estrogen (e.g., obesity), these mutant populations have a selective advantage, leading to further proliferation and increased mutation rates. The result is a progression of "latent precancers" to endometrial intraepithelial neoplasia (EIN) - a precursor of endometrial endometrioid-type adenocarcinoma.