The main risk factor is continued unopposed exposure to elevated estrogen levels. Among the different causes related to endometrial cancer are:
1- Obesity: is present in 40-50% of endometrial carcinomas in developed countries. Obese women are 2-4 times more likely to develop endometrial cancer than non-obese women.
2- Unopposed estrogen therapy (UET). The use of UET greatly increases the formation of endometrial hyperplasia and endometrial carcinoma. This risk increases in relation to the dose and duration of the exposure. The administration of progesterone during HRT eliminates the risk of both endometrial hyperplasia and carcinoma.
3- Tamoxifen: It is a selective estrogen receptor modulator (SERM) that is commonly used as an adjuvant hormone treatment in women with breast cancer. The use of tamoxifen is associated with a 2-5-fold increased risk of developing endometrial pathology, including polyps and endometrial cancer.
4- Hereditary: Endometrial carcinoma may appear in the context of a Lynch II syndrome or hereditary colorectal cancer not associated with polyposis (HNPCC). It is an autonomic dominant disorder with incomplete penetrance. Women with HNPCC have a risk of about 50% developing endometrial cancer.