In the uterus, estrogen triggers the proliferation of endometrial lining cells during each month of the menstrual cycle, followed by death of these cells during menstruation. Over a span of 40 years, from puberty to menopause, hundreds of cycles of cell division and cell death will occur.

These repeated cycles of estrogen-induced cell division tend to increase the risk of developing cancer in the same two ways as in the breast: Estrogen can stimulate the division of uterine cells that already have DNA mutations, and it also increases the chances of developing new, spontaneous mutations when estrogen stimulates cell proliferation. Whether the mutations are inherited or spontaneous, estrogen-driven proliferation will increase the number of these altered cells that can ultimately lead to the development of uterine cancer.