Unopposed estrogen hypothesis is the theoretical framework used to explain the relationship between endogenous steroid hormones and endometrial cancer risk. This hypothesis proposes that that endometrial cancer may develop as a result of the mitogenic effects of estrogens, when these are insufficiently counterbalanced by progesterone. In etiological terms, any factor that increases exposure to unopposed estrogens (such as estrogen therapy obesity, and irregular menstrual cycles) tends to increase the risk of the disease, while factors that decrease exposure to estrogens or increase progesterone levels (such as oral contraceptives or smoking) tend to be protective.