ESR1 and hyperinsulinism: However, IR and hyperinsulinemia in the body can inhibit the secretion of SHBG, thereby increasing free active estrogen in the blood circulation.[32] At the same time, hyperinsulinemia can also increase the expression of estrogen receptor and in turn enhance the function of estrogen in the endometrium.[33] As a result, excess insulin promotes the proliferation of endometrial cells under the action of estrogen, thereby increasing the risk of EC.