This study showed that age at menarche (p = 1.21e − 05; OR = 0.6852; 95% CI: 0.5784–0.8116), age at menopause (p = 0.00098; OR = 1.242; 95% CI: 1.0919–1.4127), and sex hormone–binding globulin (SHBG) levels (p = 7.4e − 07; OR = 0.5914; 95% CI: 0.4804–0.7281) have an independent causal relationship with the incidence of endometrial cancer. Here, SHBG is linked to endometrial cancer.