It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC. •Throughout women’s life, respect the balance between estrogen and progestogen.•Use combined contraception or progestin in anovulatory premenopausal women.•Prevent hyperplasia in obese women, women with polycystic ovary syndrome (PCOS), metabolic syndrome.•In MHT, adapt the dose of progestogen to dose/duration of estrogen treatment.•Inform the woman of the importance of taking the progestogen pill and check the compliance.•In menopause hormonal treatment (MHT), prefer continous treatment than sequential.