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Introduction: The addition of progestin to estrogen therapy is required for endometrial protection in menopausal women who have an intact uterus.Unfortunately emerging evidence indicates that the combined regimen is associated with an increased risk of breast cancer.It is likely that this unwanted adverse effect varies according to various regimens of hormone.Objective: To evaluate experimental and epidemiological studies pertaining to the breast cancer risk of various regimens of hormone therapy in menopausal women.Design: Literature review.Setting: Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University.Main Outcome Measures: Mammry epithelial proliferation, apoptosis and incidence of breast cancer.Results: In experimental studies, adding testosterone to hormone therapy exhibited protective effects on the breast.Tibolone had a strong preclinical evidence to support the breast safety.The combination of estradiol and either natural progesterone or dydrogesterone had moderate amount of data to support the neutral effects on the breast while the combination of estradiol and drospirenone had a limited evidence.For clinical studies level 1 of evidence supported that the use of tibolone up to 3 years decreased the risk of breast cancer in postmenopausal women.Discussion: According to available data, three promising ways to avoid the breast cancer risk arising with the use of combined estrogen and progestin are selecting to add natural progestin or dydrogesterone to estrogen therapy, adding testosterone to hormone therapy and the use of tibolone as hormone therapy.