It is well established that progestogens protect the endometrium against the proliferative effects of estrogens in postmenopausal women receiving hormone replacement therapy (HRT). Therefore, micronized progesterone and progestogens are recommended as part of combined HRT in women with an intact uterus. The protective effect of progestogens against hyperplasia and endometrial cancer does not appear to differ with different progestogens (micronized progesterone or progestogens), but appears to be affected by the regimen and thus the dose, with continuous combined treatment conferring better protection. However, the protective effect of progestogens seen in the endometrium is not replicated in the breast. Progestogens combined with estrogens are generally associated with a small increase in the risk of invasive breast cancer, which is believed to be due to a promoter effect. However, all progestogens are not equivalent in their effects on the breast and breast cancer risk. Micronized progesterone does not increase cell proliferation in breast tissue in postmenopausal women compared with synthetic medroxyprogesterone acetate (MPA). Experimental evidence suggests that the opposing effects of MPA and micronized progesterone on breast tissue are related to the non-specific effects of MPA, including glucocorticoid activity and differences in the regulation of gene expression. Therefore, for women with an intact uterus, micronized progesterone may be the optimal choice as part of combined HRT.