There have been few additional published data concerning the effects of hormone replacement therapy (HRT) on the endometrium since December 2003. The Million Women Study has confirmed the known protective effect of progestogen with both sequential and continuous combined regimens, although also reporting an increased risk of endometrial cancer with tibolone. This finding has not been found in any other study previously or in the recently reported OPAL 3-year study. Bleeding during HRT remains an important issue for patient acceptability as well as physician concern about the implications. The incidence of bleeding is related to the dose of estrogen and the development of new low-dose therapies containing 0.5 mg oral estradiol, 0.3 mg oral conjugated equine estrogens or 14 microg estradiol daily by transdermal patch is associated with less bleeding and thus greater patient acceptability as well as minimal endometrial stimulation. Intrauterine delivery of progestogen is the most logical route of administration and provides a high level of progestogen directly to the endometrium, with good endometrial suppression and lower circulating levels than by other routes. The protective effect of progestogen on the endometrium has to be balanced against the apparent adverse effect on breast cancer risk.