Endometrial hyperplasia. Risks, recognition and the search for a safe hormone replacement regimen

Endometrial hyperplasia is an acknowledged risk of unopposed estrogen replacement therapy (ERT). Several categories of hyperplasia are now recognized, among which atypical complex hyperplasia is the most likely to progress to carcinoma. Adding a synthetic progestin or natural progesterone to estrogen therapy has been shown to decrease or eliminate the endometrial risk associated with ERT. However, the addition of synthetic progestins has been associated with uncomfortable side effects, reversal of some of the cardiovascular and metabolic benefits of estrogen, and unwanted bleeding. The use of natural micronized progesterone in lieu of synthetic progestins alleviates the former two drawbacks, while careful scheduling of estrogen and progesterone dosing can eliminate the latter. In Europe, where natural progesterone has been in use for some time, a cyclic combined regimen comprising estrogen and 100 mg micronized progesterone administered on days 1-25 has been shown to provide endometrial safety, absence of bleeding and a high rate of tolerability.