Aspects of Hormone Replacement Therapy

The most important benefit of ERT may well be its cardioprotective effect. But unopposed estrogen therapy also carries the risk of inducing endometrial cancer. A compelling body of evidence indicates that adjunctive progestogen protects effectively against estrogen-induced endometrial adenocarcinoma, and that progestogen therapy is effective in the treatment of hyperplasia in most women who have taken unopposed estrogen. Yet there is concern that adjunctive progestogen may attenuate the cardioprotective effects of estrogen. It is therefore agreed that adjunctive progestogen therapy is not indicated for hysterectomized women, and should be given at the lowest effective dose to non-hysterectomized women. Phase II dose-ranging clinical trials using secretory transformation as an efficacy endpoint to estimate protective effects of different doses of progestogen against endometrial hyperplasia/adenocarcinoma are complicated by the possibility that the doses protecting against hyperplasia may differ from those producing secretory changes. Further work is needed to identify one or several progestogen-regulated markers that most closely correlate with protection against estrogen-induced endometrial cancer.