Megatrials of hormonal replacement therapy.

Despite the fact that estrogen replacement therapy has been demonstrated to be of great value to postmenopausal women, many patients are still reluctant to use it. This is primarily because of fears that sex hormone therapy increases the risk of developing uterine and breast cancer. Because retrospective epidemiological studies have failed to clarify the issue for breast cancer, ambitious prospective trials have been initiated to determine the role of hormones in the development of breast cancer and cardiovascular disease. The main studies have been the Women's Health Initiative, the Postmenopausal Estrogen/Progestin Intervention (PEPI) Trial, the Heart and Estrogen-Progestin Replacement Study (HERS), the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) and the Million Women Study. Only the PEPI Trial has been completed. It showed a substantial benefit for women using hormone replacement therapy, but was insufficiently powerful to determine whether such therapy affected the incidence of breast cancer. Despite the immense costs involved and the considerable time that must elapse before results are published, it is imperative that these major prospective studies are completed, analysed and published. Only then can physicians advise their patients in an appropriate manner.