THE ROLE OF RANDOMIZED CONTROLLED TRIALS IN ASSESSING THE BENEFITS AND RISKS OF LONG-TERM HORMONE REPLACEMENT THERAPY - EXAMPLE OF THE WOMENS HEALTH INITIATIVE

Observational studies suggest that hormone replacement therapy among p ostmenopausal women may have important benefits, particularly in relat ion to heart disease and bone fractures, but may also convey important risks, most notably for breast cancer. The magnitude of these potenti al benefits and risks and the prevalence of use of hormone replacement therapy in the United States make the question of benefits versus ris ks a very pressing public health issue. This public health importance, along with the fact that reliable answers are likely to depend on acc urate quantitative assessments of the impact of hormone replacement th erapy on a range of clinical outcomes? implies a critical role for ran domized controlled clinical trials of adequate size, duration, and qua lity in an overall replacement hormone research strategy. Some limitat ions of cohort and case-control studies of long-term hormone replaceme nt therapy are briefly mentioned toward establishing the need for the type of logistically complicated clinical trial included in the Women' s Health Initiative. This is followed by a description of the hormone replacement therapy component of the Women's Health Initiative Clinica l Trial, along with some comments on the methods to be used for benefi t-versus-risk monitoring and analysis of this trial. It is recommended that long-term hormone replacement therapy, in the form of estrogen a lone for hysterectomized women or estrogen plus progestin for women wi th a uterus, should be prescribed conservatively until more reliable d ata on risks and benefits are available from randomized controlled tri als or from other sources.