Critique of the evidence from large trials of hormone replacement therapy

Abstract

During several decades, hormone replacement therapy (HRT) was the only long-term treatment used by millions of women without any trial. A huge amount of observational studies performed on surrogate markers, animals or women has suggested that HRT reduces cardiovascular morbidity and mortality in postmenopausal women. Numerous observational studies have also suggested a slight increase of breast cancer risk. Other results from observational studies include prevention of osteoporosis, diminished colorectal cancer risk and increased venous thromboembolism risk. During the past decade, several trials have been set up, mostly to compare cancer and cardiovascular disease endpoints in HRT users and nonusers. With the early termination of part of the Women's Health Initiative (WHI) trial, the most important trial ever done on HRT, it is timely to review the evidence from such studies. Results from the main randomised trials broadly agree with findings from the majority of observational studies on the following points: reduction in incidence of osteoporotic fractures and colorectal cancer, increased incidence of venous thromboembolism and breast cancer risk and no significant change in endometrial cancer. However, the trials reported opposite results on the effect of HRT on cardiovascular risk, with a significantly increased incidence of coronary events and stroke. Furthermore, these trials tested only one drug regimen, and they do not necessarily apply to lower dosages of these drugs, to other formulations or methods of administering estrogen and progestins, or to estrogens alone.