The Women’s Health Initiative Study was a large American study which looked at health outcomes such as the incidence of cardiovascular disease, breast cancer, colorectal cancer and hip fracture in over 160,000 postmenopausal women aged between 50-79. One part of the study included a trial of MHT where women were randomised to either MHT or placebo. 27,347 women were randomised to the MHT group. The trial was stopped early in 2002 following initial results suggesting an increased risk of breast cancer, blood clots, cardiovascular disease and stroke in the HRT group.

However, one of the criteria for entry in the trial was that women could not be perimenopausal or have menopausal symptoms. As a result, most women included in the trial were older than the average woman commencing MHT for symptom control who is typically in her late 40s to mid-50s. The trial assessed disease prevention rather than symptom control ( the latter being the main indication for MHT).

Women were also given an older synthetic version of MHT which is less commonly prescribed in Europe. In addition, a proportion of women in the placebo arm of the trial were taking MHT (started outside of the trial protocol) or had a previous history of MHT use.

A long term follow-up analysis published 18 years later in 2017, showed that MHT was not associated with an increase in all-cause mortality, cancer mortality, or cardiovascular disease.