Results from WHI and HERS II - Implications for women and the prescriber of HRT Manuel Neves-e-Castro *, Go ¨ ran Samsioe, Martina Do ¨ren, Sven O Skouby On behalf of the European Menopause & Andropause Society (EMAS) 1. Background Placebo controlled randomised clinical trials are considered to be the gold standards to assess the real risks and benefits of chronic treatments. This was the case with the WHI, a study aimed at the primary prevention of cardiovascular diseases in healthy postmenopausal women. The WHI safety committee [1,2] decided to interrupt one arm of the study because women on the combined estrogen-progestin, at the end 5.2 years, had an increase in the relative risks for cardiovascular events and breast cancer, though with a lesser risk of osteoporotic fractures and colon cancer. However, interim reports on women on estrogens alone did not show adverse CV or breast cancer crossing the predetermined safety boundaries, and this part of the trial thus con- tinues. The order of magnitude of the relative risks is impressive. However, absolute risks are small per 10 000 woman / year, an abstract figure of extra- polation that does not reflect the actual results: at the end of 5.2 years there were 7968 women in the treated group and 7608 in the placebo group. Therefore, if the absolute risks are plotted as percentages, instead of the additional 8 strokes, 7 heart attacks and 8 breast cancers per 10 000 woman / year one would have, respectively, 0.8, 0.7 and 0.8 cases per 1,000 woman / years a figure that is easier to interpret. It would suggest that if 1000 women were treated during one year there would be less than one woman with an adverse effect. As the WHI investigators say ‘the increased risk of breast cancer for each woman in the WHI study who was taking the estrogen plus progestin therapy was actually very small: less than a tenth of 1 percent per year’ [3]. This is more realistic than the reported relative risk increase of 26% for breast cancer. It is reassuring that there was ‘no difference in total mortality of all causes’ and it is also a very important conclusion that only 2.5% of women in the estrogen plus progestin, had those health events [4]. Thus, ‘the absolute risk of the study arm to an individual woman is small’ [2]. ‘The absolute excess risk events included in the global index was 19 per 10 000 person/years’ [1]; that is to say that 1000 women would have to be treated during one year in order to cause two events. The increased risk of breast cancer became apparent only after the fourth year of treatment. These cancers were invasive. In the protocol of the study it is mentioned that women had to have a base line mammography [5]. Another puzzling aspect of this study is the high drop out rate of 42% in the estrogen plus progestin group that, over time, has exceeded the design projections. At the time of this report clinical * Corresponding author Maturitas 42 (2002) 255  /258 www.elsevier.com/locate/maturitas 0378-5122/02/$ - see front matter # 2002 Published by Elsevier Science Ireland Ltd. PII:S0378-5122(02)00214-1