I have always been skpetical of subgroup analyses in clinical trials, especially when they clash with the overall findings. The HRT "timing hypothesis" is a popular excuse for estrogen's failure to reduce cardiovascular disease. The validity of this theory, however, is very suspect because you have one age group (70+) where CHD, colon cancer, and total mortality are ELEVATED, but then you have another (the 50-59 group) where these risks are reduced. I ask - what drug out there prevent the very diseases it exacerbates? Frankly, the most reliable and responsible interpretation of this study is - cessation of estrogen alone therapy attenuates both the risks and benefits seen while taking the drug, except for the clear and continued 23% reduction in breast cancer.
What I find troubling though is that there is too much evidence already showing that estrogen does not prevent heart disease in anyone, especially since oral contraceptives, pregnancy, and even high dose Premarin in men with prostate cancer all markedly raise the risk of vascular events - CHD, stroke, and venous thromboembolism. And the WHI estrogen-alone trial also did an analysis for medication COMPLIANCE, and those results were very different - during the trial, according to the 2004 initial results, women who took >80% of their study pills for the entire 7.1 years had an even higher risk of stroke, embolism, and total mortality, with no reduction in heart disease (but a greater reduction in breast cancer). The follow-up results, presented in April, also showed different results based on compliance - an even larger reduction in breast cancer (32%) but also a continued elevation in stroke risk (50%). Additionally, and most importantly, NO AGE DIFFERENCES were seen for any outcome.
I wish I knew why this need to make estrogen therapy be something it is not persists. It's harmful to women and it's an affront to good science.