Sunday, October 24, 2010


Just in time for Halloween the Women’s Health Initiative (WHI) investigators are trying to scare women again (Chlebowski et al 2010 JAMA 304 1684). They did this in 2002 with the help of unknowing press and TV journalists who spread the word that hormone replacement therapy (HRT, estrogen plus progestin, Prempro) was really bad for you and you should stop taking it. These authors were wrong then and they are wrong now. The new article says that HRT not only increases the risk of breast cancer but it also causes greater mortality.

For one thing the data in this paper are what polite scientist call marginal which translates to: through it out and forget it. All of the risk data are just barely statistically significant and the absolute risks are very small which means they are of no importance to any individual woman who has taken HRT.

These very weak findings of increased risk of death are in contrast to the many studies which say just the opposite. The WHI authors explain that other studies are not as good as the WHI studies because they are not randomized placebo controlled trials, so just forget them. Well it is hard to forget 15 to 20 studies which disagree with the WHI especially since some of them are just as good as those of the WHI. The WHI people would do well to remember that their studies are far from perfect and have been criticized at length by many scientists.

For instance: Many investigators agree that the WHI study does not even qualify as a randomized placebo-controlled study which is supposed to be superior to other types of studies. The reasons for this statement are: 1. Following randomization the women were free to decide whether to continue their assigned treatment or whether to undergo diagnostic procedures. 2. Almost half of the women were aware of their treatment so there was no valid placebo group. 3. Several warnings were sent to the participants about the detection of increased risks of myocardial infarction, stroke and pulmonary embolism during the study. These problems make the WHI study no better than any observational study with all of their limitations.

In addition to all of these problems, the women in these WHI studies were 12-15 years past the onset of menopause. Thus they were without their pre-menopausal levels of estrogen and progesterone long enough to bring about changes in various bodily functions which are the precursors of disease or of undiagnosed disease. For instance, ovarian hormones are important for maintaining normal structure and function of the blood vascular system. Once vascular disease has begun hormone treatment is not likely to reverse the effects. Proper bone strength is maintained by estrogen and when estrogen is no longer secreted at menopause bones begin to lose calcium and the first stages of osteoporosis begin.

So if anyone you know is or has taken HRT tell them not to be scared. It’s only the big bad WHI monster who makes a loud noise but has no claws.

For more information see my critique of the WHI studies from 2002-2006: Clark JH (2006) Nuclear Receptor Signaling 4, e023