Fundamental flaws of the WHI

In your May issue, the article on hormone replacement therapy (“Hormone replacement therapy: The right choice for your patient?,” J Fam Pract 2005; 54:428) purports to present a knowledgeable discussion of this problem. In fact, Dr Pees does hint at some of the problems with the Women’s Health Initiative (WHI), particularly concerning some of the statistical problems and what the study really says. However, this discussion is at a very sophisticated technical level that I believe most of your readers will not appreciate.

Unfortunately, none of your discussions address even more fundamental flaws with the WHI. Dr Pees hints at one of the problems in noting that only 10% of the subjects were in the 50-to-54-year-old age group. In fact, the average age of the subjects was 63.3 years. This is more than 13 years postmenopause for the average woman, which is (or at least used to be) 50 years old. We know that something significant happens physiologically with women postmenopause, and it has been postulated that this change takes place within the first 2 years after menopause. Therefore, we know as a certainty that postmenopausal women are physiologically significantly different from premenopausal women and any study done on these women can only be applied to postmenopausal women. We also know that the incidence of cardiovascular disease and other disease entities accelerates rapidly after menopause. Therefore, postmenopausal women have a high likelihood of having subclinical disease. Based on the aforementioned issues, the WHI cannot be classified as a preventive study and, in fact, because the population used is so significantly different from the premenopausal population, that results from this study cannot be applied to any women who are placed on hormonal therapy at the time of menopause.

It should also be noted that the WHI used a steady-state estrogen and progesterone drug therapy that was not in vogue until approximately 15 years ago. This is significantly different from the cycled hormone replacement therapy prescribed prior to that time and one which many of the previous epidemiological studies are based.

Based on the 2 above methodological fatal flaws in this study, please reveal WHI for what it truly is. Also please refrain from making any statements concerning heart disease based on this study. Only when we have an appropriate study of perimenopausal women (women within the first 2 years of menopause) with a significant arm on cycled hormone therapy can we make any statement concerning the effect on cardiovascular disease any other potentially related disease or symptoms. The “expert panel consensus” released on September 2003 is inappropriate, not based on any evidence, and illustrates the lack of understanding of research design and methodology by the “experts.” Our academic rigor needs to improve significantly in the field of medicine.

David L. Weldy, MD, PhD
Mantua Family Heathcare, Mantua, Ohio