A clinician's review of the WHI-related literature

When the monitoring board of the Women's Health Initiative (WHI) canceled the estrogen-progestin arm of the study in July 2002, the effect was immediate and dramatic, as several million postmenopausal women with the full agreement of their physicians ceased taking combined hormone therapy. Soon thereafter the manufacturers of conjugated equine estrogens felt compelled to publicize a drastic restriction of the indications for their product. Little notice, except in the medical literature, was given to the continuation of the other treatment arms of the WHI, nor did the rather small (however significant) increases in risk of cardiovascular disease and breast cancer resulting from combined therapy receive widespread serious analysis. In this article, special attention is given to the population sampling involved in setting up the WHI, arm by arm, with full discussion of how these samplings compare with those in other studies--HERS, ERA, WEST, etc. All studies are scrutinized in terms of treatment regimens, follow-up, confounding factors, particularly statins and aspirin, and high drop-out rates in order to discover possible reasons for the results in the WHI for primary and secondary prevention of cardiovascular disease in the combined-therapy arm and slightly disappointing results for breast cancer. Each of the two main sections of the article, Cardiovascular Disease and Breast Cancer, concludes with a detailed summation of points derived from the often contrasting results of the various studies, which can be used in counseling patients.