Guest Editorial: What have we learned from the WHI?

May 1, 2007

After reading the latest report from the Women's Health Initiative (WHI), I've struggled with my emotional reaction. The data in this report is not new. The risk of CHD was present only in the oldest women in the trials. . .

The WHI investigators conducted a secondary analysis of the two canceled clinical trial arms, assessing cardiovascular results by age groups at randomization (50–59, 60–69, and 70–79) and according to years since menopause (<10, 10–19, and ≥20).1 An increased risk for coronary heart disease (CHD) was present only in the oldest women in the trials. The authors calculated absolute risks and found no increases for CHD, stroke, or total mortality in women aged 50 to 59. In fact, only the increase in CHD events in women 20+ years since menopause reached statistical significance. When women with prior cardiovascular disease or those older than 60 years were excluded, the risk of stroke in women less than 10 years since their menopause was not significantly increased. The authors concluded that there was no apparent increase in cardiovascular disease risk in treated women close to their menopause.

The data in this WHI report are not new. A careful reading of the original adjudicated reports reveals that the risk of CHD was present only in the oldest women in the trials.2, 3 What is new is that the WHI is finally reporting this finding to the public, almost 5 years since the first dramatic publication in July 2002.4

Do these results rule out the possibility that hormone therapy given to young postmenopausal women may prevent CHD? I think not. In the WHI, the number of women in this young age group was small, the duration of hormone exposure relatively short, and long-term follow-up is yet to be reported. The number of women aged 50 to 54 or less than 5 years since menopause was too small to allow analysis. There continues to be a growing story that adequate estrogen exposure prior to the clinical presence of atherosclerosis provides protection against cardiovascular disease. How many heart attacks and fractures will be documented in the coming years arising in the population of women who discontinued their hormone therapy following the WHI publicity?

I REMEMBER WELL sitting in a conference of about 50 academicians in July 2002, listening to Jacques Rossouw, from the National Heart, Lung, and Blood Institute and the first author of the very first WHI publication and the current report, tell us that "our intention is to make a big public splash." If that's a measure of success, they were victorious beyond their dreams. In the first year or 2 that followed, it was an intrepid few of us willing to voice criticisms of the WHI. The publicity generated by the WHI publications made decision making regarding postmenopausal hormone therapy more difficult than ever. The situation was made more acute by the absence of critical responses from academicians and medical organizations. Indeed, the immediate commentaries included adjectives such as "definitive," "unequivocal," and "solid." I received an e-mail from an assistant professor at a prominent academic medical center accusing me of "killing" women because of my criticisms of the WHI. On a memorable occasion, my wife and I were returning to our hotel after a Broadway show, when I was accosted in Times Square by a clinician from New Jersey, accusing me of denying the truth.