The Best Is Yet to Be

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http://www.usnews.com/usnews/health/art ... 6healy.htm

By Bernadine Healy

3/6/06

"All changed, changed utterly: a terrible beauty is born." These words of William Butler Yeats capture the legacy of the Women's Health Initiative, which has been a transforming force for women's well-being, a humbling experience for medicine, and--at first glance--a story whose messages seem highly contradictory. Hormones don't work--or maybe they do. Calcium and vitamin D supplements prevent hip fractures--but only sometimes.

Yes, the results seem terribly confusing at first blush. But think of it as puzzlement for a good cause. In fact, the studies have refined conventional wisdom about blanket solutions--that what works for men by definition works for women, or that what's right for one woman is right for all--and point the way to a future in which medicine will be more powerfully predictive, preventive, and personalized. Irrational exuberance has cooled about lifelong hormone replacement therapy for older women, for example. HRT brings great relief to many going through menopause, but it's not for all, and it's decidedly risky for some. On the ever moving diet front, we've learned that less fat and more fruits and vegetables won't provide everyone a bulletproof shield against disease. But such dietary changes seem to protect against premalignant colon polyps and, just possibly, breast cancer. Next, we need to ask: Would it make a difference to limit saturated fat and instead eat healthy fish and olive oils?

I think I'm being objective (even though I initiated the WHI in 1991 as director of the National Institutes of Health) when I stand in awe of the work of the talented and tenacious WHI investigators, who have prepared us to do even greater work in the future. One course of action: continued follow-up of the women who took part in the hormone, low-fat-diet, and calcium and vitamin D trials to see whether, given more time, these interventions might produce different results. Another is to mine an as-yet-untapped reserve of data collected on both the 68,132 women in these trials and the 93,676 women in the "observational" study, which regularly has gathered information on everything from their family history to their aspirin use.

Indeed, the greatest potential of the study lies in these billions of data points drawn from two generations of women, ages 50 to near 80 upon entry and representing all of America's diversity--each with her own behaviors and lifestyle, virtues and vices, moods and temperament, and physical traits. The study subjects' health and habits are monitored yearly; blood is stored on all participants, and millions of samples are now frozen and awaiting further study. As participants age and experience heart attacks, strokes, cancer, osteoporosis, depression, and Alzheimer's, scientists with advanced computing power that didn't exist when the study began can observe which women have which diseases and then look for reasons, be they genetic or behavioral or both. Besides gauging the impact of known risk factors on groups of women and on individuals, researchers will be able to search for new ones.

Markers. Investigators can examine blood samples from women who've had hip fractures, for instance, and hunt for proteins that might have signaled the danger. Or they can search for blood markers common to women with Alzheimer's or ovarian cancer. Already, researchers are scanning the genetic information of thousands of WHI participants for variations of normal genes that point to specific disease susceptibility. Once they identify these variations, scientists can begin to evaluate how women with particular characteristics respond to hormone therapy, or a modified diet, or food supplements, for example. Then, many of the puzzling elements of the clinical trials will begin to make sense. And before picking up the proverbial pen to write a prescription for estrogen, tomorrow's physician will have in hand a personal risk assessment based on a rapid gene analysis. This would increase the likelihood for the therapy to work as hoped.

Yes, this is a vision for the future, but it's not so far off. In January, the National Heart, Lung, and Blood Institute proposed to open up these databases nationwide to scientists with the best ideas about how to expand knowledge of predictors and preventers of disease. The pace of discovery is bound to accelerate, and the door will swing wide on an era of highly personalized medicine, in which both sexes should benefit from more targeted--thus more effective--therapies. That is the beauty of the gift these women are sharing, with their daughters and with us all.