So what to do now, ladies?
A decade ago, a false sense of simplicity made hormone replacement therapy a public-health elixir for postmenopausal women to fight off heart and bone diseases. Fifteen million American women had signed on for HRT; the received wisdom was that virtually all women over 50 could live out their lives with--and benefit from--estrogen pills. And not only 50-somethings: Women 70 and older, some who hadn't seen an estrogen molecule in their bodies in years, got on the estrogen bandwagon.
In the past two years, however, the government's Women's Health Initiative has delivered payloads of seemingly complex and conflicting information that has turned this HRT thinking on its head. And, in turn, this so-called mother of all clinical trials (full disclosure: I began the WHI while director of the National Institutes of Health in 1991) has cut nearly in half the number of women using HRT.
The first reports startled the medical world. They showed that five years' use of estrogen combined with progestin--the other major female sex hormone--would bring on more public-health harm than good, including increased heart attacks, strokes, breast cancer, and, in women over 65, dementia. Overnight, HRT went from being saint to sinner. Last week, another component of this massive study further muddied the waters for women: It showed that women who use estrogen alone--typically, after a hysterectomy--had no net benefit but also no net harm. Stroke risk increased in the older women, but encouragingly that was balanced by no increase in heart attack or breast cancer and strong protection against broken hips. Not all hormone treatment is the same, and individual characteristics of the women taking these drugs seem to matter.
This steady stream of unexpected findings has incited a flood of frightening and confusing reports. This whiplash is uncomfortable, but it is a healthy happening: Complex reality should trump false simplicity in the end. Lest we forget, it was solid medical research that explained why replenishing estrogen should protect against killer heart disease--and disabling osteoporosis, stroke, and Alzheimer's, the major reasons for a woman's lonely trek into a nursing home. What's more, studies of health-conscious women who diligently took HRT for years because it made them feel better showed a reduction in these diseases.
Diversity. The WHI took on the daunting task of studying the snapshot of "everywoman"--over 160,000 participants mirroring the postmenopausal population in terms of age, ethnicity, race, and socioeconomic and educational level. Women older and younger, richer and poorer, fatter and thinner, on different diets, with different risk factors; black, white, Hispanic, and Asian women, recent immigrants, those on Indian reservations, and older ladies with hair of every color signed up in droves. The result of their enthusiasm is history.
And arising out of the seeming rubble is a new medical playbook for postmenopausal women. First, hormone therapy is not a public-health potion, as once thought. To be so, benefits would have to vastly exceed risks for the majority of the population, and that's just not the case. Second, hormones should not be initiated in older women, a regular practice of the past. They are more stroke prone and more likely to have underlying blood vessel disease, which can be exacerbated by hormone treatment. Third, women who have had hysterectomies should feel reassured. For them, years of estrogen alone bring little harm, particularly with regard to breast cancer. And as for stroke, it appears that patches, which don't cause blood clotting the way oral doses do, are a logical consideration for lowering risk. Finally--and this is the take-home message--for an individual woman really troubled by menopausal symptoms or fearful about osteoporosis, the risk of HRT is tiny (less than 1 serious problem per 1,000), especially with the lower doses now available.
This is a new prescription for women's health. Women's basic biological and behavioral differences will become even clearer as we gain greater insights into the complex interactions of genetics, hormones, and factors like obesity and diet. Though hormones clearly don't belong in postmenopausal toothpaste, they are sure to be in many women's medicine cabinets--but more safely now and with better-defined purpose.
This story appears in the March 15, 2004 print edition of U.S. News & World Report.