Pros And Cons

By J. MADELEINE NASH

Poor women!" sighs University of Michigan cardiologist Dr. Lori Mosca. "Every time a new study comes out, they have to revisit the decision they've made." That decision, of course, is the one that currently confronts millions of baby-boomer women just entering their menopause years: whether or not to supplement their bodies' flagging supplies of estrogen in hopes of preventing late-in-life maladies like osteoporosis and heart disease.

Making this decision has never been easy, and last week, alas, it got harder still. According to a study published by the Journal of the American Medical Association, the estimated 8.6 million American women now taking estrogen plus progestin--the most commonly prescribed form of hormone-replacement therapy--may be running a significantly higher risk of developing breast cancer than previously suspected.

How much higher? The combination of estrogen plus progestin, the study's authors calculated, may increase one's breast-cancer risk by 8% a year, vs. 1% for women taking estrogen alone. "What was surprising was the magnitude of the increase," says epidemiologist Dr. Walter Willett of the Harvard School of Public Health. "It's rare to see such a strong effect."

The picture may not be quite so grim as it seems, however. For one thing, although the study was large--drawing from a pool of 46,355 postmenopausal women--the number of women on combined estrogen and progestin therapy was comparatively modest. For another, the rise in risk only became striking after four or more years of continuous hormone use, which further reduced the pool of subjects. In the end, out of a total of 2,082 cases of breast cancer, 101 occurred among women who were currently taking estrogen-progestin--and of these, a striking 39 occurred among the roughly 3,200 women who had continued to take both hormones for four or more years.

The rise in risk was most pronounced among lean women, who accounted for two-thirds of the 39 cases. But there was good news too: after women stopped taking the hormones, their breast-cancer risk promptly fell.

For all these reasons, says National Cancer Institute epidemiologist Catherine Schairer, the study's lead author, women should not panic, especially if they are taking estrogen-progestin for just two or three years to obtain relief from the discomfort of hot flashes and mood swings that mark the onset of menopause. Indeed, this study bears out what most experts have long believed: that short-term use of hormones can confer substantial benefits while posing relatively few risks.

Long-term hormone-replacement therapy is a different matter. Unfortunately, what is known at present about the benefits and risks of hormone replacement has largely been drawn from studies of the effects of estrogen taken alone, a therapeutic option that is now reserved for women who have undergone hysterectomies. That's because experience has shown that "unopposed estrogen," as doctors call it, elevates the risk of uterine cancer. By adding progestin to the mix, physicians have found, they can protect the uterus from malignant growth. The question Schairer and her colleagues have raised is whether this victory over one form of cancer came at the price of increased risk for another.

"We've assumed that estrogen and estrogen-progestin were the same," says UCLA breast surgeon Dr. Susan Love, a prominent critic of hormone-replacement therapy. "Suddenly we are starting to get evidence that they're not." Like many others, Love is eagerly awaiting the findings of a large clinical trial launched by the Women's Health Initiative in 1993. That trial, which involves nearly 30,000 women between the ages of 50 and 79, is specifically designed to assess the pros and cons of estrogen-progestin therapy. The first results won't be ready for five more years.

Until then, women and their physicians will have to make do with the limited information they have. "When you take hormones," says Dr. Dorothy Gohdes, an internist in Albuquerque, N.M., "you have to remember that you don't get them for nothing. There are trade-offs." A woman whose family history places her at high risk for breast cancer might decide to avoid hormone therapy even for the short term, for example, while a woman at high risk for osteoporosis or heart disease would probably be more willing to take her chances.

One encouraging development is the increasing number of options for preventing bone loss and heart disease. The American Heart Association, for example, recommends the use of cholesterol-lowering drugs as the front-line treatment of choice for women whose blood lipids remain high despite diet and exercise. Similarly, there are new drugs designed to combat bone loss, including estrogen look-alikes that appear to act as antigrowth factors in the breast. As new and better drugs become available, the case for long-term hormone replacement will weaken.

For the time being, women should not rule out long-term hormone therapy, but they should weigh the pros and cons with great care. "This is just one study," says Schairer. "I'm not going to hang my hat on it. But it does provide an impetus for women to discuss alternatives with their doctors."

--With reporting by Dr. Ian K. Smith/New York

With reporting by Dr. Ian K. Smith/New York