For the 6 million American women now on combined hormone replacement therapy, July 9 was a watershed. That was the day the National Heart, Lung and Blood Institute called an abrupt halt to what had been intended as the largest and most definitive long-term study ever conducted on HRT—using Prempro, the estrogen-progestin pill most commonly prescribed—for menopausal women.

Launched in 1993 by the National Institutes of Health, the study involved 16,000 women ages 50 to 79 and was meant to last 15 years. But by this past May it was clear that the estrogen-progestin regimen not only failed to protect against heart attacks and strokes, as many doctors believed, but also caused an increased risk of invasive breast cancer and other serious ailments. "Once the risks were certain, we couldn't justify exposing our subjects to them," says Dr. Jacques E. Rossouw, 59, a coronary expert and acting director of the Women's Health Initiative, a nationwide study that includes the hormone trial.

Almost immediately doctor's offices across the country were flooded with calls from women desperate to know whether they should toss their HRT pills. Then, just days later, a new study, showing a slight increase in ovarian cancer in women taking estrogen-only HRT, added to the confusion. To help them navigate this new terrain, Dr. Rossouw, who shares a home in Highland, Md., with his wife, Hannelore, 49, and is the father of three grown sons, spoke with PEOPLE correspondent Giovanna Breu.

What is hormone replacement therapy?

It's the administration of estrogen to postmenopausal women as a way to make up for the decline in production of their ovarian hormones. For women who have a uterus, it's combined with progesterone because estrogen alone is known to increase the risk of uterine cancer. Women who have had their uterus removed can't get that disease, of course, so they're often given straight estrogen. We're still studying the long-term effects of estrogen-only therapy.

For years women have gotten conflicting advice on whether to use HRT. Why should they accept this study as the final word?

Because until now, even though there have been about 30 hormone-therapy observational studies, their methodologies were flawed. All they did was to compare women who were taking hormones with those who were not. The problem is that women who decided to take hormones were generally more health-conscious to begin with.

Our study is the first large-scale controlled trial in healthy women in which one group of randomly selected women received hormones and the other group placebos.

Why was the study halted?

By May, when our subjects had been in the study for an average of 5.2 years, we saw a 26 percent increase in invasive breast cancer-cancer that spreads to surrounding tissue—with estrogen—progestin. There was also a significant increase in the rate of strokes, heart attacks and blood clots in legs and lungs.

What do those numbers mean for an individual woman?

Well, you have to keep them in perspective. For instance, if 10,000 women take these hormones for one year, they will have 8 more cases of breast cancer than 10,000 women who aren't on the therapy. What that translates to is that an individual woman who takes hormone therapy increases her risk of breast cancer by less than one-tenth of 1 percent per year. But if you apply these tiny risks to the 6 million women taking the drug, it means an additional 25,000 cases of breast cancer in the U.S. over a five-year period.

Birth control pills also combine estrogen and progestin. Do we have to worry about those too?

There's a lot of data on birth control pills. We're now going to combine it with our findings for further study on the possible effects of long-term hormone exposure.

So what's a woman to do about HRT?

First, consult with your doctor. The bottom line is that for most women who don't have high-risk factors—breast cancer in their immediate family, for example—the benefits of taking estrogen plus progestin for two or three years to control hot flashes, vaginal dryness and mood swings outweigh the risk. Nothing works better. But hormone therapy does not protect against heart attacks, and there are safer ways to prevent osteoporosis. So over longer periods there's little benefit—and real potential for harm.

More From This Article

Getting by Without HRT
Hormone therapy isn't for you? Experts say there are other ways to cope with life after menopause

•MENOPAUSE SYMPTOMS

Women with risk factors that rule out HRT—a family history of breast cancer or heart disease, for example—can do little about hot flashes other than avoiding alcohol and caffeine and dressing in layers, says Rossouw. Antidepressants are effective against mood swings. Estrogen creams can remedy vaginal dryness.

•OSTEOPOROSIS Diet, weight-bearing exercise and calcium supplements may be helpful. When those fail, bone-strengthening drugs such as raloxifene have been proven effective.

•HEART DISEASE HRT doesn't help and can do harm, says the study. Better preventives are exercise, proper diet and cholesterol-lowering drugs.

•HAIR AND SKIN Though HRT helps maintain supple skin and prevent thinning hair, experts say it's too risky a drug to use for cosmetic purposes alone.

•HRT ALTERNATIVES The safety of lower-dose forms of HRT is being studied. As for substitutes like soy foods and the herb black cohosh, says Rossouw, research hasn't proved that they work. And though the jury is still out on plant-derived "natural" estrogen, some are concerned that it may cause endometrial cancer.

For more on this subject, go to www.people.com or AOL (Keyword: People)