As CBS News Correspondent Maureen Maher reports, the news was startling enough to warrant press conferences around the country.
Six million American women use this hormone combination, either for short-term relief of hot flashes and other menopausal symptoms or because of doctors' long-standing assumptions that long-term use would prevent heart disease and brittle bones and generally keep women healthier longer.
In fact, there are serious risks to using the hormones for years, risks that far outweigh the few benefits, the National Institutes of Health announced Tuesday.
The hormones harm, not protect, the heart — they actually increase previously healthy women's risk of a heart attack by 29 percent and a stroke by a stunning 41 percent. They also increase women's chances of breast cancer by 26 percent.
On the good side, the hormones cut by a third the risk of colon cancer and hip fractures — but there are other, safer ways to fend off those illnesses, doctors noted.
So the NIH stopped the 16,600-woman study three years early, and is advising other women who use the estrogen-progestin combination to ask their doctors if they, too, should quit.
Letters have been mailed out to the women in the study telling them to stop taking the drugs right away.
Barbara Gubelman, who's been in the trial since it started in 1993, accepted the risks all along.
"We all knew it was an experiment and with experiments sometimes they work and sometimes they don't," she told CBS.
"We want to get the word out to women and their doctors that long-term use of this therapy could be harmful," said Dr. Jacques Rossouw, acting director of the NIH's Women's Health Initiative, which sponsored the study.
The study, published in the Journal of the American Medical Association, is the second blow this month to HRT. Doctors reported last week that the combination of estrogen and progestin does not protect women from heart disease after menopause.
"Women with a uterus who are currently taking estrogen plus progestin should have a serious talk with their doctor to see if they should continue it," Dr. Jacques Rossouw of the National Heart, Lung, and Blood Institute, who led the study, said in a statement.
"The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit," added the institute's director, Dr. Claude Lenfant.
Doctors are disappointed by the treatment's resounding failure.
"We thought it would really prevent heart disease, which is in fact the number one killer even in women," said Dr. Norman Lasser of the New Jersey Medical School. "Now we know it's not only not going to prevent it, it may make it worse."
An estimated 38 percent of women past menopause take HRT for a range of reasons, including immediate relief of symptoms including hot flashes and sexual problems, as well as to prevent osteoporosis and heart disease.
Women may still want to use the hormones for a short period to treat menopause symptoms such as hot flashes, he said. But for how long?
"There is no really safe period," he acknowledged, noting that the heart attack risk hit during women's first year taking the hormones. "As short a period as you can get away with in order to manage the menopausal transition."
Other researchers were even more negative.
"We recommend that clinicians stop prescribing this combination for long-term use," wrote Dr. Suzanne Fletcher of Harvard Medical School in an editorial accompanying the study results posted on the Web site of the Journal of the American Medical Association. "Risks from the drug add up over time."
The study's leaders stressed that women shouldn't panic because personal risk is pretty small.
In one year, for every 10,000 women who take the estrogen-progestin combination there will be eight more breast cancers, eight more strokes and seven more heart attacks — and six fewer colon cancers and five fewer hip fractures — compared with 10,000 women who didn't take the pills.
However, because millions take the hormones, those numbers can add up to thousands of illnesses, Rossouw noted.
The estrogen-progestin combination was formulated because taking estrogen alone was shown to increase the risk of ovarian cancer. For women who have had hysterectomies and who need HRT, estrogen alone may be safer, said Fletcher and Dr. Graham Colditz, both of Harvard Medical School, in a written commentary.
"The (study) provides an important answer for generations of healthy postmenopausal women to come: do not use estrogen/progestin to prevent chronic disease," the two doctors wrote.
To use estrogen or not has long been a vexing question for women entering menopause. While the study seems definitive, it doesn't settle all the questions:
What about women who use estrogen alone? The NIH is letting a second, smaller study of those women continue for now, saying so far the balance of risks and benefits remains uncertain. Only women who have had hysterectomies can use estrogen alone, because it causes uterine cancer unless balanced by progestin.
How do the risks stack up for short-term use? In the latest study, the cardiovascular risk actually jumped within the first year of use while the cancer risk didn't appear until around year four.
"The message still goes back to treat your individual needs," said study co-author Jennifer Hays of the Baylor College of Medicine. "If you can't sleep for three weeks (because of night sweats) and short-term therapy at a low dose helps you with that, quality of life is an important thing."
This study used Prempro, the most popular estrogen-progestin combination. But what about lower-dose pills or even skin patches?
Without testing each, "you can get wrong answers," cautioned study co-author Dr. Norman Lasser of the University of Medicine and Dentistry of New Jersey, who wants drug companies to do such testing. "It's going to be a while 'til we know what's safe."
Wyeth Pharmaceuticals, which makes Prempro and other estrogen supplements, said the main reason women start hormone therapy is to relieve hot flashes, night sweats or vaginal problems.
"It is important to recognize the critical role" the hormones play for those women, said Wyeth vice president Dr. Victoria Kusiak.