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Stanford Report, July 10, 2002

Hormone-replacement therapy study abruptly halted


In the largest study to date on hormone replacement, researchers have found clear evidence that healthy, post-menopausal women who take estrogen combined with progestin have a greater risk of breast cancer, heart attack, stroke and blood clots within five years of starting the hormones.

Study results were so compelling that the National Institutes of Health, sponsor of the nationwide trial, abruptly halted the estrogen/progestin trial this week -- more than three years before the scheduled end. The results surprised researchers, who had expected to find that the hormones would help protect the women from heart disease, said Marcia Stefanick, PhD, associate professor of medicine at Stanford and chair of the national steering committee for the study.

"This is definitive evidence that estrogen plus progestin does not prevent heart disease and, in fact, increases your risk for heart attacks, stroke and blood clots in the lungs and legs for those women who don't have heart disease," she said. There was no difference in death rates among women taking the hormones vs. placebo.

Stefanick said the jury is still out on whether estrogen alone is beneficial for women who have undergone a hysterectomy. That part of the study continues, as the risks and benefits of taking this hormone alone remain unclear.

The hormone studies, part of the Women's Health Initiative (WHI), involved more than 27,000 women at 40 sites around the country. Some 4,500 women are participating in a range of WHI studies at Stanford, including more than 700 in the hormone trials.

In the estrogen/progestin study, 16,608 healthy women between ages 50 and 79 were randomly assigned to take a daily dose of either the hormones or placebo. The women, from diverse ethnic backgrounds, were enrolled in the study between 1993 and 1998.

The risks started to become apparent two years into the study, when data showed higher rates of heart attack and blood clots in women taking the hormones. Study participants were alerted to these results.

It wasn't until the fourth year of the study that the breast cancer risks began to emerge. This increased risk became clear by 5.2 years. At that point, researchers determined the risks clearly outweighed the benefits and decided to end the trial.

Researchers stopped a hormone-replacement study when data clearly pointed to higher rates of heart attack, stroke, breast cancer and blood clots in women on therapy compared with those who took the placebo. Source: WHI


The study showed that for every 10,000 women on hormones:

  • Seven more women would suffer heart attacks. That means 37 women taking estrogen plus progestin would have heart attacks, compared with 30 women on placebo;
  • Eight more women would have strokes;
  • Eight more women would develop breast cancer; and
  • 18 more women would have blood clots in the legs or lungs.

In relative terms, women taking hormones were found to have a 29 percent increase in heart attacks and a 26 percent increase in breast cancer.

Stefanick said the researchers were not entirely surprised by the results showing an increase in breast cancer but were surprised that many women developed the disease so early, as they had projected that higher breast cancer rates would not show up for 10 to 15 years.

She added that the researchers did find the hormones had some benefit. For instance, the study is the first to confirm that estrogen plus progestin can reduce the incidence of hip fractures, with the fracture rate among women taking hormones reduced by one-third. The study also found that hormone therapy lowered colorectal cancer risk by 37 percent.

Given the overall results, Stefanick said women need to carefully consider whether they should begin taking the hormones -- and for how long. For instance, for women just starting to show signs of menopause, "estrogen plus progestin is by far the most effective way of preventing hot flashes, nights sweats" and other uncomfortable symptoms, she said. However, she said it remains unclear how long it is safe to stay on the pills.

"We need to acknowledge that some of these risks appeared within a year and persisted throughout the study," she said.

Currently, some 7 million women nationwide are on estrogen/progestin therapy. The researchers encourage these women to consult their physicians on whether they should continue therapy, as each woman's individual risks may differ.

As for the women in the trial, researchers say they have no way of knowing whether their risks might disappear over time, once they have discontinued the pills. The participants are being asked to continue their clinic visits so they can be monitored, receive care and help answer the remaining questions about hormone use.

Participants were notified of the latest results in a letter sent July 5 from Claude Lenfant, director of the National Heart, Lung and Blood Institute of the NIH.

The WHI trial is not related to the Heart Estrogen Replacement Study (HERS), in which researchers are following women who have already suffered a heart attack to see if hormones might prevent future heart problems.

In the latest results from HERS, reported in the July 3 issue of the Journal of the American Medical Association (JAMA), researchers found that hormone therapy did not reduce cardiovascular risks for these women.

Results of the WHI study are scheduled for publication in the July 17 issue of JAMA but due to the importance of the results, the study was posted July 9 as an expedited article on the JAMA Web site.

For more information on the trial, please visit the Women's Health Initiative at

Despite new finding, hormone replacement therapy still considered promising (5/17/00)

Hormone therapy appears to boost quality of life (2/6/02)

Women's Health Initiative