Cancer Risk Stays After Hormone Therapy

The study of more than 15,000 women who took the hormones for more than five years found that the chance of developing cancer remained elevated well after they quit, which many did after an earlier stage of the study showed that the risks outweighed the benefits.

While their increased risk of heart attacks, blood clots and strokes appeared to vanish as soon as women stopped taking the drugs, the cancer risk persisted. It appeared to be driven primarily by a continued increased rate of breast cancer but also by a new, unexpected higher risk of other malignancies, such as lung cancer, the analysis found.

"The question has been: Do the risks persist?" said Marcia Stefanick of Stanford University, who chairs the steering committee for the federally funded Women's Health Initiative. "What this clearly shows is, unfortunately, the risk for cancer continues."

Stefanick said the data appeared to show a real trend even though the breast cancer difference was not statistically significant, but other experts warned that the findings could have been the result of chance.

All the same, the findings underscore the now-standard recommendation that women who take hormones to relieve hot flashes and other effects of menopause should use the lowest possible dose for the shortest time, Stefanick said. And the millions of women who have taken the hormones should be monitored closely for cancer, especially breast cancer, she said.

"The important message is women really need to make sure they continue getting their mammograms," she said.

It remains unclear how long the increased risk persists, Stefanick said, and researchers have continued following the women to try to answer that crucial question.

"This says, 'You're not quite safe yet, but let's hope you'll be safe soon,' " she said. It is also unclear whether women who took the hormone combination for shorter periods of time or took estrogen alone face similar ongoing risks.

For years, doctors recommended that women take hormones to alleviate the symptoms of menopause and in the belief that the drugs would protect their hearts. But in 2002, researchers stunned doctors and women when they reported that the Women's Health Initiative found that the hormones actually increased the risk of heart attacks, strokes, blood clots and breast cancer.

At the time, an estimated 8 million American women were taking the estrogen/progestin combination used in the study, and the results soon prompted millions of them to stop. Until the new report, published in today's issue of the Journal of the American Medical Association, no one knew whether the higher risks would continue nevertheless.

The study involved 15,730 postmenopausal women ages 50 to 79 who took estrogen and progesterone for an average of 5.6 years. The researchers analyzed the data for an average of 2.4 years after they stopped and found that the risk of heart disease and blood clots dropped back to a level that is about the same as it is for women who had been taking a placebo. The risk of stroke also appeared to fall, but that finding was somewhat less clear.

The benefits of hormone treatment -- a lower risk of colorectal cancer and bone fractures -- also appeared to dissipate.

But the researchers were surprised to find that the overall risk of cancer was 24 percent higher in women who took hormones, compared with those who took a placebo: 281 of those who used hormones developed some type of cancer, compared with 218 in the placebo group. That appeared to be driven by a 27 percent increased risk of breast cancer, although that difference did not meet a test of statistical significance. There were 79 breast cancers in the hormone group, compared with 60 in the placebo group.

Stefanick said that "breast cancer is really driving" the overall increased cancer risk.

"People were under the impression that once you stop the hormones, your risk for breast cancer goes down," she said. "This is saying, 'No, that's not the case.' It continues. It is bad news."

The findings seem to conflict with a recent report that the rate of new breast cancer cases dropped nationally after the 2002 news about hormones. Stefanick said it could be the result of fewer women starting hormones rather than women quitting them.

Peter M. Ravdin of the University of Texas M.D. Anderson Cancer Center, who reported the falloff in new cancer cases, said the new study's findings could have been the result of chance.

"They just didn't have the statistical power to identify a decrease that we've seen in the population data," Ravdin said. "It's not convincing. All the epidemiological data argues against their results."

Other researchers said they were disturbed that there appeared to be an increased risk for other cancers.

"It is really surprising and unexpected to see more cancers overall after you stop hormone therapy," said Rowan Chlebowski of the Harbor-UCLA Medical Center, who helped run the study. "It is an unsettling thought to think that in the period after you stop hormone therapy, women are at risk for more cancers."

The findings are likely to spur research to try to understand how hormones might increase the risk of other cancers, such as lung cancer, which has not been thought to be fueled by hormones.

"This opens up a new biological question," Chlebowski said.

Other researchers noted that the increased risks found by the new analysis were very small or questionable and worried that the findings might frighten women who really need hormones for a short time.

"I see a lot of patients who are really miserable -- whose interpersonal relationships are harmed, whose careers have suffered," said Hugh S. Taylor of Yale University School of Medicine. "It's a fairly small risk, and when women hear about this, it plays to their fears. I think they are suffering needlessly because of an exaggerated risk."