HRT's Benefits for Colon Cancer in Doubt

Hormone supplements may cause women to miss early diagnosis

WEDNESDAY, March 3, 2004 (HealthDayNews) -- The safety of long-term hormone replacement therapy has taken another blow, with new data suggesting the treatment's risks may outweigh its benefits when it comes to colorectal cancer.

While long-term use of estrogen and progestin in combination does appear to lower a woman's overall risk for colon tumors, researchers say hormone replacement therapy (HRT) users who do contract colon cancer are less likely to catch it early, when it's most treatable.

Based on these findings, "I would caution women not to take hormone therapy for the purpose of preventing colon cancer," concludes oncologist Dr. JoAnn Manson of Brigham and Women's Hospital in Boston. "In fact, if anything, there's a suggestion that it could lead to a delay in [cancer] diagnosis. I think it's important for the public to be aware of this potential risk."

The study appears in the March 4 issue of the New England Journal of Medicine.

For decades, millions of U.S. women have sought short-term relief from hot flashes and other symptoms of menopause by taking supplemental estrogen, or estrogen in combination with another hormone, progestin. Early studies also suggested that long-term use -- more than four years -- might help reduce a woman's risk for osteoporosis and heart disease after menopause. Buoyed by those findings, U.S. prescriptions for HRT rose to 91 million by the year 2000.

Things changed in the summer of 2002, however, when researchers pulled the plug on the estrogen-progestin arm of the massive Women's Health Initiative (WHI) study. That study, initially planned to last 12 years and involving more than 161,000 women, was discontinued after only five years when investigators announced that women using the two-hormone treatment were at increased risk for breast cancer, heart attack and stroke.

The news caused many women to quit long-term HRT. Annual U.S. prescriptions have since fallen considerably, to 57 million by 2003.

Just this Tuesday, the estrogen-only arm of the study was discontinued after investigators at the National Institutes of Health found women using the therapy were at increased risk of stroke, with no clear benefit in terms of prevention of heart disease.

Still, many experts believed HRT might be of benefit in preventing lethal colorectal cancers, the second leading cancer killer in the United States.

Investigating the issue, researchers at Harbor-UCLA Research and Education Institute in California took a hard look at data on more than 16,000 postmenopausal women enrolled in the WHI trial. They compared rates of colorectal cancer in women taking either the estrogen-progestin combination or a placebo over a five-year period.

As expected, "there were 44 percent fewer colorectal cancers seen in the estrogen plus progestin group," says lead researcher Dr. Rowan Chlebowski. But, he adds, "surprisingly, as well, the cancers that were found [in the HRT group] were diagnosed at a much more advanced stage. That is, more of the cancers in the estrogen-progestin group had spread to either lymph nodes or to distant sites in the body, so it represented more of a life-threatening disease."

Why such late diagnoses in the HRT group? According to Chlebowski, nearly all of the women diagnosed with late-stage cancers had also experienced vaginal bleeding during the time they were taking hormone replacement therapy.

He theorizes that women on HRT and their doctors may mistake vaginal bleeding as just another side effect of HRT -- rather than a potential early sign of colon cancer.

Manson, a researcher on the original WHI study, agrees. "Women on active hormone therapy are less likely to have their colon cancer detected because they are dismissing a symptom of bleeding that could lead to earlier detection," she explains. "So the result is a larger and more advanced tumor."

But even if HRT could lower women's colon cancer risk without impairing diagnosis, Manson says she still wouldn't recommend it as long-term therapy.

"We know that combined therapy increases the risk for breast cancer," she says. "So even if there were a true reduction in risks for colon cancer, we're simply substituting breast cancer for colon cancer. That would make no sense."

National Cancer Institute recommendations now stipulate that hormone therapy not be taken for the prevention of colon cancer, she notes.

Manson stresses there appears to be no cancer risk -- for either colon or breast cancer -- from short-term (three years and under) use of HRT to control symptoms of menopause. "None of these findings reflects on the role of hormone therapy in that context," she says.

Regular screening remains key to the early detection of colon cancer, experts say. Screening methods include the fecal occult blood test, which looks for the presence of blood in stool; sigmoidoscopy, where a flexible video-equipped tube is inserted into the rectum to examine the lower part of the colon; and colonoscopy, which uses a similar but longer device to examine the entire length of the colon.

The American Cancer Society currently recommends that men and women aged 50 and over have their stool tested once every year, undergo sigmoidoscopy once every five years, and have a colonscopy once every 10 years.

More information

The U.S. Food and Drug Administration has more on menopause and hormones. The National Institutes of Health has more on the Women's Health Initiative. To learn more about colorectal cancer, visit the National Library of Medicine.

SOURCES: JoAnn Manson, M.D., chief, preventive medicine, Brigham and Women's Hospital, Boston; Rowan Chlebowski, M.D., Ph.D., medical oncologist, Harbor-UCLA Research and Education Institute, Torrance, Calif.; March 4, 2004, New England Journal of Medicine
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