Women receiving short-term combined hormone replacement therapy to combat symptoms of menopause may be at a higher risk for developing breast cancer, according to a study published today.
Previous studies have indicated increased breast cancer risks with long-term use of the hormones estrogen and progestin, but the study published today in the Journal of the American Medical Association is the first to indicate that short-term use of even less than one year may present significant risks.
“We saw the same kinds of cancers developing but found them at a more advanced stage, which in many circumstances means that the prognosis will be worse,” said the study’s lead author, Dr. Rowan T. Chlebowski of the Harbor-UCLA Research and Education Institute in Torrance, Calif.
And an increase in abnormal mammograms as early as one year after therapy begins likely makes breast cancer more difficult to detect, he said.
“The mammograms were substantially less effective,” Chlebowski said. “Some women will have severe symptoms and want to take it no matter what, but there should be a substantial number of women who have mild symptoms [and] who before thought there were no short-term risks and now may want to reconsider.”
The prevalence of abnormal mammograms “makes it very difficult to determine the safety of short-term use,” he said.
Earlier research has suggested that women receiving combined hormone therapy and who developed breast cancer would have less severe forms of the disease. But the new study suggests the estrogen and progestin combination may result in more aggressive forms of breast cancer.
The report is the latest caution to come from the largest federal clinical trial of Prempro, the combination estrogen and progestin drug that doctors once prescribed as a fail-safe remedy for postmenopausal women.
Last July, researchers discovered that an examination of more than 16,000 women ages 50 to 79 linked estrogen-progestin pills with an increased risk of breast cancer, cardiovascular disease and strokes. The discovery so alarmed researchers that they stopped the study, known as the Women’s Health Initiative.
Last month, the hormone combination was linked with a doubling of the risks of dementia and Alzheimer’s disease in women over 65.
Currently, the short-term use of combination estrogen and progestin for relief of menopausal symptoms is the recommended use of Prempro, according to the Food and Drug Administration.
Dr. Carl D’Orsi, director of the Breast Imaging Clinic at Emory University’s Winship Cancer Institute, said the study could lead to a change in the FDA’s position.
“It certainly should have an effect on people who prescribe this hormone replacement therapy,” he said. “I hope it doesn’t take five years for this to filter down. That’s some pretty scary data.”
Wyeth Pharmaceuticals, which manufactures Prempro, said it is evaluating the study. “We’ll make a determination if our labeling needs to be revised and, if so, what changes are appropriate,” said company spokeswoman Natalie de Vane. “We believe that there continues to be a very appropriate place for hormone therapy. It remains a valuable treatment option for postmenopausal woman, and hormone therapy is still the most effective treatment for relief of postmenopausal symptoms.”
The number of women taking Prempro to alleviate hot flashes, mood swings and other symptoms of menopause has declined from roughly 3.4 million to 1.2 million in the last year, she said.
More research advised
Some doctors caution that more research is needed to determine whether short-term use of the drug has substantial negative effects. The older average age of participants in this study, they said, made patients more likely to have previously undergone hormone therapy, thus making it difficult to establish a clear link between short-term therapy and cancer risks.
Dr. Wulf Utian, executive director of the North American Menopause Society, said using the hormones for short-term relief from menopause symptoms does not present significant risks.
“Every bit of data we get is important, but we should be cautious about extrapolating each piece of data we get to all women,” he said. “Each woman herself has a very complicated profile.”
“There may be situations where a woman is having very severe menopausal symptoms, and I don’t think we should say that there’s absolutely no way that this drug combination should be used,” said Dr. Peter Gann, an epidemiologist at Northwestern University. He co-authored an editorial about the studies that will also appear in today’s JAMA. “But it changes the equation, and maybe it says that those symptoms have to be pretty darn bad.”
“Even short-term use increases the likelihood of having an abnormal mammogram, something that is very traumatic for most women even when the findings are benign,” said Monica Morrow, a surgeon at Northwestern who co-authored the editorial. “For women with severe symptoms, this won’t be a deterrent. But for those with mild symptoms, I think we will see greater use of nonhormonal therapies for relief.”
Cautious use of therapy
Dr. Albert Scott Jr., president of the Atlanta Ob-Gyn Society, said his office at the DeKalb Women’s Specialists clinic has used the combination hormone therapy cautiously.
“We use it chiefly for complaints [of menopause symptoms], and if we do use it, we use it in the lowest dose that it comes in,” he said.
“I rarely prescribe combination hormone replacement therapies, because after discussing the numerous options and the benefits and the risks to women, most of them choose safer, effective options,” said Dr. Jay Kulkin, a gynecologist at the Women’s Institute for Health in North Atlanta.
A second study published in today’s JAMA involved 975 Seattle-area women ages 65 to 79. It also confirmed a link between combined hormone treatments and breast cancer and suggested estrogen-only treatment may be safer.