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More Risk Shown in Use of Estrogen

Health: New study finds long-term application of replacement therapy increases a woman's chances of getting ovarian cancer.


The drumbeat of bad news about estrogen replacement therapy continues today with the release of a new study showing that long-term use of estrogen increases the risk of ovarian cancer.

Earlier, smaller studies of such a link had shown mixed results and an American Cancer Society study last year showed that long-term estrogen use increased the risk of dying from ovarian cancer. The new National Cancer Institute study shows that the increased risk of contracting the disease is real and substantial--an 80% increase in risk for women who have used estrogen for at least 10 years and a 220% higher risk for those who have used it at least 20 years.

Both studies were epidemiological applications, however, not the randomized clinical trials that are considered the gold standard for determining risks and benefits of drugs.

The latest study did not show an increased risk among women using a combination of estrogen and progestin, but study author James V. Lacey Jr. cautioned that there were too few women in the research using the combination for conclusive results. "There simply aren't enough data to say whether taking the combined therapy has any effect on ovarian cancer," he said.

"Our results don't change the message that we have been hearing for the past week," Lacey said. "If anything, they reiterate it. Women should talk to their health-care providers before making any decisions about hormone replacement therapy."

The balance in decision-making is turning away from long-term estrogen use, said Dr. Kenneth L. Noller of Tufts University and the New England Medical Center, who wrote an editorial about the new report in today's Journal of the American Medical Assn.

"Estrogen replacement therapy certainly is not the panacea it once appeared," he wrote.

Dr. Wulf H. Utian, executive director of the North American Menopause Society, however, said that "women should not be particularly concerned" about the new findings. "Of the women starting hormone replacement therapy, 75% have stopped within 24 months, so the number taking it beyond 10 years is really quite a small number," he said.

The new study comes a week after doctors reported early results from the Women's Health Initiative, a major research effort in which 16,608 post-menopausal women were randomly assigned to take either a combination of estrogen and progestin, or a placebo. That study was terminated early when it became clear that women taking the hormones had an increased risk for breast cancer, blood clots, strokes and heart attacks.

Dr. Howard Judd of Olive View-UCLA Medical Center noted that observational studies similar to today's report had concluded that hormone replacement therapy reduced the risk of heart attack and strokes. It took a controlled clinical trial like the Women's Health Initiative to show that the therapy did not provide protection.

Judd noted that the Women's Health Initiative is also examining the risks of ovarian cancer and would probably issue a report in a few months. "If I were going to put this in perspective, I would say that the risks [reported in today's study] are modest and we anxiously await the results of randomized drug trials to address this issue. That is why the Women's Health Initiative is so important."

Hormone replacement therapy is used by about 13.5 million women in the United States. Just under 8 million use estrogen alone and the rest use a combination of estrogen and progestin. Estrogen alone is typically given only to women who have undergone hysterectomies because the drug increases the risk of uterine cancer about eightfold. Studies have shown that, for women with intact uteruses, adding progestin reduces the risk of uterine tumors.

Hormone replacement therapy is used primarily to reduce the symptoms of menopause--such as hot flashes and vaginal dryness--and to reduce the risk of osteoporosis. In recent years, however, physicians have expanded its use because of the belief that it protects against heart disease and a variety of other problems of aging. In the new study, Lacey and his colleagues followed 44,241 post-menopausal women for an average of about 20 years. They identified 329 women who developed ovarian cancer during that period.

They concluded that, overall, women who had used estrogen had a 60% increased risk. Those who used it for 10 to 19 years had an 80% increased risk, while those who used it for 20 or more years had a 220% increased risk.

Those results were similar to conclusions reached in last year's study by Dr. Carmen Rodriguez and her colleagues at the American Cancer Society. The Rodriguez study found that using estrogen for 10 years or longer doubled the risk of dying from ovarian cancer.

Experts cautioned that the absolute risk was still low. Ovarian cancer is relatively rare, striking an estimated 23,000 U.S. women each year and killing 14,000.

"If our results are true, they would translated to one to two additional cases of ovarian cancer in a group of 10,000 women taking estrogen for a year," Lacey said.

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