Estrogen Therapy Linked to Ovarian Cancer

But the risk is still very slight, doctors say

TUESDAY, July 16, 2002 (HealthDayNews) -- A new study has found that menopausal women who take the hormone estrogen face a slightly increased risk of ovarian cancer.

Ovarian cancer is a rare disease, occurring in about one in 10,000 women, or about 16,000 a year in the United States. The researchers say estrogen therapy might raise that figure to two or three women per 10,000.

The extra risk seems to accompany only estrogen therapy, and not the combination of estrogen and progestin. However, the scientists speculate they might have detected such an effect if they had looked at more women taking these two drugs. Progestin is used to block the cancer-causing effects of estrogen on the uterus, and the combination is typically taken by women who have not had their uterus removed in a hysterectomy.

The latest findings add to the turbulence left by the halting in May of a major hormone replacement trial -- part of the massive Women's Health Initiative -- after scientists found the combination of estrogen and progestin caused a small but detectable rise in the risk of invasive breast cancer, as well as stroke, heart attacks and blood clots.

Another arm of the Women's Health Initiative, looking at estrogen therapy alone, is ongoing.

Some experts say the new results, published in tomorrow's Journal of the American Medical Association, are less alarming than meets the eye.

"This will not change how I take care of menopausal patients," says Dr. Steven Goldstein, an obstetrician at New York University School of Medicine.

Unlike the Women's Health Initiative, which was designed to explore the effects of hormones, the most recent work was an observation of a large pool of women. These so-called "observational studies" are like epidemiological fishing expeditions, and can't prove cause-and-effect. Scientists therefore consider them less definitive than randomized, controlled trials -- such as the Women's Health Initiative -- in which researchers account for many potentially confounding variables and characteristics of the volunteers.

The observational finding "doesn't even remotely carry the same kind of significance or importance" as the announcement earlier this month that half the Women's Health Initiative was ended three years early, Goldstein says.

What's more, several previous studies have found either no effect of estrogen on the ovaries or a modestly higher risk of cancer. If the hormone truly spurred ovarian cancer, Goldstein says, results should show that effect consistently.

Led by James Lacey Jr., an epidemiologist at the National Cancer Institute, the new study compared rates of ovarian cancer in 44,000 women who'd participated in a major breast cancer research effort called the Breast Cancer Detection Demonstration Project.

Women who'd ever taken estrogen during menopause and beyond had a 60 percent higher risk of developing ovarian cancer compared with those who never used the hormone, the researchers found. That risk grew by 7 percent a year, nearly doubled between years 10 and 19, and more than tripled after two decades or longer of the therapy.

While those numbers may sound startling, it's too early in the research to gauge their significance, doctors say.

The results "aren't the kind of information you should use to change your clinical practice, but this is the kind of information that researchers should use to direct how they go in the future," says Dr. Susan Hendrix, an obstetrician at Wayne State University in Detroit.

Hendrix, a principal investigator with the Women's Health Initiative, says that study is also addressing whether estrogen promotes ovarian cancer. "I don't think this is ready for prime time -- it's nothing women or the public should panic about," she says.

In the study led by Lacey, women who switched from estrogen alone to the combination of estrogen and a progestin reduced the increased risk of ovarian cancer somewhat, while those who took the two hormones together from the start had no elevated risk.

Lacey says the findings were "consistent" with the results of two other studies reported in the past 18 months. One showed that women who took estrogen for at least 10 years after menopause were more likely to die from ovarian cancer than those who didn't use the treatment. However, he says, more large studies are needed to explore estrogen's effects on the ovaries, as well as that of estrogen plus progestin.

The pharmaceutical industry estimates that 8 million American women take estrogen, and another 6 million use estrogen plus a progestin, often to counter unpleasant symptoms of menopause, such as hot flashes and vaginal dryness. Those numbers are likely to change as women digest the results of the Women's Health Initiative and other studies questioning the overall benefit of the therapies.

What To Do

For more on the Women's Health Initiative, visit the National Heart, Lung, and Blood Institute. To learn more about hormone replacement therapies, try the North American Menopause Society.

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