Estrogen Therapy Boosts Clotting Risk in Postmenopausal Women

Those who had hysterectomies, took hormone were more likely to get DVT, study found

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By Amanda Gardner
HealthDay Reporter

MONDAY, April 10, 2006 (HealthDay News) -- Estrogen therapy appears to increase the risk of blood clots in the veins of postmenopausal women who have had their uterus removed.

These latest results from the Women's Health Initiative (WHI) were unexpected, even to the study's lead author.

"It surprised us all how few benefits have come out of this and how many negatives," said Dr. J. David Curb, a professor of geriatric medicine at the University of Hawaii and president/director of the Pacific Health Research Institute, both in Honolulu. "This is not where I would have predicted we would be. I was a believer [that estrogen would not increase the risk of blood clots]. The data have convinced me that I was wrong."

The risk is still less than that of estrogen plus progestin, the combination hormone therapy given if a woman still has her uterus. The study appears in the April 10 issue of the Archives of Internal Medicine.

Venous thromboembolism (VT, or blood clots in the veins) includes both deep vein thrombosis (DVT, a blood clot in a deep vein) and the potentially life-threatening pulmonary embolism (PE, a blood clot that has moved to the lungs). VT affects about one adult per 1,000 years of life.

Previous WHI data on progestin plus estrogen indicated an increased risk of VT. There also appear to be increased risks with tamoxifen and raloxifene as well as birth control pills, all of which involve giving hormones.

There was little information on the effect of estrogen alone, however.

"There was no good evidence that estrogen alone caused these events, so some people had been promoting just estrogen," Curb explained.,

This particular arm of the trial was terminated early because of increased health risks, primarily for stroke. This paper is the final data from that trial.

The researchers looked at data on 10,739 women aged 50 to 79 who had undergone a hysterectomy. The women were randomly assigned to receive either estrogen alone or a placebo, and were followed for a mean 7.1 years.

Overall, 197 women developed VT: 111 in the estrogen group and 86 in the placebo group.

"The risk of having a blood clot was close to 30 percent more for a woman on estrogen vs. not on estrogen," Curb said.

While the risk of VT was slightly higher for women receiving estrogen alone, it was quite a bit higher for DVT and not significantly higher for PE. Risks were most pronounced in the first two years. Also, risk was higher in women who were more physically active and had lower HDL ("good") cholesterol levels, and in women who had a history of VT.

Curb added that the investigators did not find many benefits, even in relief of menopausal symptoms such as hot flashes.

What does this mean, practically speaking?

"This certainly would indicate that we should be careful about giving estrogen to women, that it's not just a progestin effect which some people had predicted," Curb said. "Women have to be very cautious about taking estrogens. There may be certain women that need them for severe symptoms, but there are just multiple risks and, while each one of them is a relatively small risk for a person, they all add up."

When weighing the decision to use hormone therapy, women need to take into account their personal medical history and their family medical history, as well as the risks and benefits of the treatment, added Dr. Nieca Goldberg, chief of women's cardiac care at Lenox Hill Hospital in New York City, and author of The Women's Healthy Heart Program.

"If a woman is really experiencing significant symptoms that are inhibiting her quality of life, we try to use the safest effective recommendations," she said. "This doesn't say you shouldn't use hormone therapy because of the risk of blood clots, but that's a consideration."

Women who have a prior history of blood clots probably should not take hormones, Goldberg added.

And women also need to know the symptoms. "For DVT, it's sudden onset of pain and swelling in the calf with redness," she said. "Some of the symptoms of pulmonary embolism can be similar to a heart attack, chest pain, shortness of breath, rapid heartbeat."

Another study in the same journal found that both estrogen alone and estrogen plus progestin were associated with a higher risk of breast cancer among black women. The association was even stronger among leaner women.

Previous research had indicated there was an increased risk, but most of this research was conducted in white women.

The latest research, the Black Women's Health Study, involved 23,191 women aged 40 and up. Risk of breast cancer in women using hormones was about 58 percent higher than that of women not using hormones for 10 or more years of use. The risk went up the longer one was on hormones.

More information

For more on the Women's Health Initiative, visit the National, Heart, Lung, and Blood Institute.

SOURCES: J. David Curb, M.D., professor, geriatric medicine, University of Hawaii, and president and director, Pacific Health Research Institute, Honolulu; Nieca Goldberg, M.D., chief, women's cardiac care, Lenox Hill Hospital, New York City, and author, The Women's Healthy Heart Program; April 10, 2006, Archives of Internal Medicine

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