Estrogen therapy boosts clotting risk in postmenopausal women

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

Previous Women's Health Initiative data on progestin plus estrogen indicated an increased risk of venous thromboembolism.

There also appears to be increased risk 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 explains.

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 venous thromboembolism: 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 versus not on estrogen," Curb says.

While the risk of venous thromboembolism was slightly higher for women receiving estrogen alone, it was quite a bit higher for deep vein thrombosis and not significantly higher for pulmonary embolism. 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 venous thromboembolism.

Curb adds 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 says. "Women have to be very cautious about taking estrogens. There may be certain women who 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, adds 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 says. "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 adds.

And women also need to know the symptoms. "For deep vein thrombosis, it's sudden onset of pain and swelling in the calf with redness," she says. "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 that 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.

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c.2006 HealthDay News