HRT's Link to Higher Blood Clot Risk Confirmed

Study also finds odds higher in older, heavier women

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HealthDay Reporter

TUESDAY, Oct. 5, 2004 (HealthDayNews) -- Women who receive combination hormone therapy are at double the risk of developing blood clots in their veins, according to a major government study on the treatment.

The final results from the Women's Health Initiative (WHI), which appear in the Oct. 6 issue of the Journal of the American Medical Association, confirm previous research on the therapy. However, they also found obesity and advancing age further increase the risk of clots, known medically as venous thrombosis, even further.

"Increasing age and obesity are two of the most important lifestyle characteristics associated with thrombosis. The risks are cumulative," said study author Dr. Mary Cushman, an associate professor of medicine at the University of Vermont College of Medicine. "If you are considering giving hormones to healthy women, these are two major risk factors to consider."

Meanwhile, a second study in the journal found that a certain type of estrogen, conjugated equine estrogen, but not esterified estrogen, increased rates of venous thrombosis.

Hormone replacement therapy (HRT) is approved for the relief of hot flashes, night sweats and other menopausal symptoms, but it also carries with it the risk of blood clots, heart attacks, stroke and breast cancer. These risks led investigators to halt this segment of the WHI in July 2002. Nevertheless, a quarter of women who stopped taking hormone replacement therapy have gone back to it, according to experts.

Previous information from the WHI reported a 2.11 times increased risk of venous thrombosis based on 5.2 years of follow-up. The current study incorporates data through July 7, 2002, with an average follow-up of 5.6 years.

The trial involved 16,608 postmenopausal women between the ages of 50 and 79 who were randomly assigned to receive either conjugated equine estrogen plus progestin or a placebo.

Venous thrombosis occurred in 167 women taking hormones and in 76 women taking the placebo, representing about double the risk. The risk was even higher among older women and among overweight and obese women: 4.3 times for women 60 to 69 and 7.5 times women 70 to 79 compared with women 50 to 59. Overweight women had 3.8 times the risk, while obese women were at 5.6 times the risk compared with women of normal weight.

The absolute numbers are relatively small, though. For every 1,000 women taking estrogen plus progestin over 10 years, there will be an estimated 18 incidents of venous thrombosis.

Women with a hereditary clotting disorder known as Factor V Leiden had 6.7 times the risk of thrombosis compared with women without the mutation.

Some 2 percent of the population carry this mutation, said Dr. Philip Sarrel, emeritus professor of obstetrics and gynecology and psychiatry at Yale University School of Medicine. "It's enough people to say that this should probably be in routine testing," he added. "If that factor is present, then it's particularly sensitive to the effects of estrogen or estrogen combined with progestin and puts the risk off the scale."

None of this means that women should give up on HRT. "The paper does help guide women and their physicians in being selective in a choice of hormone therapy," Sarrel said.

The second trial in found an increased risk of venous thrombosis associated with conjugated equine estrogen (CEE), which includes horse estrogens, but not with esterified estrogen, which is made up of a combination of estrogens.

These study authors looked at perimenopausal and postmenopausal women, aged 30 to 89, who were members of a large health maintenance organization (HMO) in Washington state. The HMO's pharmacies switched from standard estrogen therapy to conjugated equine estrogen in October 1999, providing an opportunity to observe if the change resulted in any differences.

As it turned out, women currently taking CEE had a 65 percent increased risk of venous thrombosis compared with women not taking that type of estrogen, and a 78 percent increased risk over women taking esterified estrogen. Higher daily doses were associated with an even higher risk.

More information

For more on hormones and menopause, visit the U.S. Food and Drug Administration.

SOURCES: Mary Cushman, M.D., associate professor, medicine, University of Vermont College of Medicine, Burlington; Philip M. Sarrel, M.D., emeritus professor, obstetrics and gynecology and of psychiatry, Yale University School of Medicine, New Haven, Conn.; Oct. 6, 2004, Journal of the American Medical Association

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