Postmenopausal Hormone Therapy Appears to Increase Risk of Blood Clots

Estrogen therapy may increase the risk of venous thrombosis, the formation of blood clots in the veins, among postmenopausal women who have had their uterus removed, according to a study in the April 10 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Venous thromboembolism (VT), which includes the conditions deep vein thrombosis (a blood clot in a deep vein) and pulmonary embolism (a blood clot that travels to the lungs), affects about one adult per 1,000 years of life, according to background information in the article. Researchers suspect that hormone therapy may increase a woman's risk of developing VT. The largest study analyzing the relationship between hormone therapy and VT is the Women's Health Initiative (WHI), which included two large clinical trials. One WHI trial examined the effects of estrogen plus progestin and found that this combination of hormones appeared to increase the risk of VT.

J. David Curb, M.D., University of Hawaii and Pacific Health Research Institute, Honolulu, and colleagues analyzed data from the other WHI trial, in which the effect of estrogen alone was studied in 10,739 women aged 50 to 79 years.

The participants were randomly assigned to take either combined equine estrogens (a mix of several estrogens) or placebo. They were followed for an average of 7.1 years, during which 197 women developed VT, including 144 with deep vein thrombosis, 91 with pulmonary embolism and 38 with both.

Of those 197 women who developed VT, 111 were taking estrogen and 86 were taking placebo. The risk of VT was slightly higher for women receiving estrogen therapy; was significantly increased for deep venous thrombosis, but not significantly increased for pulmonary embolism; and was highest in the first two years of therapy. Estrogen therapy appeared to affect risk more in women with higher physical activity levels and lower HDL (good) cholesterol. Overall, the risk of venous thrombosis associated with estrogen therapy was lower than that associated with estrogen plus progestin in the other WHI trial.

"Our data suggest that although the absolute incidence is relatively low, the use of combined equine estrogens increases the relative risk of venous thrombosis in postmenopausal women without a uterus," the authors conclude. "Women with appropriate indications, such as short-term treatment of severe menopausal symptoms, should use combined equine estrogens only after careful consideration of the relative risks and benefits, especially if the women have other risk factors for venous thrombosis," which include older age, obesity and a history of the condition.

Arch Intern Med. 2006; 166: 772-780.
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