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Hormone therapy linked to blood clots in JAMA report

BURLINGTON, VT., October 10, 2004 -- Postmenopausal women who take the hormone therapy estrogen-plus-progestin have double the risk for a potentially fatal condition that causes blood clots to develop in the veins, according to an article in the October 6 issue of JAMA: Journal of the American Medical Association.

Venous thrombosis is a disorder in which the formation of a blood clot blocks circulation in the deep veins of the leg. These veins are responsible for returning de-oxygenated blood from the legs to the heart and lungs. The greatest risk occurs when pieces of the clot break off, travel to and lodge in the arteries that go to the lungs, which is called a pulmonary embolus.

Lead author of the study Mary Cushman, M.D., M.Sc., an associate professor of medicine at the University of Vermont College of Medicine, and colleagues examined the effects of postmenopausal hormone therapy on venous thrombosis in the presence of age and obesity - two major risk factors for thrombosis. The researchers analyzed final data from the Women's Health Initiative Estrogen Plus Progestin clinical trial, a double-blind randomized controlled trial of 16,608 postmenopausal women between the ages of 50 and 79 years, who were enrolled in 1993 through 1998 at 40 U.S. clinical centers, with 5.6 years of follow up.

As part of the study, hereditary thrombosis risk was measured in the first 147 women who developed thrombosis and in 513 women who did not develop thrombosis. Participants were randomly assigned to receive either a dose of conjugated equine estrogen plus medroxyprogesterone acetate, or a placebo.

Venous thrombosis occurred in 167 women taking estrogen plus progestin and in 76 taking placebo (twice the risk for venous thrombosis for women taking hormone therapy). Compared with women between the ages of 50 and 59 years who were taking placebo, the risk associated with hormone therapy was higher with age. Women aged 60 to 69 years experienced 4.3 times the risk and women aged 70 to 79 years experienced 7.5 times the risk. Compared with women who were of normal weight and taking placebo, the risk associated with taking estrogen plus progestin was increased among overweight (3.8 times the risk) and obese women (5.6 times the risk). Participants with the hereditary blood coagulation disorder Factor V Leiden had a 6.7 times increased risk of thrombosis compared with women in the placebo group without the genetic mutation.

"The risk for venous thrombosis with oral contraceptive use has been well quantified but we have not had this information with respect to the use of hormone therapy," said Barbara Alving, M.D., director of the Women's Health Initiative and acting director of the National Heart, Lung, and Blood Institute. "This study now clearly defines the risk of venous thrombosis in women who are taking hormone therapy for a prolonged period of time according to age, obesity, and inherited conditions that can lead to thrombosis."

"Based on projections for 10 years for 1,000 women taking estrogen plus progestin, the estimated excess number of events is 18 for venous thrombosis, six for coronary heart disease, eight for invasive breast cancer, and eight for stroke," said Cushman, a hematologist who specializes in venous thrombosis and cardiovascular risk factors found in the blood. "Now that we have confirmation of these risks, women have more information on which to base their decision about whether or not to take hormone therapy. Women and their physicians can use this information to think about the risk of treatment."

In addition to the University of Vermont, centers involved in this report included the University of Pittsburgh; the University of Washington, Seattle; Stanford University; Kaiser Permanent in Oakland, Calif.; and Leiden University Medical Center, the Netherlands. The Women's Health Initiative was funded by the National Heart, Lung and Blood Institute. Wyeth-Ayerst Research provided the study medications (active and placebo). Additional funding was provided by a grant from the Netherlands Heart Foundation.

Source: University of Vermont College of Medicine (Author: Jennifer Nachbur)

Posted: October 2004