Study Links Estrogen Pills, Blood ClotsOct 5, 2004 | AP
Estrogen-progestin pills double postmenopausal women's chances of developing dangerous blood clots, and the risk is even higher for overweight patients and those over 60, researchers say.
The findings continue the drumbeat of bad news about estrogen that has led to a sharp drop in sales of the supplements, which have long been prescribed to relieve such symptoms of menopause as hot flashes and vaginal dryness.
The results came from the Women's Health Initiative, the same government study that was halted two years ago after Prempro estrogen-progestin pills appeared to raise the risk of heart attacks, strokes and breast cancer. Later WHI data found that Premarin, an estrogen-only pill, was risky, too.
At the time the study was stopped, there were also signs that Prempro raised the risk of deep vein thrombosis, or blood clots that typically form in the legs and can be painful and even lethal. A closer, more detailed look at the WHI data, published in Wednesday's Journal of the American Medical Association, has reinforced that finding.
Researchers looked at 16,608 WHI participants ages 50 to 79 who took either Prempro or a placebo for an average of about five years. Blood clots in the legs, lungs or elsewhere occurred in 167 women on Prempro, compared with 76 on the dummy pills.
The blood clot risk was nearly four times higher in overweight women than it was in normal-weight women on dummy pills, and it was more than five times higher in obese women.
Even higher risks were found in women in their 60s and 70s, who already are more prone to blood clots because of age; and in women with a genetic flaw called factor V Leiden. The mutation causes a protein involved in clotting to be abnormally active and is present in about 5 percent of whites but is rare in other ethnic groups.
While there is a long-established link between blood clots and estrogen in birth-control pills, the link with hormones taken to relieve menopause symptoms was less certain.
Dr. Mary Cushman, a University of Vermont hematologist who led the study, said the findings indicate that overweight and older women who take hormones should be vigilant about reporting symptoms of blood clots, which include swelling, pain or both.
The symptoms "should be treated promptly because it can be a fatal episode," Cushman said.
Doctors should consider testing for the genetic flaw in women with a family history of blood clots who want to take hormones, she said.
A separate study in JAMA found no increased clot risk among women taking two different estrogen-only pills, compared with women not taking hormones.
Lead author Dr. Nicholas Smith of the University of Washington cautioned that the results, while provocative, are only preliminary and need to be duplicated in additional research.
The products studied were plant-based estrogen pills sold as Estratabs and Menest. Estratabs was taken off the market last year because of what the manufacturer said were production difficulties.
By contrast, women on Premarin, containing animal-based estrogen, faced a 65 percent higher blood clot risk than non-hormone users.
Estrogen-only pills are recommended only for women with hysterectomies because estrogen without progestin can cause uterine cancer.
Dr. Barbara Soltes, a reproductive endocrinologist at Chicago's Rush University Medical Center, was skeptical about any major differences in blood-clot risks among the various estrogen pills and said the results "won't hold water in the medical community."