TUESDAY, Jan. 18, 2005 (HealthDayNews) -- In yet another piece of bad news for hormone replacement therapy, researchers report that postmenopausal women taking estrogen therapy face an increased risk of gallbladder disease and surgery.
The effects were seen whether or not the women were also taking progestin.
This is the first time the effect had been seen in a randomized, double-blind study, considered the gold standard for scientific research.
"My own personal view is that the association is causal," said study co-author Dr. Robert B. Wallace, a professor of epidemiology at the University of Iowa College of Public Health. "This is the most persuasive level of evidence."
The findings, which appear in the Jan. 19 issue of the Journal of the American Medical Association, essentially mean that women considering hormone therapy now have one more thing they need to factor into their decision.
Some 10 percent to 15 percent of the U.S. population experiences gallstones in the gallbladder, with 1 million new diagnoses every year.
"Gallbladder disease is very common in this country," said Dr. Taylor Wootton, chairman of the clinical practice and economics committee of the American Gastroenterological Association. "Close to 1 million people have their gallbladder removed each year."
Previous observational studies had shown an association between estrogen and gallstones, but those studies lacked the weight of a randomized, double-blind study.
For this study, the researchers looked at more than 22,000 women aged 50 to 79 who participated in the Women's Health Initiative (WHI), the largest randomized, double-blind study of hormone use in postmenopausal women. None of the women had had their gallbladder removed.
The women were divided into two initial groups. Women who had undergone hysterectomies were randomized to receive either estrogen or a placebo. Women without a hysterectomy were randomized to receive estrogen plus progestin or a placebo.
The study was funded by the National Heart, Lung, and Blood Institute, with Wyeth-Ayerst Research Laboratories providing the drug and the placebo.
The women in the estrogen-only group were followed for a mean of 7.1 years, while the women in the estrogen-plus-progestin group were followed for a mean 5.6 years.
Women taking estrogen or estrogen plus progestin had a higher risk of gallbladder disease or surgery: a 67 percent higher risk with estrogen alone and a 59 percent increased risk with the combination.
The risk for inflammation of the gallbladder was 80 percent higher with estrogen and 54 percent higher with the combination. The risk for gallstones was 86 percent higher with estrogen and 68 percent higher for the combination.
Women taking estrogen alone were 93 percent more likely to have their gallbladder removed, while those taking the combination were 67 percent more likely to undergo this procedure.
Overall, the authors calculated that 323 women would need to take estrogen each year and 500 would have to take estrogen plus progestin to cause one excess adverse outcome.
The link between gallstone formation and estrogen is not entirely clear. "We don't know exactly because estrogen has so many bodily effects. Estrogen has the ability to have some physiological effect on almost every organ and system," Wallace explained.
The most likely effect, he added, is that estrogen changes the nature of bile so that it's more saturated, thereby leading to stones that block the gallbladder and duct, which in turn may lead to inflammation.
"It's not all that surprising. The question is, what do we do with this information," Wootton said. "If they are symptomatic, I would imagine most women are going to take the hormone replacement therapy. It's an increased risk, but it's not fourfold."
Still, any risk needs to be discussed with a physician. "Every time you prescribe any medication, the good and the bad needs to be discussed in a good doctor-patient relationship," Wootton pointed out.
"This isn't a fatal illness and may be a little less important, but it is important to people who have to go through surgery and convalescence, and the costs and disability that come with it," Wallace said.
The National Institute of Diabetes and Digestive and Kidney Diseases has more on gallstones.