The risks of taking hormone replacement therapy pills for menopausal women include gallbladder surgery, a large French study suggests.

Gallstone disease is common in developed countries and its complications are a major reason for hospital admissions.

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Gallstone complications are a major reason for hospital admissions. (Christopher Furlong/Getty)

Among women, those over the age of 50 are at greatest risk of gallstone disease.

Researchers in France analyzed data on 70,928 menopausal women who were asked about their use of estrogen hormone therapy every two years between 1992 and 2008. They were checking for an increased risk of gallbladder surgery, also called cholecystectomy and for complications of gallstones.

"Over five years, about one cholecystectomy in excess would be expected in every 150 women using oral estrogen therapy without a progestagen, compared with women not exposed to menopausal hormone therapy," Dr. Antoine Racine of South Paris University and his co-authors said in Monday's issue of the Canadian Medical Association Journal.

"Complicated gallstone disease should be added to the list of potential adverse events to be considered when balancing the benefits and risks associated with menopausal hormone therapy."

In France, hormone therapy is usually given in patch or gel form on the skin rather than orally as is common in North America, the United Kingdom and the Netherlands, Dr. Bette Liu of the University of New South Wales in Australia said in a journal commentary published with the study.

In the study, non-oral types of hormone replacement therapy were not associated with an increased risk of gallbladder surgery.

UK and U.S. estrogen studies similar 

Racine's team speculated that absorbing estrogens through the skin bypasses the liver. 

The liver metabolizes the hormone when it's taken orally, leading to higher cholesterol levels that are thought to increase the risk of gallstone complications.

The women participating in the study were covered by France's national health insurance plan for teachers and other educational workers. The patients mainly self-reported their use of menopausal hormone therapy and gallbladder surgery, although spot checks on a subsample using medical records suggested that the reports were accurate.

The researchers were not able to conclude whether the therapy causes gallstones, in part because they did not have enough details from the medical records to know why the surgeries were performed.

During an average of 11.5 years, 2,819 women in the study said they had gallbladder surgery.

The UK Million Women Study also suggested that estrogen therapy through the skin with gels or a patch is associated with a lower risk of gallbladder surgery than oral estrogen therapy, Liu said. "This consistency across different populations gives further weight to the findings."

The U.S. Women's Health Initiative also pointed to the same association.

"Drug regulatory bodies currently recommend that hormone therapy be prescribed only for moderate to severe menopausal symptoms and that the dose and duration of use be minimized," Liu concluded.

Data increasingly suggest that taking menopausal hormone therapy through the skin is a "more attractive option" than oral therapy, she noted.