A new study published on bmj.com reports that although hormone replacement therapy (HRT) results in an overall increase in risk of gallbladder disease, HRT administered by skin patches or gels poses a smaller risk than HRT given orally.
In 2005, about 1 million women in the UK were taking HRT – any of several medications designed to artificially raise estrogen, progesterone, and sometimes testosterone levels in menopausal women. Most women receive oral treatments. Post-menopausal women are prone to gallbladder disease, and research has shown that HRT increases the risk. However, there has not been a comparative analysis of how the risk of gallbladder disease changes depending on the method of HRT administration.
To study the different effects of HRT treatment given orally or through skin patches and gels, Dr Bette Liu (University of Oxford) and colleagues analyzed data from over 1.3 million UK women aged 50 to 69 years who participated in the Million Women Study. After an average of 6 years of follow-up, 19,889 women were admitted to a hospital with gall bladder disease, and 86% (17,190) of these required surgery to have the gall bladder removed (cholecystectomy).
Liu and colleagues confirmed previous results that indicated an increased risk of developing gallbladder disease for women receiving HRT compared to women who had never taken HRT. Regarding HRT administration methods, the researchers found that women who took HRT through a patch or gel were significantly less likely to require hospitalization for gallbladder disease and less likely to require cholecystectomy than women who received HRT in the form of tablets.
Specifically, gallbladder removal hospital admission rates per 100 women were 1.1 for women who never used HRT, 1.3 for patch or gel HRT users, and 2.0 for oral HRT users. After HRT terminated, there was a gradual reduction in the heightened risk of gallbladder disease. Still, however, even after 10 years of stopping treatment, women who had HRT still had a higher risk than women who had never had HRT.
How can we explain the observed difference in risk of developing gallbladder disease? One suggestion provided by the authors is that estrogen is absorbed differently whether HRT is given orally or through the skin (transdermally). Oral administration allows the liver to break down the hormone before entering the blood stream, while the transdermal administration is generally a lower dose that is directly entered into circulation after being absorbed through the skin. The lower risk of gallbladder disease associated with the HRT patch could be driven by these absorption differences.
The researchers conclude that, “For women who choose to use hormone replacement therapy, one cholecystectomy could be avoided for every 140 users of transdermal therapy rather than oral therapy over a five year period.”
Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study
Bette Liu, Valerie Beral, Angela Balkwill, Jane Green, Sian Sweetland, Gillian Reeves, for the Million Women Study Collaborators
BMJ (2008). 337:a386
doi:10.1136/bmj.a386.
Written by: Peter M Crosta