Estrogen Therapy for Menopause Ups Gallbladder Surgery Risk

Oral estrogen therapy for menopausal women is associated with an increased risk of gallbladder surgery, according to the results of a large-scale study conducted in France.¹
   
Previous studies from the United States and the United Kingdom have reported an increased risk of gallbladder surgery, or cholecystectomy, in women who have taken menopausal hormone therapy, but these studies were largely homogeneous in that most of the hormone therapies that were evaluated were oral formulations, according to the study authors.¹ To evaluate whether the increased risk of cholecystectomy in women taking hormone therapy is associated with other forms of menopausal hormone therapy, such as topical and gel formulations of estrogen, in addition to oral regimens, the study authors evaluated self-reported data from a large cohort of menopausal women from the French E3N study.^1,2 This sample allowed for more heterogeneity in terms of type of hormone therapy because in France, menopausal hormone therapy is generally administered transdermally through skin patches or gels.
   
Of the 70,928 women who reported data, 45,984 (64.8%) had used menopausal hormone therapy. A total of 2819 cases of cholecystectomy were reported. Compared with menopausal women who did not use hormone therapy, those who did use hormone therapy were slightly more likely to have had a cholecystectomy (adjusted hazard ratio, 1.10). However, the study authors reported that this increased risk was restricted to the use of unopposed oral estrogen therapy (adjusted hazard ratio, 1.38). Estrogen therapy administered through skin patches or gels did not increase the risk of gallbladder surgery.
   
“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,” wrote the study authors.¹
   
These findings support current recommendations that urge clinicians to minimize the doses and duration of menopausal hormone therapy, said Bette Liu, PhD, a medically trained epidemiologist and senior lecturer at the University of New South Wales, Sydney, Australia, in a related commentary.³ In addition, these findings indicate that transdermal formulations may have fewer adverse effects than oral formulations and should be considered when hormone therapy is considered necessary in menopausal women.

Pertinent Points:
- Oral estrogen use in menopausal women is associated with an increase risk of cholecystectomy.
- Estrogen therapy administered through skin patches or gels did not increase risk for gallbladder surgery.
- Complicated gallstone disease should be considered a potential adverse effect when weighing the risks and benefits of menopausal hormone therapy.
 

References:

1. Racine A, Bijon A, Fournier A, et al. Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort. CMAJ. March 18, 2013. [Epub ahead of print]
2. Clavel-Chapelon F, van Liere MJ, Guibout C, et al, for the E3N Group. E3N, a French cohort study on cancer risk factors. Etude Epidemiologique aupres de femmes de l’Education Nationale. Eur J Cancer Prev. 1997;6:473-478.
3. Liu B. Is transdermal menopausal hormone therapy a safer option than oral therapy? CMAJ. March 18, 2013. [Epub ahead of print.]