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Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort.

ABSTRACT: BACKGROUND: Studies in the United States and the United Kingdom have reported an increased risk of cholecystectomy among women exposed to menopausal hormone therapy, but with substantial heterogeneity between types of hormone treatments. We evaluated the risk of cholecystectomy associated with different regimens of menopausal hormone therapy in a large prospective cohort study. METHODS: Between 1992 and 2008, 70 928 menopausal women from the French E3N study cohort were sent questionnaires assessing their use of menopausal hormone therapy, medical history and lifestyle characteristics. The primary outcome was cholecystectomy. We analyzed the risk of cholecystectomy associated with use of menopausal hormone therapy using Cox proportional models, with age as time-scale. RESULTS: During follow-up, 45 984 (64.8%) of the participants were exposed to menopausal hormone therapy, and 2819 cholecystectomies were recorded. The use of menopausal hormone therapy was associated with an increased risk of cholecystectomy (adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.01-1.20) compared with women who were not exposed to menopausal hormone therapy. The association was restricted to unopposed oral estrogen therapy (adjusted HR 1.38, 95% CI 1.14-1.67). Over 5 years, about 1 cholecystectomy in excess would be expected in every 150 women using oral estrogen therapy without progestogens, compared with women not exposed to menopausal hormone therapy. INTERPRETATION: The risk of cholecystectomy was increased among women exposed to oral estrogen menopausal hormone therapy, especially oral regimens without a progestagen. 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.

SUBMITTER: Racine A

PROVIDER: S-EPMC3626807 | biostudies-other | 2013 Apr

REPOSITORIES: biostudies-other

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Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort.

Racine Antoine A Bijon Anne A Fournier Agnès A Mesrine Sylvie S Clavel-Chapelon Françoise F Carbonnel Franck F Boutron-Ruault Marie-Christine MC

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20130318 7

<h4>Background</h4>Studies in the United States and the United Kingdom have reported an increased risk of cholecystectomy among women exposed to menopausal hormone therapy, but with substantial heterogeneity between types of hormone treatments. We evaluated the risk of cholecystectomy associated with different regimens of menopausal hormone therapy in a large prospective cohort study.<h4>Methods</h4>Between 1992 and 2008, 70 928 menopausal women from the French E3N study cohort were sent questio ...[more]

PMID: 23509128

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Project description:BackgroundMenopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study.MethodsWe used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status.ResultsAmong MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC.ConclusionsOur results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.

Dataset Information

Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort.

Publications

Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort.

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