Hormone replacement therapy and symptomatic gallstones - a prospective population study in the EPIC-Norfolk cohort

Hormone replacement therapy (HRT) may increase the risk of symptomatic gallstones, but this association has not been investigated in a prospective study in a European population. The aim of the study was to investigate the relationship between HRT and the development of symptomatic gallstones in a free-living population.

Use of HRT was ascertained by questionnaire in 13,433 women aged 45-74 years living in Norfolk, UK, who participated in the EPIC-Norfolk Study (European Prospective Investigation Into Cancer). The use of HRT was that at the time of recruitment rather than at the point of diagnosis. Participants were followed up for the development of symptomatic gallstones. The analysis used a nested case-control method in a prospective study.

A total of 117 women developed symptomatic gallstones. Women who reported either ever using HRT, currently using HRT or who had been past users all had a greater risk of gallbladder disease than age-matched control women who had never used HRT, after adjusting for known risk factors for gallstones. Women who had ever used HRT had a risk of 1.94 (95% CI = 1.17-3.22) compared with women who had never used HRT. For past users of HRT, the risk of symptomatic gallstones was greater, the longer the duration of use (OR = 4.05, 95% CI = 1.12-14.76 for use >1 year, compared to OR = 2.04, 95% CI = 0.79-5.30 for < or =1 year).

Use of HRT was positively associated with an increased risk of symptomatic gallstones in this population. This confirms trial data and additionally shows effects of duration of use and increased risk associated with past use.