The Risk of Gallstones in Middle-Aged Women

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Abstract
It was with some surprise that we read in the article by Maclure et al. (Aug. 31 issue)1 that parity was not a risk factor in the development of symptomatic cholelithiasis in the Nurses' Health Study. Research on the pathophysiology of gallstone formation has focused in part on the effects of pregnancy as well as endogenous and exogenous estrogens on bile composition and the contractility of the gallbladder.2 Existing epidemiologic data also suggest that hormones may affect the risk of cholelithiasis. Studies in women have noted positive associations of both parity and oral-contraceptive use with cholelithiasis, although the findings have not been consistent.3 4 5 Similarly, studies of men with prostatic cancer have suggested an association of exogenous estrogens with gallstone formation.2 The effect of the use of exogenous estrogens and progesterone on the risk of gallstones, although still unclear, is therefore of potential importance and may have had a role in the interpretation of the data on parity reported by Maclure et al.1 Previous articles from the Nurses' Health Study have recorded the use of exogenous hormones6 , 7 and indicated that approximately 50 percent of this large cohort had used or were using contraceptives or estrogens. Analyses of the effects of parity on cholelithiasis both stratifying by and controlling for exogenous hormone use would be of great interest. These additional analyses would enhance the unique opportunity of the Nurses' Health Study to explore the interactions among age, obesity, parity, and exogenous hormones on the risk for symptomatic cholelithiasis.