Practitioners' oral contraception study

The effects of cigarette smoking and parity on the development of symptomatic gall bladder disease remain controversial. These relations have been examined in a cohort of 46000 women followed for up to 19 years during the Royal College of General Practitioners' (RCGP) oral contraception study. During follow up, 1087 women were recorded as experiencing their first ever episode ofsymptomatic cholelithiasis (International Classification of Diseases, 8th revision (ICD-8) 574) or cholecystitis (ICD-8 575). Smokers were more likely to develop symptomatic gall bladder disease than non-smokers (relative risk 1*19; 95% confidence intervals (95% CI) 1*06 to 1.34) and there was a significant trend with the number of cigarettes smoked daily (test for trend X2=7S58, p<001). This relation was most apparent among never users of oral contraceptives, although similar trends were found among current and former users. A significant direct relation between symptomatic gall bladder disease and parity was also found (test for trend X'=2l189, p<0001). When all were examined together a trend of increasing risk with lower social class was also found (test for trend X2=572, p=002). Current users of oral contraceptives had a moderately increased risk of symptomatic gall bladder disease (relative risk 1*15; 95% CI 0*99 to 1.34), unlike former users (relative risk 1*03; 95% CI 0'90 to 1.18). These results suggest that smoking and parity are important risk factors for the development of symptomatic gall bladder disease in women. (Gut 1994; 35: 107-1 11) Department of Therapeutics F E Murray Department of Public Health Medicine and Epidemiology R F A Logan Royal College ofGeneral Practitioners, Manchester Research Unit, Manchester P C Hannaford CR Kay Correspondence to: Dr R F A Logan, Departments of Public Health Medicine and Epidemiology, University Hospital, Nottingham NG7 2UH. Accepted for publication 19 May 1993 It is currently thought that cholesterol gall stones arise because of a triple hepatobiliary defect: cholesterol supersaturation of gall bladder bile, reduction gall bladder contractility, and increased rate of cholesterol nucleation, probably due to mucin glycoprotein hypersecretion. 2 Two recent case-control studies have suggested that smoking might protect against gall stone disease.34 Both found a halving in risk of gall stone disease for smokers compared with non-smokers. Previous reports have indicated, however, that smoking is associated with an increased risk of gall stone disease.5 Evidence for a positive association between parity and gall bladder disease is also contradictory, notwithstanding many studies of this relation.8 Pregnancy could affect each of the processes involved in gall stone formation. For example, progesterone impairs gall bladder contractility,9 and oestrogens may increase cholesterol saturation of bile'0 and gall bladder prostaglandin synthesis," and thus possibly mucin secretion by the gall bladder mucosa. A previous report from the Royal College of General Practitioners' (RCGP) oral contraception study suggested that the pill accelerated the development of symptomatic gall stone disease in women prone to the disease.'2 This report has used further data from the RCGP oral contraception study to examine the influence of smoking and parity on the development of gall stone disease.