Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer drugs.

OBJECTIVE

To study the risk of gynaecomastia associated with cimetidine, misoprostol, omeprazole and ranitidine.

DESIGN

Open cohort study with nested case-control analysis.

SETTING

General practices in United Kingdom that had computerised offices, 1989-92.

SUBJECTS: 81,535 men aged 25-84 years who received at least one prescription for cimetidine, misoprostol, omeprazole, or ranitidine during the study period.

MAIN OUTCOME MEASURES: New occurrences of idiopathic gynaecomastia diagnosed by general practitioner.

RESULTS

The relative risk of gynaecomastia for current users of cimetidine compared with non-users was 7.2 (95% confidence interval 4.5 to 11.3). Relative risks for misoprostol, omeprazole, and ranitidine were 2.0 (0.1 to 10.7), 0.6 (0.1 to 3.3), and 1.5 (0.8 to 2.6), respectively. Current users of cimetidine on a daily dose > or = 1000 mg had more than 40 times the risk of developing gynaecomastia than non-users. The period of highest risk was seven to 12 months after starting cimetidine treatment. Spironolactone (relative risk 9.3 (3.3 to 26.1)) and verapamil (9.7 (2.6 to 36.0)) were associated with a relative risk of gynaecomastia comparable to one for cimetidine.

CONCLUSIONS

Use of cimetidine, but not the three other antiulcer drugs, is associated with a substantially greater risk of gynaecomastia in men. A strong dose-response relation was present among cimetidine users.