Gynaecomastia associated with proton pump inhibitors: a case series from the Spanish Pharmacovigilance System.
OBJECTIVE
Proton pump inhibitors (PPIs) are widely used in the management of peptic ulcer and related symptoms. They have been linked to certain endocrine adverse reactions, including gynaecomastia. The aim of the present study is to investigate the association between the use of PPIs and the development of gynaecomastia.


METHODS
Reports of cases of gynaecomastia that had putatively been induced by PPIs and that had been collected by the Spanish Pharmacovigilance System via the 'yellow card' scheme, were analysed. Reporting odds ratios (RORs) were calculated as a measure of disproportionality.


RESULTS
Twenty-four cases of gynaecomastia associated with PPIs were identified in the database of the Spanish Pharmacovigilance System. Overall, there was a clear temporal sequence of events in all cases and the adverse effect disappeared after drug withdrawal in most of the cases; 14 patients were also receiving other drugs at the time of the adverse effect. The ROR for omeprazole exposure versus no exposure, but not that for other PPIs, showed a statistically significant elevation (ROR adjusted for age 5.23; 95% CI 3.32, 8.26).


CONCLUSIONS
Considering the widespread use of PPIs, gynaecomastia may affect a large number of patients. In most cases, the condition seems to be reversible with drug withdrawal. Doctors should be aware of this potential adverse reaction when prescribing PPIs to their patients over long periods of time.
Carvajal
Alfonso
A
Instituto de Farmacoepidemiología, Universidad de Valladolid, Valladolid, Spain. carvajal@ife.uva.es
Macias
Diego
D
Gutiérrez
Angélica
A
Ortega
Sara
S
Sáinz
María
M
Martín Arias
Luis H
LH
Velasco
Alfonso
A
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D016208:Databases, Factual; D006177:Gynecomastia / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009853:Omeprazole / Q000009:adverse effects; D054328:Proton Pump Inhibitors; D012189:Retrospective Studies; D013030:Spain
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D009853:Omeprazole