Abstract
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).
Conclusion: 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.
References
IMS [online]. Available from URL: http://www.imshealth.com. [Accessed 2006 July 31]
Wilton LV, Key C, Shakir SA. The pharmacovigilance of pantoprazole: the results of postmarketing surveillance on 11,541 patients in England. Drug Saf 2003; 26: 121–32
Martin RM, Dunn NR, Freemantle S, et al. The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England: cohort studies. Br J Clin Pharmacol 2000; 50: 366–72
Santucci L, Farroni F, Fiorucci S, et al. Gynaecomastia during omeprazole therapy. N Engl J Med 1991; 324: 635
Convens C, Verhelst J, Mahler C. Painful gynaecomastia during omeprazole therapy. Lancet 1991; 338: 1153
Carvajal A, Martin Arias LH. Gynaecomastia and sexual disorders after the administration of omeprazole. Am J Gastroenterol 1995; 90(6): 1028–9
Lindquist M, Edwards IR. Endocrine adverse effects of omeprazole. BMJ 1992; 305: 451–2
Adverse Drug Reactions Advisory Committee. Drug-induced gynaecomastia. Aust Adverse Drug React Bull 1997; 16: 3
Garcia Rodriguez LA, Jick H. Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer drugs. BMJ 1994; 308: 503–6
Alvarez Requejo A, Carvajal A, Begaud B, et al. Under-reporting of adverse drug reactions. Estimate based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharmacol 1998; 54: 483–8
Karch FE, Lasagna L. Toward the operational identification of adverse drug reactions. Clin Pharmacol Ther 1977; 21: 247–54
International Monitoring of Adverse Reactions to Drugs. Adverse Reaction Terminology. Uppsala: World Health Organization Collaborating Centre for International Drug Monitoring, 1992
Evans SJW. Pharmacovigilance: a science or fielding emergencies? Stat Med 2000; 19: 3199–209
Rothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its advantages over proportional reporting ratio. Pharmacoepidemiol Drug Saf 2004; 13: 519–23
van Puijenbroek EP, Bate A, Leufkens HG, et al. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf 2002; 11: 3–10
Egberts ACG, Meyboom RHB, van Puijenbroek EP. Use of measures of disproportionaly in pharmacovigilance. Three Dutch examples. Drug Saf 2002; 25: 453–8
Braunstein GD. Gynaecomastia. N Engl J Med 1993; 328: 490–5
Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709–1
Satoh T, Munakata H, Fujita K, et al. Studies on the interactions between drug and estrogen: II. On the inhibitory effect of 29 drugs reported to induced gynaecomastia on the oxidation of estradiol at C-2 or C-17. Biol Pharm Bull 2003; 26: 695–700
Human Cytochrome P450 (CYP) Allele Nomenclature Committee [online]. Available from URL: http://www.cypalleles.ki.se/cyp2c19.htm. [Accessed 2006 July 31]
Goldstein JA, Ishizaki T, Chiba K, et al. Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 1997; 7: 59–64
Desta Z, Zhao X, Shin JG, et al. Clinical significance of the cytochrome P4502C19 genetic polymorphism. Clin Pharmacokinet 2002; 41: 913–58
Claude K, Lardinois MD, Ernest L, et al. Cimetidine blocks testosterone synthesis. Arch Intern Med 1985; 154: 920–2
Satoh T, Itoh S, Seki T, et al. On the inhibitory action of 29 drugs having side effect gynecomastia on estrogen production. J Steroid Biochem Mol Biol 2002; 82: 209–16
Acknowledgements
No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study. We wish to thank all the pharmacovigilance centres in Spain and, especially, all reporting doctors and pharmacists.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Carvajal, A., Macias, D., Gutiérrez, A. et al. Gynaecomastia Associated with Proton Pump Inhibitors. Drug-Safety 30, 527–531 (2007). https://doi.org/10.2165/00002018-200730060-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-200730060-00006