According to the results of a retrospective cohort study, male patients who utilize proton pump inhibitors (PPIs) appear to be at increased risk of developing gynecomastia.

In order to quantify the risk of developing gynecomastia in male patients taking PPIs, the study authors utilized the PharMetrics Plus health claims database to obtain data on both new users of PPIs as well as new users of amoxicillin between 2006 and 2016. Cases of gynecomastia were then identified in patients who had two International Classification for Diseases 9th or 10th edition (ICD-9 and ICD-10) codes within 90 days, with the first code being the event code.

“Hazard ratios (HRs) were computed by adjusting for alcoholic cirrhosis, hyperthyroidism, testicular cancer, Klinefelter syndrome, and obesity; as well as the use of ketoconazole, risperidone, spironolactone, and androgen deprivation therapy,” the study authors explained. They added, “A sensitivity analysis defining exposure with two PPI prescriptions was also undertaken.”

A total of 220,791 new PPI users and 837,740 new amoxicillin users were identified in the study. Among these patients, 389 cases of gynecomastia were reported in the PPI group and 996 cases were reported in the amoxicillin group. The study authors reported a crude HR of 1.70 (95% CI: 1.461, 1.976) for PPI vs amoxicillin use and an adjusted HR of 1.299 (95% CI: 1.146, 1.473) for the sensitivity analysis. The number needed to harm was calculated as 1746. Adjusted HRs for patients >50 years old and ≤50 years old were reported as 1.4795 (95% CI: 1.2431, 1.7609) and 1.324 (95% CI: 1.1133, 1.5745), respectively.

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“In our study, we found that users of PPIs were 30% more likely to develop gynecomastia compared to users of amoxicillin, however the absolute risk is small, as the number needed to harm was 1746,” the study authors concluded. They added, “Nevertheless, as there are approximately 14.9 million patients who are prescribed PPIs in the United States, and assuming that half (7.5 million) of the patients receiving PPIs are men, this means that there are potentially 4295 male patients with gynecomastia.” Because of this, the study authors recommended that healthcare providers counsel male patients on the potential risk of gynecomastia prior to prescribing PPIs.


He, B. , Carleton, B. and Etminan, M. (2019), Risk of Gynecomastia with Users of Proton Pump Inhibitors. Pharmacotherapy. Accepted Author Manuscript. doi:10.1002/phar.2245