Men on Proton Pump Inhibitors at increased risk of developing gynecomastia

CANADA: Proton pump inhibitors (PPIs) are commonly prescribed for many gastrointestinal diseases. However, a recent study in the journal Pharmacotherapy has shed light on its harmful effects on men, stating that patients who take proton pump inhibitors appear to be at increased risk of developing gynecomastia.

A number of case reports have linked PPIs to gynecomastia in men, but large epidemiologic studies are lacking. Mahyar Etminan, University of British Columbia, Vancouver, Canada, and colleagues conducted this large retrospective cohort study to quantify the risk of gynecomastia with PPIs in male patients.

For the purpose, 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 9^th or 10^th 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,” explain the authors. “A sensitivity analysis defining exposure with two PPI prescriptions was also undertaken," they added.

Key findings of the study include:

• 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 crude HR for PPI use compared to amoxicillin use was 1.70.


• The adjusted HR for the sensitivity analysis was 1.299.


• 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 and 1.324 respectively.

“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.

For detailed study log on to https://doi.org/10.1002/phar.2245