{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:00:10Z","timestamp":1768280410429,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Therapeutic Evaluation Unit of the British Columbia Provincial Health Services Authority"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Proton pump inhibitors (<jats:styled-content style=\"fixed-case\">PPIs<\/jats:styled-content>) are commonly prescribed for many gastrointestinal diseases. A number of case reports have linked <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>s to gynecomastia in men, but large epidemiologic studies are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To quantify the risk of gynecomastia with PPIs in male patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the PharMetrics Plus\u2122 health claims database from the United States, a retrospective cohort study of new <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> users and new amoxicillin users from 2006 to 2016 was conducted. Diagnosis of gynecomastia was identified by the International Classification for Diseases, 9th edition (<jats:styled-content style=\"fixed-case\">ICD<\/jats:styled-content>\u20109) and 10th edition (<jats:styled-content style=\"fixed-case\">ICD<\/jats:styled-content>\u201010) codes. Cases were defined as patients with two codes for gynecomastia within 90\u00a0days, with the first code as the event code. Hazard ratios (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>s) 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. A sensitivity analysis defining exposure with two <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> prescriptions was also undertaken.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 389 cases of gynecomastia diagnosed among 220,791 new <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> users, and 996 gynecomastia cases were diagnosed among 837,740 new amoxicillin users. The crude <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> for <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use compared to amoxicillin use was 1.70 (95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>]: 1.461\u20131.976). The adjusted <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> for the sensitivity analysis was 1.299 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.146\u20131.473). The adjusted <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> was 1.4795 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.2431\u20131.7609) for patients over 50\u00a0years old and 1.324 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.1133\u20131.5745) for patients 50\u00a0years old or younger.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This large retrospective cohort study suggests that patients who used <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>s are at higher risk of developing gynecomastia. Clinicians may want to convey this information to male patients who require long\u2010term <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2245","type":"journal-article","created":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T11:14:34Z","timestamp":1552475674000},"page":"614-618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Risk of Gynecomastia with Users of Proton Pump Inhibitors"],"prefix":"10.1002","volume":"39","author":[{"given":"Bonnie","family":"He","sequence":"first","affiliation":[{"name":"Department of Medicine Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Carleton","sequence":"additional","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics University of British 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