Proton pump inhibitors and risk of hearing loss; a systematic review

Proton pump inhibitors (PPIs) are widely used medications for the treatment of gastroesophageal reflux disease (GERD) and other conditions requiring acid suppression. While generally considered safe, concerns have emerged regarding potential long-term adverse effects of PPIs, such as ototoxicity. To systematically synthesize the evidence regarding the association between PPIs usage and the risk of hearing loss. This systematic review followed PRISMA guidelines. PubMed/Medline, Embase, Scopus, and Web of Science databases were searched in May 2024 and further updated using a handsearching in December 2024. Clinical original studies evaluating the relationship between PPI usage and any type of hearing impairments were included. Exclusion criteria include non-human studies, non-English language publications, reviews, case reports, book chapters, conference abstracts, and retracted studies. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. The initial database search yielded 661 records. Four studies (total n = 208,956 participants) proceeded to full-text review and were included in the qualitative synthesis. All of the included studies demonstrated a statistically significant association between PPI use and an increased risk of hearing impairments; even after adjusting for possible confounders; however, one study found no independent association after adjusting for GERD symptoms. The findings of this systematic review reveal inconclusive results regarding the association between PPI use and hearing loss. While the limited available evidence suggests a possible increased risk, further research is needed to dissect the possible causal relationship and elucidate the underlying mechanisms.