Phosphodiesterase-5 (PDE-5) Inhibitors and Ototoxicity: A Systematic Review.
Level 1 - systematic review of randomized trials
Systematic review of randomized trials, observational studies, and basic science
PubMed 30741888 · doi:10.1097/MAO.0000000000002148
What was done
Authors conducted a systematic review following PRISMA guidelines across PubMed/MEDLINE, Scopus, and Cochrane Library through March 21, 2018. They searched for basic science, epidemiological studies, randomized controlled trials, cohort studies, case reports, reviews, meta-analyses, press releases, and newsletters evaluating the relationship between phosphodiesterase-5 (PDE-5) inhibitors and ototoxicity.
What was found
Twenty-two articles met inclusion criteria. Nine case reports were identified (all male, mean age 57.4 years, range 37–79 years), where hearing loss was unilateral in 75% (6/8) and bilateral in 25% (2/8); 22% (2/9) had tinnitus and 33% (3/9) had vestibular symptoms. Across multipatient studies, all prospective studies failed to find a significant association between PDE-5 inhibitor use and ototoxicity, and retrospective studies yielded heterogeneous results. Basic science literature showed key pathway molecules in the cochlea but suggested both ototoxic and otoprotective mechanisms.
Why it matters
Despite regulatory warnings, high-quality prospective clinical evidence does not support a clear link between PDE-5 inhibitors and sudden hearing loss.
Limits
The review included highly heterogeneous study types, including press releases and uncontrolled case reports. Audiometric data across retrospective studies were inconsistent, and well-powered double-blind placebo-controlled trials with objective audiometric tracking remain lacking.
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