Phosphodiesterase-5 (PDE-5) Inhibitors and Ototoxicity: A Systematic Review

Sayan Manna, Mingyang Liu Gray, Vivian F. Kaul, George Wanna

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Objective:This study explores the current literature regarding associations between phosphodiesterase-5 (PDE-5) inhibitors and ototoxicity and provides a detailed summary and discussion of the findings. Data Sources: A comprehensive electronic search of PubMed/MEDLINE, Scopus, and Cochrane Library for studies published from database inception through March 21, 2018. Study Selection: Basic science articles, epidemiological studies, randomized controlled trials, cohort studies, case reports, reviews, meta-analyses, press releases, and newsletters were included. The PRISMA search strategy was used to select papers. Search terms are included in the appendix ( Results: Twenty-two articles met the inclusion criteria. Among case reports, there were a total of nine patients, all male, with an average age of 57.4 years (37-79 years, SD = 13.87 years). Of the cases of hearing loss, 25% (2/8 cases) were bilateral and 75% (6/8) were unilateral; 22% (2/9) were associated with tinnitus; and 33% (3/9) had accompanying vestibular symptoms (including vertigo and dizziness). Among multipatient studies, all prospective studies failed to find a significant association between ototoxicity and PDE-5 inhibitor use. Results of the retrospective studies were also heterogeneous. Many key molecules in the PDE-5 inhibition pathway have been demonstrated to exist in the cochlea. However, mirroring the clinical studies, the basic science mechanisms have suggested both ototoxic and otoprotective effects. Conclusions: Currently, the literature is inconclusive regarding the interaction between PDE-5 inhibitor use and ototoxicity. Future study such as a double-blinded placebo controlled randomized trial with audiometric assessment would provide more sound evidence. Similarly, a unified molecular model is necessary.

Original languageEnglish
Pages (from-to)276-283
Number of pages8
JournalOtology and Neurotology
Issue number3
StatePublished - 1 Mar 2019


  • Cialis
  • Erectile dysfunction (ED)
  • Levitra
  • Ototoxicity
  • Phosphodiesterase-5 (PDE-5) inhibitor
  • Pulmonary hypertension
  • Sildenafil citrate
  • Sudden Sensorineural hearing loss
  • Tadalafil
  • Tinnitus
  • Vardenafil
  • Viagra


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