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Phosphodiesterase-5 (PDE-5) Inhibitors and Ototoxicity

A Systematic Review

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

doi: 10.1097/MAO.0000000000002148

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.

Department of Otolaryngology—Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, New York

Address correspondence and reprint requests to Vivian F. Kaul, M.D., Department of Otolaryngology—Head and Neck Surgery, One Gustave L Levy Place—Box 1189, New York, NY 10029; E-mail:

Funding and conflicts of interest: The authors have no funding, financial relationships, or conflicts of interest to disclose.

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