Risk of sudden sensorineural hearing loss in adults using phosphodiesterase type 5 inhibitors: Population-based cohort study

Pharmacoepidemiol Drug Saf. 2018 Jun;27(6):587-595. doi: 10.1002/pds.4405. Epub 2018 Mar 7.


Purpose: The objective of the study was to determine the risk of sudden sensorineural hearing loss (SNHL) associated with use of phosphodiesterase type 5 (PDE5) inhibitors.

Methods: We conducted a retrospective cohort study in the MarketScan Commercial Claims and Encounters Database including adult men who initiated a PDE5 inhibitor (n = 377,722) and 1,957,233 nonusers between 1998 and 2007. Periods of drug exposure were assessed on a weekly basis based on pharmacy billing records, assuming use of 1 dose per week (current use). Incident sudden SNHL was defined based on inpatient or outpatient visits with International Classification of Diseases, Ninth Revision, Clinical Modification codes 389.1x, 389.2x, or 388.2 plus ≥2 procedure codes for audiometric hearing testing within ±30 days of sudden SNHL diagnosis. We used age- and propensity score-adjusted Cox proportional hazards model to evaluate the risk of sudden SNHL during periods of current or recent use compared with that of nonuse. We conducted sensitivity analyses by varying the assumed drug utilization frequency and sudden SNHL case definition.

Results: We evaluated 1233 sudden SNHL cases, resulting in an incidence of 4.35, 5.58, and 2.38 per 10,000 person-years for current, recent, and nonuse of PDE5 inhibitors, respectively. Compared with nonuse, the adjusted hazard ratio was 1.25 (1.01-1.55) for current use with a risk difference of 1.97 (1.12-2.82) per 10,000 person-years. For recent use, the adjusted hazard ratio was 1.60 (1.33-1.94) and risk difference was 3.19 (2.24-4.14). Estimates were consistent across the sensitivity analyses.

Conclusions: Use of PDE5 inhibitors is associated with a small but significantly increased risk of sudden SNHL.

Keywords: erectile dysfunction; ototoxicity; pharmacoepidemiology; phosphodiesterase 5 inhibitor; sudden sensorineural hearing loss.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Databases, Factual / statistics & numerical data
  • Erectile Dysfunction / drug therapy*
  • Female
  • Hearing Loss, Sensorineural / chemically induced
  • Hearing Loss, Sensorineural / epidemiology*
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • United States / epidemiology
  • Young Adult


  • Phosphodiesterase 5 Inhibitors