Histopathologic results of long-term sildenafil administration on rat inner ear

Phosphodiesterase Type 5 Inhibitors and sudden sensorineural hearing loss

“…In the control group, the caspase 3 immunoreactivity was not observed. Thus, the authors concluded that caspase-3 immunostaining in the sildenafil group was strongly associated with an increase in apoptotic events in the cochlea, and the long-term use of sildenafil may cause hearing loss by increasing apoptosis 15 .…”

Sudden hearing loss after cialis (tadalafil) use: A unique case of cochlear hydrops

“…[4][5][6][7][8][9] Prior animal studies, however, have been conflicting and inconclusive of causation. [10][11][12][13] Until recently, our understanding of cochlear disorders was based on histologic or molecular findings in postmortem and animal studies. With advances in imaging techniques, however, magnetic resonance imaging (MRI) is now being used in the study of endolymphatic hydrops (EH) and SSNHL.…”

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

“…10 In a study that examined inner ear specimens from mice given sildenafil, increased caspase 3 immunoreactivity was observed, suggesting that apoptosis was responsible for the induced hearing impairment. 11 In contrast, another study found that daily administration of sildenafil 10 mg/kg for 30 days did not affect hearing in mice. 12 Despite these scattered reports, exact biological mechanisms responsible for PDE5 inhibitor-induced sudden SNHL are still unclear.…”

“…Using a mouse model, Hong et al showed that high dose sildenafil treatment (up to 10 mg/kg) can cause threshold shift of auditory brainstem responses and changes in transient evoked otoacoustic emissions after long‐term treatment (up to 105 days) which suggested that cochlear outer hair cells were damaged by sildenafil . In a study that examined inner ear specimens from mice given sildenafil, increased caspase 3 immunoreactivity was observed, suggesting that apoptosis was responsible for the induced hearing impairment . In contrast, another study found that daily administration of sildenafil 10 mg/kg for 30 days did not affect hearing in mice …”

“…safety signal, the FDA approved more stringent labeling alerting to the potential risk of sudden hearing loss in men by using PDE5 inhibitors. 7 Since then, additional data from mouse model, [10][11][12] case reports, [13][14][15] small clinical studies, 16,17 and pharmacovigilance 18 have been published, raising further concern. While the association is perhaps initially surprising, a plausible mechanism for PDE5 inhibitor ototoxicity involves the nitric oxide-cyclic guanosine monophosphate signaling pathway 13 that has also been implicated with ototoxicity of gentamicin and cisplatin 19,20 To date, no large postmarketing safety studies of PDE5 inhibitor ototoxicity have been reported.…”