Can long-term use of sildenafil impact cardiovascular health or cause hearing loss?
Executive summary
Long-term sildenafil use carries known cardiovascular cautions—most critically dangerous interactions (for example with nitrates) and rare reports of serious cardiac events—while population and pharmacovigilance data also link sildenafil and other PDE‑5 inhibitors to sudden sensorineural hearing loss, though causation is not firmly established [1] [2] [3]. Animal studies, case series, and real‑world adverse‑event signals strengthen concern about ototoxicity, but confounding factors and limited prospective human data mean the risk remains incompletely quantified [4] [5] [6].
1. Cardiovascular risk: established interactions and context
Sildenafil is explicitly contraindicated with nitric‑oxide donors such as nitroglycerin because the combination can cause a severe and potentially life‑threatening drop in blood pressure, and prescribing information warns caution in people with cardiovascular disease [1]. Post‑marketing surveillance has reported rare but serious cardiovascular events—myocardial infarction, ventricular arrhythmias, stroke—after sildenafil use, but regulatory and clinical reviews note that many reported cardiac events involved patients with preexisting heart disease or occurred in temporal association with sex or other risk factors, so a direct causal role for sildenafil in most cases is uncertain [1] [2]. Clinical guidance therefore emphasizes individual cardiac assessment before prescribing sildenafil and advising patients with significant heart disease about the risks of sexual activity itself as well as drug interactions [2].
2. Hearing loss: signals, case reports, and mechanistic plausibility
Since the first published case reports in 2007, sudden sensorineural hearing loss (SSNHL) temporally linked to PDE‑5 inhibitors—most often sildenafil—has been repeatedly reported in case series, pharmacovigilance analyses, and observational studies, prompting an FDA labeling change to highlight the risk [1] [6] [3]. Analyses of the FDA Adverse Event Reporting System show disproportionate reporting of hearing impairment with sildenafil and other PDE‑5 inhibitors, with signals for sudden hearing loss stronger for some agents and tinnitus reported for others [3]. Reviews and expert summaries conclude there is growing evidence and plausible physiologic mechanisms—vascular or cochlear effects—by which PDE‑5 inhibition might precipitate sensorineural injury, yet authors uniformly call for greater awareness while acknowledging limitations in the evidence base [7] [6].
3. Animal and histopathologic studies: mixed and dose‑dependent findings
Laboratory work gives conflicting signals: some rodent studies found hearing deficits after long‑term, high‑dose sildenafil exposure and histopathologic cochlear changes consistent with increased apoptosis, while other animal studies of related PDE‑5 inhibitors suggested protective effects against noise‑induced hearing loss, indicating species, dose, and model differences that complicate translation to humans [4] [5]. These preclinical data provide biological plausibility but cannot by themselves quantify risk at clinically used doses in humans or settle whether long‑term therapeutic use carries a measurable ototoxic risk [4] [5].
4. Real‑world epidemiology and clinical uncertainty
Epidemiological studies have suggested associations between PDE‑5 inhibitor use and self‑reported or clinically identified hearing impairment, with some studies finding stronger associations for sildenafil than for other drugs in the class, but observational designs leave open confounding by age, noise exposure, comorbid vascular disease, or concomitant ototoxic medications [8] [9]. Pharmacovigilance studies identify a signal, but adverse‑event reporting systems cannot determine incidence or causality; reviewers therefore call for prospective, controlled studies and for clinicians to warn patients to report sudden hearing changes promptly [3] [6].
5. Practical takeaways and open questions
Clinically, the balance is pragmatic: avoid sildenafil with nitrates and exercise caution in patients with unstable cardiac disease; be alert that rare but serious cardiovascular and auditory events have been reported, and advise patients to stop the drug and seek immediate care for sudden hearing loss or other severe symptoms [1] [10] [2]. The evidence supports concern—especially from pharmacovigilance and case literature—but not definitive proof that long‑term therapeutic sildenafil use at prescribed doses causes progressive hearing loss or cardiovascular injury in otherwise healthy people; important gaps remain, notably prospective incidence data and well‑controlled cohort studies to separate drug effects from underlying risk factors [3] [6].