Abstract
Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra related ototoxicity in humans.
Highlights
Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), was originally synthesized for angina pectoris
Mice Mice from two inbred genetic backgrounds were used in this study: C57BL/6J, which is genetically predisposed to age-related hearing loss, and FVB/N, which is not predisposed to acquire hearing loss and considered to be a ‘good hearing’ strain
We carried out longitudinal evaluation of hearing during treatment: Our results indicate that, within the mouse model, chronic, systemic (IP) administration (30 days) of sildenafil citrate at a concentration of 10 mg per kg of body weight (MPK) does not affect hearing sensitivity in C57BL/6J (Fig. 1) or FVB/N (Fig. 2)
Summary
Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), was originally synthesized for angina pectoris. It was patented in 1996, approved by the FDA in 1998, and prescribed for erectile dysfunction and pulmonary hypertension. Introduced in 50 countries with multiple PDE5i formulations (tadalafil or Cialis, vardenafil or Levitra), patents expiring globally, and investigations for off-label use, such as in cardiovascular disease [4] or altitude sickness [5,6], we may see an increase in the amount of PDE5i prescribed and more longterm side effects surfacing as a result. One specific side effect that requires further investigation is sudden sensorineural hearing loss (SSHL). SSHL is characterized by a sudden or rapid loss of hearing, often causing distress in affected patients. The incidence of SSHL is approximately 4,000 cases per year with an unknown etiology but can be attributed to multiple underlying causes, such as viral infections or ototoxic drugs [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
