In Defense of Phosphodiesterase 5 Inhibitors

Abstract

To the Editor Erectile dysfunction (ED) affects over half of all older than 40 years. 1 Until recently, when a patient would ask if taking a phosphodiesterase inhibitor for ED was dangerous, most prescribers would respond no. Our faith in this answer may be diminished somewhat following the publication of the investigation by Etminan et al. 2 In a current issue of JAMA Ophthalmology, they 2 reported an association between phosphodiesterase 5 inhibitors (PDE5Is) and an increased risk of ocular adverse events (ie, serous retinal detachment, retinal vascular occlusion, or ischemic optic neuropathy). While we would encourage continued vigilance for pharmaceutical safety, the conclusions of the authors raise concerns.First and most importantly, the risk factors for ED and serious ocular events overlap. 3,4 Just as serous retinal detachment, retinal vascular occlusion, and ischemic optic neuropathy are associated with cardiovascular and metabolic disease, vasculogenic disease remains the most common cause of ED. With inadequate arterial inflow, men are unable to achieve or maintain erections sufficient for intercourse. Indeed, the differences between the group of patients treated with PDE5Is and the enrollment and age-matched control group are severely unbalanced, and may be challenging for a multivariable model to disentangle. The rates of hypertension, diabetes, and other similar cardiovascular risk factors are much higher in the case group, which often occurs with such matching strategies using claims-based data. Moreover, by examining only a single treatment for ED (ie, PDE5i) compared with the other treatments (ie, penile suppositories, penile injections, penile implant surgery, etc), it is difficult to distinguish the culprit as the disease or the treatment.Additionally, given the important role of age and sexual hormones in ED, analyses taking younger men and serum testosterone levels into consideration could have helped to better characterize possible interactions with patients' age and hormonal profiles. PDE5Is are one of the most prescribed classes of drugs worldwide and it is imperative to understand the true risks of use given the importance for both patient and partner quality of life. 5