Phosphodiesterase 5 Inhibitor Use and Risk of Conventional and Serrated Precursors of Colorectal Cancer

Abstract

Background: Phosphodiesterase 5 (PDE5) inhibitors have been hypothesized to have chemoprotective effects in colorectal cancer. Current population-based epidemiologic evidence is, however, limited and inconsistent. Methods: Among 18,123 men in the Health Professionals Follow-up Study who had at least one lower gastrointestinal endoscopy, we evaluated the association between PDE5 inhibitor use and risk of conventional adenoma and serrated lesion between 2000 and 2010, adjusted for repeated observations and multiple risk factors. We stratified by erectile dysfunction to account for potential “confounding by indication.” Results: We documented 2,595 conventional adenomas and 1,395 serrated lesion polyps during the follow-up period. Using people without erectile dysfunction as reference group, recent PDE5 inhibitor use at baseline was not associated with lower risk of conventional adenoma [erectile dysfunction with PDE5 inhibitors: OR = 1.08; 95% confidence interval (CI) = 0.92–1.26; erectile dysfunction without PDE5 inhibitors: OR = 0.95; 95% CI, 0.85–1.06], serrated lesions (erectile dysfunction with PDE5 inhibitors: OR = 1.19; 95% CI = 0.97–1.45; erectile dysfunction without PDE5 inhibitors: OR = 1.03; 95% CI = 0.89–1.19), or advanced conventional adenomas (erectile dysfunction with PDE5 inhibitors: OR = 1.20; 95% CI = 0.94–1.53; erectile dysfunction without PDE5 inhibitors: OR = 0.95; 95% CI = 0.79–1.14). No association was found for PDE5 inhibitor use ever before as well. Conclusions: We found no evidence of an association between PDE5 inhibitor use and risk of conventional and serrated precursors of colorectal cancer. Impact: We show that PDE5 inhibitor use is not associated with precursors of colorectal cancer adjusted for medical and lifestyle risk factors among a large population of men with 10 years of follow-up.

The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta‐analysis

“…Three studies [25, 29, 34] compared sildenafil monotherapy users with nonusers of PDE5 inhibitor. Subgroup analysis did not show an association between sildenafil monotherapy and a lower risk of CRC or advanced colorectal polyps (Figure 6A; OR 0.98, CI 0.79–1.22, p = 0.86, I 2 = 66%).…”

“…Bhagavathula et al [37] reported that users of PDE5 inhibitors had a significantly reduced risk of developing CRC (RR 0.85, CI 0.76–0.95, p = 0.004). However, omission of two relevant studies [22, 29], exclusion of subgroup analysis on primary and secondary prevention and lack of prospective PROSPERO registration of the previous meta‐analysis warranted the conduction of a more comprehensive review on this subject area. The protective effect of PDE5 inhibitors on CRC risk suggested in the present study contrasts with that reported by Soriano et al [36], who found that once the confounder of erectile dysfunction was accounted for no reduced risk of CRC was observed among users of PDE5 inhibitors.…”

“…A total of 675 publications were identified using the predefined search terms, of which six were eligible for inclusion [22,25,29,[34][35][36]. Four were retrospective cohort studies [22,25,29,34] and two were case-control studies [35,36]. All studies were published between 2016 and 2021.…”

“…All studies were published between 2016 and 2021. Study populations originated from the USA [25,29], the UK [35,36] and Sweden [22,34]. There was 100%…”

“…Several cohort studies have examined the association between PDE5 inhibitors and the risk of CRC or advanced colonic polyps, with conflicting results [22,25,29]. The aim of this study was to clarify whether an association between PDE5 inhibitor use and CRC risk exists through systematic review and meta-analysis of published peer-reviewed studies.…”