Columbia, SC—PDE-5 inhibitors are approved by the FDA to treat erectile dysfunction, but a new study suggests that the drugs also might be a viable chemopreventive agent for some types of cancer.

The article in Clinical and Translational Gastroenterology cites past research indicating that PDEs (phosphodiesterases) are involved in the development and progression of colorectal cancer, with one type of PDE isozyme being the PDE-5, which is specific to cyclic guanosine monophosphate. 

Researchers from the University of South Carolina College of Pharmacy and WB Dorn Veterans Affairs Medical Center (VHA), both in Columbia, South Carolina, point out that targeting cyclic guanosine monophosphate with PDE-5 inhibitors might reduce the incidence of intestinal cancer via altering epithelial homeostasis. Citing recent preclinical studies including in vivo, in vitro, and mouse studies indicating that PDE-5 inhibitor use possibly could reduce the risk of colorectal cancer, the study team sought to examine the association between PDE-5 inhibitor use and incidence of colorectal cancer among VHA patients with erectile dysfunction.

The retrospective cohort study using the Veterans Affairs Informatics and Computing Infrastructure was conducted with data from January 2001 to December 2016. Researchers followed patients from index until the first diagnosis of colorectal cancer, death, or the end of the study. Included in the study were 192,691 patients in the PDE-5 cohort and 29,227 patients in the never-use PDE-5 cohort.

Analysis revealed that the those who had any exposure to a PDE-5 inhibitor have an 18% lower hazard of colorectal cancer (adjusted hazard ratio [HR], 0.816; 95% confidence interval [CI], 0.754-0.882). For each additional 100-mg dosage of sildenafil and 10-mg dosage of tadalafil, the hazard of colorectal cancer is reduced by 2.4% (adjusted HR, 0.976; 95% CI, 0.973-0.979) and 1.7% (adjusted HR, 0.983; 95% CI, 0.972-0.996), respectively, according to the researchers.

“PDE-5 inhibitor usage in patients with erectile dysfunction is associated with a lower hazard of colorectal cancer compared with patients not exposed to PDE-5 inhibitors,” the authors conclude.

The study team also estimates the effect of additional dosages of each specific PDE-5 inhibitor, excluding avanafil, explaining, “We found for each additional 100-mg dosage of sildenafil and each additional 10-mg dose of tadalafil, the hazard of colorectal cancer is reduced. In the subanalysis, patients who had monotherapy with sildenafil only had a decreased hazard of colorectal cancer for each additional 100 mg of treatment. However, for each additional 10 mg of vardenafil, there is a higher hazard of colorectal cancer for those on vardenafil only.”

The authors suggest that their research was the “first population-based study to examine the function of PDE-5 inhibitors along with the risk of colorectal cancer among patients with ED. Our study is unique because it (i) evaluated a national cohort of patients with ED, (ii) evaluated patients who were prescribed PDE-5 inhibitors (sildenafil, tadalafil, vardenafil, and avanafil), and (iii) evaluated PDE-5 usage 2 ways (binary and dosage).”

Recommending further research on the topic, researchers advise that “clinicians should monitor and understand the risks and benefits of PDE-5 inhibitors with the occurrence of colorectal cancer among patients with ED.”

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