LAUSR

INTRODUCTION Several treatment strategies are nowadays available for erectile dysfunction (ED) patients. Currently, oral phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line therapy for ED. However, they are effective in all treated cases with variable non-responsiveness. Many factors have been listed for this behavior, but the possibility of gene polymorphisms as an underlying cause has not been systematically investigated. OBJECTIVES This review aimed to assess the possible involvement of gene polymorphisms affecting the response to PDE5Is in men with ED. METHODS A systematic review was conducted based on a search of all relevant articles in various electronic sites such as PubMed, Medline Medical Subject Headings, Cochrane Library, Science Direct, Scopus, Embase, CINAHL, and Egyptian Knowledge Bank databases. Keywords used for relevant associations were sexual health, genes, variants, erectile dysfunction, polymorphisms, PDE5Is, and cavernous tissues. RESULTS Several studies have been carried out to determine the contribution of different encoded genes to ascertain the association between different genotypes and ED men who were non-responders for PDE5Is. 11 studies were selected for this review. In these studies, 6 investigated eNOS genetic polymorphism with variable outcomes. Only 1 study was carried out for each of the following genetic polymorphisms: phosphodiestrase 5A, G-protein β3 subunit, angiotensin converting enzyme, dimethylarginine dimethylaminohydrolase, arginase, and vascular endothelial growth factor with variable results. CONCLUSION Despite the relative shortage of available studies and the varied methodologies used, most of the research articles demonstrated a significant association between genetic polymorphism and the response to PDE5Is, especially for endothelial nitric oxide synthase polymorphism. The limited number of studies that investigated the possible effect of genetic polymorphism and the response to PDE5Is are challenged by many factors, particularly for the definition of responders and non-responders. This should be a motivating factor for researchers to perform further studies with a standardized methodology to address the influence of genetic variations on the response to PDE5Is. Mostafa T, Hassan A, Alghobary MF, et al. Effect of Genetic Polymorphism on the Response to PDE5 Inhibitors in Patients With Erectile Dysfunction: A Systematic Review and a Critical Appraisal. J Sex Med 2020;XX:XXX-XXX.