Nicolai Egholt Munk1, Jakob Schöllhammer Knudsen2, Simon Comerma-Steffensen1, Ulf Simonsen3. 1. Department of Biomedicine, Aarhus University, Aarhus, Denmark. 2. Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Biomedicine, Aarhus University, Aarhus, Denmark. Electronic address: us@biomed.au.dk.
Abstract
INTRODUCTION: On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. AIM: To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. METHODS: PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. MAIN OUTCOME MEASURES: The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). RESULTS: Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. CONCLUSION: For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, et al. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.
INTRODUCTION: On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. AIM: To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. METHODS: PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. MAIN OUTCOME MEASURES: The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). RESULTS: Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. CONCLUSION: For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, et al. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.
Authors: Pablo Garrido-Abad; Isabel Senra-Bravo; Celeste Manfredi; Esaú Fernández-Pascual; Estefanía Linares-Espinós; Manuel Fernández-Arjona; David Varillas-Delgado; Juan Ignacio Martínez-Salamanca Journal: Int J Impot Res Date: 2021-01-22 Impact factor: 2.408