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Systematic review of oral combination therapy for erectile dysfunction when phosphodiesterase type 5 inhibitor monotherapy fails

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Systematic review of oral combination therapy for erectile dysfunction when phosphodiesterase type 5 inhibitor monotherapy fails. / Munk, Nicolai Egholt; Knudsen, Jakob Schöllhammer; Comerma-Steffensen, Simon; Simonsen, Ulf.

In: Sexual Medicine Reviews, Vol. 7, No. 3, 07.2019, p. 430-441.

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@article{c27f9106b7ff4b2f9580bb38b320ffc8,
title = "Systematic review of oral combination therapy for erectile dysfunction when phosphodiesterase type 5 inhibitor monotherapy fails",
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.",
keywords = "Adrenoceptor antagonist, Androgen, Combination therapy, Erection, Phosphodiesterase type 5 inhibitor, Sildenafil",
author = "Munk, {Nicolai Egholt} and Knudsen, {Jakob Sch{\"o}llhammer} and Simon Comerma-Steffensen and Ulf Simonsen",
year = "2019",
month = "7",
doi = "10.1016/j.sxmr.2018.11.007",
language = "English",
volume = "7",
pages = "430--441",
journal = "Sexual Medicine Reviews",
issn = "2050-0513",
publisher = "Elsevier Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Systematic review of oral combination therapy for erectile dysfunction when phosphodiesterase type 5 inhibitor monotherapy fails

AU - Munk, Nicolai Egholt

AU - Knudsen, Jakob Schöllhammer

AU - Comerma-Steffensen, Simon

AU - Simonsen, Ulf

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - Adrenoceptor antagonist

KW - Androgen

KW - Combination therapy

KW - Erection

KW - Phosphodiesterase type 5 inhibitor

KW - Sildenafil

UR - http://www.scopus.com/inward/record.url?scp=85060719885&partnerID=8YFLogxK

U2 - 10.1016/j.sxmr.2018.11.007

DO - 10.1016/j.sxmr.2018.11.007

M3 - Review

C2 - 30711478

AN - SCOPUS:85060719885

VL - 7

SP - 430

EP - 441

JO - Sexual Medicine Reviews

JF - Sexual Medicine Reviews

SN - 2050-0513

IS - 3

ER -