Systematic Review Article

Phosphodiesterases 5 Inhibitors and Erectile Dysfunction Recovery after Pelvic Surgery: Future Perspectives for New Drugs and New Formulations

Author(s): Riccardo Lombardo, Giorgia Tema and Cosimo De Nunzio*

Volume 22, Issue 1, 2021

Published on: 25 September, 2020

Page: [31 - 37] Pages: 7

DOI: 10.2174/1389450121666200925145347

Price: $65

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Abstract

Background: Phosphodiesterase 5 inhibitors (PDE5I) represent the first-line treatment in the management of post-operative erectile dysfunction (ED) after pelvic oncological surgery. The aim of our study is to evaluate the available evidence on the efficacy of PDE5Is, including new formulations and penile rehabilitation post-pelvic surgery.

Evidence Acquisition: A systematic review of the literature was performed until May 2020. The following databases were searched: Scopus, Medline and Web of Science. The MeSH search was conducted by combining the following terms: ‘erectile dysfunction’, ‘radical prostatectomy’ ‘pelvic’ ‘bladder’ ‘phosphodiesterase’ inhibitors’ ‘avanafil’ ‘sildenafil’ ‘tadalafil’ ’lodenafil’ ‘mirodenafil’ ‘udenafil’ ‘vardenafil’ ‘sublingual’ ‘orodispersible’ ‘penile’ ‘rehabilitation’.

Evidence Synthesis: Sildenafil, Tadalafil, vardenafil and Avanafil improve EF compared with placebo in men with all levels of ED severity after radical prostatectomy with good tolerability. No specific recommendations can be suggested regarding the superiority of a drug over the other. The optimal dose, continuous vs. on-demand and duration of treatment, is still under investigation. In vitro and preclinical studies suggest the possible role for lodenafil, mirodenafil and oro-dispersible formulations in patients undergoing oncological pelvic surgery. Few studies demonstrated the efficacy of udenafil in improving ED after rectal surgery or radical prostatectomy. Complete recovery of EF after surgery is still an unmet need in the field of penile rehabilitation after pelvic surgery.

Conclusion: PDE5Is have a crucial role in the management of post pelvic surgery of ED. New drugs and new formulations have shown excellent results in patients with ED; however, data in patients after surgery is still scarce. Further well designed RCT should clarify the role of these new compounds and oro-dispersible formulations in the management of ED in patients undergoing pelvic surgery.

Keywords: Phosphodiesterase 5 inhibitors, surgery, pelvic, erectile dysfunction, radical prostatectomy, penile rehabilitation, orodispersible.

Graphical Abstract
[1]
Salonia A, Adaikan G, Buvat J, Carrier S, El-Meliegy A, Hatzimouratidis , et al. Sexual rehabilitation after treatment for prostate cancer—part 1: Recommendations from the fourth international consultation for sexual medicine (ICSM 2015). J Sex Med 2017; 14: 285-96.
[2]
Foo KT. From evidence-based medicine to evidence-balanced medicine for individualized and personalized care: As applied to benign prostatic hyperplasia/male lower urinary tract symptoms. Int J Urol 2017; 24: 94-5. http://www.ncbi.nlm.nih.gov/pubmed/ 28191718
[3]
De Nunzio C, Pastore AL, Lombardo R, Cancrini F, Carbone A, Fuschi A, et al. The EORTC quality of life questionnaire predicts early and long-term incontinence in patients treated with robotic assisted radical prostatectomy: Analysis of a large single center cohort. Urol Oncol Semin Orig Investig 2019; 37: 1006-3.http://www.ncbi.nlm.nih.gov/pubmed/31326315
[4]
Capogrosso P, Vertosick EA, Benfante NE, et al. Are We Improving Erectile Function Recovery After Radical Prostatectomy? Analysis of Patients Treated over the Last Decade. Eur Urol 2019; 75(2): 221-8.
[http://dx.doi.org/10.1016/j.eururo.2018.08.039] [PMID: 30237021]
[5]
Ficarra V, Novara G, Ahlering TE, Costello A, Eastham JA, Graefen M, et al. Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol 2012; 418-30.http://www.ncbi.nlm.nih.gov/pubmed/22749850
[6]
Montorsi F, Guazzoni G, Strambi LF, Da Pozzo LF, Nava L, Barbier L, et al. Recovery of spontaneous erectile function after nervesparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: Results of a prospective, randomized trial. J Urol Elsevier Inc 1997; 158: 1408-10.
[7]
Mulhall JP, Land S, Parker M, Waters WB, Flanigan RC, Burnett AL, et al. The use of an erectogenic pharmacotheraphy regimen following radical prostatectomy improves recovery of spontaneous erectile function. J Sex Med 2005; 2: 532-40.http://www.ncbi.nlm.nih.gov/pubmed/16422848
[8]
Salonia A, Adaikan G, Buvat J, Carrier S, El-Meliegy A, Hatzimouratidis K, et al. Sexual Rehabilitation After Treatment For Prostate Cancer—Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017; 14: 297-315.
[9]
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49(6): 822-30.
[http://dx.doi.org/10.1016/S0090-4295(97)00238-0] [PMID: 9187685]
[10]
Laumann EO, Paik A, Rosen RC. Sexual Dysfunction in the United States: Prevalence and Predictors. JAMA J Am Med Assoc 1999; 281: 537-44.http://www.ncbi.nlm.nih.gov/pubmed/17365514
[11]
Peng Z, Yang L, Dong Q, Wei Q, Liu L, Yang B. Efficacy and safety of tadalafil once-a-day versus tadalafil on-demand in patients with erectile dysfunction: A systematic review and meta-analyses. Urol Int 2017; 99: 343-52.https://www.karger.com/Article/FullText/477496
[http://dx.doi.org/10.1159/000477496]
[12]
Montorsi F, Brock G, Stolzenburg JU, et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT). Eur Urol 2014; 65(3): 587-96.
[http://dx.doi.org/10.1016/j.eururo.2013.09.051] [PMID: 24169081]
[13]
Montorsi F, Oelke M, Henneges C, Brock G, Salonia A, d’Anzeo G, et al. Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy. Eur Urol 2016; 70: 529-37. http://www.ncbi.nlm.nih.gov/ pubmed/26947602
[http://dx.doi.org/10.1016/j.eururo.2016.02.036]
[14]
Schwartz EJ, Wong P, Graydon RJ. Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol 2004; 171: 771-4. http://www.ncbi.nlm.nih.gov/pubmed/ 14713808
[15]
Padma-Nathan H, McCullough AR, Levine LA, et al. Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int J Impot Res 2008; 20(5): 479-86.
[http://dx.doi.org/10.1038/ijir.2008.33] [PMID: 18650827]
[16]
Pavlovich CP, Levinson AW, Su LM, et al. Nightly vs on-demand sildenafil for penile rehabilitation after minimally invasive nerve-sparing radical prostatectomy: results of a randomized double-blind trial with placebo. BJU Int 2013; 112(6): 844-51.
[http://dx.doi.org/10.1111/bju.12253] [PMID: 23937708]
[17]
Kim DJ, Hawksworth DJ, Hurwitz LM, et al. A prospective, randomized, placebo-controlled trial of on-Demand vs. nightly sildenafil citrate as assessed by Rigiscan and the international index of erectile function. Andrology 2016; 4(1): 27-32.
[http://dx.doi.org/10.1111/andr.12118] [PMID: 26663669]
[18]
Montorsi F, Brock G, Lee J, et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol 2008; 54(4): 924-31.
[http://dx.doi.org/10.1016/j.eururo.2008.06.083] [PMID: 18640769]
[19]
Li J, Peng L, Cao D, He L, Li Y, Wei Q. Avanafil for the Treatment of men With Erectile Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Mens Health 2019; 13.
[20]
Mulhall JP, Burnett AL, Wang R, McVary KT, Moul JW, Bowden CH, et al. A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy. J Urol 2013; 189: 2229-36.http://www.ncbi.nlm.nih.gov/pubmed/23219537
[21]
Sperling H, Gittelman M, Norenberg C, Ulbrich E, Ewald S. Efficacy and Safety of an Orodispersible Vardenafil Formulation for the Treatment of Erectile Dysfunction in Elderly Men and Those with Underlying Conditions: An Integrated Analysis of Two Pivotal Trials. J Sex Med 2011; 8: 261-71. http://www.ncbi.nlm.nih. gov/pubmed/20807322
[22]
Scaglione F, Donde S, Hassan TA, Jannini EA. Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction: Pharmacology and clinical impact of the sildenafil citrate orodispersible tablet formulation. Clin Ther Excerpta Medica Inc 2017; 370-7.http://www.ncbi.nlm.nih.gov/pubmed/28139291
[23]
Cocci A, Cito G, Urzì D, et al. Sildenafil 25 mg ODT + Collagenase Clostridium hystoliticum vs Collagenase Clostridium hystoliticum Alone for the Management of Peyronie’s Disease: A Matched-Pair Comparison Analysis. J Sex Med 2018; 15(10): 1472-7.
[http://dx.doi.org/10.1016/j.jsxm.2018.08.012] [PMID: 30245025]
[24]
Ding H, Du W, Wang H, et al. Efficacy and safety of udenafil for erectile dysfunction: a meta-analysis of randomized controlled trials. Urology 2012; 80(1): 134-9.
[http://dx.doi.org/10.1016/j.urology.2012.02.014] [PMID: 22497982]
[25]
Kim TH, Ha YS, Choi SH, et al. Factors predicting outcomes of penile rehabilitation with udenafil 50 mg following radical prostatectomy. Int J Impot Res 2016; 28(1): 25-30.
[http://dx.doi.org/10.1038/ijir.2015.28] [PMID: 26510966]
[26]
Park SY, Choi GS, Park JS, Kim HJ, Park JA, Choi JI. Efficacy and safety of udenafil for the treatment of erectile dysfunction after total mesorectal excision of rectal cancer: A randomized, double-blind, placebo-controlled trial. Surg (United States) 2015; 157: 64-71.
[http://dx.doi.org/10.1016/j.surg.2014.07.007]
[27]
Toque HA, Teixeira CE, Lorenzetti R, Okuyama CE, Antunes E, De Nucci G. Pharmacological characterization of a novel phosphodiesterase type 5 (PDE5) inhibitor lodenafil carbonate on human and rabbit corpus cavernosum. Eur J Pharmacol 2008; 591(1-3): 189-95.
[http://dx.doi.org/10.1016/j.ejphar.2008.06.055] [PMID: 18593576]
[28]
Glina S, Toscano I, Gomatzky C, de Góes PM, Júnior AN, Claro JF de A, et al. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: a phase II clinical trial. J Sex Med 2009; 6: 553-7.http://www.ncbi.nlm.nih.gov/pubmed/19040623
[29]
Glina S, Fonseca GN, Bertero EB, et al. Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: a phase III clinical trial. J Sex Med 2010; 7(5): 1928-36.
[http://dx.doi.org/10.1111/j.1743-6109.2010.01711.x] [PMID: 20214718]
[30]
Park HJ, Moon KH, Lee SW, Lee WK, Kam SC, Lee JH, et al. Mirodenafil for the Treatment of Erectile Dysfunction: A Systematic Review of the Literature. World J Mens Health 2014; 32: 18.http://www.ncbi.nlm.nih.gov/pubmed/24872948
[http://dx.doi.org/10.5534/wjmh.2014.32.1.18]
[31]
De Nunzio C, Lombardo R, Tema G, Tubaro A. Erectile dysfunction and lower urinary tract symptoms. Curr Urol Rep 2018; 61.http://www.ncbi.nlm.nih.gov/pubmed/29858709
[32]
Philippou YA, Jung JH, Steggall MJ, O’driscoll ST, Bakker CJ, Bodie JA, et al. Penile rehabilitation for postprostatectomy erectile dysfunction. Cochrane Database Syst Rev 2018; CDO12414. http://www.ncbi.nlm.nih.gov/ pubmed/30352488

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