Phosphodiesterase Type 5 Inhibitors in Postprostatectomy Erectile Dysfunction: A Critical Analysis of the Basic Science Rationale and Clinical Application

European Urology

Volumn 55, Issue 2, 2009, Pages 334-347

  Hatzimouratidis, Konstantinos ^a   Burnett, Arthur L ^b   Hatzichristou, Dimitrios ^a   McCullough, Andrew R ^c   Montorsi, Francesco ^d   Mulhall, John P ^e  

^a ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^b JOHNS HOPKINS HOSPITAL   (United States)

^c NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^e MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Erectile dysfunction; Penile rehabilitation; Phosphodiesterase type 5 inhibitors; Radical prostatectomy

Indexed keywords

LEVACECARNINE; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROPIONYLCARNITINE; PROSTAGLANDIN E1; SILDENAFIL; TADALAFIL; VARDENAFIL;

CLINICAL PRACTICE; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; ERECTILE DYSFUNCTION; EVIDENCE BASED MEDICINE; HEMODYNAMICS; HUMAN; MEDICAL ASSESSMENT; NERVE INJURY; NONHUMAN; OXYGENATION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROPHYLAXIS; PROSTATECTOMY; REHABILITATION CARE; REVIEW; SEXUAL INTERCOURSE; SYSTEMATIC REVIEW;

CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 5; ERECTILE DYSFUNCTION; HUMANS; MALE; PHOSPHODIESTERASE INHIBITORS; POSTOPERATIVE COMPLICATIONS; PROSTATECTOMY; QUALITY OF LIFE; RECOVERY OF FUNCTION; VASODILATOR AGENTS;

EID: 57649184019     PISSN: 03022838     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.eururo.2008.10.028     Document Type: Review

References (97)

1. Heidenreich A., Aus G., Bolla M., et al. EAU guidelines on prostate cancer. Eur Urol 53 (2008) 68-80
2. Stephenson R.A., Mori M., Hsieh Y.C., et al. Treatment of erectile dysfunction following therapy for clinically localized prostate cancer: patient reported use and outcomes from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study. J Urol 174 (2005) 646-650 discussion 650
3. Kundu S.D., Roehl K.A., Eggener S.E., Antenor J.A., Han M., and Catalona W.J. Potency, continence, and complications in 3,477 consecutive radical retropubic prostatectomies. J Urol 172 (2004) 2227-2231
4. Walsh P.C., Marschke P., Ricker D., and Burnett A.L. Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology 55 (2000) 58-61
5. Rabbani F., Stapleton A.M., Kattan M.W., Wheeler T.M., and Scardino P.T. Factors predicting recovery of erections after radical prostatectomy. J Urol 164 (2000) 1929-1934
6. Schover L.R., Fouladi R.T., Warneke C.L., et al. Defining sexual outcomes after treatment for localized prostate carcinoma. Cancer 95 (2002) 1773-1785
7. Zippe C.D., and Pahlajani G. Penile rehabilitation following radical prostatectomy: role of early intervention and chronic therapy. Urol Clin North Am 34 (2007) 601-618 viii
8. Hatzimouratidis K., and Hatzichristou D. Phosphodiesterase type 5 inhibitors: the day after. Eur Urol 51 (2007) 75-89 discussion 89
9. Mulhall J.P., and Morgentaler A. Penile rehabilitation should become the norm for radical prostatectomy patients. J Sex Med 4 (2007) 538-543
10. Burnett A.L. Rationale for cavernous nerve restorative therapy to preserve erectile function after radical prostatectomy. Urology 61 (2003) 491-497
11. Klein L.T., Miller M.I., Buttyan R., et al. Apoptosis in the rat penis after penile denervation. J Urol 158 (1997) 626-630
12. Daley J.T., Watkins M.T., Brown M.L., Martinez V., Cuevas P., and Saenz de Tejada I. Prostanoid production in rabbit corpus cavernosum. II. Inhibition by oxidative stress. J Urol 156 (1996) 1169-1173
13. Moreland R.B. Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence. Int J Impot Res 10 (1998) 113-120
14. Leungwattanakij S., Bivalacqua T.J., Usta M.F., et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl 24 (2003) 239-245
15. User H.M., Hairston J.H., Zelner D.J., McKenna K.E., and McVary K.T. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol 169 (2003) 1175-1179
16. Mullerad M., Donohue J.F., Li P.S., Scardino P.T., and Mulhall J.P. Functional sequelae of cavernous nerve injury in the rat: Is there model dependency?. J Sex Med 3 (2006) 77-83
17. Granchi S., Vannelli G.B., Vignozzi L., et al. Expression and regulation of endothelin-1 and its receptors in human penile smooth muscle cells. Mol Hum Reprod 8 (2002) 1053-1064
18. Muller A., Tal R., Donohue J.F., Akin-Olugbade Y., et al. The effect of hyperbaric oxygen therapy on erectile function recovery in a rat cavernous nerve injury model. J Sex Med 5 (2008) 562-570
19. Rambhatla A., Kovanecz I., Ferrini M., Gonzalez-Cadavid N.F., and Rajfer J. Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review. Int J Impot Res 20 (2008) 30-34
20. Ferrini M.G., Davila H.H., Kovanecz I., Sanchez S.P., Gonzalez-Cadavid N.F., and Rajfer J. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology 68 (2006) 429-435
21. Kovanecz I., Rambhatla A., Ferrini M., et al. Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res 20 (2008) 202-212
22. Sezen S.F., Hoke A., Burnett A.L., and Snyder S.H. Immunophilin ligand FK506 is neuroprotective for penile innervation. Nat Med 7 (2001) 1073-1074
23. Mulhall J.P., Muller A., Donohue J.F., et al. FK506 and erectile function preservation in the cavernous nerve injury model: optimal dosing and timing. J Sex Med 5 (2008) 1334-1344
24. Lagoda G., Jin L., Lehrfeld T.J., Liu T., and Burnett A.L. FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. J Sex Med 4 (2007) 908-916
25. Lagoda G., Sezen S.F., Liu T., Hoke A., and Burnett A.L. FK506-binding protein localizations in human penile innervation. BJU Int 101 (2008) 604-609
26. Iacono F., Giannella R., Somma P., Manno G., Fusco F., and Mirone V. Histological alterations in cavernous tissue after radical prostatectomy. J Urol 173 (2005) 1673-1676
27. Montorsi F., Guazzoni G., Strambi L.F., et al. Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. J Urol 158 (1997) 1408-1410
28. Mulhall J.P., Slovick R., Hotaling J., et al. Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function. J Urol 167 (2002) 1371-1375
29. Mulhall J.P., Secin F.P., and Guillonneau B. Artery sparing radical prostatectomy-myth or reality?. J Urol 179 (2008) 827-831
30. Secin F.P., Touijer K., Mulhall J., and Guillonneau B. Anatomy and preservation of accessory pudendal arteries in laparoscopic radical prostatectomy. Eur Urol 51 (2007) 1229-1235
31. Rogers C.G., Trock B.P., and Walsh P.C. Preservation of accessory pudendal arteries during radical retropubic prostatectomy: surgical technique and results. Urology 64 (2004) 148-151
32. McCullough A., Woo K., Telegrafi S., and Lepor H. Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP. Int J Impot Res 14 (2002) 462-465
33. Fraiman M.C., Lepor H., and McCullough A.R. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol 3 (1999) 109-115
34. Munding M.D., Wessells H.B., and Dalkin B.L. Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy. Urology 58 (2001) 567-569
35. Savoie M., Kim S.S., and Soloway M.S. A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer. J Urol 169 (2003) 1462-1464
36. Gontero P., Galzerano M., Bartoletti R., et al. New insights into the pathogenesis of penile shortening after radical prostatectomy and the role of postoperative sexual function. J Urol 178 (2007) 602-607
37. Briganti A., Fabbri F., Salonia A., et al. Preserved postoperative penile size correlates well with maintained erectile function after bilateral nerve-sparing radical retropubic prostatectomy. Eur Urol 52 (2007) 702-707
38. Walsh P.C., and Partin A.W. Anatomic radical retropubic prostatectomy. In: Wein A.J., Kavoussi L.R., Novick A.C., Partin A.W., and Peters C.A. (Eds). Campbell-Walsh Urology. 9th ed. (2007), Saunders Elsevier, Philadelphia, PA 2956-2978
39. Michl U.H., Friedrich M.G., Graefen M., Haese A., Heinzer H., and Huland H. Prediction of postoperative sexual function after nerve-sparing radical retropubic prostatectomy. J Urol 176 (2006) 227-231
40. Walsh P.C., Marschke P., Ricker D., and Burnett A.L. Use of intraoperative video documentation to improve sexual function after radical retropubic prostatectomy. Urology 55 (2000) 62-67
41. Montorsi F., Salonia A., Suardi N., et al. Improving the preservation of the urethral sphincter and neurovascular bundles during open radical retropubic prostatectomy. Eur Urol 48 (2005) 938-945
42. Stolzenburg J.-U., Schwalenberg T., Horn L.-C., Neuhaus J., Constantinides C., and Liatsikos E.N. Anatomical landmarks of radical prostatecomy. Eur Urol 51 (2007) 629-639
43. Kessler T.M., Burkhard F.C., and Studer U.E. Nerve-sparing open radical retropubic prostatectomy. Eur Urol 51 (2007) 90-97
44. Eichelberg C., Erbersdobler A., Michl U., et al. Nerve distribution along the prostatic capsule. Eur Urol 51 (2007) 105-111 discussion 110-1
45. Ficarra V., Cavalleri S., Novara G., Aragona M., and Artibani W. Evidence from robot-assisted laparoscopic radical prostatectomy: a systematic review. Eur Urol 51 (2007) 45-56 discussion 56
46. Rassweiler J., Hruza M., Teber D., and Su L.-M. Laparoscopic and robotic assisted radical prostatectomy - critical analysis of the results. Eur Urol 49 (2006) 612-624
47. Tooher R., Swindle P., Woo H., Miller J., and Maddern G. Laparoscopic radical prostatectomy for localized prostate cancer: a systematic review of comparative studies. J Urol 175 (2006) 2011-2017
48. Dubbelman Y.D., Dohle G.R., and Schröder F.H. Sexual function before and after radical retropubic prostatectomy: a systematic review of prognostic indicators for a successful outcome. Eur Urol 50 (2006) 711-720 discussion 718-20
49. Lee I.H., Sadetsky N., Carroll P.R., and Sandler H.M. The impact of treatment choice for localized prostate cancer on response to phosphodiesterase inhibitors. J Urol 179 (2008) 1072-1076 discussion 1076
50. Descazeaud A., Debre B., and Flam T.A. Age difference between patient and partner is a predictive factor of potency rate following radical prostatectomy. J Urol 176 (2006) 2594-2598 discussion 2598
51. Salonia A., Gallina A., Briganti A., et al. Remembered International Index of Erectile Function domain scores are not accurate in assessing preoperative potency in candidates for bilateral nerve-sparing radical retropubic prostatectomy. J Sex Med 5 (2008) 677-683
52. Salonia A., Zanni G., Gallina A., et al. Baseline potency in candidates for bilateral nerve-sparing radical retropubic prostatectomy. Eur Urol 50 (2006) 360-365
53. Burnett A.L., Aus G., Canby-Hagino E.D., et al. Erectile function outcome reporting after clinically localized prostate cancer treatment. J Urol 178 (2007) 597-601
54. Kovanecz I., Rambhatla A., Ferrini M.G., et al. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int 101 (2008) 203-210
55. Wang R. Penile rehabilitation after radical prostatectomy: where do we stand and where are we going?. J Sex Med 4 (2007) 1085-1097
56. Mulhall J., Land S., Parker M., Waters W.B., and Flanigan R.C. The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. J Sex Med 2 (2005) 532-540 discussion 540-2
57. Nandipati K., Raina R., Agarwal A., and Zippe C.D. Early combination therapy: intracavernosal injections and sildenafil following radical prostatectomy increases sexual activity and the return of natural erections. Int J Impot Res 18 (2006) 446-451
58. McCullough A.R., Levine L.A., and Padma-Nathan H. Return of nocturnal erections and erectile function after bilateral nerve-sparing radical prostatectomy in men treated nightly with sildenafil citrate: subanalysis of a longitudinal randomized double-blind placebo-controlled trial. J Sex Med 5 (2008) 476-484
59. Burnett A.L., and Lue T.F. Neuromodulatory therapy to improve erectile function recovery outcomes after pelvic surgery. J Urol 176 (2006) 882-887
60. Padma-Nathan H., McCullough A.R., Levine L.A., 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 20 (2008) 479-486
61. Giuliano F., Amar E., Chevallier D., Montaigne O., Joubert J.M., and Chartier-Kastler E. How urologists manage erectile dysfunction after radical prostatectomy: a national survey (REPAIR) by the French urological association. J Sex Med 5 (2008) 448-457
62. Bannowsky A., Schulze H., van der Horst C., Seif C., Braun P.M., and Junemann K.P. Nocturnal tumescence: a parameter for postoperative erectile integrity after nerve sparing radical prostatectomy. J Urol 175 (2006) 2214-2217
63. Bannowsky A., Schulze H., van der Horst C., Hautmann S., and Junemann K.P. Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil. BJU Int 101 (2008) 1279-1283
64. Mulhall J.P., Muller A., Donohue J.F., et al. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate. J Sex Med 5 (2008) 1126-1136
65. Ferrini M.G., Kovanecz I., Sanchez S., et al. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biol Reprod 76 (2007) 915-923
66. Vignozzi L., Filippi S., Morelli A., et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med 3 (2006) 419-431
67. Lysiak J.J., Yang S.K., Klausner A.P., Son H., Tuttle J.B., and Steers W.D. Tadalafil increases Akt and extracellular signal-regulated kinase 1/2 activation, and prevents apoptotic cell death in the penis following denervation. J Urol 179 (2008) 779-785
68. Schwartz E.J., Wong P., and Graydon R.J. Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol 171 (2004) 771-774
69. Iacono F., Prezioso D., Somma P., Chierchia S., Galasso R., and Micheli P. Histopathologically proven prevention of post-prostatectomy cavernosal fibrosis with sildenafil. Urol Int 80 (2008) 249-252
70. Gallo L., Perdona S., Autorino R., et al. Recovery of erection after pelvic urologic surgery: our experience. Int J Impot Res 17 (2005) 484-493
71. 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 54 (2008) 924-931
72. Hong E.K., Lepor H., and McCullough A.R. Time-dependent patient satisfaction with sildenafil for erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (RRP). Int J Impot Res 11 Suppl 1 (1999) S15-S22
73. Jarow J.P., Burnett A.L., and Geringer A.M. Clinical efficacy of sildenafil citrate based on etiology and response to prior treatment. J Urol 162 (1999) 722-725
74. Lowentritt B.H., Scardino P.T., Miles B.J., et al. Sildenafil citrate after radical retropubic prostatectomy. J Urol 162 (1999) 1614-1617
75. Marks L.S., Duda C., Dorey F.J., Macairan M.L., and Santos P.B. Treatment of erectile dysfunction with sildenafil. Urology 53 (1999) 19-24
76. Blander D.S., Sanchez-Ortiz R.F., Wein A.J., and Broderick G.A. Efficacy of sildenafil in erectile dysfunction after radical prostatectomy. Int J Impot Res 12 (2000) 165-168
77. Feng M.I., Huang S., Kaptein J., Kaswick J., and Aboseif S. Effect of sildenafil citrate on post-radical prostatectomy erectile dysfunction. J Urol 164 (2000) 1935-1938
78. Zippe C.D., Jhaveri F.M., Klein E.A., et al. Role of Viagra after radical prostatectomy. Urology 55 (2000) 241-245
79. Zagaja G.P., Mhoon D.A., Aikens J.E., and Brendler C.B. Sildenafil in the treatment of erectile dysfunction after radical prostatectomy. Urology 56 (2000) 631-634
80. Raina R., Lakin M.M., Agarwal A., et al. Long-term effect of sildenafil citrate on erectile dysfunction after radical prostatectomy: 3-year follow-up. Urology 62 (2003) 110-115
81. Raina R., Lakin M.M., Agarwal A., et al. Efficacy and factors associated with successful outcome of sildenafil citrate use for erectile dysfunction after radical prostatectomy. Urology 63 (2004) 960-966
82. McMahon C.G., Samali R., and Johnson H. Efficacy, safety and patient acceptance of sildenafil citrate as treatment for erectile dysfunction. J Urol 164 (2000) 1192-1196
83. Baniel J., Israilov S., Segenreich E., and Livne P.M. Comparative evaluation of treatments for erectile dysfunction in patients with prostate cancer after radical retropubic prostatectomy. BJU Int 88 (2001) 58-62
84. Martínez-Jabaloyas J.M., Gil-Salom M., Villamón-Fort R., Pastor-Hernández F., Martínez-García R., and García-Sisamón F. Prognostic factors for response to sildenafil in patients with erectile dysfunction. Eur Urol 40 (2001) 641-647 discussion 647
85. Ogura K., Ichioka K., Terada N., Yoshimura K., Terai A., and Arai Y. Role of sildenafil citrate in treatment of erectile dysfunction after radical retropubic prostatectomy. Int J Urol 11 (2004) 159-163
86. Shimizu T., Hisasue S., Sato Y., Kato R., Kobayashi K., and Tsukamoto T. Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil. Int J Urol 12 (2005) 552-557
87. Montorsi F., and McCullough A. Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data. J Sex Med 2 (2005) 658-667
88. Ohebshalom M., Parker M., Waters B., Flanagan R., and Mulhall J.P. Erectile haemodynamic status after radical prostatectomy correlates with erectile functional outcome. BJU Int 102 (2008) 592-596
89. Cavallini G., Modenini F., Vitali G., and Koverech A. Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology 66 (2005) 1080-1085
90. Brock G., Nehra A., Lipshultz L.I., et al. Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. J Urol 170 (2003) 1278-1283
91. Nehra A., Grantmyre J., Nadel A., Thibonnier M., and Brock G. Vardenafil improved patient satisfaction with erectile hardness, orgasmic function and sexual experience in men with erectile dysfunction following nerve sparing radical prostatectomy. J Urol 173 (2005) 2067-2071
92. Miles CL, Candy B, Jones L, Williams R, Tookman A, King M. Interventions for sexual dysfunction following treatments for cancer. Cochrane Database Syst Rev 2007:CD005540.
93. Montorsi F., Nathan H.P., McCullough A., et al. Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. J Urol 172 (2004) 1036-1041
94. Raina R., Nandipati K.C., Agarwal A., Mansour D., Kaelber D.C., and Zippe C.D. Combination therapy: medicated urethral system for erection enhances sexual satisfaction in sildenafil citrate failure following nerve-sparing radical prostatectomy. J Androl 26 (2005) 757-760
95. Nehra A., Blute M.L., Barrett D.M., and Moreland R.B. Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy. Int J Impot Res 14 Suppl 1 (2002) S38-S42
96. Mydlo J.H., Viterbo R., and Crispen P. Use of combined intracorporal injection and a phosphodiesterase-5 inhibitor therapy for men with a suboptimal response to sildenafil and/or vardenafil monotherapy after radical retropubic prostatectomy. BJU Int 95 (2005) 843-846
97. Gutierrez P., Hernandez P., and Mas M. Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders. Int J Impot Res 17 (2005) 354-358