Tadalafil once daily and extracorporeal shock wave therapy ...

1 ORIGINAL ARTICLET adalafil once daily and extracorporeal shock wavetherapy in the management of patients with Peyronie sdisease and erectile dysfunction: results from a prospectiverandomized trialA. Palmieri, C. Imbimbo, M. Creta, P. Verze, F. Fusco and V. MironeDepartment of Urology, University Federico II of Naples, Naples, ItalyIntroductionPeyronie s disease (PD) is a localized disorder of the con-nective tissue involving the penile tunica albuginea andthe surrounding areolar spaces that typically evolves infibrotic plaques [Bivalacquaet al.(2000)]. Patients pres-ent with three, occasionally simultaneous, chief com-plaints: a palpable plaque, painful erections and a peniledeformity [Palmieriet al.(2009)]. Moreover, PD is asso-ciated with erectile dysfunction (ED) in a percentage ofpatients ranging from 18 to 80% [Weidneret al.]

2 (1997),Levine & Latchamsetty (2002), Kadiogluet al.(2004),Mulhallet al.(2005)]. In a previous study, we demon-strated that extracorporeal shock Wave therapy (ESWT)can significantly improve erectile function (EF) inpatients with PD when compared to placebo [Palmieriet al.(2009)]. However, ED still persisted in about 50%of patients thus suggesting the need for more successfulstrategies [Palmieriet al.(2009)]. Levine demon-strated that on-demand sildenafil was an effective, safeand well tolerated first-line strategy for PD patients withED [Levine & Latchamsetty (2002)]. Recent pre-clinicalstudies characterized the antifibrotic effects of chronictreatmentwithphosphodiesterasetyp e5inhibitorsKeywords: extracorporeal shock wave therapy , Peyronie sdisease, tadalafilCorrespondence:Massimiliano Creta, MD, University Federico IIof Naples, Via S.

3 Pansini, 5, 80131 Naples, : 12 February 2011; revised 19 August 2011; accepted 18 September 2011 shock wave therapy improves erectile function in patients withPeyronie s disease. However, erectile dysfunction still persists in many aimed to investigate the effects of extracorporeal shock wave therapy plustadalafil 5 mg once daily in the management of patients with Peyronie s diseaseand erectile dysfunction not previously treated. One hundred patients wereenrolled in a prospective, randomized, controlled study. Patients were ran-domly allocated to receive either extracorporeal shock wave therapy alone for4 weeks (n= 50) or extracorporeal shock wave therapy plus Tadalafil 5 mg oncedaily for 4 weeks (n= 50).

4 Main outcome measures were: erectile function(evaluated through the shortened version of the International Index of ErectileFunction), pain during erection (evaluated through a Visual Analog Scale), pla-que size, penile curvature and quality of life (evaluated through an internalquestionnaire). Follow-up evaluations were performed after 12 and 24 both groups, at 12 weeks follow-up, mean Visual Analog Scale score, meanInternational Index of Erectile Function score and mean quality of life scoreameliorated significantly while mean plaque size and mean curvature degreewere unchanged. Intergroup analysis revealed a significantly higher mean Inter-national Index of Erectile Function score and quality of life score in patientsreceiving the combination.

5 After 24 weeks, intergroup analysis revealed a signif-icantly higher mean International Index of Erectile Function score and meanquality of life score in patients that received extracorporeal shock wave therapyplus Tadalafil . In conclusion extracorporeal shock wave therapy plus tadalafil5 mg once daily may represent a valid conservative strategy for the manage-ment of patients with Peyronie s disease and erectile journal of andrology ISSN 0105-6263 International Journal of Andrology, 2012,35, 190 195 2011 The Authors190 International Journal of Andrology 2011 European Academy of Andrology(PDE5is) in PD plaque models [Gonzalez-Cadavid &Rajfer (2009)]. Owing to its longer half-life, Tadalafil wasrecently approved for chronic administration and thisregimen was reported to be associated with improved effi-cacy and patients satisfaction [Porstet al.]

6 (2009), McMa-hon (2005)]. The aim of the present study was tocompare ESWT alone or in combination with once dailytadalafil 5 mg for the management of patients with PDand and methodsFrom February 2009 to December 2009 we conducted aprospective, randomized, controlled clinical study on 100consecutive male patients affected by PD and ED. Patientswith the following characteristics were included into thestudy protocol: disease not >12 months, age between 18and 75 years, a single penile plaque demonstrated by basaland dynamic sonography and by palpation, plaque maxi-mum size of cm2, monogamous sexual relationshipwith a female partner, presence of ED, presence of painfulerections [score 5 on a visual analog scale (VAS) with ascore ranging from 0 to 10], and penis recurvatum <30 (the last two criteria could be present as singular featureor could be associated).

7 Subjects were excluded fromenrolment for any of the following symptoms: lowerurinary tract infections, vascular disorders in the path ofthe shock waves , disorders of blood coagulation, cardiacpacemaker, premature ejaculation, hypogonadism, historyof radical prostatectomy or other pelvic surgery with sub-sequent ED, clinically significant hepatobiliary or renaldisease, diabetes mellitus, lipid disorders, smoking habit,cardiovascular diseases, current nitrate use, alcohol abuse,recent significant central nervous system injuries and pre-vious medical or surgical therapies for PD or ED. Allpatients gave their informed written consent. Subjectswere randomly assigned to receive either ESWT or ESWT plus Tadalafil 5 mg once daily for 4 weeks.

8 Patients ran-domized to receive Tadalafil were presented with oral aswell as written instructions regarding the use and poten-tial side effects of the drug. EF, presence and severity ofpainful erections, penile plaque size, penile curvaturedegree and quality of life (QoL) were assessed at baselineand follow-up evaluations by the same operator. EF wasevaluated through the shortened version of the Interna-tional Index of Erectile Function (IIEF-5) questionnaire,and ED was graded according to Rosenet al.(1999).Severity of painful erections was assessed by means of aVAS score ranging from 0 to 10, with 0 being no pain and10 being severe pain. QoL was assessed by means of astructured interview composed of five questions, each witha score ranging from 0 to 5 [Palmieriet al.]

9 (2009)]. Pla-que position was evaluated by palpation and plaque sizewas assessed by ultrasonography in the tumescence phaseduring an artificial erection induced by a standard injec-tion of alprostadil. The size of the plaque was measured asthe product of length and width in square degree of penile curvature was determined with agoniometer using photographic pictures during full artifi-cial erection. The Storz Duolith system (Storz MedicalAG, Lohstampfestrasse, Switzerland) was used for were administered once weekly for four con-secutive weeks in both groups by the same operator. Oneach ESWT session, two thousand impulses were energy flux density was mJ mm2and an emis-sion frequency was 4 Hz.

10 The probe was manually oper-ated, and the focus of energy delivery remained were performed without anaesthesia. Treat-ment complications and side effects were were asked not to take other therapies for EDand PD during the 4 weeks treatment period as well asduring the 24 weeks follow-up period. Moreover, theywere asked not to take analgesics before, during, or afterpainful erections during the same periods. Follow-up eval-uations were performed 12 weeks and 24 weeks after thefinal intervention session. Treatment preference was inves-tigated by asking patients to answer yes , no , or don tknow to the following question: Would you recommendthis treatment to a friend?