The Effect of Condoms on Penile Vibrotactile Sensitivity Thresholds in Young,Heterosexual Men

IntroductionInvestigating the ways in which barrier methods such as condoms may affect penile sensory thresholds has potential relevance to the development of interventions in men who experience negative effects of condoms on sexual response and sensation. A quantitative, psychophysiological investigation examining the degree to which sensations are altered by condoms has, to date, not been conducted.AimThe objective of this study was to examine penile vibrotactile sensitivity thresholds in both flaccid and erect penises with and without a condom while comparing men who do and those who do not report condom-associated erection problems (CAEP).MethodsPenile vibrotactile sensitivity thresholds were assessed among a total of 141 young, heterosexual men using biothesiometry. An incremental two-step staircase method was used and repeated three times for each of four conditions. Intra-class correlation coefficients (ICCs) were calculated for all vibratory assessments. Penile vibratory thresholds were compared using a mixed-model analysis of variance.Main Outcome MeasuresPenile vibrotactile sensitivity thresholds with and without a condom, erectile function measured by International Index of Erectile Function Questionnaire, and self-reported degree of erection.ResultsSignificant main effects of condoms (yes/no) and erection (yes/no) were found. No main or interaction effects of CAEP were found. Condoms were associated with higher penile vibrotactile sensitivity thresholds (F[1,124] = 17.11, P < 0.001). Penile vibrotactile thresholds were higher with an erect penis than with a flaccid penis (F[1,124] = 4.21, P = 0.042).ConclusionThe current study demonstrates the feasibility of measuring penile vibratory thresholds with and without a condom in both erect and flaccid experimental conditions. As might be expected, condoms increased penile vibrotactile sensitivity thresholds. Interestingly, erections were associated with the highest thresholds. Thus, this study was the first to document that erect penises are less sensitive to vibrotactile stimulation than flaccid penises. Hill BJ, Janssen E, Kvam P, Amick EE, and Sanders SA. The effect of condoms on penile vibrotactile sensitivity thresholds in young, heterosexual men. J Sex Med 2014;11:102–106.     

Intraoperative Cavernous Nerve Stimulation and Laser-Doppler Flowmetry during Radical Prostatectomy

IntroductionErectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity.AimTo test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation.MethodsFifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30–40 seconds biphasic constant current (10–30 mA) with 0.5 millisecond pulse duration.Main Outcome MeasuresStimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery.ResultsTen patients had stimulus induced increase in Laser Doppler flow unilaterally (N = 7) or bilaterally (N = 3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge.ConclusionThis preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery. Axelson HW, Johansson E, and Bill-Axelson A. Intraoperative cavernous nerve stimulation and Laser-Doppler flowmetry during radical prostatectomy. J Sex Med 2013;10:2842–2848     

Valproic Acid Prevents Penile Fibrosis and Erectile Dysfunction in Cavernous Nerve‐Injured Rats

IntroductionBilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases.AimsThis study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI‐induced ED and penile fibrosis.MethodsFive groups of rats (8–10 weeks, n = 10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250 mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor‐β1 (TGF‐β1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α‐SMA) antibodies.Main Outcome MeasuresWe measured ICP; HDAC3, HDAC4, fibronectin, and TGF‐β1 protein expression; penile fibrosis; penile α‐SMA content.ResultsThere was a voltage‐dependent decline (P < 0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P < 0.05) 14 days after BCNI. There was a slight increase in TGF‐β1 protein expression after BCNI. Histological analysis showed increased (P < 0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P < 0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α‐SMA between all groups. Furthermore, VPA‐treated BCNI rats had improved erectile responses to CNS (P < 0.05).ConclusionHDAC‐induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and preserves erectile function. The HDAC pathway may represent a suitable target in preventing the progression of ED occurring post‐radical prostatectomy. Hannan JL, Kutlu O, Stopak BL, Liu X, Castiglione F, Hedlund P, Burnett AL, and Bivalacqua TJ. Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve‐injured rats. J Sex Med 2014;11:1442–1451.     

Sexual Rehabilitation and Cancer Survivorship: A State of Art Review of Current Literature and Management Strategies in Male Sexual Dysfunction Among Prostate Cancer Survivors

IntroductionThe challenges for prostate cancer survivors include the surveillance of prostate cancer recurrence and management of physical, cognitive, sexual, and socioeconomic quality of life issues. Sexual function remains an important issue in men, who often continue to be interested in sex after prostate cancer treatment. The various post‐prostate cancer treatment‐related sexual dysfunctions are penile deformities and erectile dysfunction (ED); sexual desire and mental health; ejaculatory and orgasmic dysfunctions; and changes in partner relationship and dynamics.AimsThe aim of this study is to provide state of art review of the various male sexual dysfunctions in prostate cancer survivors and the management strategies in sexual rehabilitation.Methods and MaterialsA literature search for English language original and review articles either published or e‐published was performed using PubMed database. Keywords included prostate cancer, prostate cancer treatment, prostate prostatectomy (RP), sexual dysfunction, erectile dysfunction (ED), sexual desire, mental health, ejaculation, orgasmic, climacturia, and relationship.ResultsThere has been considerable volume of publication in recent years on prostate cancer‐related male sexual dysfunction. Penile deformities and ED shared similar pathophysiology and that penile smooth muscle fibrosis ultimately results in structural alterations and end‐organ failure. Penile rehabilitation using oral phosphodiesterase type 5 (PDE5) inhibitors is considered the standard of care especially in patients who received nerve‐sparing RP and should be instituted as soon as possible to protect and prevent corporal endothelial and smooth muscle damage. However, there is no consensus on the exact timing, dose, and duration of PDE5 inhibitors and its impact in non‐nerve‐sparing RP and other forms of prostate cancer treatment modalities. Current literature on hypoactive sexual desire, ejaculatory, and orgasmic dysfunctions in patients who received prostate cancer treatment is limited. Psychological and sexual counseling play an important role in rehabilitation and treatment of various forms of male sexual dysfunctions.ConclusionWhile several preventive and treatment strategies for the preservation and recovery of sexual function are available, no specific recommendation or consensus guidelines exist regarding the optimal rehabilitation or treatment protocol. While medical and surgical therapies are effective in erectile function recovery and/or preservation, psychological and sexual counseling are equally important in sexual rehabilitation. Chung E and Brock G. Sexual rehabilitation and cancer survivorship: A state of art review of current literature and management strategies in male sexual dysfunction among prostate cancer survivors. J Sex Med 2013;10(suppl 1):102–111.     

Impaired Cavernous Reinnervation after Penile Nerve Injury in Rats with Features of the Metabolic Syndrome

IntroductionThe metabolic syndrome is a cluster of cardiovascular risk factors that predispose toward the development of diseases such as diabetes. Erectile dysfunction (ED) is common in men with metabolic syndrome, but its etiology is poorly understood. Pro‐erectile nitrergic nerves innervating penile erectile tissue are also susceptible to mechanical injury during pelvic surgical procedures, which can lead to sexual dysfunction.AimsThe aims of this article are: (i) to examine erectile function in an experimental model of metabolic syndrome, the phosphoenolpyruvate carboxykinase (PEPCK)‐overexpressing rat; and (ii) to study function and cavernous reinnervation after penile nerve crush injury, which permits regeneration, in transgenic rats.MethodsWe analyzed the density of noradrenergic and nitrergic nerves and performed organ bath pharmacology to assess neurogenic activity.Main Outcome MeasuresBy analyzing changes in neural structure, function, and pharmacologic responses of cavernous tissue after nerve crush injury, we were able to reveal neurologic deficits in rats with metabolic syndrome.ResultsAnimals with features of metabolic syndrome did not develop notable changes in cavernous autonomic nerve density or nerve‐evoked smooth muscle activity. However, regeneration of nitrergic nerves after crush injury in transgenic rats was impaired compared with injured controls. This was manifested as a deficit in axon regrowth and responses to axon activation. However, unlike injured controls, injured PEPCK‐overexpressing rats did not develop a reduced maximal response to the nitric oxide (NO) donor, sodium nitroprusside. This suggests preserved NO responsiveness in tissues from rats with metabolic syndrome, despite impaired regeneration and return of function.ConclusionsThis study revealed that rats with features of metabolic syndrome display impaired cavernous nerve regeneration after penile nerve injury, but the degree of functional impairment may be attenuated due to reduced plasticity of NO signaling. This reinnervation deficit may be of clinical relevance for understanding why ED persists in some (particularly aged) men after pelvic surgery. Nangle MR, Proietto J, and Keast JR. Impaired cavernous reinnervation after penile nerve injury in rats with features of the metabolic syndrome.     

Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to Radical Prostatectomies: Results from a Cross‐Sectional Questionnaire‐Based Study

IntroductionAltered perception of orgasm, orgasm‐associated pain, penile sensory changes, urinary incontinence (UI) during sexual activity, penile shortening (PS), and penile deformity following radical prostatectomy (RP) have received increasing attention from researchers.AimThe aim of this study is to describe the prevalence and predictors of the above‐mentioned side effects.MethodsThis was a cross‐sectional questionnaire‐based study among men who had undergone RP between 3 and 36 months prior to study inclusion. Predicting factors were identified through logistic regression analyses.Main Outcome MeasuresThe primary outcome measures were prevalence rates of the above‐mentioned side effects.ResultsOverall, 316 questionnaires were available for analyses. Of the sexually active patients (n = 256), 12 (5%) reported anorgasmia, whereas 153 (60%) reported decreased orgasm intensity. Delayed orgasms were reported by 146 (57%). Twenty‐three patients (10%) had experienced pain during orgasm. UI during sexual activity were reported by 99 patients (38%). Out of the whole population, 77 patients (25%) reported sensory changes in the penis. A total of 143 patients (47%) reported a subjective loss of penile length of >1 cm. An altered curvature of the penis was reported by 30 patients (10%). Patients had increasing risk of UI during sexual activity (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.10–1.25) and orgasmic dysfunction (OR 1.09; 95% CI 1.01–1.16) with increasing International Consultation on Incontinence Questionnaire scores. Erectile dysfunction (OR 1.81; 95% CI 1.07–3.10) and a high body mass index (OR 1.10; 95% CI 1.02–1.19) increased the risk of PS after RP. Nerve‐sparing (OR 0.32; 95% CI 0.16–0.95) reduced the risk of PS.ConclusionsOrgasm‐associated problems, UI during sexual activity, penile sensory changes, PS, and penile deformity are common side effects to RP. Daytime UI, erectile dysfunction, and nerve‐sparing status can help identify patients at risk. Frey A, Sønksen J, Jakobsen H, and Fode M. Prevalence and predicting factors for commonly neglected sexual side effects to radical prostatectomies: Results from a cross‐sectional questionnaire‐based study. J Sex Med 2014;11:2318‐2326.     

Subjective Characterization of Nerve Sparing Predicts Recovery of Erectile Function after Radical Prostatectomy: Defining the Utility of a Nerve Sparing Grading System

IntroductionRadical prostatectomy (RP) is a common technique for managing prostate cancer. Concern regarding functional outcomes in patients prompted the development of nerve sparing to improve recovery of erectile function.AimTo assess if a cumulative nerve damage grading system is a more precise predictor of recovery of erectile function as compared to the current “all‐or‐none” grading system.MethodsBaseline demographic, medical history, and International Index of Erectile Function (IIEF)‐erectile function domain (EFD) scores were collected. At the time of RP, patients were assigned a nerve sparing score (NSS) by their surgeon for each neurovascular bundle (left and right) to assess the quality of intraoperative nerve sparing (1—complete preservation, 4—complete resection). Patients completed IIEF questionnaires at 24 months after RP.Main Outcome MeasuresGroup comparisons and multiple regression analyses were used to test the association between the NSS and IIEF‐EFD scores for patients with preoperative EFD scores ≥24.ResultsA total of 173 patients were included in this analysis. Mean age for patients was 59, and 62% of patients had at least one comorbidity. Baseline EFD scores were comparable between all NSS assignments. At 24 months, EFD scores were reduced by 7.2, 11.6, 13.9, and 15.4 points for patients with NSS grades of 2, 3, 4, and 5–8, respectively (P < 0.01). Multivariate analysis demonstrated lower NSS predicted recovery of erectile function at 24 months (P = 0.001), as did age (P = 0.001) and baseline EFD score (P = 0.02).ConclusionsOur data support the adoption of a subjectively assigned NSS to more precisely predict erectile function outcomes and suggest that even minor nerve trauma significantly impairs the recovery of erectile function after procedures classically regarded as having achieved bilateral nerve sparing. Further studies are needed to identify the optimal NSS system. Moskovic DJ, Alphs H, Nelson CJ, Rabbani F, Eastham J, Touijer K, Guillonneau B, Scardino PT, and Mulhall JP. Subjective characterization of nerve sparing predicts recovery of erectile function after radical prostatectomy: Defining the utility of a nerve sparing grading system.     

Spontaneous Penile Tumescence by Sparing Cavernous Tissue in the Course of Malleable Penile Prosthesis Implantation

Introduction

Spontaneous penile tumescence after penile prosthesis implantation has been sporadically reported in the literature.

Penile Rehabilitation Following Radical Prostatectomy: Predicting Success

IntroductionIt has been suggested that the institution of a pharmacologically based penile rehabilitation program in the early stages after radical prostatectomy (RP) may benefit some patients.AimThis analysis was conducted to define if predictors of successful outcome with pharmacological penile rehabilitation following RP could be identified.MethodsRetrospective statistical analysis was performed on a large database of patients who had participated in a post-RP rehabilitation program. Inclusion criteria included: presence of functional erections permitting sexual intercourse pre-RP and commencement of rehabilitation within 12 months of RP. Patients were instructed to obtain a penetration-rigidity erection on at least three occasions per week and to continue this regimen until at least 18 months after RP using either sildenafil or intracavernosal injection therapy (if oral therapy failed).Main Outcome MeasureInternational Index of Erectile Function (IIEF) and visual analog scale erectile rigidity assessment. Stepwise logistic regression analysis was used to generate predictors of erectile function (EF) outcomes with penile rehabilitation.ResultsNinety-two patients constituted the study population. Mean patient age and duration post-RP at commencement of the rehabilitation program were 59 ± 10 years and 7 ± 3 months, respectively. Sixty-seven percent of operations were bilateral nerve sparing (BNS), 11% unilateral nerve sparing (NS), and 22% non-NS. Comorbidities included hypertension 22%, dyslipidemia 30%, coronary artery disease 7%, and diabetes 2%. Preoperative mean self-reported, partner-corroborated erectile rigidity during relations was 90 ± 20%. At 18 months post-RP, 57% patients had partner-corroborated functional erections without phosphodiesterase type 5 inhibitors with a mean erectile rigidity during relations of 72 ± 16% compared with 45 ± 22% for those who denied functional erections postoperatively (P > 0.01). The IIEF-EF domain scores in these two cohorts were 21 ± 7.5 and 13 ± 9, respectively (P > 0.01). On multivariate analysis, factors that predicted failure of return of natural erections after RP having followed a rehabilitation program were age >60 years (relative risk [RR] = 1.3), non-BNS surgery (RR = 1.6), presence of >1 vascular comorbidity (RR = 2.1), commencement of rehabilitation >6 months post-RP (RR = 2.8), unsuccessful response to sildenafil at 12 months post-RP (RR = 4.5), and the use of trimix dose >50 units (RR = 8.1).ConclusionsMore than half of the patients committing to a pharmacological rehabilitation program had return of functional natural erections. Predictors of successful outcome included NS surgery, early post-RP presentation, young age, and absence of vascular comorbidities. Müller A, Parker M, Waters BW, Flanigan RC, and Mulhall JP. Penile rehabilitation following radical prostatectomy: Predicting success. J Sex Med 2009;6:2806–2812.     

Choosing the best candidates for penile rehabilitation after bilateral nerve-sparing radical prostatectomy

IntroductionControversy exists regarding the ideal candidates for penile rehabilitation after bilateral nerve‐sparing radical prostatectomy (BNSRP).AimTo test the effect of penile rehabilitation according to preoperative patient characteristics.MethodsWe included 435 consecutive patients treated with BNSRP between 2004 and 2008. Preoperative age, International Index of Erectile Function (IIEF) and Charlson Comorbidity Index (CCI) were used to subdivide patients into three groups according to foreseen risk of erectile dysfunction (ED) after surgery: low (age ≤65, IIEF‐erectile function (EF) ≥26, CCI ≤1; N = 184), intermediate (age 66–69 or IIEF‐EF 11–25, CCI ≤1; N = 115), and high (age ≥70 or IIEF‐EF ≤10 or CCI ≥2; N = 136). The Kaplan–Meier method was used to test the difference in EF recovery rates among patients left untreated after surgery (N = 193), those receiving on‐demand phosphodiesterase type 5 inhibitors (PDE5‐I; N = 147), and those treated with chronic use of PDE5‐I (taken every day or every other day for 3–6 months; N = 95). The same analyses were repeated within each risk category.Main Outcome MeasureErectile function (EF) was evaluated using the International Index of Erectile Function (IIEF). Recovery of EF after BNSRP was defined as an IIEF‐EF domain score ≥22.ResultsNo difference in terms of EF recovery was found between patients receiving on‐demand vs. daily PDE5‐I (P = 0.09) in the overall population. Similarly, comparable efficacy of the two treatment schedules (on‐demand vs. chronic) was demonstrated in patients with low and high risk of ED (all P ≥ 0.8). Conversely, daily therapy with PDE5‐I showed significantly higher efficacy for the EF recovery rate compared with the on‐demand PDE5‐I administration schedule in patients with intermediate risk of ED (3‐year EF recovery: 74% vs. 52%, respectively; P = 0.02).Conclusions.The ideal candidates for penile rehabilitation after surgery are patients at intermediate risk of ED. Briganti A, Di Trapani E, Abdollah F, Gallina A, Suardi N, Capitanio U, Tutolo M, Passoni N, Salonia A, DiGirolamo V, Colombo R, Guazzoni G, Rigatti P, and Montorsi F. Choosing the best candidates for penile rehabilitation after bilateral nerve‐sparing radical prostatectomy. J Sex Med 2012;9:608–617.     

Sexual Rehabilitation and Penile Pain Associated with Intracavernous Alprostadil after Radical Prostatectomy

IntroductionIntracavernous alprostadil injection (IAI) is widely used for sexual rehabilitation (SR) after radical prostatectomy (RP). However, the rate of spontaneous erection recovery with IAI remains unclear, and IAI causes pain that may hinder SR.AimsTo assess SR in IAI users after RP and to evaluate the course and impact on SR of postinjection penile pain.MethodsWe prospectively studied 87 patients who underwent nerve‐sparing laparoscopic RP, reported normal preoperative erectile function, and used IAI for 12 months. Patients started with 2.5 µg alprostadil and were advised to increase the dose gradually until erection hardness allowed vaginal penetration.Main Outcome MeasuresAt 6 and 12 months, the International Index of Erectile Function (IIEF‐15) and Erection Hardness Score (EHS) were determined with and without IAI, and injection‐related penile pain was assessed using a numeric rating scale. Correlations linking penile pain, IIEF‐15, and EHS scores were evaluated.ResultsThe mean alprostadil dose was 8.1 µg after 6 months and 9.9 µg after 12 months. With/without IAI, mean IIEF‐15 scores for erectile and orgasmic function and mean EHS score were 14.6/4.6, 4.1/2.1, and 2.5/0.4, respectively, after 6 months; and 17.2/5.4, 4.9/2.6, and 2.7/0.9 after 12 months. Pain scores were 3.2 ± 2.5/10 and 2.5 ± 2.5/10 after 6 and 12 months, respectively. Pain intensity correlated with erectile function (r = ?0.23), intercourse satisfaction (r = ?0.23), and overall satisfaction (r = ?0.24) after 6 months but not after 12 months. Follow‐up was short and only patients who used IAI for 12 months were included.ConclusionsIn patients who were willing and able to use IAI, erectile function improved after 1 year but remained below preoperative levels. The adverse impact of pain on SR was significant during the first 6 months and diminished over time. These data may help to counsel IAI users with painful erections. Yiou R, Cunin P, de la Taille A, Salomon L, Binhas M, Lingombet O, Paul M, and Abbou C. Sexual rehabilitation and penile pain associated with intracavernous alprostadil after radical prostatectomy.     

ORIGINAL RESEARCH—EJACULATORY DISORDERS: Quantitative Sensory Testing of Peripheral Thresholds in Patients with Lifelong Premature Ejaculation: A Case-Controlled Study

IntroductionThe main functional factors related to lifelong premature ejaculation (PE) etiology have been suggested to be penile hypersensitivity, greater cortical penile representation, and disturbance of central serotoninergic neurotransmission.AimsTo quantitatively assess penile sensory thresholds in European Caucasian patients with lifelong PE using the Genito-Sensory Analyzer (GSA, Medoc, Ramat Yishai, Israel) as compared with those of an age-comparable sample of volunteers without any ejaculatory compliant.MethodsForty-two consecutive right-handed, fully potent patients with lifelong PE and 41 right-handed, fully potent, age-comparable volunteers with normal ejaculatory function were enrolled. Each man was assessed via comprehensive medical and sexual history; detailed physical examination; subjective scoring of sexual symptoms with the International Index of Erectile Function; and four consecutive measurements of intravaginal ejaculatory latency time with the stopwatch method. All men completed a detailed genital sensory evaluation using the GSA; thermal and vibratory sensation thresholds were computed at the pulp of the right index finger, and lateral aspect of penile shaft and glans, bilaterally.Main Outcome MeasuresComparing quantitatively assessed penile thermal and vibratory sensory thresholds between men with lifelong PE and controls without any ejaculatory compliant.ResultsPatients showed significantly higher (P < 0.001) thresholds at the right index finger but similar penile and glans thresholds for warm sensation as compared with controls. Cold sensation thresholds were not significantly different between groups at the right index finger or penile shaft, but glans thresholds for cold sensation were bilaterally significantly lower (P = 0.01) in patients. Patients showed significantly higher (all P ≤ 0.04) vibratory sensation thresholds for right index finger, penile shaft, and glans, bilaterally, as compared with controls.ConclusionsQuantitative sensory testing analysis suggests that patients with lifelong PE might have a hypo- rather than hypersensitivity profile in terms of peripheral sensory thresholds. The peripheral neuropathophysiology of lifelong PE remains to be clarified. Salonia A, Saccà A, Briganti A, Carro UD, Dehò F, Zanni G, Rocchini L, Raber M, Guazzoni G, Rigatti P, and Montorsi F. Quantitative sensory testing of peripheral thresholds in patients with lifelong premature ejaculation: A case-controlled study. J Sex Med 2009;6:1755–1762.     

Preoperative Erectile Function Is an Independent Predictor for Decision to Spare Cavernous Nerves During Radical Prostatectomy

IntroductionCavernous nerve sparing (NS) is critical for recovery of erectile function (EF) as well as erectile tissue preservation following radical prostatectomy (RP). Clinical experience suggests that surgeons may opt for non‐NS RP in patients with impaired baseline EF.AimThis study was performed to define if baseline EF is an independent predictor of NS status during RP.MethodsA total of 2,323 mean (mean age 59 ± 7 years) who underwent RP at a tertiary referral academic medical center were retrospectively evaluated. Patients who underwent preoperative radiation therapy or androgen deprivation treatment were excluded.Main Outcome MeasuresPreoperative parameters evaluated included biopsy pathological characteristics, prostate‐specific antigen (PSA) level, patient age, and EF. Baseline EF was graded on a validated five‐point patient reported scale. NSS was graded intraoperatively by the surgeon, using a four‐point NS score assigned to each nerve where 1 = fully preserved, 2 = partially preserved, 3 = minimally preserved, and 4 = resected. NS surgery was defined as NSS of 1 or 2 on both sides, and nerve resection surgery was defined as NSS of 3 or greater on both sides.ResultsOn univariate analysis, factors related to nerve resection surgery included (all P < 0.01): increasing age (r = 0.16), Gleason score (r = 0.19), EF score (r = 0.21), percentage biopsy cores positive (r = 0.11), higher preoperative PSA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.23–2.40), and clinical stage ≥T2 (RR 2.17, 95% CI 1.68–2.78). On multivariable analysis, factors independently predicting for non‐NS surgery included (all P < 0.01): baseline EF (odds ratio [OR] 1.50, 95% CI 1.33–1.68), biopsy Gleason sum (OR 1.95, 95% CI 1.65–2.36), clinical T stage ≥T2 (OR 1.59, 95% CI 1.15–2.20), patient age (OR 1.07, 95% CI 1.04–1.09), and percentage of biopsy cores positive (OR 1.01, 95% CI 1.00–1.02).ConclusionsWhile unfavorable clinical and prostate biopsy characteristics predict less NS, we have shown that poorer baseline EF also independently predicts for nerve resection RP. For every point increase in EF score (that is, worsening EF) the odds of not receiving NS during surgery increase by a factor of 1.5. Although NS is not associated with worse cancer outcomes in appropriately selected patients, failure to spare nerves is associated with poor post‐operative EF, urinary continence, and increased severity of cavernous venous leak. Patient anxiety related to cancer diagnosis and impending treatment may lead to falsely‐worsened apparent EF when recent erections are assessed during a pre‐operative planning visit. For these reasons prostatectomists should consider NS based solely on factors other than patient's baseline EF, even when it is impaired. Stember DS, Nelson CJ, and Mulhall JP. Preoperative erectile function is an independent predictor for decision to spare cavernous nerves during radical prostatectomy. J Sex Med 2013;10:2101-2107.     

Penile implant utilization following treatment for prostate cancer: analysis of the SEER-Medicare database

IntroductionProstate cancer treatments, including radical prostatectomy (RP) and radiotherapy (RT), may adversely affect erectile function. Penile implant surgery is a well-recognized erectile dysfunction (ED) treatment for prostate cancer survivors who wish to remain sexually active and in whom nonsurgical treatments are ineffective or unpalatable.AimTo describe the utilization of penile implants after RP or RT for prostate cancer and to identify predictors of such use.MethodsFrom Surveillance Epidemiology and End Results cancer registry data linked with Medicare claims, we identified men aged ≥66 years diagnosed with prostate cancer in 1998–2005 who were treated with RP or RT. Utilization of penile implants was identified in Medicare claims. Multivariable logistic regression was used to identify demographic and clinical predictors of implant utilization.Main Outcome MeasuresMedicare claim for penile implant surgery, impact of demographic and clinical factors on penile implant surgery utilization.ResultsThe study group comprised 68,558 subjects, including 52,747 who had RT and 15,811 who had RP as primary prostate cancer treatment. The penile implant utilization rate was 0.8% for the entire group, 0.3% for the RT group, and 2.3% for the RP group. Predictors of penile implant utilization were initial treatment modality, younger age, and African American or Hispanic race, being unmarried and residing in the South or West.ConclusionsPenile implant utilization after prostate cancer treatment is relatively uncommon in men over 65. Men who are younger, African American or Hispanic, and those who have an RP are more likely than their peers to receive a penile implant after prostate cancer treatment. Tal R, Jacks LM, Elkin E, and Mulhall JP. Penile implant utilization following treatment for prostate cancer: Analysis of the SEER-Medicare database.     

Penile Rehabilitation after Radical Prostatectomy: Where Do We Stand and Where Are We Going?

IntroductionPostprostatectomy erectile dysfunction (ED) remains a serious quality-of-life issue. Recent advances in the understanding of the mechanism of postprostatectomy ED have stimulated great attention toward penile rehabilitation.AimThis review presents and analyzes a contemporary series of the recent medical literature pertaining to penile rehabilitation therapy after radical prostatectomy (RP).Main Outcome MeasuresThe laboratory and clinical studies related to penile rehabilitation are analyzed. The validity of the methodology and the conclusion of the findings from each study are determined.MethodsThe published and presented reports dealing with penile rehabilitation following RP in human and cavernous nerve injury in animal models are reviewed.ResultsExciting scientific discoveries have improved our understanding of postprostatectomy ED at the molecular level. The rationale for postprostatectomy penile rehabilitation appears to be logical according to animal studies. However, clinical studies have not consistently replicated the beneficial effects found in the laboratory studies. Currently available clinical studies are flawed due to short-term follow-up, small number of patients in the studies, studies with retrospective nature, or prospective studies without control. Rehabilitation programs are also facing a challenge with the compliance, which is critical for success for any rehabilitation program. At the present time, we do not have concrete evidence to recommend what, when, how long, and how often a particular penile rehabilitative therapy can be used effectively.ConclusionsLarge prospective, multicentered, placebo-controlled trials with adequate follow-up are necessary to determine the cost-effective and therapeutic benefits of particular penile rehabilitative therapy or therapies in patients following the treatment of clinically localized prostate cancer. Until such evidence is available, it is difficult to recommend any particular penile rehabilitation program as a standard of practice. Wang R. Penile rehabilitation after radical prostatectomy: Where do we stand and where are we going?     

Penile rehabilitation should become the norm for radical prostatectomy patients

IntroductionThe Journal of Sexual Medicine (JSM) held a debate at the annual fall meeting of the Sexual Medicine Society of North America (SMSNA). The motion was “Penile Rehabilitation Should Become the Norm for Radical Prostatectomy Patients.” At the suggestion of several SMSNA members, it was requested that this debate might be of interest to JSM readers in the form of a published controversy.MethodsTwo debate speakers with expertise and/or strong opinions in the area of penile rehabilitation submitted their literature-review, evidence-based opinions on the topic.Main Outcome MeasureLiterature review of laboratory basic science and clinical research studies on penile rehabilitation.ResultsPenile rehabilitation involves prophylactic procedures designed to improve oxygen delivery to penile erectile tissues, aimed at preserving erectile tissue health and minimizing erectile tissue damage that otherwise occurs during the period of neural recovery to the autonomic cavernosal nerve following radical prostatectomy. There are several studies in the sexual medicine literature on penile rehabilitation after radical prostatectomy, and the positive results appear to support this concept, the rationale, and mechanism. The use of prophylactic penile rehabilitation programs has not been fully elucidated, nor have the results been replicated in large multicenter placebo-controlled trials.ConclusionPenile rehabilitation may be performed along with counseling with the couple, vacuum erection therapy, and vacuum erection device therapy if it is the patient and partner's preference, provided that it is undertaken in a safe and effective manner and is monitored closely. Mulhall JP, and Morgentaler A. Penile rehabilitation should become the norm for radical prostatectomy patients.     

Early versus late rehabilitation of erectile function after nerve-sparing radical cystoprostatectomy: a prospective randomized study

IntroductionPharmacological rehabilitation of erectile function (EF) after nerve‐sparing radical prostatectomy was repeatedly advocated.AimTo compare early vs. late penile rehabilitation in patients with nerve‐sparing (NS) radical cystoprostatectomy based on a prospective randomized trial.MethodsEighteen patients without spontaneous erection 8 weeks after NS radical cystoprostatectomy were randomly divided into two groups; group I and II who started the erectogenic therapy at the 2nd and 6th month postoperatively, respectively. The pharmacological therapy constitutes of sildenafil citrate twice weekly to be shifted to intracavernosal injection (ICI) of prostaglandin E1 (PGE1) if not responding. The treatment continued for 6 months in both groups.Main Outcome MeasuresThe EF status was evaluated before and at the end of the treatment by International Index of Erectile Function questionnaire and penile Doppler ultrasonography (PDU).ResultsSix out of nine patients recovered unassisted erection after treatment in group I compared to three out of nine patients in group II. Two patients in group I and three patients in group II were maintained on sildenafil therapy on demand basis. The remaining four patients were dependent on ICI of PGE1. At final evaluation, a significant improvement was found in the EF, the intercourse satisfaction and overall satisfaction domains (P = 0.02, 0.03, and 0.02, respectively) in group I compared with group II. Regarding PDU findings, significant improvement in end‐diastolic velocity was elicited in the early rehabilitation group compared with the pretreatment value (P = 0.03) with no significant difference between both groups.ConclusionEarly compared with delayed erectile rehabilitation brings forward the natural healing time of potency and maintains nerve‐assisted erection. Mosbah A, El Bahnasawy M, Osman Y, Hekal IA, Abou‐Beih E, and Shaaban A. Early versus late rehabilitation of erectile function after nerve‐sparing radical cystoprostatectomy: A prospective randomized study. J Sex Med 2011;8:2106–2111.     

Sonic Hedgehog Regulates Brain‐Derived Neurotrophic Factor in Normal and Regenerating Cavernous Nerves

IntroductionThe cavernous nerve (CN) is commonly injured during prostatectomy. Manipulation of the nerve microenvironment is critical to improve regeneration and develop novel erectile dysfunction therapies. Sonic hedgehog (SHH) treatment promotes CN regeneration. The mechanism of how this occurs is unknown. Brain‐derived neurotrophic factor (BDNF) facilitates return of erectile function after CN injury and it has been suggested in cortical neurons and the sciatic nerve that BDNF may be a target of SHH.AimTo determine if SHH promotes CN regeneration through a BDNF‐dependent mechanism.MethodsSprague Dawley rats underwent (i) bilateral CN crush (N = 15); (ii) SHH treatment of pelvic ganglia (PG)/CN (N = 10); (iii) SHH inhibition in PG/CN (N = 14 rats); (iv) CN crush with SHH treatment of PG/CN (N = 10 rats); (v) CN crush with SHH treatment and BDNF inhibition (N = 14 rats); and (vi) CN injury and SHH treatment of the penis (N = 23).Main Outcome MeasuresBDNF and glial fibrillary acidic protein were quantified in PG/CN by Western, and a t‐test was used to determine differences.ResultsIn normal rats SHH inhibition in the PG/CN decreased BDNF 34% and SHH treatment increased BDNF 36%. BDNF was increased 44% in response to SHH treatment of crushed CNs, and inhibition of BDNF in crushed CNs treated with SHH protein hampers regeneration.ConclusionsSHH regulates BDNF in the normal and regenerating PG/CN. BDNF is part of the mechanism of how SHH promotes regeneration, thus providing an opportunity to further manipulate the nerve microenvironment with combination therapy to enhance regeneration. Bond CW, Angeloni N, Harrington D, Stupp S, and Podlasek CA. Sonic hedgehog regulates brain‐derived neurotrophic factor in normal and regenerating cavernous nerves. J Sex Med 2013;10:730–737.     

Expression of Caveolin-1 in Penile Cavernosal Tissue in a Denervated Animal Model after Treatment with Sildenafil Citrate

IntroductionRadical pelvic surgery is a major cause of erectile dysfunction due to iatrogenic cavernous nerve damage. Endothelial nitric oxide synthase, which generates nitric oxide (NO) in the cavernosal tissues, localizes to specialized plasma membrane invaginations known as caveolae. Growing evidence suggests that caveolae are major components of signal trafficking and that stimuli that affect the concentration of the main structural protein of caveolae, caveolin-1 influence NO signaling.AimTo evaluate caveolin-1 expression as a marker of cavernous tissue damage and determine the impact of early sildenafil administration on caveolin-1 expression in animal models of partial and total surgical penile denervation.MethodsThirty-six rats were divided into six groups (N = 6 per group) that received bilateral or unilateral penile denervation or sham surgery, with and without sildenafil 10 mg daily for 7 weeks.Main Outcome MeasuresSections were taken from the proximal middle portion of the penis of all animals. Cavernous tissue was delineated by the tunica albuginea, then the extent of immunostaining for the following parameters was quantitated to determine (i) cavernous smooth muscle layer in the cavernous space expressed as the percentage of α-smooth muscle actin (α-SMA) positive immunostaining per area and (ii) caveolin-1 expressed as a percentage of area.ResultsA marked decrease in both caveolin-1 and α-SMA expression in cavernous smooth muscle tissue and in the endothelium of rats was noted after a bilateral and unilateral neurotomy. Specimens from animals receiving sildenafil exhibited higher mean immunostaining values for both proteins in cavernous tissue. The differences were statistically significant compared with groups receiving the same surgical treatment without sildenafil.ConclusionCaveolin-1 and α-SMA expression in cavernous tissue is significantly reduced by pelvic nerve injury, and the loss is related to the extent of the neural damage. Early administration of sildenafil elicits caveolin-1 expression, which appears to preserve cavernous tissue. Becher EF, Toblli JE, Castronuovo C, Nolazco C, Rosenfeld C, Grosman H, Vazquez E, and Mazza ON. Expression of caveolin-1 in penile cavernosal tissue in a denervated animal model after treatment with sildenafil citrate. J Sex Med 2009;6:1587–1593.     

Extended Pelvic Lymph Node Dissection Does Not Affect Erectile Function Recovery in Patients Treated with Bilateral Nerve‐Sparing Radical Prostatectomy

IntroductionExtended pelvic lymph node dissection (ePLND) might be associated with damages to the pelvic plexus, potentially affecting erectile function (EF) recovery after radical prostatectomy (RP). However, the impact of the extent of pelvic lymph node dissection (PLND) on EF has never been addressed.AimThe aim of this study is to evaluate the impact of ePLND on potency recovery in patients who underwent bilateral nerve‐sparing RP (BNSRP).MethodsThe study included 396 patients with prostate cancer treated with BNSRP by two high‐volume surgeons. Patients were retrospectively divided into two groups based on PLND status: no PLND (N = 161; 40.9%) and ePLND (N = 235; 59.1%) at the time of BNSRP. All patients had preoperative functional and oncological data. Univariable and multivariable Cox regression models tested the association between ePLND and EF recovery after surgery, after accounting for confounders.Main Outcome MeasureThe International Index of Erectile Function (IIEF) was used to evaluate EF after BNSRP. Postoperative EF recovery was defined as an IIEF‐EF domain score ≥22.ResultsAt a mean follow up of 33.2 months after surgery (median 30), 183 patients (46.2%) recovered EF. Overall, postoperative EF recovery rate at 2 years was 48.4%. No significant differences were recorded when patients were stratified according to the extent of PLND (EF recovery rates at 2‐year: 46.6% vs. 49.7% for patients who did not undergo PLND vs. those treated with ePLND; P = 0.33). These results were confirmed at multivariable analyses, where only age at surgery and preoperative IIEF‐EF (all P ≤ 0.03), but not ePLND (P = 0.8), represented independent predictors of EF recovery.ConclusionsThe extent of PLND is not associated with potency after BNSRP. Conversely, other factors such as age at surgery and preoperative EF represent the major predictors of postoperative potency recovery. Therefore, when indicated, ePLND can be safely performed without compromising EF outcomes. Gandaglia G, Suardi N, Gallina A, Abdollah F, Capitanio U, Salonia A, Colombo R, Bianchi M, Chun FK, Hansen J, Rigatti P, Montorsi F, and Briganti A. Extended pelvic lymph node dissection does not affect erectile function recovery in patients treated with bilateral nerve‐sparing radical prostatectomy. J Sex Med 2012;9:2187–2194.