The Role of the Low-Intensity Extracorporeal Shockwave Therapy on Penile Rehabilitation After Radical Prostatectomy: A Randomized Clinical Trial

BackgroundErectile dysfunction (ED) after radical prostatectomy (RP) still represents a major issue. Considering the benefits recently described regarding the application of low-intensity extracorporeal shockwave therapy (LiESWT) in vasculogenic ED, questions arise about its role in the scenario of penile rehabilitation.AimTo compare the early introduction of phosphodiesterase-5 inhibitor (PDE5i) with a combination therapy enrolling both early PDE5i use and LiESWT in patients submitted to RP.MethodsThis study is a randomized clinical trial, open-label, with 2 parallel arms and an allocation ratio of 1:1. The study was registered in ReBEC (ensaiosclinicos.gov.br) Trial: RBR-85HGCG. Both arms started tadalafil at a dose of 5 mg/day right after the removal of the transurethral catheter, and the experimental group received 2,400 shocks/session-week distributed on 4 different penile regions. The full treatment consisted of 19,200 impulses across 8 weeks.OutcomesThe primary clincal end point was ≥4-point difference favoring the experimental group considering the mean International Index of Erectile Function short form (IIEF-5) at last follow-up. Any statistical difference in the IIEF-5 score between the arms was stated as the primary statistical end point.ResultsBetween September 25, 2017, and December 3, 2018, 92 men were enrolled in the study. At last follow-up, we assessed 77 patients, 41 in the control group and 36 in the intervention group. A difference between groups was detected when accessing the final median IIEF-5 score (12.0 vs 10.0; P = .006). However, the primary clinical endpoint considering a difference ≥4-point between the arms has not been reached. When performing an exploratory analysis comparing the proportion of those individuals with an IIEF-5 score ≥17, no difference between groups was noted (17.1% vs 22.2%; P = .57).Clinical ImplicationsSo far, the benefits arising from LiESWT for penile rehabilitation after RP have been uncertain.Strengths & LimitationsThis is the first trial assessing the role of LiESWT on erectile function after RP. Our study protocol included only one session per week for the experimental group, raising a query if a more intensive application could achieve better results once a statistically significant difference was found between groups. We discontinue the PDE5i use at the last session, which may have interfered in the penile vascular rehabilitation, maybe compromising the results too.ConclusionAfter therapy with 19,200 impulses therapy across 8 weeks, we found an improvement of the IIEF-5 score, but it was not enough to be considered clinically significant. More studies are warranted before any recommendation on this topic.Baccaglini W, Pazeto CL, Corrêa Barros EA, et al. The Role of the Low-Intensity Extracorporeal Shockwave Therapy on Penile Rehabilitation After Radical Prostatectomy: A Randomized Clinical Trial. J Sex Med 2020;17:688–694.     

Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial

BackgroundAlthough several reports have documented the subjective improvement of erectile function after low-intensity extracorporeal shockwave therapy (LI-ESWT) in patients with vasculogenic erectile dysfunction (ED), objective assessment data of penile hemodynamics are lacking.AimTo assess penile hemodynamics before and 3 months after LI-ESWT in a group of patients with documented vasculogenic ED.MethodsThis was a double-blinded, randomized, sham-controlled trial. Forty-six patients with ED were randomized; 30 underwent LI-ESWT and 16 had a sham procedure in double-blinded fashion. All patients underwent penile triplex ultrasonography by the same investigator immediately before and 3 months after treatment. Patient demographics, International Index of Erectile Function erectile function domain (IIEF-ED) score, and minimal clinically important difference were assessed at baseline and 1, 3, 6, 9, and 12 months after treatment.OutcomesChanges in peak systolic velocity and resistance index as measured by triplex ultrasonography at baseline and 3 months after treatment were the main outcomes of the study. Secondary outcomes were changes in the IIEF-EF score from baseline to 1, 3, 6, 9, and 12 months after treatment and the percentage of patients reaching a minimal clinically important difference during the same period for the two groups.ResultsIIEF-EF minimal clinically important differences for the active vs sham group were observed for 56.7% vs 12.5% (P = .005) at 1 month, 56.7% vs 12.5% (P = .003) at 3 months, 63.3% vs 18.8% (P = .006) at 6 months, 66.7% vs 31.3% (P = .022) at 9 months, and 75% vs 25% (P = .008) at 12 months. Mean peak systolic velocity increased by 4.5 and 0.6 cm/s in the LI-ESWT and sham groups, respectively (P < .001).Clinical ImplicationsSuch results offer objective and subjective documentation of the value of this novel treatment modality for men with vasculogenic ED.Strengths and LimitationsStrengths include the prospective, randomized, sham-controlled type of study and the assessment of penile hemodynamics. Limitations include the small sample and strict inclusion criteria that do not reflect everyday clinical practice.ConclusionThe present study confirms the beneficial effect of LI-ESWT on penile hemodynamics and the beneficial effect of this treatment up to 12 months.Kalyvianakis D, Hatzichristou D. Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial. J Sex Med 2017;14:891–897.     

The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan

IntroductionAlthough physical activity is associated with a decreased risk of erectile dysfunction (ED), the association of ED with physical function remains unclear.AimTo investigate the relationship between gait function and ED in a community-dwelling population.MethodsThis cross-sectional study analyzed 324 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. ED was assessed with the 5-Item International Index of Erectile Function (IIEF-5). The participants were divided into 2 groups: low IIEF-5 score (≤16) and high IIEF-5 score (>16). We evaluated physical function, including gait function and grip strength. Gait function was evaluated by 10-meter gait speed and 2-step score (the ratio of the maximum length of 2 strides to height). We assessed daily physical activity, comorbidities, mental status, and laboratory data. The association between physical function and a low IIEF-5 score was analyzed by multivariate logistic regression analysis.Main Outcome MeasureThe main outcome measure was to assess whether gait function was an independent indicator for erectile dysfunction.ResultsOf 324 men, 154 (48%) had a low IIEF-5 score. Grip strength, 2-step score, and 10-meter gait speed in the low IIEF-5 group were significantly inferior to those in the high IIEF-5 group. Multivariate analysis showed that the 2-step score (odds ratio = 0.08), age, and total testosterone were independently associated with a low IIEF-5.Clinical ImplicationsThis study may motivate clinicians to investigate predictive values of physical function for ED.Strengths & LimitationsThe strength of this study was the use of simple, objective, and feasible tests for gait function to assess its association with ED. The limitations of this study were selection bias, regional bias, and nature of the cross-sectional study.ConclusionsOf the gait functional tests, not the 10-meter gait speed but 2-step score was an independent indicator for the presence of ED.Okamoto T, Hatakeyama S, Imai A, et al. The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan. J Sex Med 2019; 16:1922–1929.     

Functional Variations in the NOS3 Gene Are Associated With Erectile Dysfunction Susceptibility,Age of Onset and Severity in a Han Chinese Population

BackgroundImpaired function of endothelial nitric oxide synthase (eNOS) is involved in the pathologic processes of erectile dysfunction (ED), and three functional polymorphisms (G894T, T-786C, and a tandem repeat of 27 bp in intron 4) in the NOS3 gene, which encodes eNOS, are associated with the clinical characteristics of ED in several populations.AimTo investigate the effect of these variations of NOS3 on ED phenotypes and the response to sildenafil in a Han Chinese population.MethodsThis case-control study enrolled 112 patients with ED and 156 age-matched healthy men. Their medical history and laboratory data were collected. ED severity and response to sildenafil were assessed using the five-item International Index of Erectile Function (IIEF-5) score. Routine polymerase chain reaction and Sanger sequencing were used to genotype the three polymorphisms of NOS3.OutcomesThe frequencies of alleles, genotypes, and haplotypes of the loci in patients and controls; the IIEF-5 scores of patients carrying the risk and non-risk genotype; and the frequencies of risk and non-risk genotypes in patients with different ages at onset and responses to sildenafil were assessed.ResultsThe frequencies of drinkers and diabetic and hyperlipidemic patients in the ED group were higher than those in the age-matched control group (P < .05). The distributions of alleles (G894T, P < .005; T-786C, P < .015), genotypes (G894T, P < 0.015; T-786C, P < .010), and haplotypes (G894T/T-786C, P < .015) of the NOS3 polymorphisms were significantly different between patients with ED and controls. An increased risk for earlier onset of ED was observed in the G894T risk genotype carriers (odds ratio = 3.572; P < .020). Patients with the risk genotype of T-786C exhibited lower IIEF-5 scores than patients with the non-risk genotype (8.2 ± 4.5 vs 12.2 ± 5.0; P < .015). The influence of the T-786C or G894T genotype on the response to sildenafil was not observed.Clinical TranslationThe detectable effect of NOS3 functional polymorphisms on ED suggests their application potential as a molecular biomarker in predicting ED susceptibility and severity in the Han Chinese population.Strengths & LimitationsThis study provides strong evidence that NOS3 functional variation is an independent risk factor for ED in the Han Chinese population, which should be confirmed in larger cohorts considering the limited number of subjects in this study.ConclusionThese results are the first to identify a clear association between NOS3 functional variation and ED susceptibility, age at onset, and severity in the Han Chinese population.Yang B, Liu L, Peng Z, et al. Functional Variations in the NOS3 Gene Are Associated With Erectile Dysfunction Susceptibility, Age of Onset and Severity in a Han Chinese Population. J Sex Med 2017;14:551–557.     

Can the International Index of Erectile Function (IIEF-5) be used as a diagnostic tool to the severity of vasculogenic erectile dysfunction?

ObjectiveThe objective of this observational study was to compare the International Index of Erectile Function (IIEF-5) with penile duplex in the diagnosis of vasculogenic erectile dysfunction severity. 150 subjects complaining of erectile dysfunction for >6 months have been divided into two groups according to their response to intracavernous injection (ICI) test; 50 patients who showed good response ? (E4) and one hundred patients who showed poor response ? (E4) up to maximum dose of 1 cc Quadmix with abnormal penile duplex. The results of the duplex are correlated to the IIEF-5 score of the patients.FindingsThere is statistically significant difference between mean value of IIEF-5 in both good and poor responders (P-value = 0.0000), significant difference between mean value of (age, duration, PSV, EDV, diameter of artery after injection, percent of increase in arterial diameters and RI) between the good and poor responders. There was no evidence of statistically significant difference between mean value of IIEF-5 in both arteriogenic and venogenic subgroups of poor responders group. There was neither evidence of statistically significant correlations between IIEF-5 and penile duplex results in both good and poor responders groups, nor between IIEF-5 and penile duplex results in arteriogenic and venogenic and combined subgroups.ConclusionIIEF-5 might not be a suitable diagnostic tool of the severity of vascular affection in ED.     

Acceptance and Commitment Therapy to Increase Adherence to Penile Injection Therapy-Based Rehabilitation After Radical Prostatectomy: Pilot Randomized Controlled Trial

IntroductionDespite the importance of using penile injections as part of a penile rehabilitation program, men have difficulty complying with these programs.AimTo test a novel psychological intervention based on Acceptance and Commitment Therapy for erectile dysfunction (ACT-ED) to help men utilize penile injections.MethodsThis pilot randomized controlled trial (RCT) recruited men who were beginning a standard care (SC) structured penile rehabilitation program following radical prostatectomy. The SC program instructed patients to use penile injections 2 to 3 times per week. Participants were randomized to SC+ACT-ED or SC+enhanced monitoring (EM). Over 4 months, patients in the SC+ACT-ED group received SC plus 4 ACT sessions and 3 ACT phone calls; those in the EM group received SC plus 7 phone calls from an experienced sexual medicine nurse practitioner. Participants were assessed at study entry and at 4 and 8 months. For this pilot study, the goal was to determine initial efficacy (ie, effect sizes, where d = 0.2 is small, d = 0.5 is medium, and d = 0.8 is large).Main Outcome MeasurePrimary outcomes were feasibility and use of penile injections. Secondary outcomes were ED treatment satisfaction (ie, Erectile Dysfunction Inventory of Treatment Satisfaction, or EDITS), sexual Self-Esteem and Relationship (SEAR) quality, sexual bother (SB), and prostate cancer treatment regret.ResultsThe 53 participants were randomized (ACT, n = 26; EM, n = 27). The study acceptance rate was 61%. At 4 months, the ACT-ED group utilized more penile injections per week (1.7) compared to the EM group (0.9) (d = 1.25; P = .001) and was more adherent to penile rehabilitation compared to the EM group (ACT, 44%; EM, 10%; relative risk [RR], 4.4; P = .02). These gains were maintained at 8 months for injections per week (ACT, 1.2; EM, 0.7; d = 1.08; P = .03) and approached significance for adherence (ACT, 18%; EM, 0%; P = .10). At 4 months, ACT-ED, compared to EM, reported moderate effects for greater satisfaction with ED treatment (d = 0.41; P = .22), greater sexual self-esteem (d = 0.54; P = .07) and sexual confidence (d = 0.48; P = .07), lower sexual bother (d = 0.43; P = .17), and lower prostate cancer treatment regret (d = 0.74; P = .02). At 8 months, moderate effects in favor of ACT-ED were maintained for greater sexual self-esteem (d = 0.40; P = .19) and less treatment regret (d = 0.47; P = .16).Clinical ImplicationsACT concepts may help men utilize penile injections and cope with the effects of ED.Strengths and LimitationsStrengths include use of an innovative intervention utilizing ACT concepts and pilot RCT. Limitations include the pilot nature of the study (eg, small samples size, lack of statistical power).ConclusionACT-ED is feasible and significantly increases the use of penile injections. ACT-ED also shows promise (moderate effects) for increasing satisfaction with penile injections and sexual self-esteem while decreasing sexual bother and prostate cancer treatment regret.Nelson CJ, Saracino RM, Napolitano S, et al. Acceptance and Commitment Therapy to Increase Adherence to Penile Injection Therapy-Based Rehabilitation After Radical Prostatectomy: Pilot Randomized Controlled Trial. J Sex Med 2019; 19:1398–1408.     

Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film

BackgroundA new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT).AimTo assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT.MethodsFrom May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks.OutcomesThe International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11–16), or mild (IIEF-15 score = 17–25).ResultsAll patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = −0.19; P < .01). For the ODF formulation, the median CGI-I score was 3.5 (interquartile range [IQR] = 2.5–4.5) and the median PGI-I score was 3.0 (IQR = 2.0–4.0). The median action time was 20.0 minutes (IQR = 15.0–30.0) and the median mouth time was 60.0 seconds (IQR = 30.0–120.0).Clinical ImplicationsThe ODF formulation of a widely known drug, with the same safety and effectiveness of the FCT, was better appreciated by patients in overall satisfaction.Strengths and LimitationsThis is the first clinical trial to assess the efficacy of a new formulation of sildenafil in patients with ED. The limitations of the study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the “additional” side effects of the ODF formulation compared with FCT are reported.ConclusionThe new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy.Cocci A, Capece M, Cito G, et al. Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film. J Sex Med 2017;14:1606–1611.     

Male Sexual Function in New Zealand: A Population-Based Cross-Sectional Survey of the Prevalence of Erectile Dysfunction in Men Aged 40–70 Years

BackgroundSexual function declines with age and erectile dysfunction (ED) is a common condition worldwide; however, prevalence rates vary markedly between populations and reliable data specific to New Zealand (NZ) are lacking.AimTo assess the prevalence of ED in NZ men using a population-based cross-sectional survey.MethodsPostal questionnaires were sent, according to a modified Dillman method, to a randomly selected age-stratified population-based sample of 2,000 men 40 to 70 years old obtained from the electoral roll. Self-reported erectile function was assessed using the five-item International Index of Erectile Function (IIEF-5) and the single-question self-assessment tool.OutcomesThe prevalence of ED is presented as crude, age-adjusted to the distribution of the NZ population, and standardized to the World Health Organization World Standard Population (WSP). Associations between sexual function and age were analyzed using χ² test.ResultsThe response rate was 30% (599) and 28% (562) were complete for analysis. The crude prevalence of ED was 42% (22% mild, 10% mild to moderate, 6% moderate, and 4% severe), the age-adjusted prevalence was 38%, and the WSP-adjusted prevalence was 37%. Among men reporting ED, 16% were medically diagnosed and 22% were treated. ED affected 24% of men in their 40s, 38% in their 50s, and 60% in their 60s (P < .001). Age was associated with a significant increase in diagnosed ED (P = .001), treated ED (P = .006), dissatisfaction with current sexual function (P < .001), associated anxiety or depression (P = .023), and a decrease in sexual activity (P < .001).Clinical TranslationApproximately one in three NZ men 40 to 70 years old might have ED. Although comparable to overseas populations, this prevalence is high.Strengths and LimitationsThis study provides the most reliable, comprehensive, and current information on ED and its risk factors in NZ men. Strengths include the large sample, the use of random selection from a population-based sampling frame, established effective survey methods, and the validated IIEF-5. Limitations include the inability of cross-sectional data to determine causation, non-sampling errors associated with the population-based sampling frame, the low response rate, the inability to assess non-respondents, the possibility of men with ED who were sexually inactive not responding or not completing the IIEF-5, and the inherent inability to rule out recall bias.ConclusionED is a marker of subclinical cardiovascular disease. The high prevalence and low levels of diagnosis and treatment indicate a lost opportunity for timely intervention to delay or prevent the progression toward clinical disease.Quilter M, Hodges L, von Hurst P, et al. Male Sexual Function in New Zealand: A Population-Based Cross-Sectional Survey of the Prevalence of Erectile Dysfunction in Men Aged 40–70 Years. J Sex Med 2017;14:928–936.     

Male and Female Sexual Dysfunction in Pediatric Cancer Survivors

BackgroundPediatric cancer survivors suffer indirect long-term effects of their disease; however, there is a paucity of data regarding the effect of pediatric cancer survivorship on sexual function.AimTo assess the prevalence and risk factors associated with sexual dysfunction among pediatric cancer survivors.MethodsPediatric cancer survivors were recruited to complete an online survey using the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-5), both validated questionnaires to assess female sexual dysfunction (FSD) and erectile dysfunction (ED). Patient demographics, oncologic history, prior treatment, and sexual habits were also queried. Logistic regression was used to evaluate risk factors for sexual dysfunction, and Mann-Whitney U test was used to identify factors associated with individual domains of the FSFI.OutcomesThe main outcome measures were FSFI and IIEF-5 score, which are used to diagnose FSD (FSFI<26.55) and ED (IIEF-5<22).ResultsA total of 21 (72.4%) female respondents and 20 (71.4%) male respondents were sexually active and completed the survey and FSFI or IIEF-5 questionnaire, respectively. Mean (±SD) age was 23.7 (4.1) years, and average age at diagnosis was 9.1 (5.0), with no difference between genders. Overall, 25.0% (5/20) of male and 52.4% (11/21) of female pediatric cancer survivors reported sexual dysfunction (P = .11). Oncologic history and prior treatment were not associated with sexual function. Females who reported difficulty relaxing during intercourse in the last 6 months had higher odds of reporting sexual dysfunction (odds ratio: 13.6, 95% confidence interval: 1.2–151.2, P = .03). Subgroup analysis of FSFI domains found that previous radiation therapy was correlated with decreased lubrication and satisfaction during intercourse, whereas previous treatment to the pelvic region significantly reduced satisfaction and increased pain during intercourse.Clinical ImplicationsFemale pediatric cancer survivors have higher odds of reporting sexual dysfunction after treatment and should be screened appropriately to provide early intervention and to mitigate risk.Strength & LimitationsOur study includes validated questionnaires to assess FSD and ED and queries specific characteristics to assess their association with sexual dysfunction. However, the study is limited by sample size and its cross-sectional survey design.ConclusionsThe prevalence of female sexual dysfunction in this cohort is higher than that in the general population of equivalent-aged individuals, and clinicians should be aware of these potential long-term sequelae.Greenberg DR, Khandwala YS, Bhambhvani HP, et-al. Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. J Sex Med 2020;17:1715–1722.     

Factors Associated With Patient-Reported Penile Length Loss After Radical Cystoprostatectomy in Male Patients With Bladder Cancer

BackgroundThe perception of penile length loss is common in male patients undergoing radical prostatectomy; however, this has not been described after radical cystoprostatectomy (RC).AimTo evaluate perceptions of penile length loss in male patients after RC and contributing factors.MethodsPatients completed an institutional review board–approved questionnaire comprised the International Index of Erectile Function (IIEF-5) and supplemental questions including perceived changes in penile length after RC. Multivariable analysis was performed to determine associations between the perception of penile length loss and the amount of length lost with patient and surgery-specific factors.OutcomesThe rate of patient-reported penile length loss and factors contributing to this perception was the outcome of this study.ResultsFrom October 2017 to January 2019, 151 patients completed the questionnaire. The median age at cystectomy was 66.1 years (interquartile range [IQR]: 59.4–73.3), and the median duration of follow-up was 28.3 months (IQR: 13–74.1). Preoperative IIEF-5 was available in 55 patients with a median score of 14 (IQR: 3–20). The median IIEF-5 score at time of survey completion was 3 (IQR: 1–18). The majority of patients (55.1%) reported a perceived loss of penile length, 20.4% reported no loss, and 24.5% were unsure. Of those who quantified their loss in penile length, 54.6% reported losses of an inch or more. Neurovascular preservation was not found to protect against penile length loss but did correlate with a reduction in the amount reported lost (P = .008). Multivariable logistic regression analysis identified increasing IIEF-5 score at time of survey completion to protect against a perceived loss in penile length (odds ratio: 0.924, 95% confidence interval: 0.878–0.973, P = .0025), whereas increasing body mass index was associated with a loss in perceived penile length (odds ratio: 1.198, 95% confidence interval: 10.53–1.383, P = .0060).Clinical ImplicationsThe perception of penile length loss is a commonly held belief in patients after RC, and many patients will perceive losses that exceed 1 inch (2.54 cm).Strengths and LimitationsThis study is the first series to describe the perception of penile length loss after RC. It is strengthened by the study population's size, heterogeneity, and patient-reported results. It is limited by lack of objective measurements of stretched penile length.ConclusionsRC can result in significant sexual dysfunction including the perceived loss of penile length.Loh-Doyle JC, Han J, Ghodoussipour S. Factors Associated With Patient-Reported Penile Length Loss After Radical Cystoprostatectomy in Male Patients With Bladder Cancer. J Sex Med 2020;17:957–963.     

ORIGINAL RESEARCH–SURGERY: Treatment of Penile Deep Dorsal Venous Leakage of Erectile Dysfunction by Embedding the Deep Dorsal Vein of the Penis: A Single Center Experience with 17 Patients

IntroductionThe common surgery for venous leakage was not very successful; unsatisfactory long-term results have reduced the indications for venous surgery for erectile dysfunction (ED).AimsTo assess the outcomes of embedding the deep dorsal vein of the penis (EDDVP), a new surgical technique used in patients with penile deep dorsal venous leakage of ED.MethodsBetween December 2001 and November 2007, 17 patients diagnosed with penile deep dorsal venous leakage of ED underwent embedding the deep dorsal vein of the penis.Main Outcome MeasuresAll cases were available for follow up by using the abridged 5-item version of the International Index of Erectile Function (IIEF-5) scoring system and penile color Doppler ultrasound. Dynamic cavernosography were also assessed in three patients at 3 months postoperatively.ResultsAfter surgery, 14 patients were able to achieve satisfactory intercourse and three had sufficient erection after oral sildenafil (50–100 mg). The IIEF-5 scoring changed from a preoperative mean IIEF-5 score of 8.8 ± 3.9 to 20.8 ± 4.1 (P < 0.05). Peak systolic velocity (average of right and left cavernosal arteries) changed from 41.9 ± 7.7 cm/second to 44.2 ± 9.2 cm/second (P > 0.05), resistance index changed from 0.79 ± 0.1 to 1.00 ± 0.0 (P < 0.05), and venous velocity changed from 8.4 ± 4.0 cm/second to 0.0 ± 0.0 cm/second (P < 0.05). Dynamic cavernosography demonstrated a smooth flow of the deep dorsal vein during the flaccid phase. During the tumescent phase, the deep dorsal vein of the penis was compressed between the dilated sinusoidal spaces and the tunica albuginea and resulted in venous drainage blockade. And then the hardness of erection was improved and maintained.ConclusionsThe new surgical technique of EDDVP is a simple operative procedure, which seems to be efficient in the treatment of penile deep dorsal venous leakage of ED. Zhang B, Chen J, Xiao H, Zhang Y, Cai L, Tao X, Qi T, and Ban D. Treatment of penile deep dorsal venous leakage of erectile dysfunction by embedding the deep dorsal vein of the penis: A single center experience with 17 patients. J Sex Med 2009;6:1467–1473.     

Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1

IntroductionErectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED.AimTo evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1.MethodsIn this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame’s Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher’s exact tests were used to compare the groups, and regression analyses were used to show predictors of ED.Main Outcome MeasureSexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED.ResultsED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED.Clinical ImplicationsNeurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men.Strengths & LimitationsThe statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED.ConclusionHormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals.de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV–1. J Sex Med 2019; 16:1763–1768.     

Impact of Kidney Transplantation on Male Sexual Function: Results from a Ten-Year Retrospective Study

BackgroundThe effects of kidney transplantation on male sexual function are controversial.AimTo evaluate the impact of kidney transplantation on erectile and ejaculatory function and to assess a possible correlation between some selected characteristics of patients and their erectile and ejaculatory function after renal transplantation.MethodsAn observational retrospective analysis was conducted on male patients who had undergone kidney transplantation from January 2009 to April 2019. A prospectively maintained database was used to collect all data. Patients were evaluated before kidney transplant and 6 and 12 months after kidney transplant. Male patients undergoing renal transplantation for any cause who were sexually active with a stable partner were included in the study.OutcomesThe main outcome measures included the International Index of Erectile Function (IIEF-15) and the 4-item version of Male Sexual Health Quality–Ejaculation Disorders (MSHQ-EjD Short Form) questionnaires. The first 3 questions of the MSHQ-EjD Short Form were used to assess the ejaculatory function, whereas the fourth question was used to evaluate the ejaculation bother.ResultsA total of 95 patients were eligible in the study. The evaluation of sexual function was available in 56 patients (58.9%). Mean IIEF-15 significantly decreased at 6 months (P < .001) remaining unchanged at 12 months (P = .228). Mean MSHQ-EjD Short Form (1–3) significantly decreased at 6-month follow-up (P < .001) and at 12-month follow-up (P = .024). Mean MSHQ-EjD Short Form (4) was significantly increased compared with the baseline at both 6 and 12 months (P < .05). IIEF-15 was significantly related to the MSHQ-EjD Short Form at 6-month and 12-month follow-up (P < .001). Age, diabetes, hypertension, smoking, pretransplantation testosterone, time for transplantation, baseline IIEF-15, and baseline MSHQ-EjD Short Form (1–3) were significantly associated (P < .05) with both IIEF-15 and the MSHQ-EjD Short Form (1–3) at 6-month and 12-month follow-up after kidney transplantation.Clinical ImplicationsImprovement of knowledge regarding the effects of kidney transplantation on sexual function and about the patient characteristics related to sexual health after transplantation.Strength & LimitationsThis is the first article that analyzes in depth the ejaculatory function in patients who had undergone kidney transplantation assessing ejaculation with a validated questionnaire. The main limitation is the retrospective design of the study.ConclusionKidney transplantation appears to have a negative impact on sexual health, significantly worsening both erectile and ejaculatory functions. Age, diabetes, hypertension, smoking, pretransplantation testosterone levels, time for transplantation, as well as erectile and ejaculatory function before transplant were significantly related to erectile and ejaculatory functions after renal transplantation.Spirito L, Manfredi C, Carrano R, et al. Impact of Kidney Transplantation on Male Sexual Function: Results from a Ten-Year Retrospective Study. J Sex Med 2020;17:2191–2197.     

An Evaluation of a Clinical Care Pathway for the Management of Men With Nonorganic Erectile Dysfunction

IntroductionThere exists little literature on the outcomes of the medical management of men with erectile dysfunction (ED) with no overt organic etiology.AimThis study was conducted to assess the outcomes of men with nonorganic ED treated medically.MethodsAll patients had normal hormone profiles and vascular assessment. All were given a trial of a phosphodiesterase type 5 inhibitor (PDE5i). If no improvement was experienced, intracavernosal injection (ICI) therapy was administered. All patients were encouraged to seek a consultation with a mental health professional.Main Outcome MeasurePatient demographics, medical comorbidities, hormone and hemodynamics assessments, and change in International Index of Erectile Function scores of patients were recorded.Results116 men with a mean age or 38 ± 19 (range 16?57) years were studied. 21% had mild ED, 47% had moderate ED, and 32% had severe ED. 21% had seen a psychiatrist. 81% of patients responded to PDE5i with a penetration hardness erection on follow-up (mean duration of 7 ± 3 months postcommencement of PDE5i). However, only 68% of these were capable of a consistently good response. The mean Erectile Function domain score on PDE5i for the entire group improved from 18 ± 11 to 22 ± 6 (P = .01), and for PDE5i responders it was 27 ± 4 (P < .001). 28% of men (22 PDE5i failures and 10 with a mixed response to PDE5i) attempted ICI, all obtaining consistently functional erections. At a mean time point of 11 ± 5 months, 83% of those responding to PDE5i had ceased using PDE5i due to a lack of need. 11% of those using ICI continued to use them 6 months after starting ICI; the remainder had been transitioned back to PDE5i. Of the 29 patients in the latter subgroup, 66% were no longer using PDE5i consistently due to a lack of need.Clinical ImplicationsNot all men with nonorganic ED respond to PDE5i initially and many of those who respond do so only intermittently; such patients are potentially curable, using erectogenic pharmacotherapy for erectile confidence restoration, most men are capable of being weaned from drug therapy.Strengths & LimitationsThe strengths of the study are the large number of patients and the use of serial validated instruments to assess erectile function outcomes. As a weakness, despite normal hormone and vascular assessments, the diagnosis of nonorganic ED is still a presumptive one.ConclusionMedical management of nonorganic ED utilizing the process of care model results in cure in a large proportion of such patients. The transient use of ICI in some patients permits successful PDE5i rechallenge.Jenkins LC, Hall M, Deveci S, et al. An Evaluation of a Clinical Care Pathway for the Management of Men With Nonorganic Erectile Dysfunction. J Sex Med 2019;16:1541–1546.     

Longitudinal Risk of Developing Cardiovascular Diseases in Patients With Erectile Dysfunction—Which Patients Deserve More Attention?

BackgroundErectile dysfunction (ED) is widely considered as an early manifestation of cardiovascular diseases (CVDs), sharing similar risk factors.AimAssess rates and predictors of developing CVD and/or hypertension (HTN) over a long-term follow-up period using user-friendly and clinically reliable tools in men presenting with ED but without CVD/HTN or known vascular risk factors at baseline.MethodsData from 108 patients presenting between 2005 and 2011 with ED were analyzed. All patients were free from CVD and/or HTN (CVD/HTN) at baseline. Patients completed the International Index of Erectile Function (IIEF) at baseline and were followed up every 6 months with clinical assessment or phone interview. Kaplan-Meier analyses estimated the probability of developing CVD/HTN over time. Cox-regression models tested the association between patient baseline characteristics (for example, age, Charlson Comorbidity Index, baseline IIEF-EF, ED severity, alcohol intake, smoking), response to phosphodiesterase type-5 inhibitors (PDE5is), and the risk of developing CVD/HTN.ResultsOf all, 43 (40%) patients showed IIEF-EF scores suggestive of severe ED; 37 (39%) and 59 (61%) were nonresponders and responders to PDE5i, respectively. Median (interquartile range) age was 51 (41, 61) years. Median (interquartile range) follow-up was 95 (86-106) months. Overall, the estimated risk of developing CVD/HTN was 15% (95% confidence interval [CI]: 9-27) at 10-year assessment. Men with baseline severe ED had a higher risk of developing CVD/HTN (34%; 95% CI: 17-59, P = .03) at 10 years than patients with mild to moderate ED (5% [95% CI: 2-14]). At the Cox regression analysis, severe ED (Hazard ratio [HR], 4.62; 95% CI: 1.43, 8.89; P = .01) and baseline IIEF-EF score (HR, 0.92; 95% CI: 0.86, 0.99; P = .02) were associated to the risk of CVD/HTN overtime. Conversely, age and nonresponders to PDE5is (HR, 0.92; 95% CI: 0.32, 2.68; P = .9) were not associated to a risk of CVD/HTN over time.Clinical ImplicationsThe use of an easy and user-friendly tool, as the IIEF-EF domain score, would allow to reliably assess which men with ED at first presentation may deserve a different, more specific and detailed cardiologic investigation to prevent inauspicious CV events.Strengths & LimitationsA single-center-based, observational longitudinal study, raising the possibility of selection biases are the main limits.ConclusionsPatients with severe ED and lower baseline IIEF-EF but no vascular risk factors at first presentation have more than 30% risk of developing CVD/HTN in 10-year time. Those patients may benefit from medical preventive strategies to lowering the risk of CV events and HTN.Pozzi E, Capogrosso P, Boeri L, et al. Longitudinal Risk of Developing Cardiovascular Diseases in Patients With Erectile Dysfunction—Which Patients Deserve More Attention?. J Sex Med 2020;17:1489–1494.     

Associations of VEGF Gene Polymorphisms With Erectile Dysfunction and Related Risk Factors

BackgroundRepeated evidence from animal models suggests a strong link between vascular endothelial growth factor (VGEF) and penile vasculature and erectile function because VEGF can alter the physiologic pathways involved in the regulation of penile vasomotor tone.AimTo investigate three VEGF polymorphisms and their link to erectile dysfunction (ED).MethodsWe enrolled 688 Taiwanese men with a mean age of 55.6 years (SD = 4.5) during a free health screening. All participants provided complete medical histories and underwent physical examinations. Fasting blood samples were obtained for biochemical analysis and hormone profiling. The allelic discrimination of three VEGF gene polymorphisms (460T/C [rs833061], 1154G/A [rs1570360], and 2578A/C [rs699947]) was performed using validated TaqMan single-nucleotide polymorphism genotyping assays.OutcomesSubjects underwent assessment using the simplified five-item International Index of Erectile Function to diagnose and assess ED severity.ResultsThe results showed that diabetes mellitus (odds ratio [OR] = 3.27, P < .01), hypertension (OR = 3.47, P < .01), and having the VEGF 2578A allele (OR = 1.54, P = .01) were the three most independent risk factors for ED. In univariate analysis, all three VEGF polymorphisms (460C, 1154A, and 2578A) were significantly associated with a higher prevalence of coronary artery disease (P < .01) and greater frequencies of hypertension were found in carriers of the 1154A allele and the 2578A allele (P = .01). Multiple logistic regression analysis showed a significant association between VEGF 2578A allele carrier status and ED (OR = 1.54, 95% CI = 1.10∼2.15, P = .01). Furthermore, the prevalence and severity of ED were significantly increased with an increment of the 2578A allele number (P < .05).Clinical ImplicationsVEGF 2578C/A gene polymorphisms could be a genetic susceptibility factor for the development of ED.Strength and LimitationThis is the first study to investigate the genetic susceptibility of VEGF polymorphisms to ED. This study was cross-sectional with a lack of functional and molecular production investigations. Data on the association among conditions might not allow definitive conclusions about causal links.ConclusionThis study showed that VEGF 2578A allele carriers in a Taiwanese population are at greater risk for ED.Lee Y-C, Huang S-P, Tsai C-C, et al. Associations of VEGF Gene Polymorphisms With Erectile Dysfunction and Related Risk Factors. J Sex Med 2017;14:510–517.     

Vascular Risk Factors as Predictors of Sexual Function Following Coronary Artery Bypass Graft

IntroductionA strong association between cardiovascular risk factors and erectile dysfunction (ED) was suggested. Coronary artery bypass grafting (CABG) is the gold standard for surgical myocardial revascularization.AimWe herein evaluate the impact of vascular risk factors on postoperative sexual functions in patients undergo CABG.Main Outcome MeasuresED severity by the International Index of Erectile Function (IIEF-5) and penile duplex study.MethodsThe present study included 100 patients who underwent CABG. The patients were evaluated by an abridged form of the IIEF-5 questionnaire, followed by CABG. Six months after surgery the erectile function of all patients was revaluated utilizing the IIEF-5.ResultsNumber of risk factors was significantly associated with postoperative change in IIEF-5 score (P = 0.02). A post hoc analysis of the association revealed that patients with one risk factor were significantly more likely to have increased IIEF-5 scores (N = 18), whereas those with two or more risk factors were significantly more likely to have decreased IIEF-5 scores (N = 21, P < 0.05). Furthermore, those with no risk factors were significantly more likely to be stable (N = 8) compared with those with more than two risk factors, who were more likely to have decreased scores (P < 0.05). The hierarchical logistic regression results showed that when examining all risk factors simultaneously, because of multicollinearity, only hyperlipidemia was significantly associated with postoperative ED (odds ratio [OR] = 11.33, confirdence interval [CI] = 1.25, 102.82). Frequency of intercourse was also significantly associated with postoperative ED after controlling for risk factors (OR = 0.71, CI = 0.52, 0.97).ConclusionsThis data clearly shows that the number of cardiovascular risk factors is an essential predictive factor for sexual function following surgery. Only hyperlipidemia may play a predictive role for the future sexual function of patients undergo CABG. Mohamed OA, Hamed HA, Roaiah MF, Helmy T, Mahran A, and Bennett CJ. Vascular risk factors as predictors of sexual function following coronary artery bypass graft. J Sex Med 2009;6:2017–2023.     

Change in Frequency and Predictors of Erectile Dysfunction With Changes in the International Index of Erectile Function-Erectile Function Domain Score in Patients With ST-Elevation Myocardial Infarction: A Prospective,Longitudinal Study

BackgroundErectile dysfunction (ED) has been proposed as an early indicator for future coronary and peripheral vascular disease.AimWe aimed to investigate the longitudinal change in proportion and predictors for ED with changes in erectile function domain (EFD) of the International Index of Erectile Function-15 (IIEF-15) in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI).MethodsBetween December 2018 and June 2019, 286 male patients aged between 40 and 70 years who were treated with PPCI for STEMI were included. The patients were asked to complete the IIEF-EFD form 3 days after the procedure for the evaluation of baseline erectile functions. During follow-up 3 months after the index procedure, the patients were asked to refill the IIEF-EFD form. Both baseline and third-month IIEF-EFD scores were calculated, and the patients were classified into ED severity groups as per the IIEF-EFD scores. A linear mixed model was used to identify predictors of ED at 3 months.OutcomesThis study identifies the prevalence and predictors of ED with STEMI who underwent PPCI.ResultsThe median age was 54 (range 48–61) years. The median IIEF-EFD scores at 3 days and 3 months were 25.5 (range 20.0–27.0) and 22.00 (range 18.25–25.00), respectively. Half of the patients were found to have ED with varying severity as per baseline IIEF-EFD scores. This rate increased to 79% at the 3-month follow-up visit. The IIEF-EFD scores of the patients decreased over time (P < .001). Advanced age (β = −0.603, se = 0.192, P = .002), presence of three-vessel coronary artery disease (β = −3.828, se = 0.783, P < .001), and diabetes (β = −2.934, se = 0.685, P < .001) were found to be inversely associated with the IIEF-EFD scores.Clinical ImplicationsAdvanced age, presence of three-vessel disease, and diabetes mellitus are the indicators of sexual rehabilitation needs in patients after STEMI.Strengths & LimitationsThis is the first study investigating the predictor variables for the development of ED after coronary artery disease treatment. The limitations include the lack of evaluation of anxiety and depression and the measurements of testosterone levels.ConclusionThe prevalence of ED was high among patients with coronary artery disease, and the frequency of ED increased during 3-month follow-up. Advanced age, three-vessel disease, and diabetes were significant predictors of ED with changes in IIEF-EFD score in patients with STEMI who underwent PPCI.Karabay E, Karsiyakali N, Cinier G, et al. Change in Frequency and Predictors of Erectile Dysfunction With Changes in the International Index of Erectile Function-Erectile Function Domain Score in Patients With ST-Elevation Myocardial Infarction: A Prospective, Longitudinal Study. J Sex Med 2020;17:1101–1108.     

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind,Randomized, Placebo-Controlled Clinical Trial

BackgroundCombination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach.AimTo conduct the first double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of combination therapy with low-intensity shockwave therapy (LiST) and tadalafil vs LiST and placebo in patients with mild or mild-to-moderate vasculogenic ED.MethodsFifty sexually active patients fulfilling the eligibility criteria were randomly assigned to 6 sessions of LiST twice weekly for 3 weeks and tadalafil (n = 25) or placebo (n = 25) once daily for 4 weeks. Patients were evaluated at 1, 3, and 6 months after completion of the treatment protocol.OutcomesThe primary outcome was the mean change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain between the 2 groups at 3 months after treatment. Erectile function was also assessed at 1 and 6 months. The number of patients attaining a minimal clinically important difference (MCID) in the IIEF-EF, as well as the safety of combination therapy were evaluated.ResultsAdjusting for the baseline values, IIEF-EF improved by 0.8 points more (95% confidence interval [CI] = ?0.2 to 1.9, P = .12) at 1 month, 1 point more (95% CI = 0.1–1.9, P = .02) at 3 months and 1.7 points more (95% CI = 0.8–2.7, P < .001) at 6 months in patients treated with combination therapy compared to monotherapy. The number of patients attaining a MCID in the IIEF-EF between the 2 groups improved significantly only at the 3-month evaluation. No adverse events were reported during the whole study period.Clinical ImplicationsCombination of LiST twice weekly for 3 weeks and tadalafil 5 mg once daily for 4 weeks may further ameliorate mild or mild-to-moderate vasculogenic ED compared to LiST monotherapy.Strengths & LimitationsWe conducted the first randomized trial exploring the role of LiST and tadalafil in the management of ED. Conversely, our study lacks external validity due to its single-center design.ConclusionThe addition of daily low-dose tadalafil during application of LiST may further improve erectile function compared to application of LiST as a standalone treatment in patients with mild or mild-to-moderate vasculogenic ED. Still, further high-quality studies are warranted to corroborate our findings.Mykoniatis I, Pyrgidis N, Zilotis F, et al. The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2022;19:106–115.