Does climate impact inflatable penile prosthesis infection (IPP) risk? Assessment of temperature and dew point on IPP infections.

BACKGROUND: Variations in climate have been associated with a greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome; however, limited data exist on the impact of climate on inflatable penile prosthesis (IPP) infections. AIM: We sought to evaluate the impact of climate on the risk of IPP infections in a large international, multicenter cohort. METHODS: We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Implant infections were defined as infections requiring device explantation. A univariate logistic regression analysis was undertaken. OUTCOMES: Our primary outcome was implant infection. RESULTS: A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. There was a fairly even distribution of implants performed in each season. A total of 103 (1.9%) infections were recorded. There were 32 (31.1%) IPP infections in patients who underwent surgery in the summer, followed by 28 (27.2%) in the winter, 26 (25.2%) in the spring, and 17 (16.5%) in the fall. No statistically significant differences were recorded in terms of season (P = .19) and month (P = .29). The mean daily temperature (P = .43), dew point (P = .43), and humidity (P = .92) at the time of IPP placement was not associated with infection. CLINICAL IMPLICATIONS: These findings provide reassurance to prosthetic urologists that infection reduction strategies do not need to be tailored to local climate. STRENGTHS AND LIMITATIONS: Climate data were not directly recorded for each hospital, but rather based on the monthly averages in the city where the surgery was performed. CONCLUSION: The climate at time of IPP placement and time of year of surgery is not associated with IPP infection risk.

A Low or High Physical Activity Level Does Not Modulate Prostate Tumor Tissue Protein Synthesis Rates.

INTRODUCTION: Physical activity level has been identified as an important factor in the development and progression of various types of cancer. In this study, we determined the impact of a low versus high physical activity level on skeletal muscle, healthy prostate, and prostate tumor protein synthesis rates in vivo in prostate cancer patients. METHODS: Thirty prostate cancer patients (age, 66 ± 5 yr; body mass index, 27.4 ± 2.9 kg·m -2 ) were randomized to a low (<4000 steps per day, n = 15) or high (>14,000 steps per day, n = 15) physical activity level for 7 d before their scheduled radical prostatectomy. Daily deuterium oxide administration was combined with the collection of plasma, skeletal muscle, nontumorous prostate, and prostate tumor tissue during the surgical procedure to determine tissue protein synthesis rates throughout the intervention period. RESULTS: Daily step counts averaged 3610 ± 878 and 17,589 ± 4680 steps in patients subjected to the low and high physical activity levels, respectively ( P < 0.001). No differences were observed between tissue protein synthesis rates of skeletal muscle, healthy prostate, or prostate tumor between the low (1.47% ± 0.21%, 2.74% ± 0.70%, and 4.76% ± 1.23% per day, respectively) and high (1.42% ± 0.16%, 2.64% ± 0.58%, and 4.72% ± 0.80% per day, respectively) physical activity group (all P > 0.4). Tissue protein synthesis rates were nearly twofold higher in prostate tumor compared with nontumorous prostate tissue. CONCLUSIONS: A short-term high or low physical activity level does not modulate prostate or prostate tumor protein synthesis rates in vivo in prostate cancer patients. More studies on the impact of physical activity level on tumor protein synthesis rates and tumor progression are warranted to understand the potential impact of lifestyle interventions in the prevention and treatment of cancer.

The 'Mini-Jupette' technique for climacturia: a systematic review.

Background: The leakage of urine during sexual arousal, known as climacturia, is an under-recognized clinical condition often overshadowed by erectile dysfunction in men who have undergone radical prostatectomy. Objectives: This study aims to determine and evaluate the role of the Mini-Jupette technique and its alternatives in the treatment of climacturia. Data sources and methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. We searched Medline via PubMed, Scopus, and the Cochrane Library databases until October 2022. Results: We included seven studies involving 120 patients with climacturia. Different types of grafts were used, ranging from synthetic mesh to autologous grafts. In all seven studies, the use of the Adrianne Mini-Jupette (AMJ) and its alternatives showed a high percentage of improvement in climacturia, with reported complete resolution ranging from 65% to 93%. Regarding postoperative complications, one study reported the highest sling explantation rate at 11% (4/38), while other studies reported complications ranging from subjective symptoms such as dysuria and perineal pain to the need for subsequent artificial urinary sphincter placement. Conclusion: The AMJ sling and its variations are low-cost, time-efficient, and relatively safe procedures with high patient satisfaction rates among those treated for climacturia.

Single Dilation in Primary Inflatable Penile Prosthesis Placement Is Associated With Fewer Corporal Complications Than Sequential Dilation.

OBJECTIVE: To assess the difference in outcomes between single dilation (SingD) and sequential dilation (SeqD) in primary penile implantation, hypothesizing that patients who undergo SeqD had higher rates of noninfectious complications. METHODS: We performed a multicenter, retrospective study of men undergoing primary inflatable penile prosthesis placement. Intraoperative complications and postoperative noninfectious outcomes were assessed between the two groups. Multivariable analysis was performed to identify predictors of complications. RESULTS: A total of 3293 patients met inclusion criteria. After matching, there were 379 patients who underwent SingD and 379 patients who underwent SeqD. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length (20 cm with interquartile range [IQR] 18-21 cm vs 20 cm with IQR 18-20 cm respectively, P = .4). On multivariable analysis, SeqD (OR 5.23 with IQR 2.74-10, P < .001) and older age (OR 1.04 with IQR 1.01-1.06, P = .007) were predictive of postoperative noninfectious complications. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length. SeqD and older age were predictive of postoperative noninfectious complications. CONCLUSION: During inflatable penile prosthesis placement in the uncomplicated patient without fibrosis, SingD is a safe technique to utilize during implantation that will minimize postoperative adverse events, and promote device longevity without loss of cylinder length.

Long-term assessment of the safety and effectivity of the mini-jupette sling: 5-year follow-up of the original series.

Background: In 2017, a prospective multicenter, multinational, investigational pilot study was conducted examining outcomes using a novel surgical technique, the Mini-Jupette sling, for the management of erectile dysfunction (ED) patients with climacturia and/or minimal stress urinary incontinence (SUI) after prostate procedures. Climacturia has been reported in up to 64% of patients following radical prostatectomy (RP). We sought to report the 5-year outcomes from this original cohort to assess long-term safety and effectivity of the mini-jupette sling in the treatment of ED and concomitant mild SUI and/or climacturia. Methods: This is a single-arm, multicenter, retrospective, observational study. We identified patients who were enrolled in the previous multicenter study with post-RP ED and climacturia and/or mild SUI- 2 PADS PER DAY (PPD) and underwent inflatable penile prosthesis (IPP) insertion with simultaneous placement of a mini-jupette sling. Data were collected including current PPD, subjective improvement in climacturia/SUI, complications, need for revision of IPP or additional urinary incontinence surgery, and date of most recent follow-up. SPSS was used for statistical analysis. Results: Of the original 38 patients, 5 have since died and 10 were lost to follow-up with 23/38 (61%) patients available for evaluation of long-term outcomes. The average follow-up time was 59 months (SD =8.8) with a mean age of 69 years (SD =6.8). Most patients (n=21, 91%) had subjective improvement of SUI and climacturia. One patient with persistent bothersome incontinence underwent artificial urinary sphincter (AUS) placement in 2018 with no complications, while the other is still considering a repeat procedure due to minor but persistent SUI. The mean PPD decreased from 1.4 preoperatively to 0.4 at a mean of 5 years of follow-up. Most patients reported satisfaction in their urinary symptoms with 91% and 73% reporting improvement in SUI and climacturia respectively, compared to 86% and 93% respectively in the original series. One (4.3%) patient had an IPP revision for pump malfunction. There were no device infections reported. Conclusions: The mini-jupette sling appears to be a safe and effective procedure with durable improvements in SUI and climacturia at 5 years of follow-up.

Three-dimensional printed hydrogel model vs cadaver: comparing inflatable penile prosthesis training and evaluation.

BACKGROUND: Penile prosthesis implantation offers a durable, safe, and effective treatment option for male erectile dysfunction; however, many urologists feel apprehensive and uncomfortable placing penile prostheses due to limited training, low surgical experience, and intra- and postoperative complication management. AIM: To compare a previously validated hydrogel inflatable penile prosthesis (IPP) training model with cadaver simulations across 4 main categories: anatomic replication and realism, procedural replication and realism, educational effectiveness, and efficacy and safety. METHODS: An overall 88 participants (15 attendings, 18 fellows, and 55 residents) performed guided IPP placements on a cadaver and a hydrogel model. Based on a 5-point Likert scale, postsurveys were used to assess the participants' opinions regarding anatomic replication and realism, procedural replication and realism, educational effectiveness, and safety between the hydrogel model and cadavers. OUTCOMES: A direct head-to-head scenario was created, allowing participants to fully utilize the hydrogel model and cadaver, which ensured the most accurate comparison possible. RESULTS: A total of 84% agreed that the hydrogel model replicates the relevant human cadaveric anatomy for the procedure, whereas 69% agreed that the hydrogel tissue resembles the appearance of cadaveric tissue. Regarding the pubic bone, outer skin, corporal bodies, dartos layer, and scrotum, 79%, 74%, 82%, 46%, and 30% respectively agreed that the hydrogel tissue resembled the texture/behavior of cadavers. Furthermore, 66% of participants agreed that the hydrogel model replicates all the procedural steps. Specifically, participants agreed that the model replicates the skin incision/dartos dissection (74%), placement of stay suture and corporotomy (92%), corporal dilation (81%), measurement of prosthetic size (98%), reservoir placement (43%), IPP placement (91%), scrotal pump placement (48%), and skin closure (51%). Finally, 86%, 93%, and 78% agreed that the hydrogel model is useful for improving technical skills, as a teaching/practicing tool, and as an evaluation tool, respectively. To conclude, 81% of participants stated that they would include the hydrogel model platform in their current training. CLINICAL IMPLICATIONS: By replicating the IPP procedure, the hydrogel model offers an additional high-fidelity training opportunity for urologists, allowing them to improve their skills and confidence in placing penile prostheses, with the goal of improving patient surgical outcomes. STRENGTHS AND LIMITATIONS: The hydrogel training model allows users to perform the entire IPP placement procedure with high anatomic realism and educational effectiveness, maintaining many of the high-fidelity benefits seen in cadavers while improving safety and accessibility. CONCLUSION: Ultimately, this high-fidelity nonbiohazardous training model can be used to supplement and bolster current IPP training curriculums.

Simultaneous implant of inflatable penile prosthesis and artificial urinary sphincter: a single high-volume center experience.

Erectile dysfunction and stress urinary incontinence are both an important sequel after local therapy for prostate cancer, such as radical prostatectomy and radiotherapy. The implant of an inflatable penile prosthesis or an artificial urinary sphincter is an option if other treatments fail in both cases. There is a lack of literature regarding a simultaneous dual implantation. The aim of this study is to describe per- and postoperative morbidity and functional results. We included 25 patients operated between January 2018 and August 2022. Data were collected retrospectively. Standardized questionnaires for evaluating satisfaction were administered. There was a median operative time of 45 min (IQR 41.25-58). No intra-operative complications were seen. Four patients needed revision surgery, all of them regarding the sphincter prosthesis. One of these patients had additional revision surgery due to leakage of the penile implant reservoir. There were no infectious complications. There was a median follow-up time of 29 months (IQR 9.5-43). There was a satisfaction rate of 88% with patients and 92% with partners. Postoperative pads per day were reduced to zero or one in 96% of patients. We conclude that the dual implantation of an inflatable penile prosthesis and an artificial urinary sphincter was a safe and effective treatment in our series for patients with conservative treatment-refractory stress urinary incontinence and erectile dysfunction.

AUA-recommended Antibiotic Prophylaxis for Primary Penile Implantation Results in a Higher, Not Lower, Risk for Postoperative Infection: A Multicenter Analysis.

PURPOSE: Our aim was to determine if the AUA-recommended prophylaxis (vancomycin + gentamicin alone) for primary inflatable penile prosthesis surgery is associated with a higher infection risk than nonstandard regimens. MATERIALS AND METHODS: We performed a multicenter, retrospective study of patients undergoing primary inflatable penile prosthesis surgery. Patients were divided into those receiving vancomycin + gentamicin alone and those receiving any other regimen. A Cox proportional-hazards model was constructed adjusted for major predictors. A subgroup analysis to identify the appropriate dosage of gentamicin was also performed. RESULTS: A total of 4,161 patients underwent primary inflatable penile prosthesis placement (2,411 received vancomycin + gentamicin alone and 1,750 received other regimens). The infection rate was similar between groups, 1% vs 1.2% for standard vs nonstandard prophylaxis. In the multivariable analysis, vancomycin + gentamicin (HR: 2.7, 95% CI: 1.4 to 5.4, P = .004) and diabetes (HR: 1.9, 95% CI: 1.03 to 3.4, P = .04) were significantly associated with a higher risk of infection. Antifungals (HR: 0.08, 95% CI: 0.03 to 0.19, P < .001) were associated with lower risk of infection. There was no statistically significant difference in infection rate between weight-based gentamicin compared to 80 mg gentamicin (HR: 2.9, 95% CI: 0.83 to 10, P = .1). CONCLUSIONS: Vancomycin + gentamicin alone for antibiotic prophylaxis for primary inflatable penile prosthesis surgery is associated with a higher infection risk than nonstandard antibiotic regimens while antifungal use is associated with lower infection risk. A critical review of the recommended antimicrobial prophylactic regimens is needed. Prospective research is needed to further elucidate best practices in inflatable penile prosthesis antimicrobial prophylaxis.

The effect of penis size on partner sexual satisfaction: a literature review.

Larger penis size has been associated with a sign of strength, masculinity, and social standing. Little study has examined the relationship between men's penis size and their partners' sexual satisfaction. The purpose of the present study was to detail and evaluate the effect of penis size on partner sexual satisfaction with a design of narrative literature review. A systematic search of MEDLINE/PubMed was conducted to discover relevant studies on this issue. Currently, available studies show incomplete results between the penis size and partners' sexual satisfaction and are limited by methodological drawbacks, including small sample's size. The link between penis size and the sexual satisfaction of the partner need to be supported by more robust scientific evidence.

Satisfaction rates of inflatable penile prosthesis in men who have sex with men are high.

Men with erectile dysfunction (ED) have high patient satisfaction after placement of inflatable penile prostheses (IPP). The impact on satisfaction and quality of life has never been studied in men who have sex with men (MSM). This study sought to assess the satisfaction rates and quality of life of MSM after placement of IPP for ED. This study was a multi-institutional, retrospective study that enrolled adult men who self-identified as MSM and underwent IPP placement. Two questionnaires were administered at one time point post-operatively, the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Results of these questionnaires were analyzed with descriptive statistics. Forty-nine MSM were assessed retrospectively with median age of 62 years with average follow-up of 15.2 months. Median EDITS score was 93.2/100 (range, 70.5-100). Median overall QoLSPP score was 72/80 (58-79), with median scores of 22/25 (16-25), 19/20 (13-20), 18/20 (12-20), and 14/15 (9-15), for the functional, personal, relational, and social domains respectively. Overall, MSM report high satisfaction rates and quality of life after IPP placement. A better understanding of the needs and demands of this patient population may lead to improved patient satisfaction and quality of life.

Majority of erectile dysfunction patients would have preferred earlier implantation of their penile prosthesis: validation of the recently changed EAU guidelines.

Until 2019, the European Association of Urology guidelines recommended the implantation of a penile prosthesis as a third-line therapy, which has since then changed to "if other treatments fail or depending on the patient's preference". Primary endpoint was to assess whether patients with a penile prosthesis and their partner would have preferred earlier implantation. Secondary endpoints were the reason why patient and partner wanted earlier implantation, how much earlier they wanted it, satisfaction of patient and partner and if patient and partner would have recommended the intervention. We selected patients with a virgin inflatable penile prosthesis operated between April 2013 and December 2019. We included 155 patients and 65 partners. Telephonic interview was conducted in a structured manner. Further data were collected retrospectively. The preference for earlier implantation was reported in 59.4% of patients and 46.2% of partners. Of them, respectively 53.2% and 46.6% would have wanted the prosthesis more than 5 years earlier. Satisfaction was seen in 83.2% of patients and 73.8% of partners. Respectively 82.6% and 78.4% of patients and partners would recommend the procedure. Our results indicate that a more patient-oriented approach with good counseling is desirable and that the "three-level" concept must be abandoned.

Penile prosthesis in the medically complex patient: a narrative review.

Background and Objective: Penile prosthesis surgery is considered a safe and effective treatment for patients with erectile dysfunction. Implantation in the medically complex patient can be a challenge. The benefits of treatment must outweigh the possible risks or complications. A description of possible problems and how to cope with them is given in this narrative review. Methods: Literature search was performed in January 2023 using different search prompts in PubMed. These articles, excluding non-English and non-full text articles, were listed by the two authors and afterwards, the most relevant ones were included. Key Content and Findings: This article is divided into five important topics. We evaluated different comorbidities such as spinal cord injury, diabetes mellitus and cardiovascular disease, in which preoperative work-up and counseling is of significant importance. A detailed description of these comorbidities and how to handle these can be found in each section. In addition to the preoperative aspect in organ transplant patients, problems during surgery can arise, e.g., with the reservoir placement. Similarly, in patients with previous pelvic surgery, an ectopic reservoir placement can prevent possible complications. Conclusions: Preoperative diagnostics are crucial and prosthetic surgery should be done by an experienced high-volume surgeon with a diverse range of surgical techniques at his disposal.

Current practices regarding corporotomy localization during penoscrotal inflatable penile implant surgery: a multicenter cohort study.

Literature concerning corporotomy location in multicomponent inflatable penile prosthetic surgery via a penoscrotal approach is scarce if not nonexistent. Aim of our study was to report practices in low-, moderate-, and high-volume penile implant centers regarding corporotomy location and evaluate its potential impact on intraoperative and short-term postoperative complications. Data from 18 (13 European and 5 American) implant centers were collected retrospectively between September 1st, 2018 and August 31st, 2019. Variables included: intraoperative proximal and distal corpus cavernosum length measurement, total corporal length measurement, total penile implant cylinder length, and length of rear tip extenders. Eight hundred and nine virgin penile implant cases were included in the analysis. Mean age of participants was 61.5 ± 9.6 years old. In total, 299 AMS 700™ (Boston Scientific, USA) and 510 Coloplast Titan® (Minneapolis, MN USA) devices were implanted. The mean proximal/distal corporal measurement ratio during corporotomy was 0.93 ± 0.29 while no statistical difference was found among low-, moderate-, and high-volume penile implant centers. A statistically significant correlation between lower proximal/distal measurement ratio and higher age (p = 0.0013), lower BMI (p < 0.0001), lower use of rear tip extenders (RTE) (p = 0.04), lower RTE length (p < 0.0001), and absence of diabetes (p = 0.0004) was reported. In a 3-month follow up period, 49 complications and 37 revision procedures were reported. This is the first study reporting the current practices regarding corporotomy location during IPP placement in a multicenter cohort, particularly when including such a high number of patients. Nevertheless, the retrospective design and the short follow up period limits the study outcomes. Corporotomy location during penoscrotal IPP implantation does not correlate with intraoperative or short-term postoperative complication rates. Future studies with longer follow up are needed in order to evaluate the association of corporotomy location with long-term complications.

ESSM Position Statement on Surgical Treatment of Peyronie's Disease.

INTRODUCTION: Patients with Peyronie's disease may experience significat distress. The choice of treatment depends on a variety of factors, including the stage of the disease, the presence of pain, severity and direction of the curvature, penile length and the quality of erectile function. AIM: To review the evidence associated with surgical treatment of Peyronie`s Disease and provide clinical recommendations on behalf of the European Society for Sexual Medicine. 131 peer-reviewed studies and systematic reviews, which were published from 2009 to 2019 in the English language, were included. METHODS: MEDLINE, Google Scholar and EMBASE were searched for randomized clinical trials, meta-analyses, open-label prospective and retrospective studies. MAIN OUTCOME MEASURE: The panel provided statements on clinically relevant questions including patient involvement in the decision process, indications for surgery, choice of the approach, and the management of patient expectations. A comparison of the different grafts used in patients who have undergone plaque incision/excision and grafting in order to identify an ideal graft, has been carried out. The prevalence of postoperative complications has been summarized. Levels of evidence were provided according to the Oxford 2011 criteria and Oxford Centre for Evidence-Based Medicine recommendations. RESULTS: In order to allow shared decision making, a patient preoperative counselling regarding the pros and cons of each intervention is recommended. In particular, adverse effects of surgical treatments should be discussed to set realistic understanding and expectations of surgical outcomes and ultimately improve postoperative satisfaction rates. Surgical treatment should be only offered in the chronic phase of the condition, when the deformity and/or degree of erectile dysfunction, prevent patients from engaging in satisfying sexual interaction, or if the deformity is the cause of severe bother. CONCLUSIONS: Current European Society for Sexual Medicine recommendations cover several aspects of Peyronie's disease treatment. These recommendations aim both to ensure patients and partners have accurate and realistic expectations of their treatment options, as well as to formulate algorithms to guide clinician management pathways. Osmonov D, Ragheb A, Ward S et al, ESSM Position Statement on Surgical Treatment of Peyronie's Disease. Sex Med 2022;10:100459.

Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis.

Importance: Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. Objective: To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED. Data Sources: Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020. Study Selection: Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included. Data Extraction and Synthesis: Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients. Results: A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high. Conclusions and Relevance: This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.