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Background: Despite the existence of conservative therapies for Peyronie's disease (PD), surgery is commonly utilized for the treatment of bothersome curvatures due to its potential effectiveness, although it carries intrinsic risks and may not universally lead to satisfactory outcomes., Aim: To explore the rate and factors influencing patients' willingness to undergo surgery for PD., Methods: Data were prospectively collected in 5 European academic centers between 2016 and 2020. Data included age, time from PD onset, penile pain, curvature degree, difficulty at penetration, hourglass deformity, erectile dysfunction (ED), and previous treatments. All patients were offered conservative treatments, either medications or injections. Tunical shortening or lengthening procedures were offered as an alternative to conservative treatments, when indicated. Penile prosthesis was offered to those with concomitant ED. Patients' attitudes with surgery were recorded. Logistic regression analyses tested the profile of patients who were more likely to be willing to undergo surgery., Outcomes: Patients' willingness to undergo surgery for PD., Results: This study included 343 patients with a median age of 57.3 years (IQR, 49.8-63.6) and a median penile curvature of 40.0° (IQR, 30.0°-65.0°). Overall, 161 (47%) experienced penetration difficulties and 134 (39%) reported ED. Additionally, hourglass deformity and penile shortening were reported by 48 (14%) and 157 (46%), respectively. As for previous treatments, 128 (37%) received tadalafil once daily; 54 (16%) and 44 (13%), intraplaque verapamil and collagenase injections; and 30 (9%), low-intensity shock wave therapy. Significant curvature reduction (≥20°) was observed in 69 (20%) cases. Only 126 (37%) patients were open to surgery for PD when suggested. At logistic regression analysis after adjusting for confounders, younger age (odds ratio [OR], 0.97; 95% CI, 0.95-1.00; P = .02), more severe curvatures (OR, 1.04; 95% CI, 1.03-1.06; P < .0001), and difficulty in penetration (OR, 1.88; 95% CI, 1.04-3.41; P = .03) were associated with a greater attitude to consider surgical treatment., Clinical Implications: The need for effective nonsurgical treatments for PD is crucial, as is comprehensive patient counseling regarding surgical risks and benefits, particularly to younger males with severe curvatures., Strengths and Limitations: Main limitations are the cross-sectional design and the potential neglect of confounding factors., Conclusions: Patients with PD, having a lower inclination toward surgery, emphasize the need for effective nonsurgical alternatives and accurate counseling on the risks and benefits of PD surgery, particularly for younger men with severe curvatures., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Peyronie's disease (PD) is characterized by pain, deformity, sexual dysfunction, and psychological bother. Several treatments are available with varying levels of efficacy, and significant limitations exist with the currently available literature., Aim: To explore modern-era methodological challenges inherent to PD research as they pertain to intervention studies., Methods: We performed a critical review of the PD intervention literature to identify common methodological challenges with emphasis on aspects of patient assessment and treatment outcomes, study design, and statistical analysis. The key objective was to provide an impetus on which to build future research protocols, rather than focus on weaknesses with any individual studies., Main Outcome Measure: Expert opinion was used to summarize limitations with commonly reported objective outcomes such as penile curvature, girth, and length along with imaging modalities and objective questionnaires. Appropriate study design and statistical analysis were also reviewed to discuss common pitfalls in the PD literature., Results: There are multiple shortcomings inherent to studying objective PD outcomes such as penile curvature, girth, and length. These include lack of standardized protocols for preintervention and postintervention assessment, interobserver and intraobserver variability, and lack of consistent definitions for what defines an objective outcome as clinically "meaningful" for patients. Similarly, imaging studies including penile ultrasound are subject to marked variation, thereby limiting their utility to measure predefined primary or secondary study outcomes including cavernosal artery hemodynamics and penile plaque size. Objective and validated questionnaires such as the Peyronie's Disease Questionnaire and International Index of Erectile Function require that patients have recently engaged in sexual activity, which is challenging for many patients as a result of penile deformity with PD. Finally, careful study design and statistical analysis (including appropriate study power) are imperative to ensure reliable results. Current shortcomings in the majority of studies contribute to the low level of evidence available for most PD interventions., Clinical Implications: Future PD intervention studies should focus on optimizing study design and statistical analysis. Furthermore, authors must incorporate standardized protocols for assessing preintervention and postintervention outcomes., Strength & Limitations: The current analysis and recommendations for future study are based on the expertise and opinion of the manuscript authors., Conclusion: Multiple areas of weakness in study design, statistical analysis, and patient outcomes assessment limit the reliability of data derived from PD intervention studies in the modern era. The global themes identified herein should serve as a basis upon which to build future research protocols. Ziegelmann MJ, Trost LW, Russo GI, et al. Peyronie's Disease Intervention Studies: An Exploration of Modern-Era Challenges in Study Design and Evaluating Treatment Outcomes. J Sex Med 2020;17:364-377., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Low-intensity shockwave therapy (LISWT) has been investigated for the treatment of uroandrological disorders including erectile dysfunction (ED), Peyronie's disease (PD) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with controversial findings., Aim: To review the evidence on LISWT for ED, PD, and CP/CPPS and provide clinical recommendations on behalf of the European Society of Sexual Medicine., Methods: Medline and Embase databases were searched for randomized clinical trials (RCTs), meta-analyses and open-label prospective or retrospective studies investigating the effect of LISWT on ED, PD, or CP/CPPS., Outcomes: The panel provided statements on clinically relevant questions concerning LISWT: (i) treatment efficacy, (ii) treatment protocol, (iii) clinical indications, and (iv) safety. The level of evidence was provided according to the Oxford 2011 criteria and graded using the Oxford Centre for Evidence-Based Medicine recommendations., Results: 11 RCTs and 5 meta-analyses investigated LISWT for ED. RCTs provided controversial results on the efficacy of LISWT and were affected by high heterogeneity and the small number of patients included. Pooled-data analysis showed an overall positive effect in terms of erectile function improvement but reported small estimates and included a largely heterogeneous cohort of patients. 4 RCTs and 1 meta-analysis assessed LISWT for PD. All trials showed positive findings in terms of pain relief but no effect on penile curvature and plaque size. Inclusion criteria vary widely among studies, and further investigation is needed. 5 RCTs investigated LISWT for CP/CPPS. Data showed a possible effect on pain relief, although there is no evidence supporting that pain relief was maintained or any improvement in pain over time., Clinical Implications: LISWT needs to be further investigated in the context of sexual medicine and is almost but not yet ready for clinical practice., Strengths and Limitations: All studies have been evaluated by a panel of experts providing recommendations for clinical practice., Conclusions: LISWT is a safe and well-tolerated procedure but its efficacy for the treatment of ED is doubtful and deserves more investigation. Patients reporting pain associated with PD may benefit from LISWT, although no effect is expected on disease progression. LISWT is not a primary treatment for CP/CPPS, but it may be considered as an option to relieve pain. Capogrosso P, Frey A, Jensen CFS, et al. Low-Intensity Shock Wave Therapy in Sexual Medicine-Clinical Recommendations from the European Society of Sexual Medicine (ESSM). J Sex Med 2019;16:1490-1505., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Medical treatment of Peyronie's disease (PD) in terms of intralesional therapy is still a matter of debate., Aim: To compare the efficacy of different classes of intralesional therapy with a network meta-analysis (NMA) method., Methods: The search was conducted using documents published in PubMed, Scopus, and Web of Science databases until September 30, 2017. We included randomized controlled trials comparing at least 1 intralesional therapy with a placebo therapy or with another drug for the treatment of PD. All intralesional therapies have been considered: collagenase Clostridium histolyticum (CCH), hyaluronic acid, verapamil, and interferon α-2b., Main Outcome Measure: Outcomes of the study are the mean change in penile curvature (PC) and in erectile function (EF) assessed with the International Index of Erectile Function questionnaire., Results: In total, 8 comparisons matched with the inclusion criteria, which includes 1,050 patients. With regard to PC (degree) improvement, hyaluronic acid and verapamil showed worse outcomes when compared with CCH (-6.66 and -2.30) and interferon α-2b (-6.75 and -2.38). When considering improvement in EF, hyaluronic acid, verapamil and interferon α-2b showed a slight increase in mean change when compared with CCH (+2.39, +1.77, and +0.65). Moreover, verapamil and interferon α-2b showed slightly worse mean change in comparison to hyaluronic acid (+0.62 and +1.74), whereas interferon α-2b was worse than verapamil (-1.12)., Clinical Implications: Based on this NMA, empirical therapy for PD should be avoided to offer the patients the best treatment in terms of level of evidence., Strengths & Limitations: In this NMA, we have provided, for the first time, evidence of the efficacy between different intralesional therapies for the treatment of PD. We were not able to compare all specific outcomes (ie, pain, plaque size, patient satisfaction) of PD, because of the lack of homogeneity across relevant studies. Moreover, because of the few included studies, a meta-regression analysis of predictive factors of treatment response was not calculated., Conclusion: This is the first meta-analysis comparing all available intralesional treatments for PD. CCH and interferon α-2b showed the best outcome in terms of PC, whereas hyaluronic acid was most efficient in relation to EF. Russo GI, Cacciamani G, Cocci A, et al. Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis. J Sex Med 2019;16:289-299., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The effectiveness of phosphodiesterase type 5 (PDE5) inhibitors over the conservative management of Peyronie's disease (PD) has been widely questioned., Aim: To determine the role of sildenafil 25 mg film formulation twice a day (S25 b.i.d.) in the improvement of curvature after treatment of collagenase of Clostridium hystoliticum (CCH) in penile curvature owing to PD., Methods: From April 2017 to April 2018, 161 consecutive patients were treated with S25 b.i.d. + CCH or CCH alone. Adjustment variables consisted of age, penile curvature, and the 15-question International Index of Erectile Function (IIEF-15) questionnaire at baseline using 1:1 propensity-score matching. Overall, 50 patients were considered subdivided into the following: 25 patients who received S25 b.i.d. + CCH (group A) and 25 who received CCH alone (group B). Patients received CCH injection using a shortened protocol and vacuum device in both groups., Main Outcome Measure: The primary outcome of the study was the change in penile curvature after treatment, and secondary outcomes were the change in sexual function (IIEF-15) and in the Peyronie's Disease Questionnaire (PDQ) and its subscores, PDQ-PS (psychosexual symptoms), PDQ-PP (penile pain), and PDQ-SB (symptom bother)., Results: Overall, mean penile curvature was 47.0° (SD 21.88), the mean IIEF-EF (erectile function) was 23.56 (SD 4.10), and the mean PDQ was 27.06 (SD 13.55). After the treatment, we observed a mean change for penile curvature of 25.6 (SD 9.05) in group A and -25.6 (SD 9.7) in group B (P < .01), for IIEF-EF of 2.28 (SD 2.33) in group A and 1.36 (SD 1.77) in group B (P = .03), for PDQ-PS of -3.04 (SD 2.95) in group A and of -2.12 (SD 2.06) in group B (P = .11), for PDQ-PP of -1.0 (SD 4.48) in group A and of -0.88 (SD 2.04) in group B (P = .60), for PDQ-SB of -5.84 (SD 4.58) in group A and of -4.16 (SD 4.45) in group B (P = .60), and for Female Sexual Function Index of 3.8 (SD 2.45) in group A and of 2.72 (SD 2.28) in group B (P = .14). We found a rate of global satisfaction of 70.83% in group A and of 84.0% in group B (P = .27)., Clinical Implications: Addition of S25 b.i.d. to CCH is superior to CCH alone for improving penile curvature and erectile function., Strength & Limitations: This is the first study comparing sildenafil + CCH vs CCH alone for the treatment of PD. Lack of randomization and direct verification of appropriate use of penile modeling could be considered limitations., Conclusion: In this study, combination therapy was superior in terms of penile curvature and erectile dysfunction improvement. Cocci A, Cito G, Urzì D, et al. Sildenafil 25 mg ODT + collagenase Clostridium hystoliticum vs collagenase Clostridium hystoliticum alone for the management of Peyronie's disease: A matched-pair comparison analysis. J Sex Med 2018;15:1472-1477., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Collagenase Clostridium histolyticum (CCH; Xiapex) injections represent the only licensed medical treatment for Peyronie's disease (PD)., Aim: To evaluate the efficacy and safety of CCH injections in men with stable PD, using a modified treatment protocol and to assess partners' bother improvement in a large cohort of White-European sexually active heterosexual men treated in a single tertiary-referral center., Methods: All the 135 patients enrolled underwent a thorough assessment, which included history taking, physical examination, and pharmacologically induced artificial erection test (intra-cavernous injection) to assess the degree of penile curvature (PC) at baseline and after the completion of the treatment. Patients with calcified plaque and/or ventral curvature were excluded. All patients underwent a modified treatment protocol, which consisted of 3 intra-lesional injections of 0.9 mg of CCH performed at 4-week intervals at the point of maximum curvature. After each injection, patients were instructed to follow a strict routine involving daily penile stretching in the intervals between injections., Outcomes: International Index of Erectile Function (IIEF)-15, Global Assessment of PD, PD questionnaires (PDQ), and Female Sexual Function Index (FSFI) questionnaire were performed at baseline and at the end of treatment., Results: Overall, 135 patients completed the study protocol. Before treatment, 18 (13.33%) partners showed a degree of sexual dysfunction. Baseline median IIEF-15, FSFI, and PDQ scores were, respectively, 59.0, 35.0, and 23.0. Overall, both IIEF-total and all domains significantly improved after treatment (all P < .01). A PC mean change of 19.07 (P = .00) was measured. At the univariate linear regression analysis, IIEF-15, IIEF-erectile function, IIEF-sexual desire, and IIEF-intercourse satisfaction were positively associated with FSFI (all P ≤ .03); conversely, PDQ-penile pain, PDQ-symptom bother, and post-treament penile curvature (P ≤ .04) were associated with a decreased FSFI score. Furthermore, median change of PC was significantly associated with median change of FSFI (r = 0.25; 95% CI 0.02-0.11; P = .004). Global satisfaction after treatment was 89.6% (121/135)., Clinical Translation: This modified CCH treatment protocol could improve both patients' and partner's sexual function., Strength and Limitations: This was an open-label, single-arm clinical study, without placebo. where only heterosexual couples in stable relationships were included. Furthermore, no real assessment of female sexual distress was carried out and long-term sexual function in both patients and female partners were not taken into account., Conclusions: The modified treatment schedule with CCH injections for stable PD has a positive impact on both patients' and partners' sexual function in heterosexual couples with a stable sexual relationship. Cocci A, Russo GI, Salonia A, et al. Predictive Factors of Patients' and Their Partners' Sexual Function Improvement After Collagenase Clostridium Histolyticum Injection for Peyronie's Disease: Results From a Multi-Center Single-Arm Study. J Sex Med 2018;15:716-721., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: A 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)., Aim: To assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT., Methods: From 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., Outcomes: The 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)., Results: All 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 Implications: The 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 Limitations: This 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., Conclusion: The 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., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Diabetic neuropathy secondary to diabetes mellitus type 1 (DM1) is responsible for retrograde ejaculation (RE) in 5-18% of cases. Medical treatment of RE is based either on increasing the sympathetic tone of the bladder or on decreasing the parasympathetic activity. However, the onset of side effects and the lack of response should be considered., Aims: The aim of this study was to analyze long-term outcome of endourethral injection of volume-forming material (VFM) of collagen type 2 into bladder neck submucosa in patients with RE secondary to DM1., Methods: Twenty-four patients with complete RE refractory to imipramine and DM1 were included in the study. Patients were single-blinded randomized according to a computer-generated random sequence with a 1:1 ratio in two treatment groups, namely group A (endourethral collage type 2 injection) and group B (endourethral saline water injection). New technique includes an endoscopic injection of VFM such as collagen (Correcting MIT®, Ltd. minimally invasive technologies, Moscow, Russia) into bladder neck submucosa. Primary endpoint of the study was the reduction of semen antegrade volume (mL). Secondary endpoints were considered as the changes of antegrade count (millions/mL), antegrade total motility (%), antegrade progressive motility (%), State-Trait Anxiety Inventory, Beck Depression Questionnaire and International Index of Erectile Function (IIEF-5). Pregnancy rate was calculated in each group., Results: Twenty-three patients completed the study. In group A, significant differences from baseline to 12 months were observed relative to antegrade volume (mL) (mean difference: 0.71, P < 0.05), antegrade count (millions/mL) (mean difference: 45.6, P < 0.05), antegrade total motility (%) (mean difference: 15.4, P < 0.05) and antegrade progressive motility (%) (mean difference: 8.4, P < 0.05). In group A, we observed significant differences in terms State-Trait Anxiety Inventory (mean difference: -20.5, P < 0.05) and Beck Depression Inventory (mean difference: -8.4, P < 0.05) with significant differences compared with group B. We observed significant improvements in group A vs. group B when considering primary and secondary endpoints of the study, but not for the IIEF-5., Conclusion: Correction of RE in DM1 patients could be achieved with endourethral injection of collagen type 2., (© 2015 International Society for Sexual Medicine.)

Introduction: Sexual dysfunction (SD) is prevalent in multiple sclerosis (MS) patients and affects quality of life. Furthermore, lower urinary tract dysfunction (LUTD) is common in MS patients., Aims: This study aims to evaluate the relationship between SD, neurological disability, depression, anxiety, and urodynamic alterations in patients with MS and LUTD., Methods: From January 2011 to September 2013, 135 consecutive patients with MS in remission phase and LUTD underwent first urodynamic examination, according to the International Continence Society criteria. Depression and anxiety were evaluated with the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A), neurological impairment was assessed using the Expanded Disability Status Scale (EDSS), and SD was investigated with the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-15)., Main Outcome Measures: Multivariate logistic regression analyses were carried out to identify variables for predicting female sexual dysfunction (FSD) (FSFI < 26.55), male SD (IIEF-15 < 60), or moderate-severe erectile dysfunction (IIEF-EF ≤ 16), after adjusting for confounding factors., Results: Total IIEF-15 and all subdomains (all P < 0.01), total FSFI, FSFI-arousal, FSFI-lubrication, and FSFI-orgasm (all P < 0.05) were lower in subjects with EDSS ≥ 4.5. We found inverse relationship between IIEF-15 and relative subdomains with EDSS (all P < 0.01) and between FSFI and relative subdomains with EDSS (all P < 0.01), HAM-D (all P < 0.01), and HAM-A (all P < 0.01). Continuous EDSS (odds ratio [OR] = 1.54; P = 0.03) and categorical EDSS (≥4.5) (OR = 6.0; P = 0.03), HAM-D (OR = 4.74; P = 0.03), and HAM-A (OR = 4.10; P = 0.02) were significantly associated with FSD (FSFI < 26.55). Detrusor overactivity (DO) was an independent predictor of moderate-severe ED (IIEF-EF ≤ 16) (OR = 2.03; P < 0.01), and of FSD (OR = 9.73; P = 0.04)., Conclusions: Neurological disability, depression and DO are significantly predictive of SD in MS patients, irrespective of gender. An EDSS ≥ 4.5 may significantly predict the presence of SD., (© 2014 International Society for Sexual Medicine.)

Introduction: Several studies have linked the association between lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and the presence of insulin resistance (IR) due to an underlined metabolic syndrome (MetS)., Aim: This study aims to determine the relationship between IR, sexual function, and LUTS and to demonstrate the ability of IR in predicting ED and severe LUTS., Methods: Between January 2008 to January 2013, 544 consecutive patients with benign prostatic hyperplasia-related LUTS were enrolled. LUTS and sexual function of the patients were evaluated by the International Index of Erectile Function (IIEF) and the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation. IR was defined as a homeostasis model assessment (HOMA) index of 3 or greater., Main Outcome Measures: Uni- and multivariate logistic regression analysis was performed to assess significant predictors of severe LUTS (IPSS ≥ 20) and ED (IIEF-Erectile Function [IIEF-EF] <26), including MetS component, prostate volume, prostate-specific antigen, total testosterone, and HOMA index., Results: IR patients resulted in higher values of IPSS (19.0 vs. 15.0; P<0.01), IPSS-storage (6.0 vs. 5.0; P<0.01), IPSS-voiding (12.0 vs. 9.0; P<0.01), total prostate volume (54.8 vs. 36.5; P<0.01), and lower values of IIEF-EF (17.0 vs. 20.0; P<0.01), IIEF-Intercourse Satisfaction (3.0 vs. 10.0; P<0.01), IIEF-Orgasmic Function (8.0 vs. 9.0; P<0.01), IIEF-Overall Satisfaction (6.0 vs. 8.0; P<0.01), and total testosterone (3.83 vs. 4.44; P<0.01). IR was demonstrated to be a strong predictor of ED (IIEF-EF <26) (odds ratio [OR] =6.20, P<0.01) after adjusting for confounding factors. Finally, IR was also an independent predictor of severe LUTS (IPSS ≥ 20) (OR=2.0, P<0.01) after adjusting for confounding factors., Conclusions: IR patients are at high risk of having severe LUTS and contemporary sexual dysfunctions. We strongly suggest to prevent LUTS and ED by reducing insulin resistance., (© 2014 International Society for Sexual Medicine.)