Mulhall, John P.

ABSTRACTBackgroundDespite an increasing number of publications on Peyronie’s disease (PD), evidence-based clinical decision-making remains challenging due to the small number of well-designed clinical trials.AimTo perform a critical analysis of reporting quality in PD systematic reviews (SR) and meta-analyses (MA).MethodsStudy protocol registration was performed on the Open Science Framework platform. In January 2021, a systematic electronic search of the Medline/PubMed, Embase, Ovid, Scopus, Joanne Briggs Institute, and Cochrane databases was performed. Search terms included “Peyronie’s disease” and “systematic review OR meta-analysis OR meta-analysis.” Eligibility criteria were English-language, relevance to PD and specification of “systematic review” or “meta-analysis” in the title or abstract. Oxford Center for Evidence-Based Medicine levels of evidence were used to classify original studies reviewed within each publication. Risk of bias was assessed using the ROBIS tool. Data were tabulated and reported as means with standard deviation, median with interquartile range and t-testing as appropriate. Strength of association between variables was calculated using Pearson correlation coefficient. Statistical analyses were performed on RStudio (version 1.4.1106).OutcomesOutcomes included review type, level of evidence, authorship, journal, publication date, “A MeaSurement Tool to Assess systematic Reviews” (AMSTAR-2) score and “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) score.ResultsFrom 1974 to 2021, 340 articles were identified. After review, 17 full length articles were included. Thirteen were SR, 2 MA and 2 was combined. Significant heterogeneity was seen in evidence level of included studies. There was median 54% adherence to AMSTAR-2 criteria and 74% adherence to PRISMA criteria. Overall AMSTAR-2 confidence rating was Critically Low in 11 of 17 studies. Correlation analysis revealed very high positive association between AMSTAR 2 and PRISMA adherence (+0.95). ROBIS revealed “High” concern regarding methods used to collect data and appraise 12/17 studies (71%), and “High” concern regarding synthesis and findings in 8 of 17 studies (47%).Clinical ImplicationsMany SR include markedly heterogenous levels of evidence and fail to meet accepted methodological criteria for reporting.Strengths and LimitationsMain strengths include extensive literature review and analysis of standardized study reporting. One limitation is that aggregate scoring of AMSTAR-2 and PRISMA is not intended as primary method of quality assessment; however effect was minimized by reporting critical domains, overall quality assessments and specifics on globally poorly reported domains.ConclusionMore high quality randomized controlled PD trials are necessary; SR and MA should focus on these studies alone.

Abstract Introduction Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential “cure” for ED. Aim The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption. Methods A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet rich plasma (PRP), and restorative related technologies like low-intensity shockwave therapy (LiSWT). Main Outcome Measures Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures. Results To date there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, though technologies such as LiSWT have established relative safety. Conclusions Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice.

Abstract Background Erectile dysfunction (ED) is a common condition that may affect men of all ages; in 1999, a Process of Care Model was developed to provide clinicians with recommendations regarding the evaluation and management of ED. Aim To reflect the evolution of the study of ED since 1999, this update to the process of care model presents health care providers with a tool kit to facilitate patient interactions, comprehensive evaluation, and counseling for ED. Methods A cross-disciplinary panel of international experts met to propose updates to the 1999 process of care model from a global perspective. The updated model was designed to be evidence-based, data-driven, and accessible to a wide range of health care providers. Outcomes This article summarizes the resulting discussion of the expert meeting and focuses on ED evaluation. The management of ED is discussed in an article by Muhall et al (J Sex Med 2018;15:1280-1292). Results A comprehensive approach to the evaluation of ED is warranted because ED may involve both psychological and organic components. The updated process of care model for evaluation was divided into core and optional components and now focuses on the combination of first-line pharmacotherapy and counseling in consideration of patient sexual dynamics. Clinical Implications Patient evaluation for ED should encompass a variety of aspects, including medical history, sexual history, physical examination, psychological evaluation, laboratory testing, and possibly adjunctive testing. Strengths & Limitations This update draws on author expertise and experience to provide multi-faceted guidance for the evaluation of ED in a modern context. Although a limited number of contributors provided input on the update, these experts represent diverse fields that encounter patients with ED. Additionally, no meta-analyses were performed to further support the ED evaluation guidelines presented. Conclusion Comprehensive evaluation of ED affords health care providers an opportunity to address medical, psychological/psycho-social, and sexual issues associated with ED, with the ultimate goal being effective management and possibly resolution of ED. While some or all techniques described in the updated model may be needed for each patient, evaluation should in all cases be thorough.

Abstract Introduction Erectile dysfunction (ED) is a common condition the treatment of which over the years has expanded from specialty care settings to various other clinical settings. A Process of Care Model was developed in 1999 to provide primary care physicians with guidance in the diagnosis and management of ED. Aim This update to the Process of Care Model aims to reflect current ED management practices, because the study of ED has changed since 1999. Methods Updates to the Process of Care Model were developed during a meeting of international experts from diverse disciplines. The updated model is data-driven, evidence-based, and relevant to a wide range of healthcare providers. Main Outcome Measures This article summarizes the results of the expert meeting and focuses on ED management. The evaluation of ED is discussed in a separate article. Results The updated model presents modification of risk factors and correction of comorbidities frequently associated with ED as critical parts of patient management. Patients should be encouraged to make positive lifestyle changes such as improving diet and increasing physical exercise. Lifestyle changes may be accompanied by the first-line medical therapies of sexual counseling and therapy, which takes into consideration patient sexual dynamics and pharmacotherapy with phosphodiesterase 5 inhibitors (PDE5Is). Clinical Implications The updated model provides guidance regarding risk factors associated with ED, their modification, sexual counseling, and PDE5I selection, dosing, and patient education. Strengths and Limitations This update leverages the extensive clinical expertise and experience of the authors to provide updated, comprehensive guidance for ED management. The model reflects the views and experiences of a limited number of contributors; however, these authors draw upon a diverse array of clinical specialties and are regarded as experts in their fields. Additionally, no meta-analyses were performed to further support the ED evaluation guidelines presented. Conclusion Effective management of ED may be achieved through a combination of patient risk factor modification and first-line therapy, taking into consideration any patient comorbidities known to be associated with ED. Treatment goals should be individualized to restore sexual satisfaction to the patient and/or couple and improve quality of life based on the patient’s expressed needs and desires.

ABSTRACT Introduction Male hypogonadism is a common condition, with an increasing body of literature on diagnosis, implications, and management. Given the significant variability in testosterone (T) from a physiologic and assay perspective, a thorough understanding of factors affecting T values and study methodology is essential to interpret reported study outcomes appropriately. However, despite the large number of publications on T, there are no reference materials consolidating all relevant and potentially confounding factors necessary to interpret T studies appropriately. Aims To create a resource document that reviews sources of T variability, free vs total T, assay techniques and questionnaires, and study methodology relevant to interpreting outcomes. Methods A PubMed search was performed of all the T literature published on T variability, assay techniques, and T-specific questionnaires. Results were summarized in the context of their impact on interpreting T literature outcomes and methodology. Main Outcome Measures Effect of various factors on T variability and their relevance to study methodology and outcomes. Results Several factors affect measured T levels, including aging, circadian rhythms, geography, genetics, lifestyle choices, comorbid conditions, and intraindividual daily variability. The utility of free T over total T is debatable and must be compared using appropriate threshold levels. Among various assay techniques, mass spectrometry and equilibrium dialysis are gold standards. Calculated empirical estimates of free T also are commonly used and accepted. Hypogonadism-specific questionnaires have limited utility in screening for hypogonadism, and their role as objective end points for quantifying symptoms remains unclear. Numerous aspects of study methodology can directly or indirectly affect reported outcomes, including design (randomized, prospective, retrospective), duration, populations studied (age, comorbid conditions), low T threshold, therapeutic agent used, objective measurements and end points selected, and statistical interpretation. Conclusion Critical appraisal of the T literature requires an understanding of numerous factors resulting in T variability, study design and methodology, and limitations of assay techniques and objective measurement scales.

ABSTRACT Introduction Peyronie’s disease (PD) is characterized by fibrotic plaque formation within the tunica albuginea, leading to penile deformity, angulation, painful erections, and often, erectile dysfunction. There is limited knowledge of its etiology and pathophysiology. Currently, there is no standardization for reporting the evaluation and treatment outcomes. No consensus exists on the ideal management of PD. Aim The aim of this study is to review the use of radiation therapy (RT) for the treatment of PD. Methods This study used a review of the literature and informed expert opinion. Main Outcome Measures The main outcome measures are the reported improvement with regard to pain, curvature, plaque size, and erectile function as well as a review of the safety profile of RT. Results Radiation has been used for the empirical treatment of PD with mixed results throughout the literature. Low-dose RT in the early stages of PD seems to be effective in patients with painful erections not improving with time or with the use of oral or intralesional therapies. Comparison with other current medical therapies is difficult due to the absence of criteria for therapeutic success and the absence of randomized, controlled trials. Multiple studies have demonstrated varied results in terms of curvature reduction, plaque volume, and sexual functioning. The absence of the use of validated means of measuring penile deformity and sexual function, the limited relevance of plaque and pain improvement combined with the potential negative consequences of radiation on erectile tissue structure and function lead us to make a recommendation that RT not be used for the management of PD. Conclusions In clinical practice, mixed success for RT has led to the recommendation against its use as a treatment modality for PD.

ABSTRACT Introduction Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. Aim To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. Methods An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. Results Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men’s and women’s individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie’s disease; and priapism. Conclusions Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.