Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

PURPOSE: There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. MATERIALS AND METHODS: An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. RESULTS: The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. CONCLUSIONS: Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Delineating patient errors in an intracavernosal injection program.

BACKGROUND: Intracavernosal injection therapy (ICI) is a well-established therapeutic strategy for men with erectile dysfunction. Complications are often related to patient error when performong ICI. AIM: The objective of this study was to examine patient errors in an established patient training program for performing ICI and identify factors that could predict major errors. METHODS: Patients enrolled in our ICI program are trained on technical aspects, and dose titration is begun. Patients are given explicit instructions during training, both verbally and in written form. Records were reviewed for men using ICI for ≥6 months. Multivariable analysis was used to define predictors of major errors. OUTCOMES: Errors were listed as minor (zero-response injection, penile bruising, expired medication) and major (errors potentially leading to priapism: dose self-titration, double injecting). RESULTS: Overall, 1368 patients met the inclusion criteria and were included in the analysis. The mean patient age was 66 ± 22 (range 29-91) years. Regarding education, 41% of patients had graduate-level education, 48% had college education, and 11% high school education. Mean follow-up was 3.2 ± 7.6 (range 0.5-12) years. The agents used were trimix (62%), bimix (35%), papaverine (2%), and prostaglandin E1 monotherapy (1%). At least 1 error occurred during self-administration in 42% of patients during their time in the program. Errors included zero response to medication due to technical error (8% of patients), penile bruising (34%), use of an expired bottle (18%), self-titration (5%), and double injecting (4% of patients); 12% of men committed ≥1 error during their time in the program. On multivariable analysis, independent predictors of the occurrence of a major error included: young age, graduate-level education, and <12 months of injection use. CLINICAL IMPLICATIONS: To the best of our knowledge, this is the first reported study to investigate ICI errors and risk factors. The identification of factors predictive of major errors allows for more tailored and intensive training in this subset of patients. STRENGTHS AND LIMITATIONS: Strengths of this study include a large patient population (1386 men) with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions, enhances the accuracy and reliability of the results. Despite the strengths of the study, recall bias may be a limitation concern. CONCLUSION: The majority of patients were error free, and the majority of the errors were minor in nature. Major errors occurred in <10% of patients. Younger age, graduate-level education, and less experience with ICI were independent predictors of major errors.

Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency.

BACKGROUND: Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD). AIM: We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline. METHODS: The study population consisted of a group of men who within 3 months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100 ng/dL or above 1000 ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography-tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100 ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels. OUTCOMES: The majority of men showed no significant difference in T levels between morning and afternoon. RESULTS: In total, 506 men with a median age of 65 years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels. CLINICAL IMPLICATIONS: There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon. STRENGTHS AND LIMITATIONS: Strengths of the study include the number of subjects and the use of liquid chromatography-tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30 years. CONCLUSION: In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels.

Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

BACKGROUND: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Erectile response profiles of men using PDE5 inhibitors combined with intracavernosal injections as part of a penile rehabilitation program after radical prostatectomy.

BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism occurring. AIM: We explored the risk of priapism and prolonged erections in men in our post-radical prostatectomy (RP) penile injection program who were using regular PDE5 inhibitor and intracavernosal injections (ICIs) as part of their rehabilitation program. METHODS: The study cohort included men on penile injection therapy who (1) were taking tadalafil 5 mg daily or taking sildenafil 25 mg on noninjection days, (2) had an RP, (3) were using their respective PDE5 inhibitor regularly at the time of penile injection training, and (4) complied with the program instructions regarding penile injection use. Demographics, comorbidity details, PDE5 inhibitor dose and utilization, and injection dose and utilization data were collected. All patients underwent in-office injection training and used trimix (papaverine/phentolamine/prostaglandin E1) as the intracavernosal medication. OUTCOMES: Priapism was defined as a patient self-reported penetration hardness erection ≥4 hours in duration, while prolonged erection was defined as a penetration hardness erection lasting ≥2 hours. RESULTS: A total of 112 tadalafil users and 364 sildenafil users were compared. Mean age and duration post-RP were 62 ± 14 years and 5.2 ± 12 months, respectively, and there was no difference between tadalafil and sildenafil groups. The mean trimix dose was tadalafil 24 ± 24 units and sildenafil 31 ± 37 units (P < .05). Priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users (P = .47). Excluding those men experiencing priapism on any occasion, those with any reported penetration hardness erection lasting ≥2 hours were 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users (P < .01). A total of 53% of these prolonged erections occurred within the first 6 injections at home (no difference between tadalafil and sildenafil groups). CLINICAL IMPLICATIONS: We emphasize the need for continued monitoring and education on proper injection techniques to minimize the risk of adverse events in ICI and PDE5 inhibitor combination therapy. STRENGTHS & LIMITATIONS: This study has a relatively large patient population with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions for priapism and prolonged erections, enhances the accuracy and reliability of the results. However, there are some limitations, such as social desirability, confounding factors, and recall bias. CONCLUSION: There is no significant difference in the incidence of priapism in an ICI program in which men combine ICI with tadalafil or sildenafil. However, tadalafil patients had a higher rate of prolonged erections, which was found to occur mostly early during the titration phase.

Understanding the sexual health perceptions, concerns, and needs of female partners of prostate cancer survivors.

BACKGROUND: Prostate cancer (PCa) and its treatments can have a significant negative impact on the sexual health of survivors and couples, but few studies have specifically examined the impact of PCa-related sexual dysfunction on female partners of survivors. AIM: Our objective was to perform a qualitative study to comprehensively characterize female partners' perceptions of the implications of PCa on their sex lives, as well as partners' sexual health concerns and unmet needs. METHODS: We conducted semi-structured telephone interviews about sexual health and unmet needs with female partners of PCa survivors recruited from multiple clinical locations and support groups for PCa caregivers from September 2021 to March 2022. Interviews were audio-recorded, transcribed verbatim, and independently coded. Participants were recruited until thematic saturation was achieved. OUTCOMES: Outcomes of this study were female partner sexual health concerns and unmet needs. RESULTS: Among 12 participants, the median age was 65 (range 53 to 81) years, 9 were White, the median time since their partner's PCa diagnosis was 2.25 years (range 11 months to 20 years), and a majority reported that their partner had undergone radical prostatectomy, radiation, and/or hormonal therapy. Major emergent themes pertained to the significant impact of age- and PCa-related sexual dysfunction on female sexual quality of life, the dyadic nature of sexual dysfunction and recovery, the role of the partner in coping with and adjusting to sexual dysfunction, difficulties communicating about sexual dysfunction in an intimate relationship, a lack of physician-led sexual health counseling and support, and the benefit of peer interactions and proactive information seeking in addressing unmet sexual health needs. CLINICAL IMPLICATIONS: Future efforts should continue to explore the impact of PCa on partner sexual health and address unmet needs through sexual health education and support. STRENGTHS AND LIMITATIONS: In this study, we identified female partners' sexual health concerns both related to and independent of PCa survivor sexual health. Limitations include exclusion of male partners of survivors and potential responder bias, as partners who agreed to participate may have experienced more sexual health concerns. CONCLUSION: We found that female partners experience PCa-related sexual dysfunction as a couple's disease, grief due to age- and PCa-related sexual losses, and a lack of physician-led sexual health counseling and information. Our results highlight the importance of including partners of PCa survivors in the sexual recovery process and of developing sexual care programs to address partners' unmet sexual health needs.

Preservation of male fertility in patients undergoing pelvic irradiation.

As the number of cancer survivors increases, so does the demand for preserving male fertility after radiation. It is important for healthcare providers to understand the pathophysiology of radiation-induced testicular injury, the techniques of fertility preservation both before and during radiation, and their role in counseling patients on the risks to their fertility and the means of mitigating these risks. Impaired spermatogenesis is a known testicular toxicity of radiation in both the acute and the late settings, as rapidly dividing spermatogonial germ cells are exquisitely sensitive to irradiation. The threshold for spermatogonial injury and subsequent impairment in spermatogenesis is ~ 0.1 Gy and the severity of gonadal injury is highly dose-dependent. Total doses < 4 Gy may allow for recovery of spermatogenesis and fertility potential, but with larger doses, recovery may be protracted or impossible. All patients undergoing gonadotoxic radiation therapy should be counseled on the possibility of future infertility, offered the opportunity for semen cryopreservation, and offered referral to a fertility specialist. In addition to this, every effort should be made to shield the testes (if not expected to contain tumor) during therapy.

TrueNTH Sexual Recovery Intervention for couples coping with prostate cancer: Randomized controlled trial results.

BACKGROUND: Despite significant sexual dysfunction and distress after localized prostate cancer treatment, patients typically receive only physiologic erectile dysfunction management. The authors performed a randomized controlled trial of an online intervention supporting couples' posttreatment recovery of sexual intimacy. METHODS: Patients treated with surgery, radiation, or combined radiation and androgen deprivation therapy who had partners were recruited and randomized to an online intervention or a control group. The intervention, tailored to treatment type and sexual orientation, comprised 6 modules addressing expectations for sexual and emotional sequelae of treatment, rehabilitation, and guidance toward sexual intimacy recovery. Couples, recruited from 6 sites nationally, completed validated measures at the baseline and 3 and 6 months after treatment. Primary outcome group differences were assessed with t tests for individual outcomes. RESULTS: Among 142 randomized couples, 105 patients (mostly surgery) and 87 partners completed the 6-month survey; this reflected challenges with recruitment and attrition. There were no differences between the intervention and control arms in Patient-Reported Outcomes Measurement Information System Global Satisfaction With Sex Life scores 6 months after treatment (the primary outcome). Three months after treatment, intervention patients and partners reported more engagement in penetrative and nonpenetrative sexual activities than controls. More than 73% of the intervention participants reported high or moderate satisfaction with module content; more than 85% would recommend the intervention to other couples. CONCLUSIONS: Online psychosexual support for couples can help couples to connect and experience sexual pleasure early after treatment despite patients' sexual dysfunction. Participants' high endorsement of the intervention reflects the importance of sexual health support to couples after prostate cancer treatment. LAY SUMMARY: This study tested a web-based program supporting couples' sexual recovery of sexual intimacy after prostate cancer treatment. One hundred forty-two couples were recruited and randomly assigned to the program (n = 60) or to a control group (n = 82). The program did not result in improvements in participants' satisfaction with their sex life 6 months after treatment, but couples in the intervention group engaged in sexual activity sooner after treatment than couples in the control group. Couples evaluated the program positively and would recommend it to others facing prostate cancer treatment.

Disorders of Ejaculation: An AUA/SMSNA Guideline.

PURPOSE: Men who ejaculate before or shortly after penetration, without a sense of control, and who experience distress related to this condition may be diagnosed with premature ejaculation (PE), while men who experience difficulty achieving sexual climax may be diagnosed with delayed ejaculation (DE). The experience of many clinicians suggest that these problems are not rare and can be a source of considerable embarrassment and dissatisfaction for patients. The role of the clinician in managing PE and DE is to conduct appropriate investigation, to provide education, and to offer available treatments that are rational and based on sound scientific data. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to March 1, 2019), the Cochrane Central Register of Controlled Trials (through January 2019) and the Cochrane Database of Systematic Reviews (through March 1, 2019). An update search was conducted on September 5, 2019. Database searches resulted in 1,851 potentially relevant articles. After dual review of abstracts and titles, 223 systematic reviews and individual studies were selected for full-text dual review, and 8 systematic reviews and 59 individual studies were determined to meet inclusion criteria and were included in the review. RESULTS: Several psychological health, behavioral, and pharmacotherapy options exist for both PE and DE; however, none of these pharmacotherapy options have achieved approval from the United States Food and Drug Administration and their use in the treatment of PE and DE is considered off-label. CONCLUSION: Disturbances of the timing of ejaculation can pose a substantial impediment to sexual enjoyment for men and their partners. The Panel recommends shared decision-making as fundamental in the management of disorders of ejaculation; involvement of sexual partner(s) in decision making, when possible, may allow for optimization of outcomes.

The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline.

PURPOSE: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. METHODOLOGY: A comprehensive search of the literature on acute ischemic priapism and non-ischemic priapism (NIP) was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. A search of the literature on NIP, recurrent priapism, prolonged erection following intracavernosal vasoactive medication, and priapism in patients with sickle cell disease was conducted by Pacific Northwest Evidence-based Practice Center for articles published between 1946 and February 19, 2021. Searches identified 4117 potentially relevant articles, and 3437 of these were excluded at the title or abstract level for not meeting inclusion criteria. Full texts for the remaining 680 articles were ordered, and ultimately 203 unique articles were included in the report. RESULTS: This Guideline provides a clinical framework for the treatment (non-surgical and surgical) of NIP, recurrent ischemic priapism, and priapism in patients with sickle cell disease. The treatment of patients with a prolonged erection following intracavernosal vasoactive medication is also included. The AUA guideline on the diagnosis of priapism and the treatment of acute ischemic priapism was published in 2021. CONCLUSIONS: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention when indicated. NIP is not an emergency and treatment must be based on patient objectives, available resources, and clinician experience. Management of recurrent ischemic priapism requires treatment of acute episodes and a focus on future prevention of an acute ischemic event. Sickle cell disease patients presenting with an acute ischemic priapism event should initially be managed with a focus on urologic relief of the erection; standard sickle cell assessment and interventions should be considered concurrent with urologic intervention. Treatment protocols for a prolonged, iatrogenic erection must be differentiated from protocols for true priapism.

The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer.

BACKGROUND: Prostate-specific antigen (PSA) secretion is a testosterone (T) dependent process. Published data suggest that a low T level is an independent predictor of higher-grade prostate cancer (PC). AIM: To evaluate the relationship between T and PSA in patients with PC. METHODS: All men diagnosed with PC with a recorded pre-treatment total T level measurement were included in this analysis. We analyzed demographic, clinical, and pathological data. Patients were stratified according to pretreatment PSA levels: <2 ng/mL, 2-4 ng/mL, >4 ng/mL. Low T was defined as total T < 10.4 nmol/L (300 ng/dL), very low T < 6.9 nmol/L (200 ng/dL). OUTCOMES: T levels by PSA groups according to the PC pathology. RESULTS: In this retrospective study, mean patient age was 61 years among 646 men. The distribution by PSA group was: 8% (<2), 17% (2-4), and 76% (>4). The mean T level across the entire cohort was 13 nmol/L (374 ng/dL). Overall, 30% had a T level < 10.4 nmol/L (300 ng/dL). The mean total T level by PSA group was: <2 ng/mL, 7 nmol/L (206 ng/dL); 2-4 ng/mL, 13 nmol/L (362 ng/dL); >4 ng/mL, 14 nmol/L (393 ng/dL), P < .001. PSA <4 ng/mL was a significant predictor of low T in men with PC GS ≥8. PSA <2 ng/mL was a significant predictor of very low T independent of the PC pathology. CLINICAL IMPLICATIONS: These findings suggest that clinicians should consider measuring T levels when a patient diagnosed with PC GS ≥8 and PSA level <4 ng/mL, and for each patient with PSA level <2 ng/mL independent of the PC pathology. STRENGTHS & LIMITATIONS: Our study has several strengths including (i) inclusion of a large population of men, (ii) use of a database which is audited and reviewed for accuracy annually, and (iii) use of an accurate T assay (LCMS). Nonetheless, there are limitations: (i) the subjects of the study are from a single institution, and (ii) we did not measure free T levels. CONCLUSION: In men with PC with GS ≥8, PSA level <4 ng/mL predicts low T. PSA <2 ng/mL predicts very low T independent of the PC pathology. Flores JM, Bernie HL, Miranda E, et al. The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer. J Sex Med 2022;19:471-478.

A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature.

BACKGROUND: Despite 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. AIM: To perform a critical analysis of reporting quality in PD systematic reviews (SR) and meta-analyses (MA). METHODS: Study 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). OUTCOMES: Outcomes 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. RESULTS: From 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 IMPLICATIONS: Many SR include markedly heterogenous levels of evidence and fail to meet accepted methodological criteria for reporting. STRENGTHS AND LIMITATIONS: Main 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. CONCLUSION: More high quality randomized controlled PD trials are necessary; SR and MA should focus on these studies alone. Bole R, Gottlich HC, Ziegelmann MJ, et al. A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature. J Sex Med 2022;19:629-640.

Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy.

BACKGROUND: Prior studies suggest that men with good erectile function shortly after radical prostatectomy (RP) can subsequently have worsened erectile function. AIM: To determine the prevalence and predictors of early erectile function recovery post-RP and of worsening erectile function after initial erectile function recovery. METHODS: We retrospectively queried our institutional database. Men who underwent RP during 2008-2017 and who completed the International Index of Erectile Function erectile function domain both pre-RP and serially post-RP, constituted the population. Functional erections were defined as International Index of Erectile Function (IIEF)-6 erectile function domain scores ≥24. We analyzed factors predicting functional erections at 3 months post-RP as well as factors predicting a decrease in functional erections between 3 and 6 months, defined as ≥2-point drop in the erectile function domain. Multivariable logistic regression models were used to identify predictors of early erectile function recovery and also of subsequent decline. OUTCOMES: Erectile function recovery rates at 3 months post-RP and predictive factors; rates of erectile function decline between 3-6 months and associated predictors. RESULTS: Eligible patients comprised 1,655 men with median age of 62 (IQR 57, 67) years. Bilateral nerve-sparing (NS) surgery was performed in 71% of men, unilateral NS in 19%, and no NS in 10%. Of this population, 224 men (14%; 95% CI 12%, 15%) had functional erections at 3 months post-RP. On multivariable analysis, significant predictors of early erectile function recovery included: younger age (OR 0.93, P < .001), higher baseline erectile function domain score (OR 1.14, P < .001) and bilateral NS (OR 3.81, P = .002). The presence of diabetes (OR 0.43, P = .028) and a former smoking history (OR 0.63, P = .008; reference group: never smoker) was associated with the erectile dysfunction at 3 months post-RP. Of the men with early functional erections, 41% (95% CI 33%, 48%) had a ≥ 2-point decline in erectile function between 3 and 6 months. No factors were identified as predictors for this decline. CLINICAL IMPLICATIONS: Only a small proportion of men have functional erections at 3 months post-RP and a notable number of them will experience a decline in erectile function between 3 and 6 months. STRENGTHS AND LIMITATIONS: Strengths: large patient population and the use of validated questionnaire. LIMITATIONS: single-center retrospective study. CONCLUSION: A minority of men had functional erections 3 months post-RP, about half of whom had a decline in erectile function by month 6. We recommend appropriately counseling post-RP patients on the risk of such a decline in erectile function. Salter CA, Tin AL, Bernie HL, et al. Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy. J Sex Med 2022;19:1790-1796.

Luteinizing Hormone Suppression Profiles in Men Treated With Exogenous Testosterone.

BACKGROUND: Due to the negative feedback mechanism involved in the hypothalamic-pituitary-gonadal axis, testosterone therapy (TTh) may result in suppression of luteinizing hormone (LH) secretion, but clinical experience demonstrates the level of LH suppression is variable. AIM: We sought to define the relationship between TTh and LH levels, specifically predictors of LH suppression in men on TTh. METHODS: We performed a retrospective analysis of a prospectively maintained database of patients with testosterone deficiency (TD) treated with TTh. Patient demographic and clinical data including vascular risk factor (VRF) status were collected. Serum total T and LH levels before TTh and after ≥3 months (m) were recorded. LH suppression was defined as serum LH level <1.0 IU/ml. MAIN OUTCOME MEASURES: Predictors of LH suppression were searched though a series of logistic regression models assessing suppression status at the final observation, and then a series of Cox proportional hazards models assessing time to first suppression were performed. RESULTS: A total of 227 patients with mean age of 58±14 years at time of TTh initiation were included in our analysis. Just under half of subjects received transdermal T as the only modality (n = 101, 44%), while one third (n = 77, 34%) received intramuscular only, and the remainder (n = 49, 22%) received both modalities during follow-up. The mean baseline LH level was 10 ± 12 IU/ml. The percent of men who had baseline LH level above 1 IU/ml and at any given point of TTh was 84% and 78%, respectively, thus 22% of men had suppressed LH levels on TTh considering the definition of LH <1 IU/ml. Most men (73%) had a suppressed LH level of <1 IU/ml at least once during follow-up. In the final adjusted model for LH suppression, intramuscular route (OR = 2.44), baseline LH (OR = 0.94), estradiol (OR = 1.05) remained significant. CLINICAL IMPLICATIONS: LH suppression profiles may be relevant for dose titration during TTh and perhaps to minimize testicular atrophy. STRENGTHS & LIMITATIONS: A strict definition for TD was applied using LCMS for T measurements and patients had long-term follow-up. CONCLUSION: While 73% of patients had at least one LH <1 IU/ml during TTh, only 22% maintained suppressed throughout the treatment. Miranda EP, Schofield E, Matsushita K, et al. Luteinizing Hormone Suppression Profiles in Men Treated With Exogenous Testosterone. J Sex Med 2022;19:1359-1365.

Unmet Sexual Health Needs of Patients and Female Partners Following Diagnosis and Treatment for Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) and its treatment can have significant and pervasive sexual side effects for patients and their partners; however, partner needs are not well understood, and most resources do not incorporate partner priorities. AIM: Our objective was to perform a qualitative study to identify unmet sexual needs of patients and female partners after PCa diagnosis. METHODS: We conducted a qualitative study of posts to the Inspire Us TOO Prostate Cancer Online Support and Discussion Community. Overall, 6,193 posts were identified in the Sexual Health & Intimacy forum of the community, of which 661 posts were from female authors. A random sample of 10% (n = 66) of posts from female partners and an equal number of randomly selected posts from male patients were analyzed. OUTCOMES: We assessed sexual health themes among patients and female partners. RESULTS: Multiple themes emerged that were unique to female partners of PCa survivors. These included expanding the sexual repertoire, feeling invisible, contextualizing sexual intimacy within the broader picture of survival, and addressing relationship concerns. Patients and their partners also shared common sexual health themes, including coming to terms with changes in sexual function and frustration with clinicians. Both patients and their partners use online health communities to get support and share their experiences with sexual recovery and use of sexual aids. Psychosocial treatments were infrequently mentioned, and may be particularly helpful to address partner concerns. CLINICAL IMPLICATIONS: A common concern for couples was not receiving sufficient information from healthcare providers regarding sexual side effects from PCa and its treatment. STRENGTHS AND LIMITATIONS: Strengths of the study include leveraging a unique data source to address an understudied topic of sexual health concerns among partners after PCa diagnosis. However, members of an online community may not be representative of all couples facing PCa. Also, this analysis is limited to female partners of patients with PCa, and further study is underway to examine the sexual health needs among gay and bisexual couples. CONCLUSION: Both patients and female partners have many unmet sexual health needs during PCa survivorship, and designing interventions to incorporate partner perspectives may improve the management of sexual side effects of PCa for couples. Li R, Wittmann D, Nelson CJ, et al. Unmet Sexual Health Needs of Patients and Female Partners Following Diagnosis and Treatment for Prostate Cancer. J Sex Med 2022;19:1797-1803.

Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum.

INTRODUCTION: Penile curvature is the most common abnormality that is observed by men with Peyronie's disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients. AIM: To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH. METHODS: We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements. OUTCOMES: Degrees of the curvature changes between the baseline and after the cycles of CCH. RESULTS: A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7). CLINICAL IMPLICATIONS: We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment. STRENGTHS AND LIMITATIONS: This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled. CONCLUSION: Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees. Flores JM, Nascimento B, Punjani N, et al. Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum. J Sex Med 2022;19:1680-1686.

Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel.

BACKGROUND: Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. AIM: We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients' and partners' sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. METHODS: The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995-2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment, according to the nomenclature of the American Urological Association (AUA). Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). OUTCOMES: Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. RESULTS: The guidelines account for patients' cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. CLINICAL IMPLICATIONS: The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. STRENGTHS & LIMITATIONS: The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. CONCLUSION: The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research. Wittmann D, Mehta A, McCaughan E, et al. Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel. J Sex Med 2022;19:1655-1669.

Acute Ischemic Priapism: An AUA/SMSNA Guideline.

PURPOSE: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction. MATERIALS AND METHODS: A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report. RESULTS: This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement. CONCLUSIONS: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I.

PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.