Krause corpuscles are genital vibrotactile sensors for sexual behaviours.

Krause corpuscles, which were discovered in the 1850s, are specialized sensory structures found within the genitalia and other mucocutaneous tissues1-4. The physiological properties and functions of Krause corpuscles have remained unclear since their discovery. Here we report the anatomical and physiological properties of Krause corpuscles of the mouse clitoris and penis and their roles in sexual behaviour. We observed a high density of Krause corpuscles in the clitoris compared with the penis. Using mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed that both Krause corpuscle afferent types are A-fibre rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light-touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate sexually dimorphic mating behaviours.

Female erectile tissues and sexual dysfunction after pelvic radiotherapy: A scoping review.

Sexual function is a vital aspect of human health and is recognized as a critical component of cancer survivorship. Understanding and evaluating the impacts of radiotherapy on female sexual function requires precise knowledge of the organs involved in sexual function and the relationship between radiotherapy exposure and sexual tissue function. Although substantial evidence exists describing the impact of radiotherapy on male erectile tissues and related clinical sexual outcomes, there is very little research in this area in females. The lack of biomedical data in female patients makes it difficult to design studies aimed at optimizing sexual function postradiotherapy for female pelvic malignancies. This scoping review identifies and categorizes current research on the impacts of radiotherapy on normal female erectile tissues, including damage to normal functioning, clinical outcomes of radiation-related female erectile tissue damage, and techniques to spare erectile tissues or therapies to treat such damage. An evaluation of the evidence was performed, and a summary of findings was generated according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. Articles were included in the review that involved normal female erectile tissues and radiotherapy side effects. The results show that little scientific investigation into the impacts of radiotherapy on female erectile tissues has been performed. Collaborative scientific investigations by clinical, basic, and behavioral scientists in oncology and radiotherapy are needed to generate radiobiologic and clinical evidence to advance prospective evaluation, prevention, and mitigation strategies that may improve sexual outcomes in female patients.

Ejaculatory and erectile function outcomes following holmium laser enucleation of the prostate.

PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is a surgical treatment option for benign prostatic hyperplasia (BPH). Many men develop retrograde ejaculation postprocedure, but there is conflicting evidence regarding sexual function outcomes post-HoLEP. We sought to examine significant variations in patient-reported erectile and ejaculatory function within 12 months post-HoLEP. MATERIALS AND METHODS: We conducted a retrospective study for patients who underwent HoLEP between Nov 2018 and Feb 2022. Of the reviewed patients, 277 patients met inclusion criteria and completed pre and postoperative questionnaires, which included the Male Sexual Health Questionnaire- Ejaculatory Dysfunction (MSHQ-EJD) and the International Index of Erectile Function/Sexual Health Inventory for Men (IIEF-5/SHIM). Surveys were provided to patients up to 12 months postprocedure. Demographics and comorbidities associated with sexual dysfunction were collected. Responses to each question were analyzed to detect sub-categorical variations in sexual function as the secondary objective. Data was analyzed by using a linear mixed model. RESULTS: There was a significant decline in total scores for the MSHQ-EJD (8.70 pre-HoLEP vs. 6.58 post HoLEP, p ≤ 0.001) including a significant decline (p < 0.005) in questions 1-3 which assess ejaculatory ability, strength, and volume. There was not a significant decline in question 4 which assesses bother (2.552 pre-HoLEP vs. 3.119 post-HoLEP, p = 0.526). There was not a significant decline in the IIEF-5/SHIM postoperatively (11.51 pre-HoLEP vs. 13.327 post-HoLEP, p = 0.498). CONCLUSIONS: Patients undergoing HoLEP do not experience a decline in erectile function. Patients do experience a decline in ejaculatory function but did not find this bothersome.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

BACKGROUND: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. AIM: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). METHODS: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. OUTCOMES: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. RESULTS: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. CLINICAL IMPLICATIONS: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. STRENGTHS AND LIMITATIONS: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CONCLUSION: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

A novel strategy to induce penile erection during penile doppler ultrasound: oral sildenafil administration plus alprostadil injection.

OBJECTIVES: To evaluate the efficacy of a novel approach to achieve the optimal penile erection during the penile doppler ultrasound (PDU) examination, which was oral sildenafil combined alprostadil injection. MATERIALS AND METHODS: A total of 60 ED patients were enrolled in our prospective study, and they were randomly assigned to two group with different PDU order. The approaches assisted the PDU included two models, mode A meaning injection of 15 µg alprostadil and model B meaning oral sildenafil 100 mg plus injection of 15 µg alprostadil. The PDU parameters were measured continuously before induced erection, and 5, 10, 15, 20, 25 min. RESULTS: Each group included 30 ED patients with similar clinical characteristics. After pooling the results together, the PSV, EDV, and RI were all improved significantly, when adding the oral sildenafil administration to assist PDU. Also, the clinical response of oral sildenafil administration plus alprostadil injection was better than that in alprostadil injection alone (p = 0.016). The arterial ED were decreased from 31.67% to 15.00% with the P value 0.031, and the mixed ED was also decreased statistically (23.33% vs 8.33%, p = 0.024). CONCLUSION: Oral sildenafil administration plus alprostadil injection could improve the diagnostic accuracy of PDU.

Penile erection and cardiovascular function: effects and pathophysiology.

Penile erection (PE) is a hemodynamic event that results from a neuroendocrine process, and it is influenced by the cardiovascular status of the patient. However, it may also modulate an individual's cardiovascular events. The present study provides the mechanisms involved in the association of PE and cardiovascular function. Erection upsurges the cardiac rate, blood pressure, and oxygen uptake. Sex-enhancing strategies, such as phosphodiesterase inhibitors, alprostadil, and testosterone also promote vasodilatation and cardiac performance, thus preventing myocardial infarction. More so, drugs that are used in the treatment of hypertensive heart diseases (such as angiotensin system inhibitors and ß-blockers) facilitate vasodilatation and PE. These associations have been linked with nitric oxide- and testosterone-dependent enhancing effects on the vascular endothelium. In addition, impaired cardiovascular function may negatively impact PE; therefore, impaired PE may be a pointer to cardiovascular pathology. Hence, evaluation of the cardiovascular status of an individual with erectile dysfunction (ED) is essential. Also, employing strategies that are used in maintaining optimal cardiac function may be useful in the management of ED.

Efficacy and safety of PDE5 inhibitors in middle-aged and old patients with and without hypogonadism.

PURPOSE: Although several reviews have evaluated the use of PDE5 inhibitors (PDE5i) for treating erectile dysfunction (ED), their specific use in middle-aged and old patients has not been fully evaluated. Given that elderly patients with ED often have a complex combination of systemic and sexual health risk factors, the safety and efficacy of PDE5i in such a context are hereby reviewed. MATERIALS AND METHODS: A thorough examination of existing literature has been conducted on PubMed. RESULTS: PDE5i has good safety and efficacy, but the situation is more complex for patients with hypogonadism than those with normal testosterone levels, with reduced responsiveness to PDE5i. In this case, combination therapy with testosterone is recommended, safe and effective. CONCLUSIONS: Eliminating or reducing reversible risk factors and controlling or slowing the development of irreversible factors is an important foundation for using PDE5i to treat ED in all patients, especially middle-aged and elderly ones.

MicroRNA-503-5p protects streptozotocin-induced erectile dysfunction in diabetic rats by downregulating SYDE2.

Plentiful studies have clarified miRNAs take on a key role in the sexual dysfunction of diabetic rats. This study aimed to figure out microRNA (miR)-503-5p/SYDE2 axis' latent mechanisms in streptozotocin-induced diabetic rat sexual dysfunction. A model of erectile dysfunction (ED) in diabetic rats was established by injecting streptozotocin. MiR-503-5p and SYDE2 in ED rats were altered by injection of miR-503-5p mimic or si/oe-SYDE2. The targeting link between miR-503-5p and SYDE2 was testified. ICP/MAP value was tested by pressure sensor; Penile capillary abundance was assessed; Penile cGMP and AGEs were detected; penile smooth muscle cell apoptosis was assessed; MiR-503-5p and SYDE2 were tested. In streptozotocin-induced ED rats, miR-503-5p was reduced and SYDE2 was elevated. Elevating miR-503-5p or silencing of SYDE2 can enhance penile erection rate, ICP/MAP value, capillary abundance, and cGMP but reduce AGEs and penile smooth muscle cell apoptosis rate in ED rats. Strengthening SYDE2 with elevating miR-503-5p turned around the accelerating effect of elevated miR-503-5p on penile erection in ED rats. SYDE2 was a downstream target gene of miR-503-5p. MiR-503-5p protects streptozotocin-induced sexual dysfunction in diabetic rats by targeting SYDE2.

More Efficient Approach: Independent Diagnostic Value of Audiovisual Sexual Stimulation for Psychogenic Erectile Dysfunction.

The diagnostic value of audiovisual sexual stimulation (AVSS) for psychogenic erectile dysfunction (ED) is still unclear. We investigated the independent diagnostic value and optimal cut-off parameter of AVSS for psychogenic ED. All participants had received the AVSS test and nocturnal penile tumescence and rigidity (NPTR) monitoring at least twice. ED patients were divided into psychogenic ED and organic ED according to NPTR examination. The diagnostic accuracy of AVSS parameters was evaluated with the receiver operating characteristic (ROC) curve, and the Youden index was employed to determine the optimal diagnostic cut-off values. A total of 346 patients with ED and 60 healthy men were included in this study, among which 162 and 184 cases of psychogenic and organic ED were identified based on NPTR, respectively. When comparing the two ED groups, the area under the curve (AUC) of AVSS parameters was 0.85-0.89. Six-selected AVSS parameters could precisely diagnose psychogenic ED, exhibiting increased diagnostic specificity compared with corresponding sensitivity. When comparing psychogenic ED with the control group, the AUC of the tumescence of the tip was superior to the AUC other parameters (0.81 vs. 0.58, 0.66, 0.59, 0.53, 0.68), and the best determined diagnostic cut-off value was the tumescence of the tip < 29.87%. Independent AVSS could diagnose psychogenic ED objectively and effectively, and its diagnostic value was highest when 1.50% ≤ tumescence of the tip < 29.87%.

Penile Elastography Versus Penile Duplex Ultrasonography in Diagnosing Non-Responders to Intracavernosal Injection: A Prospective Cohort Study.

OBJECTIVES: The current study aims to investigate the value of penile elastography in assessing the fibrotic changes in the corpora cavernosa. PATIENTS AND METHODS: Eighty participants were included in the study. These were divided into two equal groups: a study group (group 1) included patients with ED who did not respond to intracavernosal injection (ICI), and an age-matched control group (group 2) included age-matched subjects with normal erection. All subjects answered an International Index of Erectile Function-5 (IIEF-5) questionnaire. The first group was evaluated by two ICI trials of 1 mL Quadmix, each took place 1 week apart, followed by a color duplex/Doppler ultrasonography (CDDU) scan using also a 1 mL Quadmix. All the above was done a week before the penile shear wave elastography (SWE) scan. It comprised a 12-section scan of both corpora cavernosa. Each corpus was scanned in three different segments (proximal, mid-shaft, and distal), and in both longitudinal and transverse axes. RESULTS: Comparisons of the laboratory data were non-significant, apart from the glycosylated hemoglobin which proved significant (P value <.001) in both groups. Also, the IIEF-5 scores were significantly lower in the study group (P value <.001). Significantly higher SWE readings (indicating higher fibrotic) were found in the study group compared with the control group in almost all of the scanned segments and their combinations (P value <.05). CONCLUSION: SWE can effectively assess the fibrotic changes occurring in the corpora cavernosa. Hence, SWE could be utilized as a modality that helps diagnose patients with ED.

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase.

Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCß2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.

The PINNACLE Study: A Double-blind, Randomized, Sham-controlled Study Evaluating the Optilume BPH Catheter System for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: The Optilume BPH Catheter System is a novel drug/device combination minimally invasive surgical therapy for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The PINNACLE study is a prospective, randomized, double-blind, sham-controlled clinical trial evaluating the safety and efficacy of Optilume BPH against a sham surgical procedure. MATERIALS AND METHODS: Eligible patients were men 50 years or older with symptomatic benign prostatic hyperplasia and a prostate size between 20 and 80 g. Subjects were randomized 2:1 to receive treatment with Optilume BPH or a sham surgical procedure. Blinding was maintained for subjects in both arms and evaluating personnel through 1 year postprocedure. Follow-up assessments included the International Prostate Symptom Score, uroflowmetry, and other quality-of-life and sexual function assessments. RESULTS: A total of 148 men were randomized (100 active, 48 sham) at 18 centers in the U.S. and Canada. Subjects randomized to receive Optilume BPH saw a reduction in International Prostate Symptom Score of 11.5±7.8 points at 1 year posttreatment, as compared to a reduction of 8.0±8.3 points at 3 months in the sham arm. Flow rate was dramatically improved after treatment with Optilume BPH, with an improvement of +10.3 mL/s from baseline to 1 year (+125%). CONCLUSIONS: Treatment with Optilume BPH provides immediate and sustained improvements in obstructive symptoms and flow rate while preserving erectile and ejaculatory function. Treatment is well tolerated and can be done in an office or ambulatory setting.

Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats.

INTRODUCTION: Male sexual potency and vigor are a complex neuroendocrine process and an important component of well-being. Psychological stress is one of the leading causes of male impotence worldwide. Therefore, to better understand the effects of psychological stress on male sexual potency, vigor, and the physiology of erection, we used the rat restraint stress (RS) model, which can most aptly simulate psychological stress. METHODS: Adult male SD rats were exposed to RS for 1.5 or 3 h/day for 30 days. Neuromodulators and hormones of sexual potency and penile erection were quantified using ELISA kit. The histoarchitecture of the penis was examined using Masson trichrome staining. Immunoblotting and immunofluorescence were used to assess the expression and immunolocalization patterns of penile erection markers. To assess sexual potency and vigor, a noncontact erection and a copulatory test were performed. RESULTS: RS exposure decreased the circulatory levels of gonadotropins and testosterone while increasing the serum corticosterone level. RS exposure altered the histomorphology of the penis by decreasing the smooth muscle/collagen ratio and increasing oxidative stress in penile tissue. Furthermore, RS adversely affected NO availability for penile erection by decreasing the neurotransmitter acetylcholine and other erection facilitatory markers such as p-Akt, nNOS, eNOS, and cGMP, while increasing the inhibitory marker PDE5α in the penis. RS exposure significantly reduced the frequencies of mount, intromission, and ejaculation, whereas it prolonged sexual exhaustion by increasing latencies of postejaculatory mount, intromission, and ejaculation. CONCLUSION: The current findings suggest that psychological stressors, such as RS, cause erectile dysfunction in adult male rats by modulating the hypothalamic-pituitary-testicular axis, oxidative balance, penile fibrosis, and the NO/cGMP/PDE5α pathway of penile erection.

Efficacy of RestoreX after prostatectomy: open-label phase of a randomized controlled trial.

OBJECTIVE: To report open-label phase data from a recent randomized controlled trial (RCT), after previous data from that study showed improved penile length and erectile function among post-prostatectomy men treated with Restorex penile traction therapy (RxPTT). MATERIALS AND METHODS: An RCT (NCT05244486) was performed to evaluate RxPTT vs no treatment (Tx) for 5 months, which was followed by a 3-month open-label phase. Men were stratified based on as-treated data: Group 1 = No Tx; Group 2 = No Tx → Tx; Group 3 = Tx → No Tx; Group 4 = Tx. Assessments included stretched penile length and standardized (International Index of Erectile Function [IIEF]) and non-standardized questionnaires. RESULTS: A total of 82 men were enrolled (mean age 58.6 years) with 9-month data available in 45 of the men. Baseline characteristics were similar among the cohorts. Comparing Group 1 and Group 4 (respectively), notable differences included: IIEF Erectile Function domain (IIEF-EF) score (-8 vs -0.5; P = 0.16), penile length (-0.1 vs +1.7 cm; P < 0.01), intracavernosal injection use (86% vs 14%; P < 0.01), Sexual Encounter Profile (SEP) Question 2 (50% vs 100%; P < 0.01), SEP Question 3 (33% vs 100%; P < 0.01). Men who crossed over to Tx (Group 2) failed to achieve equivalent improvements in length (+0.5 cm) or sexual function (IIEF-EF score -6) compared to men treated early (Groups 3 and 4). Those who crossed over to no treatment after initial treatment (Group 3) experienced preserved length (+1.8 cm), and erectile function (IIEF-EF score +0) despite therapy discontinuation. CONCLUSIONS: Use of RxPTT beginning 1 month post-prostatectomy results in improved penile length and erectile function, with benefits maintained after discontinuing therapy. If confirmed, these results represent the first postoperative therapy shown in a RCT to improve erectile function post-prostatectomy. External validation is warranted.

Effect of aerobic exercise on erectile function: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The health benefits of regular aerobic exercise are well established, although there is limited high-quality evidence regarding its impact on erectile function. AIM: To determine the effect of aerobic exercise on erectile function in men and to identify factors that may influence this effect. METHODS: This systematic review and meta-analysis included randomized controlled trials that evaluated the effects of aerobic exercise on erectile function via the Erectile Function domain of the International Index of Erectile Function (IIEF-EF). The mean difference in IIEF-EF scores between the aerobic exercise and nonexercising control groups was estimated by a random-effects meta-analysis. Meta-regression was used to evaluate the association of moderator variables on meta-analysis results. OUTCOMES: The IIEF-EF score is reported on a 6-30 scale, with higher values indicating better erectile function. RESULTS: Among 11 randomized controlled trials included in the analysis, aerobic exercise resulted in statistically significant improvements in IIEF-EF scores as compared with controls, with a mean difference of 2.8 points (95% CI, 1.7-3.9; P < .001) and moderate heterogeneity among studies (I2 = 53%). The effect of aerobic exercise on erectile function was greater in men with lower baseline IIEF-EF scores, with improvements of 2.3, 3.3, and 4.9 points for mild, moderate, and severe erectile dysfunction, respectively (P = .02). The meta-analysis results were not influenced by publication bias or individual study effects. CLINICAL IMPLICATIONS: Health care providers should consider recommending regular aerobic exercise as a low-risk nonpharmacologic therapy for men experiencing erectile difficulties. STRENGTHS AND LIMITATIONS: The primary strength of this review was the generation of level 1 evidence on a topic of general interest regarding sexual health in men. However, the included studies evaluated diverse groups, which may complicate data interpretation for specific segments of the population. CONCLUSION: Regular aerobic exercise can improve the erectile function of men, particularly those with lower baseline IIEF-EF scores.

Pathway analysis of microarray data from corpora cavernosal tissue of patients with a prostatectomy or Peyronie disease in comparison with a cavernous nerve-injured rat model of erectile dysfunction.

INTRODUCTION: Patients with a prostatectomy are at high risk of developing erectile dysfunction (ED) that is refractory to phosphodiesterase type 5 inhibitors. The cavernous nerve (CN) is frequently damaged during prostatectomy, causing loss of innervation to the penis. This initiates corpora cavernosal remodeling (apoptosis and fibrosis) and results in ED. AIM: To aid in the development of novel ED therapies, the current aim was to obtain a global understanding of how signaling mechanisms alter in the corpora cavernosa with loss of CN innervation that results in ED. METHODS: Microarray and pathway analysis were performed on the corpora cavernosal tissue of patients with a prostatectomy (n = 3) or Peyronie disease (control, n = 3). Results were compared with an analysis of a Sprague-Dawley rat CN injury model (n = 10). RNA was extracted by TRIzol, DNase treated, and purified by a Qiagen Mini Kit. Microarray was performed with the Human Gene 2.0 ST Array and the RU34 rat array. Differentially expressed genes were identified through several analytic tools (ShinyGO, Ingenuity, WebGestalt) and databases (GO, Reactome). A 2-fold change was used as the threshold for differential expression. OUTCOMES: Pathways that were altered (up- or downregulated) in response to CN injury in the prostatectomy patients and a rat CN injury model were determined. RESULTS: Microarray identified 197 differentially expressed protein-coding genes in the corpora cavernosa from the prostatectomy cohort, with 100 genes upregulated and 97 genes downregulated. Altered signaling pathways that were identified that affect tissue morphology included the following: neurologic disease, cell death and survival, tissue and cellular development, skeletal and muscle development and disorders, connective tissue development and function, tissue morphology, embryonic development, growth and proliferation, cell-to-cell signaling, and cell function and maintenance. These human pathways have high similarity to those observed in the CN-injured rat ED model. CLINICAL IMPLICATIONS: Significant penile remodeling continues in patients long after the acute surgical injury to the CN takes place, offering the opportunity for clinical intervention to reverse penile remodeling and improve erectile function. STRENGTHS AND LIMITATIONS: Understanding how signaling pathways change in response to CN injury and how these changes translate to altered morphology of the corpora cavernosa and ensuing ED is critical to identify strategic targets for therapy development. CONCLUSION: Altered signaling in pathways that regulate tissue homeostasis, morphogenesis, and development was identified in penes of patients with a prostatectomy, and competitive forces of apoptosis and proliferation/regeneration were found to compete to establish dominance after CN injury. How these pathways interact to regulate penis tissue homeostasis is a complex process that requires further investigation.

Caveolin-1 scaffolding domain peptide prevents corpus cavernosum fibrosis and erectile dysfunction in bilateral cavernous nerve injury-induced rats.

BACKGROUND: Corpus cavernosum (CC) fibrosis significantly contributes to post-radical prostatectomy erectile dysfunction (pRP-ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has gained significant concern as a potent antagonist of tissue fibrosis. However, applying CSD peptide on bilateral cavernous nerve injury (BCNI)-induced rats remains uninvestigated. AIM: The aim was to explore the therapeutic outcome and underlying mechanism of CSD peptide for preventing ED in BCNI rats according to the hypothesis that CSD peptide may exert beneficial effects on erectile tissue and function following BCNI through limiting collagen synthesis in CC smooth muscle cells (CCSMCs) and CC fibrosis. METHODS: After completing a random assignment of male Sprague Dawley rats (10 weeks of age), BCNI rats received either saline or CSD peptide treatment, as opposed to sham-operated rats. The evaluations of erectile function (EF) and succedent collection and histological and molecular biological examinations of penile tissue were accomplished 3 weeks postoperatively. In addition, the fibrotic model of CCSMCs was used to further explore the mechanism of CSD peptide action in vitro. OUTCOMES: The assessments of EF, SMC/collagen ratio, α-smooth muscle actin, caveolin-1 (CAV1), and profibrotic indicators expressions were conducted. RESULTS: BCNI rats exhibited significant decreases in EF, SMC/collagen ratio, α-SMA, and CAV1 levels, and increases in collagen content together with transforming growth factor (TGF)-ß1/Smad2 activity. However, impaired EF, activated CC fibrosis, and Smad2 signaling were attenuated after 3 weeks of CSD peptide treatment in BCNI rats. In vitro, TGF-ß1-induced CCSMCs underwent fibrogenetic transformation characterized by lower expression of CAV1, higher collagen composition, and phosphorylation of Smad2; then, the delivery of CSD peptide could significantly block CCSMC fibrosis by inactivating Smad2 signaling. CLINICAL IMPLICATIONS: Based on available evidence of CSD peptide in the prevention of ED in BCNI rats, this study can aid in the development and clinical application of CSD peptide targeting pRP-ED. STRENGTHS AND LIMITATIONS: This study provides data to suggest that CSD peptide protects against BCNI-induced deleterious alterations in EF and CC tissues. However, the available evidence still does not fully clarify the detailed mechanism of action of CSD peptide. CONCLUSION: Administration of CSD peptide significantly retarded collagen synthesis in CCSMCs, limited CC fibrosis, and prevented ED via confrontation of TGF-ß1/Smad signaling in BCNI rats.

Predictors of hinge effect in patients with Peyronie's disease.

BACKGROUND: Patients with Peyronie's disease present with a variety of penile deformities. Those with hinge effect can experience bothersome buckling of the erection and instability during penetrative sex; however, the actual characteristics and clinical implications are not fully understood. AIM: To determine the factors that cause hinge effect and to assess the role on surgical intervention. METHODS: This retrospective review included 1223 consecutive patients who were examined by a single surgeon and had a complete penile duplex evaluation with curvature and hinge assessment. Baseline demographics, penile duplex findings, and clinical outcomes were used to assess for predictors of hinge effect. OUTCOMES: Analyses were performed to assess preoperative predictors of hinge effect and surgical intervention. RESULTS: Hinge effect was observed at the time of penile duplex Doppler examination in 33% of patients. Circumferential girth discrepancy at point of indentation (odds ratio [OR] 1.82; P < .001), rigidity of erection (OR, 0.82; P = .002), and degree of primary curvature (OR, 1.03; P < .001) predicted the presence of hinge effect. When controlling for rigidity, a girth discrepancy >1 cm did appear to be associated with a hinge. CLINICAL IMPLICATIONS: Circumferential girth discrepancy >1 cm, regardless of erectile rigidity, can be associated with hinge effect. STRENGTHS AND LIMITATIONS: As a strength, this study included the largest cohort of patients with Peyronie's disease, all of whom were examined in a rigorous and uniform manner via the same operative counseling. However, the study is limited by its retrospective nature and potential for selection and observer bias, given that the treating physician was also assessing all penile deformities as well as performing operative intervention. CONCLUSIONS: The presence of hinge effect can cause instability of erections during penetrative sex. Multiple factors may predispose patients to a hinge effect, including the quality of erection and severity of curvature. But when controlling for rigidity, a girth discrepancy >1 cm did appear to be associated with a hinge. While many factors, such as baseline erectile dysfunction and severity of curvature, are important in determining the optimal surgical intervention, assessing for preoperative hinge effect also influenced the surgical approach.

Shaeer's corporal rotation IV: length-preserving correction of congenital ventral penile curvature.

BACKGROUND: For cases with severe penile curvature, the loss in length with shortening techniques or the loss in rigidity with incision grafting can compromise the results, hence the advent of Shaeer's corporal rotation III technique, which corrects the most severe degrees of ventral penile curvature without loss in length, though with a certain degree of narrowing. AIM: We sought to describe Shaeer's corporal rotation IV, aiming at correction of moderate-to-severe ventral penile curvature with minimal shortening, minimal narrowing, and minimal mobilization of the neurovascular bundle, among other improvements such as using thicker suture material to decease recurrence while inverting the surgical knots. METHODS: Forty-two patients with congenital ventral penile curvature were selected for the study with a curve ranging from 60° to 90°. Patients were randomized into 1 of the 2 groups: Shaeer's corporal rotation III (SCR-III) and SCR-IV. In SCR-IV, rotation is used to correct the main brunt of curvature, up to 70% to 80% of the curve. Plication is used to correct the residual curvature up to 100% straightness. This keeps the rotation points fewer and closer to the midline, thereby minimizing narrowing and mobilization of the neurovascular bundle. OUTCOMES: Both groups were compared with regard to intraoperative erection angle, length, and girth, before and after rotation, as well as subjectively reported postoperative recurrence, penile sensitivity, satisfaction, and IIEF. RESULTS: The postcorrection angle was zero for all cases in the 2 groups. Dorsal length decreased by 3% in the SCR-IV group compared with 0.5% in the SCR-III group (2.5% difference). The difference in circumference between the narrowest and widest points was 2% in the SCR-IV group vs 9.3% in the SCR-III group (7.3% difference). The average operative time was 19.2% shorter with SCR-IV. Girth asymmetry was reported in 1 (4.8%) of 21 patients in the SCR-IV group compared with 15 (71.4%) of 21 in the SCR-III group. Partial hyposensitivity of the penis was reported in 9.5% in the SCR-IV group compared with 19% in the SCR-III group. CLINICAL IMPLICATIONS: SCR-IV is an improvement over former versions of the technique, with higher patient satisfaction. STRENGTHS AND LIMITATIONS: A strength of the study is the long follow-up period. Limitations include being a single-center study and reliance on patient reporting to evaluate recurrence and satisfaction. CONCLUSION: The SCR-IV technique corrects moderate and severe degrees of congenital ventral penile curvature, with little or no compromise in penile length, girth, or sensitivity.