-
Acta Biomaterialia Sep 2023Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN)...
Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN) during prostatectomy is the main cause of postoperative erectile dysfunction (ED). In this study, the capability of a personalized bioactive fibrous membrane to regenerate injured CN was investigated. The fibrous membrane bioactivity is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. In a rat model of bilateral CN crush, the implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function, showing a significantly increased number of smooth muscle cells and content of endothelial and neuronal nitric oxide synthases (eNOS; nNOS). In addition, the bioactive fibrous membrane promotes nerve regeneration by increasing the number of myelinated axons and nNOS-positive cells, therefore reversing the CN fibrosis found in untreated rats or rats treated with a bare fibrous membrane. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments for CN injuries. It may constitute an effective treatment for prostate cancer patients suffering from ED after being subject to radical prostatectomy. STATEMENT OF SIGNIFICANCE: The present work introduces a unique strategy to address post-surgical ED resulting from CN injury during pelvic surgery (e.g., radical prostatectomy, radical cystoprostatectomy, abdominoperineal resection). It comprises a bioactive and cell-free fibrous implant, customized to enhance CN recovery. Pre-clinical results in a rat model of bilateral CN crush demonstrated that the bioactive fibrous implant can effectively heal injured CN, and restore penile structure and function. This implant selectively binds NGF from patient fluids (i.e. urine) due to its functionalized surface and high surface area. Moreover, its local implantation reduces adverse side effects. This tailored regenerative approach has the potential to revolutionize the treatment of ED in prostate cancer patients following radical prostatectomy, overcoming current treatment limitations.
Topics: Male; Humans; Rats; Animals; Rats, Sprague-Dawley; Nerve Growth Factor; Penile Erection; Erectile Dysfunction; Penis; Prostatectomy; Prostatic Neoplasms; Disease Models, Animal
PubMed: 37467838
DOI: 10.1016/j.actbio.2023.07.015 -
Clinical Interventions in Aging 2023Erectile dysfunction (ED) is a multifactorial medical disorder often neglected in clinical practice between elderly men, defined as the inability to achieve and/or...
BACKGROUND
Erectile dysfunction (ED) is a multifactorial medical disorder often neglected in clinical practice between elderly men, defined as the inability to achieve and/or maintain a penile erection sufficient for satisfactory sexual intercourse and a common clinical entity among men and associated with impaired quality of life and cardiovascular diseases in elderly men. The aim of this study is to evaluate the association between ED and clinical, demographic and behavioral parameters in elderly men.
METHODS
A total of 2436 males aged 60 years and over who participated in the health screening between January 2008 and December 2018 were included in this study. Laboratory exams, clinical and behavior profiles were analyzed. Logistic regression models were used.
RESULTS
Men with ED were older (65.87±5.49 vs. 63.85±4.05 years old. p<0.001), higher prevalence of physical inactivity (23.8 vs. 19%, p = 0.039) and had a higher body mass index (BMI; 28.36±4.06 vs. 27.72±3.89 kg/m. p<0.001) than men without ED. The multivariate model shown that hypertension (p = 0.001), diabetes mellitus (p<0.001), lower urinary tract symptoms (LUTS), depressive symptoms (p<0.001) and age (p<0.001), were strongly associated with ED.
CONCLUSION
The main risk factors associated with ED in elderly men were hypertension, diabetes mellitus, LUTS, depressive symptoms and age.
Topics: Aged; Male; Humans; Middle Aged; Erectile Dysfunction; Cross-Sectional Studies; Quality of Life; Brazil; Risk Factors; Hypertension
PubMed: 37448757
DOI: 10.2147/CIA.S405121 -
Investigative and Clinical Urology Jul 2023In this study, we aimed to evaluate the clinical utility of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and...
PURPOSE
In this study, we aimed to evaluate the clinical utility of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and monocyte/high-density lipoprotein cholesterol ratio (MHR) in predicting response to a phosphodiesterase type 5 inhibitor (PDE5i) when used as the first-line medical treatment of erectile dysfunction (ED).
MATERIALS AND METHODS
This study prospectively included 185 patients who were diagnosed with ED and started PDE5i treatment. After PDE5i treatment, 107 (57.8%) patients with an International Index of Erectile Function-5 (IIEF-5) score below 22 were assigned to Group 1, and 78 (42.2%) patients with an IIEF-5 score of 22 or above were assigned to Group 2. The outcome measures of the study were demographic characteristics and inflammation markers between the groups.
RESULTS
The mean IIEF-5 change after PDE5i treatment was 6.1±4.2 points in Group 1 and 11.5±3.2 points in Group 2 (p=0.001). The mean age was 54.6±9.2 years in Group 1 and 47.8±10.3 years in Group 2 (p<0.001), and the median fasting blood glucose values of Groups 1 and 2 were 105 (36) mg/dL and 97 (23) mg/dL, respectively (p=0.010). The LMR and MHR values were 2.39±0.23 and 13.8±7, respectively, for Group 1, and 2.03±0.22 and 17±6.6, respectively, for Group 2 (p=0.044 and p=0.002, respectively). On multivariable analysis, younger age and increased MHR were independent predictors of benefit from PDE5i treatment.
CONCLUSIONS
This study showed that only MHR as an inflammatory biomarker was an independent predictor for response to PDE5i in the treatment of ED. Also, several factors were predictive of treatment failure.
Topics: Male; Humans; Middle Aged; Erectile Dysfunction; Phosphodiesterase 5 Inhibitors; Penile Erection; Treatment Outcome; Biomarkers
PubMed: 37417566
DOI: 10.4111/icu.20230013 -
Revista Internacional de Andrologia 2023Studies have reported that coronavirus disease 2019 (COVID-19) may cause erectile dysfunction (ED), however, its role in the pathophysiology of ED has not yet been fully...
INTRODUCTION
Studies have reported that coronavirus disease 2019 (COVID-19) may cause erectile dysfunction (ED), however, its role in the pathophysiology of ED has not yet been fully elucidated. We aimed to elucidate COVID-19's effects on cavernosal smooth muscle, which has a pretty important role in erection physiology, by corpus cavernosum electromyography (cc-EMG).
MATERIALS AND METHODS
Twenty-nine male patients aged 20-50 years who applied to the urology outpatient clinic due to ED were included in the study. Nine patients that had COVID-19 and were treated as outpatients were classified as group 1, 10 patients who were hospitalized due to COVID-19 were classified as group 2, and 10 patients who did not have COVID-19 were classified as the control group (group 3). Patients underwent diagnostic evaluation including International Index of Erectile Function (IIEF)-5 form, penile color Doppler ultrasonography (CDUS), cc-EMG, and fasting serum levels of reproductive hormones (07-11am).
RESULTS
According to penile CDUS and hormonal values results, there was no significant difference between the groups. According to cc-EMG results, amplitudes and relaxation capacities of the cavernosal smooth muscle of patients in group 3 were significantly higher than those in the other groups.
CONCLUSIONS
COVID-19 can cause ED not only by psychogenic and hormonal factors but also with cavernosal smooth muscle damage.
CLINICAL TRIAL REGISTRATION NUMBER
NCT04980508.
Topics: Humans; Male; COVID-19; Erectile Dysfunction; Muscle, Smooth; Penile Erection; Pilot Projects; Young Adult; Adult; Middle Aged
PubMed: 37413939
DOI: 10.1016/j.androl.2023.100366 -
BioRxiv : the Preprint Server For... Jun 2023Krause corpuscles, first discovered in the 1850s, are enigmatic sensory structures with unknown physiological properties and functions found within the genitalia and...
Krause corpuscles, first discovered in the 1850s, are enigmatic sensory structures with unknown physiological properties and functions found within the genitalia and other mucocutaneous tissues. Here, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of the mouse penis and clitoris and project to a unique sensory terminal region of the spinal cord. Using electrophysiology and calcium imaging, we found that both Krause corpuscle afferent types are A-fiber rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Optogenetic activation of male Krause corpuscle afferent terminals evoked penile erection, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males as well as reduced sexual receptivity of females. Thus, Krause corpuscles, which are particularly dense in the clitoris, are vibrotactile sensors crucial for normal sexual behavior.
PubMed: 37398085
DOI: 10.1101/2023.06.14.545006 -
The World Journal of Men's Health Apr 2024Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota...
PURPOSE
Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota of ED and healthy males.
MATERIALS AND METHODS
A total of 43 ED patients and 16 healthy controls were enrolled in the study. The 5-item version of the International Index of Erectile Function (IIEF-5) with a cutoff value of 21 was used to evaluate erectile function. All participants underwent nocturnal penile tumescence and rigidity test. Samples of stool were sequenced to determine the gut microbiota.
RESULTS
We identified a distinct beta diversity of gut microbiome in ED patients by unweighted UniFrac analysis (R²=0.026, p=0.036). Linear discriminant analysis effect size (LEfse) analysis showed Actinomyces was significantly enriched, whereas , group, , , and were depleted in ED patients. showed a significant negative correlation with the duration of qualified erection, average maximum rigidity of tip, average maximum rigidity of base, tip tumescence activated unit (TAU), and base TAU. , group, , and were significantly correlated with the IIEF-5 score. and were positively related with average maximum rigidity of tip, average maximum rigidity of base, ΔTumescence of tip, and Tip TAU. Further, a random forest classifier based on the relative abundance of taxa showed good diagnostic efficacy with an area under curve of 0.72.
CONCLUSIONS
This pilot study identified evident alterations in the gut microbiome composition of ED patients and found was negatively correlated with erectile function, which may be a key pathogenic bacteria.
PubMed: 37382280
DOI: 10.5534/wjmh.220278 -
Toxins Jun 2023Intracavernosal injections of botulinum toxin A (BTX/A ) may be effective for difficult-to-treat erectile dysfunction (ED). This is a retrospective case series study of...
Safety and Effectiveness of Repeated Botulinum Toxin A Intracavernosal Injections in Men with Erectile Dysfunction Unresponsive to Approved Pharmacological Treatments: Real-World Observational Data.
Intracavernosal injections of botulinum toxin A (BTX/A ) may be effective for difficult-to-treat erectile dysfunction (ED). This is a retrospective case series study of the effectiveness of repeated off-label BTX/A (onabotulinumtoxinA 100U, incobotulinumtoxinA 100U or abobotulinumtoxinA 500U) in men with ED and insufficient response to phosphodiesterase type 5 inhibitors (PDE5-Is) or prostaglandinE1 intracavernosal injections (PGE1 ICIs), defined as an International Index of Erectile Function-Erectile Function domain score (IIEF-EF) < 26 on treatment. Further injections were performed on patients' requests, and the files of men who underwent at least two injections were reviewed. The response to BTX/A was defined as the achievement of the minimally clinically important difference in IIEF-EF adjusted to the severity of ED on treatment at baseline. Out of 216 men treated with BTX/A and PDE5-Is or PGE1-ICIs, 92 (42.6%) requested at least a second injection. The median time since the preceding injection was 8.7 months. In total, 85, 44 and 23 men received, respectively, two, three and four BTX/A . The overall response rate was 77.5%: 85.7% in men with mild ED, 79% for moderate ED and 64.3% for severe ED on treatment. The response increased with repeated injections: 67.5%, 87.5% and 94.7%, respectively, after the second, third and fourth injections. Post-injection changes in IIEF-EF were similar across injections. The time from injection to request for a further injection varied little. Four men reported penile pain at the time of injection (1.5% of all injections), and one experienced a burn at the penile crus. Repeated BTX/A injections combined with PDE5-Is or PGE1-ICIs produced an effective and durable response, with acceptable safety.
Topics: Male; Humans; Erectile Dysfunction; Penile Erection; Alprostadil; Retrospective Studies; Botulinum Toxins, Type A; Phosphodiesterase 5 Inhibitors; Treatment Outcome
PubMed: 37368683
DOI: 10.3390/toxins15060382 -
Nature Communications Jun 2023Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of...
Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.
Topics: Animals; Humans; Male; Mice; Rats; Adrenomedullin; Erectile Dysfunction; Penile Erection; Penis; Retrospective Studies; YAP-Signaling Proteins; Transcriptional Coactivator with PDZ-Binding Motif Proteins
PubMed: 37353497
DOI: 10.1038/s41467-023-39009-z -
Medicine Jun 2023Erectile dysfunction (ED) is common in middle-aged and elderly men, affecting more than 100 million males worldwide. Most ED cases can be attributed to organic and/or...
An atypical erectile dysfunction patient with infertility treated with penile prosthesis implantation and testicular epididymal sperm aspiration (TESA)-intracytoplasmic sperm injection (ICSI): A case report.
RATIONALE
Erectile dysfunction (ED) is common in middle-aged and elderly men, affecting more than 100 million males worldwide. Most ED cases can be attributed to organic and/or psychological factors. Here we report an atypical ED case with no clear manifestation fitting the diagnosis for recognized types of ED.
PATIENT CONCERNS
The 35-year-old male is unable to have normal erection since puberty, and unable to complete intercourse with his wife. He had no history of trauma, surgery or psychiatric/psychological disease. The patient has a normal male karyotype. There is no significant finding in physical examination, nocturnal penile tumescence test, and ultrasound measurement of penis vascular functions. The serum levels of major hormones are all in normal ranges.
DIAGNOSES
Atypical ED, psychogenic ED not excluded; infertility.
INTERVENTIONS
Oral phosphodiesterase inhibitors Tadalafil (20 mg, BIW) or Sildenafil (50 mg, BIW) had no effect in this patient. Penile prosthesis implantation helped the patient to acquire normal sexual life, but did solve the ejaculation failure and infertility. Motile sperms were obtained by testicular epididymal sperm aspiration under the guidance of ultrasound, and intracytoplasmic sperm injection was performed with occytes retrieved from his wife.
OUTCOMES
The patient sexual life was significantly improved after penile prosthesis implantation; the patient wife is currently in the first trimester of pregnancy as the result of in vitro fertilization.
CONCLUSIONS
The no response to phosphodiesterase type 5 inhibitors (PDE5) treatment may suggest an impediment of PDE5-related pharmacological pathways or the presence of defect/injury in the neural system. This special case raises a question if some patients with persistent ED may have similar manifestations and can be treated with the same procedures.
Topics: Aged; Middle Aged; Pregnancy; Female; Male; Humans; Adult; Erectile Dysfunction; Penile Implantation; Sperm Injections, Intracytoplasmic; Sperm Retrieval; Semen; Infertility
PubMed: 37352063
DOI: 10.1097/MD.0000000000034023 -
Archives of Sexual Behavior Oct 2023The notions that manhood is hard to attain, easy to lose, and needs to be proven via public action constitute precarious manhood beliefs (PMB). PMB is a new concept and...
The notions that manhood is hard to attain, easy to lose, and needs to be proven via public action constitute precarious manhood beliefs (PMB). PMB is a new concept and it remains unclear whether and how PMB relate to erectile dysfunction (ED) in cisgender men. The ability to achieve an erection remains considered as a cornerstone of masculinity and sexual performance can be conceived as a proof of one's masculinity. In this context, ED can be received as sexual failure and a threat to a man's masculinity and sense of adequacy. For these reasons, the hypothesis that PMB are associated with ED warranted empirical testing. In an anonymous online survey focusing on men's mental health conducted in German-speaking countries of Europe, 507 cisgender men (M = 44.2, SD = 15.2) completed measures on PMB, sexual function, self-stigma, social desirability, and conformity to traditional masculinity ideology (TMI). Multilinear regression analysis with stepwise introduction of relevant covariates evaluated potential associations between PMB and ED. Of a 507 cisgendered male sample, 63.1% reported an increased risk for ED based on previously established cutoff points. Elevated levels of PMB endorsement among the men predicted reduced sexual and erectile function in all models, even when accounting for relevant control variables such as age, education, self-stigma, social desirability, or conformity to TMI. Group comparisons revealed that the men suffering from ED showed higher levels of PMB endorsement but not self-stigma nor TMI relative to men without ED. PMB are significantly associated with ED. While determining causality will require further study, our results may support the hypothesis that higher levels of PMB endorsement may lead to increased tension to perform sexually, resulting in increased psychological pressure and a higher risk to develop ED.
Topics: Male; Humans; Adult; Adolescent; Erectile Dysfunction; Masculinity; Sexual Behavior; Men's Health; Penile Erection
PubMed: 37351710
DOI: 10.1007/s10508-023-02640-4