Prospective, randomized, placebo-controlled, two-arm study to evaluate the efficacy of coadministration of garlic as a hydrogen sulfide donor and tadalafil in patients with erectile dysfunction not responding to tadalafil alone - A pilot study.

OBJECTIVE: The objective is to evaluate the efficacy of coadministration of garlic (as a hydrogen sulfide [H2S] donor) and tadalafil for patients with ED using a placebo-controlled, prospective, randomized, two-arm pilot study in patients responding poorly to tadalafil alone. MATERIALS AND METHODS: The patients with complaints of ED (with normal penile Doppler) who failed to maintain sustained improvement in erectile function with tadalafil were recruited after excluding those with comorbidities. The study sample was randomized into two groups. Group A received garlic 5 g twice a day orally and Group B received a placebo twice daily orally for 4 weeks. Both groups continued tadalafil 5 mg in the night for 4 weeks. Their erectile function was assessed at the beginning and at the end of 4 weeks using the International Index of Erectile Function (IIEF-EF), erectile function domain and compared. A value of P ≤ 0.05 was considered statistically significant. RESULTS: Nineteen patients in Group A (mean age 37.5 ± 10.6 years) and 16 patients in Group B (mean age 39.6 ± 9.6 years) participated in the pilot study conducted from May 2022 to August 2022. The participants treated with garlic (as an H2S donor) as a coadministrant had statistically significant improvement in IIEF-EF score (P ≤ 0.0001) at the end of 4 weeks compared to placebo. CONCLUSIONS: Garlic (as an H2S donor) as adjunctive therapy was beneficial in our study participants responding poorly to tadalafil alone.

[The role of seminal vesicles in male sexual function].

The seminal vesicle is an important accessory gland of the male reproductive system. In the past, some scholars focused more on its role in the fertilization process and neglected its relationship with male sexual function. Researches show that the seminal vesicle is involved in multiple processes such as sexual desire, penile erection, and ejaculation. Treatment of sexual dysfunction by medication targeting the seminal vesicle has achieved certain therapeutic effects. This article discusses the relationship between the seminal vesicle and sexual function in terms of physiopathology, clinical study and basic research, hoping to provide some new ideas on the clinical diagnosis and treatment of sexual dysfunction.

Scoping review exploring advancements in topical agent therapies for erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is a common issue that affects older men and is often associated with various health conditions. Phosphodiesterase 5 inhibitors are commonly used to treat ED; however, their effectiveness may be limited, or the medication may be contraindicated. Therefore, topical gels are being developed as an alternative option for the pharmacologic treatment of ED. OBJECTIVES: This review aimed to provide an overview of the efficacy and safety of topical agents for the treatment of ED. METHODS: The PubMed, Cochrane, Embase, and Web of Science databases were searched. Articles were included that investigated ED and topical agents operating through the skin of the penis, evaluated the effectiveness of the treatment, and involved patients randomized into groups. RESULTS: Topical alprostadil, glyceryl trinitrate (MED2005), and an over-the-counter formulation (MED3000) were used as alternative treatments for ED in 7 articles, which included 3475 patients. Topical alprostadil induced an erection in 67% to 75% of patients. Adequate erections for vaginal penetration were reported in 38.7% of the alprostadil-treated patients vs 6.9% of the placebo-treated patients. Topical alprostadil significantly and dose dependently improved the total score change on the International Index of Erectile Function as compared with the placebo. MED2005 exhibited a rapid onset of action, with nearly 70% effectiveness within 10 minutes. MED3000 met the minimal clinically important difference threshold of a 4-point increase on the erectile function domain of the International Index of Erectile Function, with an improvement of 5.73 points in 24 weeks. Topical therapy for ED also had acceptable safety profiles. CONCLUSION: Topical agents via various mechanisms are effective and well-tolerated treatments for ED. A fast-acting drug that significantly reduces side effects as compared with other options has been discovered. However, its efficacy relative to current first-line therapies remains unclear. Topical agents present a viable therapeutic alternative for individuals who are unable or unwilling to take oral phosphodiesterase 5 inhibitors.

[Treatment of hypoxia-induced ED in high-altitude areas by transcutaneous low-frequency electrical stimulation based on the parameters obtained from visualized precision electrophysiological diagnosis].

OBJECTIVE: To investigate the effects of visualized precision electrophysiological diagnosis and transcutaneous low-frequency electrical stimulation (TES) on hypoxia-induced ED in high-altitude areas. METHODS: This study included 152 ED patients from high-altitude hypoxic areas treated by TES based on the parameters obtained from visualized precision electrophysiological diagnosis. We followed up the patients for 1 to 3 months and compared their IIEF-5 scores, nocturnal penile tumescence and rigidity (NPTR) and infrared thermal metabolic technology (TMT)-based temperature of the whole body and diseased parts before and after treatment. RESULTS: All the patients successfully completed 1 to 3 courses of TES. There were no statistically significant differences in the IIEF-5 scores (P<0.05) and penile tip optimal erection rigidity and duration (P<0.01) of the patients before and after treatment. TMT images indicated a temperature change of >1.5 ℃ in the penis and bilateral inguinal regions after treatment, suggesting the effectiveness of electrical stimulation. No recurrence was observed during the follow-up. CONCLUSION: TES based on the parameters obtained from visualized precision electrophysiological diagnosis has a definite effect on hypoxia-induced ED by enhancing oxygen supply to the penile corpus cavernosum and improving its function and structure.

Efficient use of penile Doppler ultrasound for investigating men with erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction is the most common type of erectile dysfunction, and penile Doppler ultrasound (PDUS) is a useful tool to assess erectile hemodynamics in the clinician's effort to discuss prognosis and management strategies with the patient. AIM: We herein describe the PDUS protocol used at our center, including indications, technique, and data interpretation. METHODS: We describe our institutional experience with PDUS and discuss it in the context of a contemporary review of the literature for this investigation. OUTCOME: Our institutional PDUS protocol. RESULTS: To perform PDUS properly, adequate training, equipment, setting, technique, and interpretation are critical. The accuracy of PDUS is entirely predicated on achieving complete cavernosal smooth muscle relaxation. A redosing protocol optimizes the reliability and reproducibility of the hemodynamic data acquired during PDUS. A rigidity-based assessment is performed, and patients are scanned according to the erection rigidity achieved (full hardness) or by administration of maximum dose of the vasoactive agent. Peak systolic velocity is considered a measure of arterial inflow (normal, >30 cm/s), while end diastolic velocity evaluates the veno-occlusive mechanism (normal, <5 cm/s). After the procedure, the patient is evaluated to confirm detumescence. If the patient has a persistent penetration rigidity erection, intracavernosal phenylephrine is administered; however, if detumescence is not achieved with intracavernosal phenylephrine injections alone, corporal aspiration is potentially performed. CONCLUSION: PDUS is a valuable minimally invasive tool for erectile hemodynamics assessment and an accurate assessment of such, provided that complete cavernosal smooth muscle relaxation is achieved.

Quality of Life Evaluation after Partial Penile Amputation for Penile Cancer.

BACKGROUND: Penile cancer is most prevalent in developing countries. Both the physiological and psychological consequences for the patient are critical. These consequences result from both the cancer diagnosis and the treatment's effects. OBJECTIVE: The objective of this study was to evaluate the quality of life (QoL) of patients who have undergone partial penile amputation in terms of general well-being, sexual function, and urinary function. MATERIALS AND METHODS: This retrospective observational study included 32 patients who underwent partial penile amputation. The european organisation for research and treatment of cancer core quality of life questionnaire (EORTC QLQ C-30) questionnaire was completed postoperatively. Erectile function and satisfaction were assessed retrospectively after partial penile amputation using the International Index of Erectile Function-15. RESULTS: The mean age of the patients was 54.03 ± 16.02 years. The mean scores for erectile function, orgasm, sexual desire, satisfaction, and overall satisfaction were 16.28 ± 10.83, 7.50 ± 3.30, 5.72 ± 3.35, 8.84 ± 4.77, and 9.12 ± 0.83 preoperatively, and 14.03 ± 8.61, 6.88 ± 2.97, 5.72 ± 3.35, 7.94 ± 4.09, and 7.81 ± 1.00 postoperatively. Mean erectile function, orgasm, satisfaction, and overall satisfaction were significantly decreased postoperatively compared with preoperatively. Erectile function and overall satisfaction improved more in younger years from the preoperative to the postoperative period, whereas they improved less in older years. CONCLUSION: Although partial penile amputation for penile cancer provides adequate local disease management, appropriate counseling is crucial, especially when the QoL concerns general well-being, sexual function, and urinary function.

Résumé Contexte:Le cancer du pénis est plus répandu dans les pays en développement. Les conséquences physiologiques et psychologiques pour le patient sont cruciales. Ces conséquences résultent à la fois du diagnostic de cancer et des effets du traitement.Objectif:L'objectif de cette étude était d'évaluer la qualité de vie (QdV) des patients ayant subi une amputation partielle du pénis en termes de bien­être général, de fonction sexuelle et de fonction urinaire.Matériels et méthodes:Cette étude observationnelle rétrospective a inclus 32 patients ayant subi une amputation partielle du pénis. Le questionnaire de base sur la qualité de vie de l'organisation européenne pour la recherche et le traitement du cancer (EORTC QLQ C­30) a été complété en postopératoire. La fonction érectile et la satisfaction ont été évaluées rétrospectivement après une amputation partielle du pénis à l'aide de l'indice international de la fonction érectile­15.Résultats:L'âge moyen des patients était de 54,03 ± 16,02 ans. Les scores moyens pour la fonction érectile, l'orgasme, le désir sexuel, la satisfaction et la satisfaction globale étaient de 16,28 ± 10,83, 7,50 ± 3,30, 5,72 ± 3,35, 8,84 ± 4,77 et 9,12 ± 0,83 en préopératoire, et de 14,03 ± 8,61, 6,88 ± 2,97, 5,72. ± 3,35, 7,94 ± 4,09 et 7,81 ± 1,00 en postopératoire. La fonction érectile moyenne, l'orgasme, la satisfaction et la satisfaction globale étaient significativement diminués en postopératoire par rapport au préopératoire. La fonction érectile et la satisfaction globale se sont améliorées davantage dans les années plus jeunes, de la période préopératoire à la période postopératoire, alors qu'elles se sont moins améliorées dans les années plus âgées.Conclusion:Bien que l'amputation partielle du pénis pour le cancer du pénis permette une prise en charge locale adéquate de la maladie, un conseil approprié est crucial, en particulier lorsque la qualité de vie concerne le bien­être général, la fonction sexuelle et la fonction urinaire.

miR-200a-3p-enriched MSC-derived extracellular vesicles reverse erectile function in diabetic rats by targeting Keap1.

BACKGROUND: The administration of mesenchymal stem cells (MSCs) through intracavernous injection is a potential therapeutic approach for managing diabetes mellitus-induced erectile dysfunction (DMED). However, pulmonary embolism and tumorigenicity are fatal adverse events that limit the clinical application of MSCs. In this study, we examined the therapeutic efficacy and potential mechanism of MSC-derived extracellular vesicles (MSC-EVs). METHODS: In this study, forty 8-week-old male SpragueDawley (SD) rats were utilised. In the control group, ten rats were administered an intraperitoneal injection of PBS. STZ (60 mg/kg) was intraperitoneally injected into the remaining rats to establish a diabetes mellitus (DM) model. Afterwards, the diabetic rats were divided into three groups at random: the DM group (intracavernosal injection of PBS), the EVs group (intracavernosal injection of MSC-EVs), and the EVs-200a group (intracavernosal injection of miR-200a-3p-enriched extracellular vesicles). Erectile function was determined by measuring intracavernous pressure in real time and utilising electrical stimulation of the cavernous nerves. The smooth muscle content was evaluated through the investigation of penile tissue using immunofluorescence staining, Masson's trichrome staining, and western blotting after euthanasia. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels in the corpus cavernosum were measured via ELISA. In vitro, hydrogen peroxide (H2O2) was used to induce oxidative stress. The viability of corpus cavernosum smooth muscle cells (ccSMCs) incubated with or without H2O2 was measured using a CCK8 assay. Flow cytometry was used to assess the levels of reactive oxygen species (ROS) and apoptosis in ccSMCs. Furthermore, a dual-luciferase reporter assay was performed to validate the relationship between miR-200a-3p and Keap1. RESULTS: Reversal of erectile function was observed in the EVs groups, especially in the EVs-200a group. DM increased the MDA level and decreased the SOD and GSH levels. In the DM group, the expression of alpha-smooth muscle actin (α-SMA) and smooth muscle 22 alpha (SM22α) was decreased, and the expression of osteopontin (OPN) was increased. Western blotting revealed decreased Nrf2, HO-1, and Bcl2 expression and increased Keap1, Bax and cleaved caspase3 expression in the cavernous tissue. miR-200a-3p-enriched extracellular vesicles (EVs-200a) reversed these changes and inhibited the loss of smooth muscle content and cavernous fibrosis. In vitro, H2O2 induced high ROS levels in ccSMCs and increased apoptosis, and these effects reversed by EVs-200a. H2O2 reduced Nrf2, HO-1, and Bcl2 expression and increased Keap1, Bax and cleaved caspase-3 expression, and these effects were reversed by MSC-EVs, especially EVs-200a. The of dual-luciferase reporter assay results indicated that miR-200a-3p directly targeted Keap1 in a negative manner. CONCLUSION: MSC-EVs, especially EVs-200a, alleviated erectile dysfunction in diabetic rats through the regulation of phenotypic switching, apoptosis and fibrosis. Mechanistically, miR-200a-3p targeted the Keap1/Nrf2 pathway to attenuate oxidative stress in diabetic rats.

Heparin-binding epidermal growth factor-like growth factor improves erectile function in streptozotocin-induced diabetic mice.

BACKGROUND: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) serves as a pro-angiogenic factor; however, there is to our knowledge currently no reported research on the relationship between HB-EGF and diabetic erectile dysfunction (ED). AIM: In this study we aimed to determine whether HB-EGF can improve the erectile function of streptozotocin-induced diabetic mice and to explore the related mechanisms. METHODS: Eight-week-old male C57BL/6 mice were used for diabetes induction. Diabetes mellitus (DM) was induced by low-dose injections of streptozotocin (50 mg/kg) for 5 consecutive days. Eight weeks after streptozotocin injections, DM was determined by measuring blood glucose and body weight. Diabetic mice were treated with two intracavernous administrations of phosphate-buffered saline (20 µL) or various doses of HB-EGF (days -3 and 0; 1, 5, and 10 µg in 20 µL of phosphate-buffered saline). The angiogenesis effect of HB-EGF was confirmed by tube formation and migration assays in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was measured by electrical stimulation of the cavernous nerve, as well as histological examination and Western blot analysis for mechanism assessment. OUTCOMES: In vitro angiogenesis, cell proliferation, in vivo intracavernous pressure, neurovascular regeneration, cavernous permeability, and survival signaling were the outcomes measured. RESULTS: Expression of HB-EGF was reduced under diabetic conditions. Exogenous HB-EGF induced angiogenesis in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was decreased in the DM group, whereas administration of HB-EGF resulted in a significant improvement of erectile function (91% of the age-matched control group) in association with increased neurovascular content, including cavernous endothelial cells, pericytes, and neuronal cells. Histological and Western blot analyses revealed a significant increase in the permeability of the corpus cavernosum in DM mice, which was attenuated by HB-EGF treatment. The protein expression of phospho-Akt Ser473 and phosphorylated endothelial nitric oxide synthase Ser1177 increased after HB-EGF treatment. CLINICAL IMPLICATIONS: The use of HB-EGF may be an effective strategy to treat ED associated with DM or other neurovascular diseases. STRENGTHS AND LIMITATIONS: Similarly to other pro-angiogenic factors, HB-EGF has dual roles in vascular and neuronal development. Our study focused on broadly evaluating the role of HB-EGF in diabetic ED. In view of the properties of HB-EGF as an angiogenic factor, its dose concentration should be strictly controlled to avoid potential side effects. CONCLUSION: In the diabetic ED mouse model in this study erectile function was improved by HB-EGF, which may provide new treatment strategies for patients with ED who do not respond to phosphodiesterase 5 Inhibitors.

Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.

PURPOSE: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). MATERIALS AND METHODS: Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. RESULTS: Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. CONCLUSIONS: Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

Clinical outcomes of the Burnett "snake" maneuver shunt modification for ischemic priapism.

BACKGROUND: Major ischemic priapism (IP) is defined as a persistent penile erection for >4 hours. IP may cause serious complications, especially if prompt resolution is not achieved. Therefore, selecting the most effective and usable shunt technique is crucial in IP cases that are refractory to medical therapy. AIM: To compare the effectiveness and complication risks of distal corporoglanular shunt procedures with and without the Burnett "snake" maneuver. METHODS: We conducted a retrospective study of patients who presented with IP and underwent surgical treatment at our institution between 2005 and 2021. The patients were categorized into 2 groups: group 1 (n = 26) underwent distal shunt + Burnett snake maneuver, and group 2 (n = 56) underwent distal shunt-only. Clinical history, parameters of IP, details of medical and surgical treatments, and follow-up information were evaluated. OUTCOMES: Outcomes included differences in IP resolution and recurrence, functional erections, and complications between corporoglanular shunt procedures with and without the Burnett snake maneuver. RESULTS: In group 1, 24 of 26 patients (92.3%) experienced priapism resolution with a single surgical intervention, while this outcome was observed in 30 of 56 patients (53.6%) in group 2 (P < .001). Notably, priapism recurrence was significantly lower in group 1, occurring in 1 of 24 patients (4.2%), as opposed to 8 of 30 patients (26.6%) in group 2 (P < .001). Of the patients with documented sexual function status at follow-up, functional erections (capable of penetration with or without phosphodiesterase 5 inhibitors) were noted in 6 of 14 patients (42.8%) in group 1 and 13 of 26 patients (50%) in group 2 (P = .66). CLINICAL IMPLICATIONS: This study provides valuable insights regarding technical aspects of distal shunt procedures with and without the Burnett snake maneuver for treating major IP episodes. These results can help surgeons with clinical decision making for patients who present with IP. STRENGTH AND LIMITATIONS: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, challenges in controlling confounding variables, and the lack of validated questionnaire scores for erectile function evaluation. CONCLUSION: Our study demonstrates that modifying distal shunt procedures using the Burnett snake maneuver significantly improves priapism resolution and effectively prevents further priapism episodes without introducing additional complications or erectile function loss, thereby distinguishing it from distal shunt-only procedures.

A low testosterone level impairs erectile function by increasing endocan expression in rat penile corpus cavernosum.

BACKGROUND: The mechanism by which a state of low testosterone leads to erectile dysfunction (ED) has not been determined. Endocan is a novel marker of endothelial function. However, whether endocan is involved in the regulation of erectile function under low testosterone levels remains unclear. AIM: In this study we sought to determine whether a low-testosterone state inhibits erectile function by regulating endocan expression in the endothelial cells of the rat penile corpus cavernosum. METHODS: Thirty-six male Sprague-Dawley rats aged 8 weeks were randomly assigned to 6 groups (n = 6 per group) as follows: (1) control, (2) castration, (3) castration + testosterone treatment (treated with 3 mg/kg testosterone propionate per 2 days), (4) control + transfection (4 weeks after castration, injected with lentiviral vector (1 × 108 transduction units/mL, 10 µL), (5) castration + transfection, or (6) castration + empty transfection. One week after the injection, we measured the maximal intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone and nitric oxide (NO) levels, and the expression of endocan, phospho-endothelial NO synthase (p-eNOS), eNOS, phospho-protein kinase B (p-AKT), and AKT in the rat penile corpus cavernosum. OUTCOMES: Under a low-androgen state, the expression of endocan in the rat penile corpus cavernosum was significantly increased, which inhibited the AKT/eNOS/NO signaling pathway and resulted in ED. RESULTS: In the castration group, the expression of endocan in the rat penile corpus cavernosum was significantly higher than that in the control group (P < .05). Additionally, the levels of p-AKT/AKT, p-eNOS/eNOS, and NO in the rat penile corpus cavernosum and ICPmax/MAP were significantly lower in the castration group than in the control group (P < .05). In the castration + transfection group compared with the castration group there was a significant decrease in the expression of endocan (P < .05) and an increase in the ratios of p-AKT/AKT, p-eNOS/eNOS, and ICPmax/MAP (P < .05) in the rat penile corpus cavernosum. CLINICAL IMPLICATIONS: Downregulating the expression of endocan in the penile corpus cavernosum may be a feasible approach for treating ED caused by hypoandrogenism. STRENGTHS AND LIMITATIONS: The results of this study indicte that endocan may affect NO levels and erectile function through multiple signaling pathways, but further experiments are needed to clarify the relationship between endocan and androgens. CONCLUSION: A low-testosterone state inhibits the AKT/eNOS/NO signaling pathway by increasing the expression of endocan in the rat penile corpus cavernosum and impairing erectile function in rats. Decreasing the expression of endocan in the penile corpus cavernosum can improve erectile function in rats with low testosterone levels.

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction.

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock-out mice (ADA-/-, A1-/-, A2a-/-, A2b-/-, and A3-/-), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine-induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age-related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus-induced ED. In single-cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock-out abolishes adenosine-induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF-1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60-6583 improves erectile function and down-regulates HIF-1α and TGF-ß. Administering Dipyridamole (40 mg Kg-1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine-induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

Preoperative high serum total testosterone levels predict preserved postoperative sexual function in patients after nerve-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To assess the association among preoperative total testosterone levels, postoperative sexual function, and prognosis after robot-assisted radical prostatectomy. METHODS: Patients who underwent robot-assisted radical prostatectomy in our institution were included in the study. Based on preoperative total testosterone levels, they were divided into low (<3.0 ng/mL) and high (≥3.0 ng/mL) total testosterone groups. Sexual function was evaluated using the International Index of Erectile Function scores, Expanded Prostate Cancer Index Composite scores, and the potency rate from preoperatively to 12 months after surgery. Oncological outcomes were evaluated based on biochemical recurrence. RESULTS: Out of 233 patients included, no significant difference in sexual function was found between the high (n = 183) and the low (n = 50) total testosterone groups at any point before or after surgery. However, in nerve-sparing cases, preservation in postoperative sexual function was observed only in the high total testosterone group (International Index of Erectile Function scores and Expanded Prostate Cancer Index Composite sexual function scores, at any point after surgery, p < 0.05; potency rate, at 3, 6, and 12 months after surgery; p < 0.05). Additionally, the high total testosterone group showed better biochemical recurrence-free survival than the low total testosterone group (p = 0.008). CONCLUSIONS: In the high total testosterone group, preservation in sexual function was observed after the nerve-sparing procedure, while the biochemical recurrence rate was low. Therefore, patients with high levels of total testosterone may be advised to consider nerve-sparing interventions.

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.

Comparison of erectile and ejaculatory functional outcomes between unilateral and bilateral cavernosal rupture in penile fractures.

This study aimed to compare the erectile and ejaculatory functional outcomes of unilateral and bilateral ruptures of the corpus cavernosum in penile fractures. Sixty patients' data were analyzed retrospectively between June 2020 and January 2023. The patients were divided into two groups based on the affected corpus cavernosum (unilateral and bilateral). Preoperative and postoperative 3rd-, 6th-, and 12th-month self-estimated intravaginal-ejaculation-latency-time (IELT), and international index of erectile function-erectile function (IIEF-EF) scores as well as the presence of urethral injury were compared. Bilateral corpus cavernosum fractures were detected in 18.3% of the patients. The IIEF-EF scores of both groups at 3rd-, 6th-, and 12th-month were found to be significantly lower than the preoperative scores (unilateral group:24.1 ± 2.7 vs 23.2 ± 3.5 and 23.3 ± 3.4, respectively, p = 0.011 and 0.014, respectively; bilateral group: 24 ± 1.9 vs 23 ± 1.8 and 23.2 ± 1.5, respectively, p = 0.027 and 0.047, respectively). No significant difference was found between the preoperative and the postoperative 12th month IIEF-EF scores in either group (unilateral group: 24.1 ± 2.7 vs 23.4 ± 3.6, p = 0.207;bilateral group:24 ± 1.9 vs 23.2 ± 1.5, p = 0.057). The self-estimated IELTs of both groups at the postoperative 3rd, 6th, and 12th months demonstrated a significant increase from the preoperative values (unilateral group: 221.6 ± 81.8 vs 252 ± 94.6, 256.5 ± 97.6, and 250.5 ± 104.8, respectively, p < 0.001; bilateral group:241.8 ± 61.6 vs 278.1 ± 55.4, 281.8 ± 56.1, and 283.6 ± 54.2, respectively, p = 0.041, 0.030, and 0.047, respectively). The changes in self-estimated IELTs and IIEF-EF scores between the preoperative period and the postoperative 3rd, 6th, and 12th-months were compared, and no statistical difference was found between patients with unilateral and bilateral corpus cavernosum fractures (p > 0.05). In conclusion, no significant difference in erectile function was found in either group at the 12-month follow-up, and the self-estimated IELTs were found to be prolonged in both groups. Furthermore, no difference was noted between the groups at any follow-up. To explain the effects of unilateral and bilateral injuries on erectile and ejaculatory functions, further studies with a larger-number of patients are necessary.

Spontaneous erectile function recovery among young men with erectile dysfunction taking tadalafil 5 mg once a day.

BACKGROUND: Daily (once a day [OaD]) tadalafil intake is a valuable option for men favoring spontaneous over scheduled sexual intercourse. AIM: The study sought to assess the rate of and the clinical factors associated with spontaneous, medication-free erectile function (EF) recovery after discontinuation of tadalafil 5 mg OaD in a cohort of young men seeking first medical help for psychogenic erectile dysfunction (ED) as their primary complaint. METHODS: Data from 96 consecutive patients <50 years of age seeking first medical help for ED and prescribed tadalafil 5 mg OaD were analyzed. Patients completed the International Index of Erectile Function (IIEF) and underwent baseline penile color Doppler ultrasound. Follow-up involved clinical assessments or phone interviews. Spontaneous medication-free EF recovery was defined as IIEF EF domain score >22 after tadalafil discontinuation, prompting cessation of follow-up. Descriptive statistics compared tadalafil OaD responders and nonresponders. Cox regression hazard models explored the association between baseline characteristics and EF recovery risk post-drug discontinuation. Kaplan-Meier analyses estimated EF recovery probability over time. OUTCOMES: The primary outcome was EF recovery after discontinuation of tadalafil 5 mg OaD. RESULTS: Overall, median age was 39 (interquartile range [IQR], 32-45) years. Of all, 82 (85.4%) patients achieved EF recovery after tadalafil OaD discontinuation, while 14 (14.6%) patients were identified as nonresponders. Median tadalafil usage time (from beginning to discontinuation) was 3 (IQR, 2-11) months. The most common treatment-emergent adverse event was headache in 9 (9.4%) patients. Nonresponders were older (43 [IQR, 42-45] years vs 38 [IQR, 31-44] years; P = .03), had higher body mass index (25.5 [IQR, 23.4-29.9] kg/m2 vs 23.6 [IQR, 21.8-25.9] kg/m2; P = .04), and reported lower baseline IIEF EF domain scores (12 [IQR, 7-15] vs 15 [IQR, 10-22]; P = .02) than responders. Nonresponders and responders did not differ in terms of baseline ED severity, Charlson comorbidity index, smoking, alcohol consumption, regular physical exercise, and color Doppler ultrasound parameters. Upon Cox regression analysis, younger age (hazard ratio, 0.95; 95% confidence interval, 0.92-0.99; P = .01) was associated to EF recovery, after adjusting for baseline ED severity, body mass index, smoking, and Charlson comorbidity index ≥1. The Kaplan-Meier analysis displays the probability of EF recovery over time, indicating rates of 43%, 60%, and 72% at 3-, 6-, and 12-month follow-up intervals, respectively. CLINICAL IMPLICATIONS: Tadalafil 5 mg OaD is an effective short-term treatment for psychogenic ED, allowing its discontinuation after achieving a normal medication-free EF. STRENGTHS AND LIMITATIONS: The main limitations are the limited number of participants and the potential neglect of confounding factors. CONCLUSION: Almost 1 out of 2 young men with primary psychogenic ED who were prescribed with tadalafil 5 mg OaD recovered spontaneous medication-free EF after 3 months of treatment. Overall, the younger the patient was, the higher the chance there was of spontaneous EF recovery after drug discontinuation.

Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K/AKT/eNOS signaling pathway.

Erectile dysfunction is a complex and common complication of diabetes mellitus, which lacks an effective treatment. The repairing role of vascular endothelium is the current research hotspot of diabetic mellitus erectile dysfunction (DMED), and the activation of PI3K/AKT/eNOS pathway positively affects the repair of vascular endothelium. The herbal extract isorhamnetin has significant vasoprotective effects and has great potential in treating DMED. This study aimed to clarify whether isorhamnetin has an ameliorative effect on DMED and to investigate the modulation of the PI3K/AKT/eNOS signaling pathway by isorhamnetin to discover its potential mechanism of action. In vivo experiments were performed using a streptozotocin-induced diabetic rat model, and efficacy was assessed after 4 weeks of isorhamnetin gavage administration at 10 mg/kg or 20 mg/kg. Erectile function in rats was assessed by maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), and changes in corpus cavernosum (CC) fibrosis, inflammation levels, oxidative stress levels, and apoptosis were assessed by molecular biology techniques. In vitro experiments using high glucose-induced corpus cavernosum endothelial cells were performed to further validate the anti-apoptotic effect of isorhamnetin and its regulation of the PI3K/AKT/eNOS pathway. The findings demonstrated that isorhamnetin enhanced erectile function, decreased collagen content, and increased smooth muscle content in the CC of diabetic rats. In addition, isorhamnetin decreased the serum levels of pro-inflammatory factors IL-6, TNF-α, and IL-1ß, increased the levels of anti-inflammatory factors IL-10 and IL-4, increased the activities of SOD, GPx, and CAT as well as the levels of NO, and decreased the levels of MDA in corpus cavernosum tissues. Isorhamnetin also increased the content of CD31 in CC tissues of diabetic rats, activated the PI3K/AKT/eNOS signaling pathway, and inhibited apoptosis. In conclusion, isorhamnetin exerts a protective effect on erectile function in diabetic rats by reducing the inflammatory response, attenuating the level of oxidative stress and CC fibrosis, improving the endothelial function and inhibiting apoptosis. The mechanism underlying these effects may be linked to the activation of the PI3K/AKT/eNOS pathway.