Search

Background: Since the outbreak of coronavirus disease 2019, it has had a serious impact on people's physical and mental health. However, in our clinical work, we have found that the erectile function of coronavirus disease 2019 patients with neurological decline was often seriously affected., Objectives: To further explore the relationship between erectile dysfunction and neurological dysfunction caused by coronavirus disease 2019., Materials and Methods: We conducted a survey from August 2022 to February 2023 at the First Affiliated Hospital of Anhui Medical University and the Third People's Hospital of Linyi City. A total of 251 subjects with a history of coronavirus disease 2019 infection were included. Symptoms and changes in erectile function after the coronavirus disease 2019 infection were collected and assessed using the International Index of Erectile Function-5 scale and several targeted questions., Results: In this study, we found that in patients infected with novel coronavirus, the proportion of erectile dysfunction was higher in those with neurological manifestations such as olfactory and taste impairment or psychological symptoms such as anxiety., Discussion: We found that neurological decline and psychological factors were independent and significant risk factors for erectile dysfunction caused by coronavirus disease 2019., Conclusion: Patients with neurological damage or psychiatric symptoms are more likely to have erectile dysfunction, suggesting that the 2019 novel coronavirus may affect erectile function by damaging nerves. This provides a new insight into the mechanism of erectile dysfunction., (© 2024 American Society of Andrology and European Academy of Andrology.)

Purpose: Comparing post-radical prostatectomy erectile function rates among different techniques has always been a challenge in urology. This difficulty is due to the heterogeneity of studies, mainly in relation to the type of erectile function classification criteria used. The aim is to apply a new evidence-gathering methodology, called reverse systematic review, to compare erectile function rates among retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robot-assisted radical prostatectomy, considering the diversity of classification criteria., Methods: A search was carried out in eight databases between 2000 and 2020 through systematic review studies referring to retropubic radical prostatectomy, laparoscopic radical prostatectomy, or robot-assisted radical prostatectomy (80 systematic reviews). All references used in these systematic reviews were captured by referring to 910 papers in a global database called EVIDENCE. A total of 268 studies related to post-prostatectomy erectile function rates were selected for the final analysis, totaling 465 cohorts or reports referring to 131,350 patients., Results: Note that, 119 (25.6%) reports for retropubic radical prostatectomy, 143 (30.7%) reports for laparoscopic radical prostatectomy, and 203 (43.7%) reports for robot-assisted radical prostatectomy were found. Mean overall erectile function rates, respectively for retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robot-assisted radical prostatectomy, were: 16%, 12%, and 35% at 1 month, 22%, 26%, and 42% in 3 months; 30%, 44%, and 54% at 6 months, 41%, 55%, and 59% at 12 months, and 58%, 52%, and 67% at more than 18 months. The most used erectile function criterion was Erection Sufficient for Intercourse (74.1%), followed by Sexual Health Inventory for Men > 21 (5.5%), and Sexual Health Inventory for Men > 16 (3.7%). Erection Sufficient for Intercourse showed the lowest discrepancy in erectile function rates in each period compared to the global average, for each technique, demonstrating less ability to influence the final results, favoring any of the techniques., Conclusions: The reverse systematic review demonstrated that the robot-assisted radical prostatectomy showed higher rates of erectile function recovery at all times analyzed (1->18 months), in relation to the retropubic radical prostatectomy and laparoscopic radical prostatectomy. The Erection Sufficient for Intercourse criterion was the most used in the literature and showed the lowest bias capable of influencing the results and favoring any of the techniques and might be the fairest option for future comparisons., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Erectile dysfunction has been associated with leisure sedentary behavior in several epidemiological and observational studies. However, the interpretation of these findings is difficult due to residual confounding or reverse causality., Objectives: To explore the causal association between leisure sedentary behavior and erectile dysfunction, and to explore the underlying mechanism using Mendelian randomization., Materials and Methods: In the present study, publicly available large-scale genome-wide association studies of leisure sedentary behaviors (television watching, computer use, and driving), erectile dysfunction, sex hormones (total testosterone, bioactive testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and sex hormone binding globulin), biomarkers of endothelial function (C reactive protein, E-selectin, and matrix metalloproteinase 7), and psychiatric symptoms (depression and anxiety) were used to perform two-sample Mendelian randomization analyses. The inverse variance weighting method was the main method used to estimate the association, and sensitivity analyses were also performed., Results: A greater risk of erectile dysfunction was significantly associated with a higher genetic susceptibility to leisure computer usage (odds ratio = 3.57; 95% confidence interval = 1.78-7.16; p < 0.001). No evidence was obtained to suggest that watching television or driving for leisure increased the risk of erectile dysfunction. No association was found between computer use and depression, anxiety, C reactive protein, E-selectin, matrix metalloproteinase 7, or other sex hormones, with the exception of follicle-stimulating hormone levels (odds ratio = 0.29; 95% confidence interval = 0.12-0.69; p = 0.01). No indication of heterogeneity or pleiotropy was identified by sensitivity analysis., Discussion: Extended computer usage for leisure raised the likelihood of developing erectile dysfunction, which may be associated to lower follicle-stimulating hormone levels; however, the role of endothelial dysfunction and psychological disorders in the development of erectile dysfunction should not be underestimated. Moderate physical activity may help to correct the dysfunction., Conclusion: The present study offered substantial evidence for a positive causal association between computer use and the risk of erectile dysfunction. However, a definitive causal association needs to be established by further research., (© 2024 American Society of Andrology and European Academy of Andrology.)

Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Diabetes mellitus-induced erectile dysfunction (DMED) has become a common disease in adult men that can seriously reduce the quality of life of patients, and new therapies are urgently needed. miRNA-100 has many targets and can induce autophagy and reduce fibrosis by inhibiting the mTOR pathway and the TGF-β pathway. However, no research has been conducted with miR-100 in the field of DMED, and the specific mechanism of action is still unclear., Objectives: To ascertain the effects of miR-100 on corpus cavernosum tissue of DMED rats and vascular endothelial cells in a high glucose environment and to elucidate the relevant mechanisms in autophagy, fibrosis and inflammation to find a new approach for the DMED therapy., Methods: Thirty rats were divided into three groups: the control group, the DMED group, and the DMED + miR-100 group. Using intraperitoneal injections of streptozotocin, all rats except the control group were modeled with diabetes mellitus, which was verified using the apomorphine (APO) test. For rats in the DMED + miR-100 group, rno-miR-100-5p agomir (50 nmol/kg, every 2 days, 6 times in total) was injected via the tail vein. After 13 weeks, the erectile function of each rat was assessed using cavernous manometry, and the corpus cavernosum tissue was harvested for subsequent experiments. For cellular experiments, human coronary microartery endothelial cells (HCMEC) were divided into four groups: the control group, the high-glucose (HG, 40 mM) group, the HG + mimic group, and the HG + inhibitor group. The cells were cultured for 6 days and collected for subsequent experiments 2 days after transfection., Results: Diabetic modeling impaired the erectile function in rats, and miR-100 reversed this effect. By measuring autophagy-related proteins such as mTOR/Raptor/Beclin1/p62/LC3B, we found that miR-100 could suppress the expression of mTOR and induce autophagy. The analysis of the eNOS/NO/cGMP axis function indicated that impaired endothelial function was improved by miR-100. By evaluating the TGF-β1/CTGF/Smad2/3 and NF-κB/TNF-α pathways, we found that miR-100 could lower the level of inflammation and fibrosis, which contributed to the improvement of the erectile function. Cellular experiments can be used as supporting evidence for these findings., Conclusion: MiR-100 can improve the erectile function by inhibiting mTOR and thus inducing autophagy, improving the endothelial function through the eNOS/NO/cGMP axis, and exerting antifibrotic and anti-inflammatory effects, which may provide new ideas and directions for the treatment of DMED., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear., Objective: This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush., Materials and Methods: The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate-buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate-buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting., Results: The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway., Discussion and Conclusion: Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18-month-old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Surgical exploration and closure of the tunica albuginea is the recommended treatment for penile fractures. The recovery of sexual function is the main result that surgeons and patients pursue., Objective: We sought to evaluate the sexual health effects of a surgically corrected penile fracture. Secondarily, we sought to identify risk factors that may influence long-term sexual function and their effects on genital body image satisfaction., Methods: A retrospective analysis of patients who underwent surgical correction of penile fractures between 2007 and 2022 in a tertiary center was performed. Lesion characteristics, weeks until the resumption of sexual activity, and post-operative sexual function were recorded. The presence of glans hypoesthesia, penile deformation, penile nodule palpation, and self-satisfaction with body image were assessed., Results: Sixty-nine patients with a mean age of 42.30 ± 12.98 years and a median follow-up of 70 (20-134) months were identified. Sexual intercourse was recorded as a percentage. Penile deformation was the most common complication, appearing in 14.5% of patients, erectile dysfunction in 5.8%, penile nodules in 4.3%, and glans hypoesthesia in 2.9%. The median post-operative International Index of Erectile Function-5 was 24 (21.5-24). Self-satisfaction with body image had a median of 9 and was negatively associated with bilateral lesions and penile deformation., Discussion and Conclusion: Distal fractures could be linked to erectile dysfunction and glans hypoesthesia. Surgical correction of penile fractures shows positive functional and self-reported outcomes, and the potential andrological complications rarely necessitate specific treatment., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: Erectile dysfunction (ED), premature ejaculation (PE), and low libido (LL) are reported as the most common male sexual dysfunctions., Objective: To evaluate the prevalence of ED, PE, and LL and associations with lifestyle risk factors and comorbidities in middle-aged men., Materials and Methods: This study included a population-based random sample of 2500 50-year-old men who completed validated questionnaires, including the International Index of Erectile Function, the Erection Hardness Score, the Sexual Complaints Screener, and further questionnaires. Multiple logistic regression of outcomes ED, PE, and LL was used to model the association with explanatory factors., Results: The prevalence of at least one sexual dysfunction was 30%. 21%, 5.2%, and 7.2% of men had ED, PE, and LL, respectively. The risk of ED increased with PE (odds ratio [OR]: 1.94, 95% confidence interval [95%CI]: 1.22-3.08), LL (OR: 2.04, 95%CI: 1.26-3.29), higher waist circumference (OR: 2.23, 95%CI: 1.67-2.96), and lower urinary tract symptoms (LUTS) (OR: 1.88, 95%CI: 1.39-2.55), partnership was associated with a lower risk (OR: 0.57, 95%CI: 0.39-0.85). The risk of PE increased with ED (OR: 1.94, 95%CI: 1.23-3.07), partnership (OR:5.42, 95%CI: 1.30-22.60), depression (OR: 2.37, 95%CI: 1.09-5.14), and LUTS (OR: 2.42, 95%CI: 1.52-3.87), and decreased with physical activity (OR: 0.44, 95%CI: 0.21-0.93). The risk of LL increased with ED (OR: 2.09, 95%CI: 1.31-3.34) and poorer self-rated health (OR: 2.97, 95%CI: 1.54-5.71)., Discussion and Conclusions: Roughly one in three 50-year-old men experience some form of sexual dysfunction and risk factors identified in this study underline the multifactorial nature of ED, PE, and LL. Many risk factors are modifiable which underlines the role of patient education. Modifiable risk factors should be addressed in patient education and men should take active measures to remove the risk posed by these factors., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: The minimally invasive infrapubic approach (MIIA) for inflatable penile prosthesis (IPP) placement has shown favorable peri-operative safety and efficacy profile, but scarce data exist on long-term follow-up., Objectives: We investigated the safety and efficacy of IPP implantation via the MIIA after a minimum 5-year follow-up., Materials and Methods: We identified data of implanted patients prospectively included in our institutional database. Complications and functional outcomes were assessed by using validated tools. Specifically, quality of life and patient satisfaction were evaluated by the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Kaplan-Meier method was used to analyze IPP survival (defined as a working IPP)., Results: Overall, 67 patients implanted by MIIA with a median (IQR) age of 64 years (61-70) were included. The median (IQR) follow-up duration was 71 months (63-80). Fifteen (22%) patients experienced complications: minor (Clavien ≤2) events included changes in penile sensitivity (n = 1; 1.5%), orgasmic dysfunction (n = 1; 1.5%), pain (n = 5; 7%), urinary tract infection (n = 2; 3%), and chronic discomfort (n = 1; 1.5%); major (Clavien 3) complications were represented by mechanical failure (n = 3; 4.5%), IPP infection (n = 1; 1.5%), and cylinder protrusion (n = 1; 1.5%). The estimated IPP survival was 94% (95% CI, 91.4-96.6), 92.5% (95% CI, 89.7-95.3), and 92.5% (95% CI, 89.7-95.3) at 3, 5, and 7 years after implantation, respectively. In patients using the device at follow-up (n = 61; 91%), median (IQR) scores for QoLSPP domains demonstrated favorable functional outcomes and patient satisfaction: functional 21 (19-23), personal 16 (15-18), relational 14 (12-15), and social 12 (11-14)., Discussion and Conclusion: This study represents the longest follow-up using validated tools to assess the outcomes of IPP implantation via MIIA so far. IPP placement via MIIA confirms to be safe and to offer high satisfaction to both patients and partners at mid-term evaluation., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: The odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase-5 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis., Objectives: To assess the efficacy of bone morphogenetic protein 2 in stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic-induced erectile dysfunction., Materials and Methods: The induction of diabetes mellitus was performed by streptozotocin (50 mg/kg daily) administered intraperitoneally for 5 successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post-inductions, animals were allocated to one of five groups: a control group, a streptozotocin-induced diabetic mouse group receiving two intracavernous 20 μL phosphate-buffered saline injections, or one of three bone morphogenetic protein 2 groups administered two injections of bone morphogenetic protein 2 protein (1, 5, or 10 μg) diluted in 20 μL of phosphate-buffered saline within a 3-day interval between the first and second injections. The erectile functions were assessed 2 weeks after phosphate-buffered saline or bone morphogenetic protein 2 protein injections by recording the intracavernous pressure through cavernous nerve electrical stimulation. Angiogenic activities and nerve regenerating effects of bone morphogenetic protein 2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured mouse cavernous endothelial cells. Moreover, fibrosis-related factor protein expressions were evaluated by western blotting., Results: Erectile function recovery to 81% of the control value in diabetic mice was found with intracavernous bone morphogenetic protein 2 injection (5 μg/20 μL). Pericytes and endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with bone morphogenetic protein 2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of mouse cavernous endothelial cells. Bone morphogenetic protein 2 protein enhanced cell proliferation and reduced apoptosis in mouse cavernous endothelial cells and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high-glucose conditions. Furthermore, bone morphogenetic protein 2 suppressed fibrosis by reducing mouse cavernous endothelial cell fibronectin, collagen 1, and collagen 4 levels under high-glucose conditions., Conclusion: Bone morphogenetic protein 2 modulates neurovascular regeneration and inhibits fibrosis to revive the mouse erection function in diabetic conditions. Our findings propose that the bone morphogenetic protein 2 protein represents a novel and promising approach to treating diabetes-related erectile dysfunction., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: It has been shown that methylation in the promoter region of eNOS can downregulate eNOS expression resulting in the endothelial dysfunction. However, it is unclear whether low androgen levels and type 1 diabetes cause ED by methylating the promoter region of eNOS in the penile corpus cavernosum., Objective: To clarify the effects of type 1 diabetes and hypo-androgen status on the methylation level of the promoter region of the eNOS gene in penile cavernous tissue and their relationship with the erectile function., Methods: Fifty-eight eight-week-old male Sprague-Dawley rats were randomly divided into six groups (n = 6): sham operation group, castration group, castration+testosterone (cast+T) group, normoglycemia group, diabetic group, and diabetic+methyltransferase inhibitor (5-aza-dc, 1.5 mg/kg) group. The ICPmax/MAP, serum T, the concentration of nitric oxide (NO), the expression of DNMT1, DNMT3a, DNMT3b, and eNOS, and the methylation level of the eNOS promoter region in penile corpus cavernosum of rat were examined 4 weeks after surgery in the sham-operated group, the castration group, and the castration + testosterone replacement group. Those tests were examined after 6 weeks using of methylation inhibitors in the normoglycemic group, the diabetic group, and the diabetic + methylation inhibitor group., Results: ICPmax/MAP, DNMT1, DNMT3a, DNMT3b, eNOS, and NO levels were significantly lower in castrated rats than in sham and cast+T rats (P < 0.05). ICPmax/MAP, eNOS, and NO levels were lower, and DNMT1, DNMT3a, and DNMT3b expression levels were significantly increased in the diabetic group compared with the normoglycemic and diabetic+methyltransferase inhibitor groups (P < 0.05). There was no significant difference in the methylation level of the promoter region of eNOS in penile cavernous tissue of castrated rats compared with the sham group or the testosterone replacement group. The methylation level of the promoter region of eNOS in penile cavernous tissue was significantly higher in the diabetic group than in the normoglycemic group and diabetic+methyltransferase inhibitor group (P < 0.05)., Conclusion: Although low androgen status inhibited the level of methyltransferase in rat penile cavernous tissue, did not affect the level of methylation in the promoter region of eNOS. Hyperglycemia inhibits the NO level in the penile cavernous tissue and the erectile function of rats by upregulating the methyltransferase level in the penile cavernous tissue and the methylation level in the promoter region of eNOS. Methylation inhibitors can partly improve the erectile function in type 1 diabetic rats., (© 2023 American Society of Andrology and European Academy of Andrology.)

Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (β-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Erectile dysfunction is a condition with a high incidence among adult men. Lycopene has been shown to lower blood glucose and reduce weight in diabetic patients because of its antioxidant and anti-inflammatory properties. However, the association between lycopene and the incidence of erectile dysfunction is unclear., Objective: The aim of this study was to examine the dietary lycopene intake and its association with erectile dysfunction risk in the US population., Materials and Methods: We investigated the lycopene intake of adult participants with complete information on clinical variables from the National Health and Nutrition Examination Survey between 2001 and 2004. Dose-response curve analysis was applied to explore the association between lycopene intake and erectile dysfunction. Logistic regression models were used to adjust for confounders. Different ethnicities, body mass index level, hypertension status, diabetes status, and smoking status were analyzed as subgroups. Propensity score matching was employed to eliminate the effects of potential confounders to confirm the reliability of the results., Results: A total of 3265 participants with lycopene consumption data were included in our study, including 931 individuals with erectile dysfunction and 2334 without erectile dysfunction during National Health and Nutrition Examination Survey 2001-2004. We found more consumption of lycopene in the non-erectile dysfunction group than in the erectile dysfunction group. Dose-response curve analysis revealed a significant negative association between lycopene intake and erectile dysfunction prevalence. After adjusting for age, race, cigarette smoking, body mass index, annual family income, education, physical activity, hypertension, diabetes, depression, and testosterone level, we found that increased lycopene intake reduced the odds ratio of erectile dysfunction. Low lycopene intake was positively related to erectile dysfunction in almost all subgroups, especially in Mexican American, non-Hispanic white, body mass index <25, hypertension positive, diabetes mellitus negative, and smoke negative. Furthermore, the results were confirmed in the 1:1 matched group., Conclusion: Our national data suggest that lower dietary lycopene intake is positively associated with an increased risk of erectile dysfunction in US men., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: Diabetes mellitus-induced erectile dysfunction is difficult to treat. The oxidative stress created by diabetes mellitus is a major cause of injuries to the corpus cavernosum, thereby resulting in erectile dysfunction. Near-infrared laser has already been shown to be effective in treating multiple brain disorders because of its antioxidative stress effect., Objectives: To investigate whether a near-infrared laser improves the erectile function of diabetes mellitus-induced erectile dysfunction rats through its antioxidative stress effect., Materials and Methods: Knowing its advantage of reasonable deep tissue penetration and good photoactivation on mitochondria, a near-infrared laser with wavelength of 808 nm was used in the experiment. Since the internal and external corpus cavernosum were covered by different tissue layers, the laser penetration rates of the internal and external corpus cavernosum were measured separately. Different radiant exposure settings were applied: in the initial experiment, 40 male Sprague-Dawley rats were randomly assigned to five groups, normal controls, and streptozotocin-induced diabetes mellitus rats that 10 weeks later received various radiant exposures (J/cm 2 ) from the near-infrared laser (DM0J(DM+NIR 0 J/cm 2 ), DM1J, DM2J, and DM4J) in the subsequent 2 weeks. Erectile function was then assessed 1 week after near-infrared treatment. It was found that the initial radiant exposure setting was not optimal according to the Arndt-Schulz rule. We performed a second experiment using a different radiant exposure setting. Forty male rats were randomly divided into five groups (normal controls, DM0J, DM4J, DM8J, and DM16J), and the near-infrared laser was again applied according to the new setting, and erectile function was assessed as in the first experiment. Histologic, biochemical, and proteomic analyses were then conducted., Results: Recovery of erectile function of varying degrees was observed in the near-infrared treatment groups, and radiant exposure of 4 J/cm 2 achieved optimal results. The DM4J group showed improvement in mitochondrial function and morphology in diabetes mellitus rats, and it was found that oxidative stress levels were significantly reduced by near-infrared exposure. The tissue structure of the corpus cavernosum was also improved by near-infrared exposure. The proteomics analysis confirming multiple biologic processes were changed by diabetes mellitus and near-infrared., Discussion and Conclusion: Near-infrared laser activated mitochondria, improved oxidative stress, repaired the damage to penile corpus cavernosum tissue structures caused by diabetes mellitus, and improved erectile function in diabetes mellitus rats. These results thus raise the possibility that human patients with diabetes mellitus-induced erectile dysfunction may respond to near-infrared therapy in a manner that parallels the responses we observed in animal study., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: Sexual dysfunctions, particularly erectile dysfunction, are common in men living with HIV, whose organic and psychological components remain to be clarified. The aim of the study is to investigate the impact of risk factors of sexual dysfunctions, including organic, relational, and psychological determinants of erectile function, in men living with HIV younger than 50 years old., Methods: A cross-sectional, observational study was conducted in men living with HIV < 50 years. The questionnaire International Index of Erectile Function-15 was used to assess the prevalence and degree of erectile dysfunction. The structured interview of erectile dysfunction was used to explore the organic (Scale 1), relational (Scale 2), and psychological (Scale 3) components of erectile dysfunction. Total testosterone, estradiol, and dihydrotestosterone were measured by liquid chromatography-tandem-mass spectrometry; free testosterone was calculated by the Vermeulen equation., Results: A total of 313 consecutive men living with HIV were prospectively enrolled (median age 47.0 years; median HIV-infection duration 16.2 years). 187 patients (59.7%) had erectile dysfunction, with a higher prevalence of non-heterosexual (138 out of 187, 73.8%) than heterosexual patients (p = 0.003). Patients with erectile dysfunction showed a worse score of structured interview of erectile dysfunction scale 3 compared to patients without erectile dysfunction (p = 0.025); the International Index of Erectile Function-15 was inversely related to structured interview of erectile dysfunction scale 3 (p = 0.042). No difference was found for sex steroids (total testosterone, estradiol, free testosterone, and dihydrotestosterone) between men living with HIV with and without erectile dysfunction. In the multivariate analysis sexual orientation, and lack of stable relationships were major determinants for erectile dysfunction. Only 35 of 187 patients with erectile dysfunction (18.7%) reported the use of erectile dysfunction medications., Conclusions: Within the multidimensional network of erectile dysfunction in men living with HIV, the psychological component is predominant, highlighting the contribution of peculiar factors related to HIV distress (e.g., fear of virus transmission, stigma) rather than gonadal status and other classical risk factors. In contrast to the high prevalence, only a few patients reported the use of erectile dysfunction medications suggesting a general under-management of such issues., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Erectile dysfunction and atherosclerosis are common cardiovascular complications in diseases. Clinical associations between erectile dysfunction and atherosclerosis have been noticed, but the specific mechanisms are not illustrated adequately., Objectives: The aim of the study was to further mine associated pathological mechanisms and genetic alterations of atherosclerosis in diabetes mellitus-related erectile dysfunction., Materials and Methods: Significant atherosclerosis-related genes were identified from transcriptome data of diabetes mellitus-related erectile dysfunction and atherosclerosis-related gene sets from DisGeNET and GeneCard databases. Functional enrichment and immune infiltration analyses were performed to clarify the biological roles and pathways as well as immune responses of significant atherosclerosis-related gene sets. A protein-protein interaction network was constructed, and gene clusters were performed. Then, data of diabetic plaques and high-glucose cavernosum endothelial cells were analyzed for validation. And hub atherosclerosis-related gene sets were identified. Finally, expressed pattern of hub atherosclerosis-related gene sets were explored by single-cell profiling and immune analysis., Results: In total, 202 significant atherosclerosis-related gene sets including 100 upregulated and 102 downregulated genes were identified. These genes were related to endothelial cell migration, inflammatory response, regulation of oxidative stress, and immune response. In immune infiltration, immature dendritic cells and monocytes showed differential expression between the diabetes mellitus-related erectile dysfunction and control groups, A protein-protein interaction network containing 135 nodes was constructed. A hub atherosclerosis-related gene set signature consisting of HBEGF, LOX, NQO1, and VLDLR was obtained by multi-omics validation. In addition, Functional enrichment analysis revealed that hub atherosclerosis-related gene sets were involved in oxidoreductase activity and extracellular matrix organization., Discussion and Conclusion: We explored atherosclerosis-related genetic changes and signaling pathways in diabetes mellitus-related erectile dysfunction. HBEGF, LOX, NQO1, and VLDLR were identified as hub atherosclerosis-related gene sets. These may serve as potential biomarkers for the clinical management of atherosclerosis and preventing further cardiovascular risks in diabetes mellitus-related erectile dysfunction., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: The COVID-19 is an ongoing health problem with millions of cases and deaths worldwide. Although the virus is transmitted with droplets through the respiratory system, the involvement of different organs has been reported., Objectives: The pandemic caused urological procedures to be postponed when patient is infected with SARS-CoV-2. However, the reliability of 1 month postpone period and long-term complications of the virus, such as a possible erectile dysfunction (ED) is not clarified. We aimed to compare the corpus cavernosum of patients 1 and 7 months after COVID-19 infection with control patients who had not COVID-19 and search for SARS-CoV-2 in tissues using immunohistochemistry and electron microscopy., Materials and Methods: Three groups of subjects underwent penile prosthesis implantation and Nesbit procedure for Peyronie's disease 1 and 7 months after COVID-19 infection and control group without previous COVID-19 infection. We searched for SARS-CoV-2 in penile tissue using RT-PCR, electron microscopy and immunohistochemistry., Results: Electron microscopy and immunohistochemical staining showed SARS CoV-2 virus in the penile corpus cavernosum of patients 1 month after COVID-19 recovery. Immunohistochemical staining intensity correlated with the severity of previous infection. Transmission electron microscopy revealed intracellular virtual particles of about 80 nm with a typical morphology of prominent spikes and electron-dense dots of nucleocapsid in addition to vesicles filled with virus-like particles. Cells showed increased membrane trafficking. The 1 month after COVID-19 group showed an increased number of fibroblasts. The 7 months after COVID-19 group had similar morphology and immunoreactivity as control group., Discussion: This is the first study of late post-COVID examination of penis and the second study of early post-COVID examination of corpus cavernosum. For 1 month post-COVID patients, the aetiology of ED could be the viral infection that is also affecting corpora cavernosa. We hypothesize that viral infection affects the endocytic and exocytic pathways, hence the metabolic activity of cells that can be the reason of altered functions in some post-COVID patients., Conclusion: This study is important because it did not detect any virus residue in the tissue samples at the seventh month. In addition, we can say that the penile surgeries should be postponed more than 1 month after the COVID infection according to this study. But, there is a need for new studies with large series and high levels of evidence that can show how long the virus remains in the corpus cavernosum. Patients should be followed in this respect., (© 2022 American Society of Andrology and European Academy of Andrology.)

Purpose: The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM., Materials and Methods: This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence., Results: Overall, mean age was 62.5 ± 9.4 years (range: 20-75) and mean BMI was 28.4 ± 4.8 kg/m 2 (range: 18.4-46.6). The mean IIEF-5 score was 15.4 ± 5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i., Conclusions: This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: The management of diabetes mellitus-induced erectile dysfunction (DMED) is progressively becoming tricky due to the surge in the number of patients and the poor efficiency of phosphodiesterase type 5 inhibitors in DMED. Paeonol (Pae), as a traditional Chinese medicine, has been more and more widely used in the treatment of diabetic complications. However, whether Pae could be a potential therapeutic drug of DMED needs to be further evaluated., Objectives: To investigate the pharmacological effect and possible mechanism of Pae in the treatment of DMED., Methods: Intraperitoneal streptozotocin injection and an apomorphine test were used to construct the model of DMED. Seventeen DMED rats were divided into two groups: DMED group (n = 8) and DMED+Pae group (Pae; 100 mg/kg/d; oral administration; n = 9). In addition, there were still 10 normal age-matched male rats as control group. Four weeks later, the cavernous nerve electric stimulation was carried out to measure the erectile response. Moreover, the corpus cavernosum smooth muscle cells (CCSMCs) were primarily isolated and exposed to high glucose (HG) stimulation, Pae treatment and glycyrrhizin (GL; the selective inhibitor of HMGB1). After an incubation for 1 week, the CCSMCs were harvested for detection., Results: The impairment of erectile function was observed in DMED rats compared with control samples, accompanied by the upregulation of HMGB1/RAGE/NF-κB Pathway. The lower nitric oxide and cGMP level and the higher level of inflammation, fibrosis, and apoptosis were also observed in DMED rats. It showed contrast that Pae treatment could improve the erectile function, as well as histologic alteration and related molecular changes. In addition, Pae could downregulate the HMGB1/RAGE/NF-κB pathway to regulate the apoptosis and inflammation levels of CCSMCs in high-glucose conditions, which is similar to the results of GL treatment., Conclusion: Pae alleviated ED in DMED rats, likely by inhibiting HMGB1/RAGE/NF-κB Pathway, inflammatory, apoptosis, and fibrotic activity, and moderating endothelial dysfunction. Our study provide evidence for a potential new therapy for DMED., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: Peyronie's disease (PD) is a fibrosing disorder of the penis resulting in plaque formation and penile deformity that negatively affect sexual and psychosocial function of patients. A multifactorial etiology of PD is assumed with diabetes mellitus (DM) being a potential risk factor., Objectives: The aim of this narrative review was to investigate diabetes role in PD pathophysiology, diagnosis, and treatment., Materials and Methods: A non-systematic narrative review of original articles, meta-analyses, and randomized trials was conducted, including articles in the pre-clinical setting to support relevant findings., Results: Diabetes is one of the most common comorbidity observed in PD patients, with a prevalence of about 11% and a strong association with erectile dysfunction (ED). DM is associated with both a higher risk of developing PD and has also an impact on the outcomes of PD's treatments., Discussion: Evidence from literature underlines that metabolic alterations typical of DM are pivotal factors in the development of PD and resistance to its medical treatment., Conclusion: The role of DM in development of PD is still debated, while its role in PD development is not completely clear, there is a clear impact of DM on PD treatment outcomes., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED., Objectives: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED., Methods: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into three groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection., Results: We found that erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100., Conclusion: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4 is may be beneficial to the management of DMED., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: Erectile dysfunction (ED) is a very common complication in men with diabetes mellitus (DM). Low-intensity extracorporeal shockwave therapy (Li-ESWT) offers a promising nonsurgical treatment option for ED. A systematic scoping review investigating the outcomes of Li-ESWT in diabetic men with ED has not yet been performed., Objectives: To systematically review animal and clinical studies related to the use of Li-ESWT for treatment of DM-related ED., Data Sources: PubMed, Embase, The Cochrane Library, Scopus, and Web of Science were searched, unrestricted by dates or study design., Materials and Methods: We included qualitative studies, quantitative studies, primary research studies, meta-analyses, and research letters written in English. Full text reviewing was completed in all animal and human studies discussing Li-ESWT for the treatment of ED in subjects with DM. Data extracted included the journal citation, publication year, country of origin, study design, and a summary of the pertinent findings., Results: Our search yielded nine clinical studies and 10 animal studies. The results of the clinical studies suggest that Li-ESWT is a safe and effective treatment in men with well-controlled DM and moderate or better ED. However, the benefit is less durable in diabetic men than nondiabetic men. The results of the animal studies suggest that Li-ESWT can significantly improve erectile function in diabetic rat models with ED., Conclusions: The examined studies present encouraging results for the use of Li-ESWT to treat diabetic men with ED. Future studies, particularly robust randomized controlled trials, are necessary to confirm these findings and provide long-term follow-up., (© 2022 American Society of Andrology and European Academy of Andrology.)

Objective: It has been understood that COVID-19, which has become a global pandemic in a short time, is a disease affecting multiple organs and systems. Some of the organs and systems affected by the disease also play a role in the pathophysiology of erectile dysfunction (ED), which led us to consider the possible effects of the disease on the erectile function. In this study, we aimed to evaluate changes in the erectile functions of patients with COVID-19 among those that had previously diagnosed with mild and moderate ED in our urology outpatient clinic., Material and Methods: Eighty-one patients aged 18-65 years who were confirmed to have COVID-19 were included in the study. According to disease severity, these patients were divided into two groups as mild (non-hospitalized, n = 60) and moderate (hospitalized but did not require intensive care, n = 21). The patients' pre- and post-disease scores in the five-item International Index of Erectile Function (IIEF-5) ​​and hormone panel results were compared., Results: The changes in the IIEF-5 scores of the patients from the pre-disease to the post-disease period were statistically significant for both the mild and moderate groups (p < 0.05). When these changes were compared between the mild and moderate groups, the difference was not statistically significant (p = 0.156). There was also no statistically significant change in the testosterone, follicle-stimulating, luteinizing, and prolactin hormone levels before and after the disease., Conclusion: In this study, we determined that SARS-CoV-2 infection caused deterioration in existing ED in sexually active male individuals, regardless of the severity of the disease., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: The high prevalence of erectile dysfunction (ED) in patients with type 2 diabetes mellitus (DM2) is a challenging clinical problem. Researches on extracellular vesicles from urine-derived stem cells (USC-EVs) have shown that they have significant therapeutic effects in a variety of diseases by injection including ED. Hyaluronic acid (HA) is especially useful for delivering bioactive molecules. This study investigated the effects and related mechanisms of local administration of human USC-EVs combined with HA (USC-EVs-HA) on a rat model of DM2ED., Methods: UCSs were extracted from human urine samples and identified for preparation of the corresponding USC-EVs. The effects of high glucose and USC-EVs on human umbilical vein endothelial cells (HUVECs) were assessed in vitro using a CCK-8 assay to determine cell proliferation and pick the most appropriate concentration for subsequent experiments. Scratch and tube formation assays were performed to assess the function of HUVECs. Quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of genes such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and superoxide dismutase-2 (SOD2). HA, USC-EVs, and USC-EVs-HA were prepared at concentrations and then administered topically to DM2ED rats multiple times. Intracavernous pressure and mean arterial pressure were measured to assess erectile function in rats. Masson, Tunel, Immunohistochemistry, and Western blot analysis were performed to assess the fibrosis and endothelial function in corpus cavernosum, respectively., Results: Compared with the control group, the proliferation, migration ability, and tube-forming ability of HUVECs decreased in high glucose environment, while USC-EVs could optimize the function of HUVECs, reverse the expression of apoptotic genes, and enhance the antioxidant capacity. USC-EVs-HA showed improvement in ED compared to the HA and USC-EVs groups, and the 10-dose group was better than the 5-dose group. Histologically, the USC-EVs-HA group significantly improved apoptosis, angiogenesis, and smooth muscle regeneration in the corpus cavernosum compared to the HA group., Conclusions: The topical application of USC-EVs-HA in the treatment of DM2ED rats has been proved effective. The potential mechanism might to promote the proliferation of endothelial cells and smooth muscle in the corpus cavernosum, which leads to the remodeling of erectile function. And multiple dosing at intervals may make the effect more pronounced., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: In different animal models, a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) reduced inflammation, oxidative stress and fibrosis which were involved in the pathogenesis of erectile dysfunction (ED), but whether NaBu could improve ED in an experimental animal model of benign prostate hyperplasia (BPH) was not known., Objective: To investigate the preventive effect of NaBu on ED in a partial bladder outlet obstruction (PBOO) rat model., Materials and Methods: PBOO was induced by partial urethral obstruction. NaBu (20 mg/kg/day) was administered orally to rats for 6 weeks after creation of PBOO. In vivo erectile responses, in vitro relaxation and contraction responses in cavernosal tissue were measured. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to determine the gene and protein expression. Inflammation, fibrosis, and localization of proteins were evaluated using histological techniques. HDAC activity and tumor necrosis factor (TNF)-α levels were measured in penile tissues., Results: NaBu improved decreased intracavernosal pressure/mean arterial pressure, nitrergic and endothelium-dependent relaxation responses, and contractile responses to phenylephrine and electrical field stimulation in the PBOO group without affecting increased bladder weight. Increased endothelial nitric oxide synthase (eNOS), transforming growth factor (TGF)-β1, and nuclear factor kappa B (NF-κB) gene levels in PBOO group were ameliorated by NaBu treatment. The administration of NaBu to PBOO rats significantly increased neuronal NOS (nNOS) and decreased TGF-β1 protein expression. The nuclear/cytosolic ratio of NF-κB demonstrated a decrease in PBOO and all treatment groups compared to control. A significant increase in the nuclear-to-cytoplasmic ratio of nuclear factor erythroid 2-related factor 2 (Nrf2) after PBOO was reduced by the treatment. Both eNOS and inducible NOS (iNOS) protein expression, together with TNF-α levels did not differ in the penile tissue of all groups. In histological analysis, increased TGF-β1 protein expression and fibrosis, as well as decreased nNOS protein in PBOO, were reversed by the treatment. NaBu did not normalize moderate inflammation in obstructed rats. An increase in the HDAC activity in PBOO was significantly suppressed by NaBu., Discussion: Inhibition of the HDAC activity by NaBu in penile tissue could ameliorate fibrosis-associated changes induced by PBOO., Conclusion: NaBu promotes recovery of erectile function, and also significantly prevents penile fibrosis and normalizes TGF-β1 and nNOS protein expression in a rat model of PBOO. The HDAC pathway may present a promising target to prevent ED in patients with BPH., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: Erectile function is usually impaired after radiation therapy in prostate cancer patients. eNOS is a key enzyme in the process of erection. Mitochondria-associated membranes (MAMs) are closely contacted with the production and bioactivity of eNOS., Objective: To study the mechanism of icariin improves the erectile function of rats treated with prostate radiation by controling the expression of MAMs in penile corpus cavernosum., Methods: Twenty 8-week-old healthy male SD rats were randomized to four groups: control group, radiation therapy (RT) group, icariin (10 mg/kg/d gavage) group, and RT + icariin (10 mg/kg/d gavage) group (n = 5). In RT group and RT + icariin group, rats were irradiated with X-rays to the prostate region (total dose 37.5 gray; 7.5 gray/day for 5 days). The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), NO concentration and the level of IP 3 R1, PACS2, FACL4, nNOS, p-eNOS, and eNOS in rats' penile cavernous tissue was determined 9 weeks after radiation therapy., Results: Compared with the control group and the RT + icariin group, the ICPmax/MAP of the RT group was remarkably reduced (p < 0.05). The levels of p-eNOS/eNOS, nNOS and the concentration of NO in the penile cavernous tissue of the penis in the RT group were remarkably decreased compared to the control group and the RT + icariin group (p < 0.05). The levels of IP 3 R1, PACS2, and FACL4 in penile cavernous tissue of the RT group were significantly higher than those in the control group and the RT + icariin group (p < 0.05)., Conclusions: After prostate X-ray radiotherapy in rats, the formation of MAMs may be increased by increased expression of IP 3 R1, PACS2, and FACL4 in penile cavernous tissue, resulting in impaired erectile function. Icariin might increase p-eNOS/eNOS and improve erectile function in rats after prostate radiotherapy by inhibiting the expression of IP 3 R1, PACS2, and FACL4., (© 2022 American Society of Andrology and European Academy of Andrology.)

Introduction: Sexual function is often impaired in patients with chronic illnesses. Several patients with chronic gastrointestinal and liver disorders have been shown to suffer from sexual dysfunction, and celiac disease is a highly prevalent gastroenterological disorder., Aim: The aim of this study was to investigate the sexual function incidence and the risk factors for sexual dysfunction in both male and female celiac disease patients., Methods: Two hundred and eighty-four patients (170 females, 114 males) participated in this cross-sectional observational study in an anonymous manner. Female sexual function was assessed through the Female Sexual Function Index questionnaire. Male sexual function was assessed through the International Index of Erectile Function-5 questionnaire. Clinical-demographic variables were recorded. We investigated differences in the patient-reported outcomes among the different subgroups and whether there were clinical-demographic predictors of sexual dysfunction in our setting., Main Outcome Measures: Prevalence and assessment of sexual dysfunction in celiac disease patients., Results: In the female group, 85 subjects (50%) had a total score compatible with sexual dysfunction: 43 (61.42%) showed low desire, 79 (46.47%) showed arousal disorder, 66 (38.82%) lubrication disorder, and 84 (49.41%) inability of obtaining an orgasm. Also, a large proportion of our female patients, 161 (94.70%), showed sexual discomfort during intercourse. In the male group, 79 patients (62.2%) showed scores compatible with normal erectile function, eight (7.01%) had mild erectile dysfunction, 24 (21.05%) mild to moderate erectile dysfunction, and three (2.63%) presented severe erectile dysfunction. Altered body mass index was significantly associated with sexual dysfunction both in male and female patients. Early age at diagnosis was a significant predictor of sexual dysfunction in male celiac disease patients., Conclusions: A significant proportion of celiac disease patients present sexual dysfunction. Early age at diagnosis and high body mass index seem to predict sexual dysfunction in this clinical setting. Assessment of sexual function should be part of the initial evaluation of celiac disease patients in order to establish a prompt diagnosis and early treatment., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Neurogenic erectile dysfunction (NED) caused by cavernous nerve (CN) injury is a typical complication after pelvic surgery, which lacks efficient treatments. Acetyl-L-carnitine (ALCAR) has been proven to promote nerve repair., Objectives: To investigate the effect and potential mechanism of ALCAR in the treatment of NED., Materials and Methods: Thirty-two rats were randomly divided into bilateral CN injury (BCNI) group, BCNI + lower-dose ALCAR (50 mg/kg/day) group, BCNI + higher-dose (100 mg/kg/day) group, and sham-operated group. Erectile function was assessed 14 days after daily intraperitoneal injection of ALCAR or placebo. The penile tissues were gathered for subsequent histological and molecular biological analysis. Rat Schwann cell (SC) line S16 was used to verify the mechanism of ALCAR in vitro., Results: We found that the erectile function of the rats in the BCNI group was severely impaired, which was improved considerably in both BCNI+ALCAR-LD and BCNI+ALCAR-HD groups. Also, we observed decreased smooth muscle and increased collagen content in the corpus cavernosum in the BCNI group. The expressions of fibrosis markers transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and Smad 2/3 were significantly up-regulated in the BCNI group. The above changes were alleviated after the administration of lower and higher-dose ALCAR. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate pathway (cGMP) was promoted and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was inhibited in the corpus cavernosum of BCNI rats after ALCAR treatment, accompanied by increased neuronal nitric oxide synthase (nNOS) and down-regulated tyrosine hydroxylase (TH). In vitro, ALCAR promoted the migration and proliferation of SC and increased the expression of 22-kD peripheral myelin protein and nerve growth factor (NGF). Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site., Discussion and Conclusion: ALCAR could promote nerve repair and regeneration, inhibit penile fibrosis, and improve penile erection by promoting the proliferation and migration of SC and the secretion of NGF. Our study confirms that ALCAR may be a potential treatment strategy for NED., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: The recognition of the erectile dysfunction pathogenesis is essential to identify the appropriate erectile dysfunction management. As vascular erectile dysfunction could be a manifestation of a systemic arterial damage, the watershed in the erectile dysfunction diagnostic framework is the discrimination between psychological erectile dysfunction and vascular erectile dysfunction. However, reliable tools to directly diagnose psychological erectile dysfunction are currently lacking., Objective: To identify which parameters could predict psychological erectile dysfunction. Moreover, we suggest a new intracavernosal injection procedure to optimize the erectile dysfunction diagnostic workup., Materials and Methods: A retrospective, real-world analysis was carried out including all men who underwent intracavernosal injection procedure at the Modena Andrology Unit from 2018 to 2021. A first intracavernosal injection procedure with 5 µg of prostaglandin E-1 (PGE-1) was performed. In the absence of a full drug-induced erection (immediate or delayed), an echo-color Doppler penile evaluation after administration of PGE-1 10 µg was conducted, measuring intracavernosal blood flows, to document a possible vascular etiology. Hormonal evaluations were performed., Results: Out of 179 enrolled patients, 70.4% showed psychological erectile dysfunction, 21.7% vascular erectile dysfunction, and 7.8% hormonal genesis. Multinomial logistic regression analysis identified absence of cardiovascular disease (p = 0.017), presence of spontaneous morning erections (p = 0.018), and normal penile erections with masturbation (p = 0.035) as predictors of psychological erectile dysfunction. Clinically, normal intracavernosal injection test response was detected in 86 patients and abnormal response in 93 subjects. Among the latter, 54 patients experienced a delayed response. The combination of intracavernosal injection test with late penile erections evaluation was able to diagnose psychological erectile dysfunction (sensitivity 97%, specificity 100%), avoiding unnecessary retesting., Discussion: We propose a two-step intracavernosal injection procedure that allows to recognize psychological erectile dysfunction with a high sensitivity/specificity, saving costs and time, and limiting adverse events. Moreover, the presence of spontaneous morning erections and valid penile erections after masturbation could guide the diagnostic workup, indirectly identifying those patients deserving of a deeper evaluation of vascular health., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury., Objectives: In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide-hydroxamic-7 acid (SAHA), for 2 weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways., Materials and Methods: Seventy 12-week-old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10 mg/kg JNKi, CNCI treated with daily oral administration of 25.0 mg/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase-3 activity assay, and western blot analysis., Results: CNCI alone resulted in significantly reduced intracavernosal pressure/mean arterial pressure (MAP) and area under the curve/MAP, decreased smooth muscle (SM)/collagen ratio and SM content, higher caspase-3 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)-β, fibronectin, and c-Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile-responses and SM/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM/collagen ratio compared to the single agent treatment. SM content, caspase-3 activity, and c-Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF-β., Discussion and Conclusions: The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC/TGF-β and JNK pathways., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: In the literature, there is not sufficient data on factors affecting the development of complications in patients with penile fracture after early surgical intervention., Objectives: To investigate the predictors of long-term complications in patients who underwent immediate surgical repair for penile fracture., Materials/methods: This clinical study included a total of 31 cases of penile fracture in which surgical treatment was performed within the first 24 h and penile fracture was confirmed during the operation. The patients with and without late complications were compared in terms of parameters such as age, tear size of the tunica albuginea of the penis, bilateral involvement of the corpora cavernosa involvement, urethral injuries, and duration from penile fracture to surgery., Results: The median age of the patients was 42 years (interquartile range: 34-51 years). The median time from penile fracture to surgery was 13 h (8-18 h). The median tear size was 16 mm (11-21 mm). Late complications were seen in 13 (41.9%) patients in the post-operative period. Erectile dysfunction developed in five (16.1%) patients in the post-operative period. There was no statistically significant relationship between age, tear size, time from penile fracture to surgery, and bilateral corporeal involvement in terms of erectile dysfunction development. Painful erections, penile deviations, urethral strictures, tunical scars, and re-fracture were the other late complications. There was a significant relationship between the development of any complication and time from penile fracture to surgery (p = 0.028) and tear size (p = 0.031). In the receiver operating characteristic analysis of complication development, the cut-off value for the time from penile fracture to surgery was 13.5 h., Discussion and Conclusion: We found that the longer time interval between penile fracture and surgery worsened the patient outcomes. In addition, tear size was determined to be a predictor for long-term complications. In our opinion, early treatment of penile fracture can prevent severe complications in these cases., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: It has been reported that the risk of erectile dysfunction (ED) is significantly higher in patients with obstructive sleep apnea (OSA), compared with patients without OSA. However, there is limited evidence on whether surgical treatments in patients with OSA could decrease ED risk., Objectives: To assess the impact of surgical treatments for OSA on the risk of ED by analysis of claims data from the Taiwan National Health Insurance Research Database between 1997 and 2012., Material and Methods: We identified 20,675 male adults with newly diagnosed OSA during the study period; 16,040 patients ever received surgical treatments (treated cohort) and 4635 patients never received surgical treatments (untreated cohort). According to 3:1 propensity score matching, we analyzed 8337 patients in the treated cohort and 2779 controls in the untreated cohort. We estimated the incidence rates (IRs) and hazard ratios (HRs) of incident ED in both cohorts through the end of 2012., Results: In a total study follow-up of 64,916 person-years, 396 (3.6%) patients developed impotence. The IRs of ED for the treated and untreated cohorts, respectively, were 55.8 (95% confidence interval [CI], 55.6-55.9) and 76.1 (95% CI, 76.0-76.3) per 1000 person-years. Multivariate Cox proportional hazard analysis showed that surgical treatments for OSA patients were associated with a lower risk for ED (adjusted HR, 0.79; 95% CI, 0.64-0.98). Multivariate stratified analysis further verified that significant risk reduction of ED was present in OSA patients without hypertension, diabetes, hyperlipidemia, hyperuricemia, obesity, chronic kidney disease, and chronic liver disease., Conclusions: We found that OSA patients who received surgical treatments were associated with a lower risk for developing ED by 21%., (© 2021 American Society of Andrology and European Academy of Andrology.)

Diabetes mellitus (DM), a chronic metabolic disease characterised by elevated levels of blood glucose, is among the most common chronic diseases. The incidence and prevalence of DM have been increasing over the years. The complications of DM represent a serious health problem. The long-term complications include macroangiopathy, microangiopathy and neuropathy as well as sexual dysfunction (SD) in both men and women. Erectile dysfunction (ED) has been considered the most important SD in men with DM. The prevalence of ED is approximately 3.5-fold higher in men with DM than in those without DM. Common risk factors for the development of DM and its complications include sedentary lifestyle, overweight/obesity and increased caloric consumption. Although lifestyle changes may help improve sexual function, specific treatments are often needed. This study aims to review the definition and prevalence of ED in DM, the impact of DM complications and DM treatment on ED and, finally, the current and emerging therapies for ED in patients with DM., (© 2021 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Whether and to what extent an association exists between hyperuricemia and erectile dysfunction (ED) has not yet been fully determined., Objective: To define pooled prevalence estimates and correlates of erectile dysfunction in men with hyperuricemic disorders., Materials and Methods: A thorough search of Medline, Scopus, and Cochrane Library databases was performed. Data were combined using random-effects models and the between-study heterogeneity was assessed by Cochrane's Q and I 2 tests. A funnel plot was used to assess publication bias., Results: Overall, 8 studies included gave information about 85,406 hyperuricemic men, of whom 5023 complained of erectile dysfunction, resulting in a pooled erectile dysfunction prevalence estimate of 33% (95% Confidence Interval: 13-52%; I² = 99.9%). The funnel plot suggested the presence of a publication bias. At the meta-regression analyses, among the available covariates that could affect estimates, only type 2 diabetes mellitus was significantly associated with a higher prevalence of erectile dysfunction (β = 0.08; 95% Confidence Interval: 0.01, 0.15, p = 0.025). At the sub-group analysis, the pooled erectile dysfunction prevalence decreased to 4% (95% Confidence Interval: 0%-8%) when only the largest studies with the lowest prevalence of type 2 diabetes mellitus were included and increased up to 50% (95% Confidence Interval: 17%-84%) when the analysis was restricted to studies enrolling smaller series with higher prevalence of type 2 diabetes mellitus., Conclusions: A not negligible proportion of men with hyperuricemia can complain of erectile dysfunction. While a pathogenetic contribution of circulating uric acid in endothelial dysfunction cannot be ruled out, the evidence of a stronger association between hyperuricemia and erectile dysfunction in type 2 diabetes mellitus points to hyperuricemia as a marker of systemic dysmetabolic disorders adversely affecting erectile function., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: Icariside II (ICA II), an active flavonoid monomer, has been proven to restore post-prostatectomy erectile dysfunction in rats; however, the high cost of extraction from natural plants limits the application of ICA II., Objective: To investigate the therapeutic effect and possible mechanism of action of YS-10, a new flavonoid compound, which was designed and synthesized based on the structure of ICA II in a rat model in of cavernous nerve injury., Materials/methods: Eight of 32 adult male Sprague-Dawley rats were selected as the normal control (NC) group and received vehicle treatment. The remaining rats were subjected to bilateral cavernous nerve injury (BCNI) and randomized into three groups: BCNI group, BCNI + ICA II group (2.5 mg/kg/day), and BCNI + YS-10 group (2.5 mg/kg/day). The total procedure lasted for 21 days, followed by a washout period of 3 days. All animals were evaluated for erectile function, and tissues were harvested for histopathological analyses., Results: It was observed that in YS-10 group, the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP) and the area under the ICP/MAP curve were effectively enhanced. The maximum ICP/MAP increased by 30% in the YS-10 group (0.86 ± 0.085) compared with the BCNI group (0.66 ± 0.058), which is close to 82% of the NC group (1.05 ± 0.033). Histopathological changes demonstrated significant reduction of smooth muscle atrophy, collagen deposition, and endothelial and neural dysfunction after YS-10 treatment, which have no statistical differences compared with ICA II group. Additionally, high-protein expression levels of β-Catenin and cyclin D1 were observed in the treatment groups., Conclusion: YS-10, a novel synthesized flavonoid compound, could effectively improve erectile dysfunction in rats after BCNI by alleviating pathological impairments; this effect may associate with the upregulation of β-Catenin and cyclin D1 in Wnt signaling pathway., (© 2021 American Society of Andrology and European Academy of Andrology.)

This study aimed to explore the possibility of miR-423-5p modified adipose-derived stem cell (ADSCs) therapy on streptozotocin (STZ)-induced diabetes mellitus erectile dysfunction (DMED) rats. MiR-423-5p was knocked down in ADSCs. ADSCs, NC-miR-ADSCs and miR-ADSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). Normal and high glucose media were supplemented. The supernatant and HUVECs were collected for assessment of eNOS and VEGFa expression, cell proliferation, and apoptosis. HUVECs co-cultured with ADSCs or miR-ADSCs exhibited higher eNOS and VEGFa protein expression levels compared to DM groups. MiR-ADSCs enhanced HUVEC proliferation compared to the ADSCs and NC-miR-ADSCs. Lower apoptotic rates were observed when HUVECs were co-cultured with miR-ADSCs, compared to ADSCs and NC-miR-ADSCs. Fifteen male Sprague-Dawley (SD) rats aged 12 weeks were induced to develop diabetes mellitus by intraperitoneal injection with STZ, and five healthy SD rats were used as normal controls. Eight weeks after developing diabetes, the rats received ADSCs and miR-ADSCs via injection into the corpora cavernosa, whereas normal controls and DM controls were injected with saline. Erectile function and histological assessment of penile tissues were performed 8 weeks after injection. The ICP/MAP indicated that erectile function was impaired in the DM rats compared with the normal group. Injection of ADSCs and miR-ADSCs improved erectile function significantly and was associated with the overexpression of eNOS and VEGFa. MiR-423-5p knockdown in ADSCs ameliorated high glucose-mediated damage to HUVECs and improved erectile function in DM rats by inducing eNOS and VEGFa overexpression, indicating that miR-423-5p may be a potential target in the treatment of DMED., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Erectile dysfunction (ED), as the hallmark of endothelial dysfunction, could be a short- or long-term complication of COVID-19. Additionally, being ED a clinical marker and predictor of non-communicable chronic diseases, particularly cardiovascular, subjects with ED could potentially have a higher risk of contracting COVID-19., Objectives: To investigate the prevalence of ED among subjects with a reported diagnosis of COVID-19 and to measure the association of COVID-19 and ED., Materials and Methods: We reviewed data from the Sex@COVID online survey (performed between April 7 and May 4, 2020, in Italy) to retrieve a sample of Italian male sexually active subjects with reported SARS-CoV-2 infection. A matching sample of COVID-19-negative male sexually active subjects was also retrieved using propensity score matching in a 3:1 ratio. The survey used different standardized psychometric tools to measure effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of Italian subjects., Results: One hundred subjects were included in the analysis (25 COVID-positive; 75 COVID-negative). The prevalence of ED, measured with the Sexual Health Inventory for Men, was significantly higher in the COVID+ group (28% vs. 9.33%; p = 0.027). Logistic regression models confirmed a significant effect of COVID-19 on the development of ED, independently of other variables affecting erectile function, such as psychological status, age, and BMI [OR 5.66, 95% CI: 1.50-24.01]. Likewise, subjects with ED were more likely to have COVID-19, once corrected for age and BMI [OR 5.27, 95% CI: 1.49-20.09]., Discussion and Conclusion: On top of well-described pathophysiological mechanisms, there is preliminary evidence in a real-life population of ED as a risk factor of developing COVID-19 and possibly occurring as a consequence of COVID-19. Universal vaccination against the COVID-19 and the personal protective equipment could possibly have the added benefit of preventing sexual dysfunctions., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: There is increasing evidence that periodontitis may affect male sexual health (MSH) (erectile function, production of sex hormones, and semen quality). However, a limited number of clinical studies demonstrate the association between MSH and periodontitis., Objectives: The aim of this study was to explore the relationship between periodontitis and MSF., Materials and Methods: A comprehensive systematic review of the published literature in MEDLINE, PubMed, Scopus, Cochrane, EMBASE, and Web of Science databases from the earliest available online indexing year until October 2020 was performed, in accordance with the PRISMA guidelines. Keywords related to periodontitis were combined with words describing MSH., Result: A total of 19 studies were included and discussed in the systematic review. The number of study participants ranged from 53 to 197,136 individuals, aged between 18 and 95 years (mean age, 41.2 years). Six studies did not report the age of the participants. Out of nine studies, eight found a significant association between erectile dysfunction (ED) and periodontitis. Only three studies evaluated the association between sex hormone levels and periodontitis, and two of these studies showed that patients with periodontitis are expected to exhibit higher levels of testosterone. Finally, out of five studies, two demonstrated a significant association between semen quality and periodontitis., Discussion: The findings in this review were limited by the quality and the few available studies. Results from the observational studies might have been affected by recall bias and confounded by cofactors., Conclusion: The results of this systematic review revealed a significant association between periodontitis and ED, although the responsible mechanisms remain unclear. The potential associations between sex hormone levels, semen quality, and periodontitis are yet to be demonstrated. In order to improve patient management, dentists and physicians need to be aware of the association between male sexual health problems and periodontitis., (© 2020 American Society of Andrology and European Academy of Andrology.)

Objective: This study was performed to explore the effects of metabolic memory on diabetic erectile dysfunction (ED), especially the severity and response to treatment., Methods: Through medical records and follow-up by telephone, 67 patients meeting the criteria with a clinical diagnosis of ED and a diabetic history of more than 5 years were enrolled for erectile function analysis. They were divided into a glycemic control group, a glycemic non-control group and a metabolic memory group according to glycemic levels and treatments for diabetes in the past 5 years, and they were treated with phosphodiesterase type 5 (PDE5) inhibitors for 4 weeks. Erectile function and efficacy were assessed by the International Index for Erectile Function (IIEF), the Erection Hardness Score (EHS), and the Sexual Encounter Profile (SEP)., Results: The patients in the glycemic control group performed better in erectile function than those in the other groups. The patients in the glycemic control group received a significantly greater score on both the EHS and the five domains of the IIEF than did the patients in the glycemic non-control group and the metabolic memory group (all P < .001). There were also statistically significant differences favoring the glycemic control group (P < .05) in SEP2 and SEP3 success rates. However, there were no significant differences between the metabolic memory group and the glycemic non-control group in these erectile function assessments (P > .05). Significant negative correlations were seen between HbA1c levels at the time of consultation and the scores on the IIEF-EF and the EHS (Pearson r-values of -0.338 with P = .005 and -0.273 with P = .025, respectively). HbA1c levels at the first diagnosis of diabetes mellitus (DM) were also significantly negatively correlated with scores on the IIEF-EF and the EHS with greater Pearson correlation coefficients (Pearson r-values of -0.478 with P < .001 and -0.392 with P = .001, respectively). Significant improvements on each of the erectile function assessments were observed among diabetic patients with ED, but no significant difference in efficacy was observed between each group., Conclusions: The phenomenon of metabolic memory did have a significant influence on ED in men with diabetes, associated with the severity of ED but not the response to medical treatment. Early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control., Patients Summary: In this report, we looked at the erectile functions of 67 patients with a clinical diagnosis of ED and a diabetic history of more than 5 years. We found that early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. We further found that the effects were associated with the severity of ED but not the response to medical treatment in men with diabetes., (© 2020 American Society of Andrology and European Academy of Andrology.)

Background: Radical prostatectomy induces some degree of cavernous nerve injury (CNI) and causes denervation-induced pathologic changes in cavernous vasculature, regardless of the advances in surgical techniques and robotic procedures. The precursor for nerve growth factor (proNGF) is known to be involved in neuronal cell apoptosis and microvascular dysfunction through its receptor p75 NTR ., Objectives: To determine the expression of proNGF/p75 NTR and the efficacy of proNGF neutralizing antibody (anti-proNGF-Ab) in a mouse model of ED induced by CNI., Materials and Methods: Age-matched 12-week-old C57BL/6 mice were distributed into three groups: sham group and bilateral CNI group treated with intracavernous injections of PBS (20 μL) or of anti-proNGF-Ab (20 µg in 20 μL of PBS) on days -3 and 0. Two weeks after treatment, erectile function was measured by electrical stimulation of cavernous nerve. Penis tissues from a separate group of animals were harvested for further analysis. We also determined the efficacy of anti-proNGF-Ab on neural preservation in major pelvic ganglion (MPG) ex vivo., Results: We observed increased penile expression of proNGF and p75 NTR after CNI. Intracavernous administration of anti-proNGF-Ab increased nNOS and neurofilament expression probably by enhancing the production of neurotrophic factors, such as neurotrophin-3, NGF, and brain-derived neurotrophic factor. Anti-proNGF-Ab preserved the integrity of cavernous sinusoids, such as pericytes, endothelial cells, and endothelial cell-to-cell junctions, possibly by controlling angiogenic factors (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor) and induced endogenous eNOS phosphorylation in CNI mice. And finally, treatment with anti-proNGF-Ab rescued erectile function in CNI mice. Anti-proNGF-Ab also enhanced neurite sprouting from MPG exposed to lipopolysaccharide., Discussion and Conclusion: The preservation of damaged cavernous neurovasculature through inhibition of the proNGF/p75 NTR pathway may be a novel strategy to treat radical prostatectomy-induced erectile dysfunction., (© 2020 American Society of Andrology and European Academy of Andrology.)

To explore how alterations in the phosphodiesterase type 5 (PDE5) signalling pathway and oxidative stress correlate with changes in the expression of relaxation and contraction molecules and erectile dysfunction (ED) in the corpus cavernosum smooth muscle (CCSM) of spontaneously hypertensive rats (SHR). In this study, SHR and Wistar-Kyoto (WKY) rats were used. Erectile function was determined by apomorphine test and electrical stimulation (ES) of cavernous nerve. Masson's trichrome staining and confocal microscopy were performed. Nitric oxide synthase (NOS), PDE5, phosphorylated-PDE5 and α1-adrenergic receptor (α1AR) were determined by RT-PCR and Western blotting while oxidative stress in CC was determined by colorimetric analysis. SHR exhibited obvious ED. CC of SHR showed less SM but more collagen fibres. The expression of NOS isoforms in SHR was significantly decreased while all α1AR isoforms were increased. In addition, PDE5 and phosphorylated-PDE5 were down-regulated and its activity attenuated in the hypertensive rats. Meanwhile, the SHR group suffered oxidative stress, which may be modulated by endoplasmic reticulum stress and NADPH oxidase up-regulation. Dysregulation of NOS and α1AR, histological changes and oxidative stress in CC may be associated with the pathophysiology of hypertension-induced ED. In addition, PDE5 down-regulation may lead to the decreased efficacy of PDE5 inhibitors in some hypertensive ED patients and treatment of oxidative stress could be used as a new therapeutic target for this type of ED., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: For a large proportion of patients with spinal cord injury, sexuality and reproduction are important issues. However, sparse data exist regarding available treatment options for this patient population., Objectives: We sought to review performance and safety rates of all currently available treatment options for erectile dysfunction in spinal cord injury men., Materials and Methods: A systematic literature review without time restrictions was performed using PubMed/EMBASE database for English-, Italian-, German-, and Spanish-language articles. Articles' selection was performed according to the PRISMA guidelines. Relevant papers on erectile dysfunction in spinal cord injury patients were included in the final analyses., Results and Discussion: Overall, 47 studies were eligible for inclusion in this review. Of these, most evidence dealt with phosphodiesterase 5-inhibitors and intracavernous drug injection. Both treatment options are associated with high levels of performance and with patients/partners' satisfaction; side effects are acceptable. Overall, penile prostheses and vacuum erection devices are in general less approved by spinal cord injury patients and are correlated with increased rates of complications in comparison with phosphodiesterase 5-inhibitors and intracavernous drug injection. Sacral neuromodulation, transcutaneous electrical nerve stimulation, and intraurethral suppositories have been poorly studied, but preliminary studies did not show convincing results., Conclusion: The best treatment options for erectile dysfunction in spinal cord injury patients emerged to be phosphodiesterase 5-inhibitors and intracavernous drug injection. The choice of erectile dysfunction treatment should be based on several aspects, including residual erectile function, spinal cord injury location, and patients' comorbidities. Future studies assessing the applicability of less well-studied treatments, as well as evaluating innovative options, are needed in this specific population., (© 2020 American Society of Andrology and European Academy of Andrology.)

Background: Severe peripheral angiopathy in patients with diabetes is a major contributing factor for low response rate to phosphodiesterase-5 inhibitors., Objectives: To examine whether and how Dickkopf3 (DKK3), a secreted modulator of the Wnt pathway that known to be involved in endothelial cell repair and vascular progenitor cell migration, restores erectile function in diabetic mice., Methods: Eight-week-old C57BL/6 mice received intraperitoneal injections of streptozotocin (50 mg/kg for 5 days). Eight weeks after the diabetes was induced, the efficacy of DKK3 was determined by three independent experiments: experiment 1 (DKK3 peptide [5 μg in 20 μL PBS]); experiment 2 (DKK3 plasmid DNA with electroporation [10, 40, or 100 μg in 20 μL PBS, respectively]); and experiment 3 (DKK3 adenovirus [1 × 10 7 , 1 × 10 8 , 1 × 10 9 virus particles per 20 μL, respectively]). Erectile function was measured by electrical stimulation of the cavernous nerve one week (for peptide) or two weeks (for genes) after treatment. The angiogenic activity of DKK3 was determined in diabetic penis in vivo and in primary cultured mouse cavernous endothelial cells (MCECs) in vitro., Results: The cavernous expression of DKK3 protein was significantly lower in the diabetic mice than in controls. DKK3 peptide or adenovirus significantly improved erectile function in diabetic mice (70% of the control values). DKK3 adenovirus profoundly restored cavernous endothelial cell and pericyte contents and increased endothelial junction proteins in diabetic mice in vivo. DKK3 peptide induced upregulation of angiogenic factors (angiopoietin-1, vascular endothelial growth factor, and basic fibroblast growth factor) and accelerated tube formation in MCECs cultivated under the high-glucose condition in vitro., Conclusion: DKK3 restored cavernous vascular integrity and improved erectile function in diabetic mice. Therapeutic cavernous angiogenesis by the use of DKK3 will be a promising therapeutic strategy to treat diabetic erectile dysfunction., (© 2020 American Society of Andrology and European Academy of Andrology.)

Background & Aims: Phosphodiesterase-5 inhibitors (PDE-5-I) are used for treatment of erectile dysfunction (ED), which is common in patients with cirrhosis. They may improve portal hypertension (PH), but contradictory data on efficacy and side-effects have been reported. Non-selective beta blockers (NSBB) reduce portal pressure, but might aggravate ED. Thus, we evaluated the combination of PDE-5-I with NSBB and its impact on PH and ED in experimental cirrhosis., Methods: ED was assessed in cirrhotic patients (n = 86) using standardized questionnaire. Experimental cirrhosis was induced by bile-duct-ligation or carbon-tetrachloride intoxication in rats. Corpus cavernosum pressure - a surrogate of ED -, as well as systemic and portal haemodynamics, were measured in vivo and in situ after acute administration of udenafil alone or in combination with propranolol. mRNA and protein levels of PDE-5 signalling were analysed using PCR and western Blot., Results: ED in humans was related to severity of liver disease and to NSBB treatment. PDE-5 was mainly expressed in hepatic stellate cells and upregulated in human and experimental cirrhosis. Propranolol reduced corpus cavernosum pressure in cirrhotic rats and it was restored by udenafil. Even though udenafil treatment improved PH, it led to a reduction of mean arterial pressure. The combination of udenafil and propranolol reduced portal pressure and hepatic resistance without systemic side-effects., Conclusions: ED is common with advanced cirrhosis and concomitant NSBB treatment. The combination of PDE-5-I and NSBB improves ED and PH in experimental cirrhosis., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: The prevalence of erectile dysfunction (ED) increases progressively with age, but its potential pathophysiology has not been fully demonstrated. Hence, this article was aimed to identify the functional and morphological characterization of the corpus cavernosum in aged rats and to evaluate the effects of the Angiotensin II type 1 receptor antagonist losartan on age-related ED (AED)., Material and Methods: A total of 40 young and aged Sprague Dawley rats were randomly divided into four groups (n = 10 per group): young rats as normal controls (YNC) group; aged rats with normal erectile function (ANC) group; aged rats with ED (AED) group; and a losartan-treated AED (AED + Losartan) group. The treated group received losartan (30 mg/kg) once daily oral gavage for 4 weeks. Erectile function was measured by the ratio of peak intracavernous pressure (ICP)/mean arterial pressure (MAP), and relevant tissues were harvested for transmission electron microscopy, Immunohistochemistry, Masson's trichrome staining, TUNEL, caspase-3 activity assay and Western blot., Results: The AED group exhibited decreases in erectile response and increases in the role of apoptosis, fibrosis as well as oxidative stress, compared with the control groups. After daily administration of losartan for four weeks, it could slightly restore erectile function and significantly attenuate corporal apoptosis, fibrosis, and oxidative stress of AED. However, the result was still not comparable with that of the control groups. Moreover, the expression levels of p-Bad/Bad and p-AKT/AKT were significantly lower, whereas the expression levels of Bax/Bcl-2, Nrf2/Keap-1, Fibronectin, HO-1, and caspase-3 activity were significantly higher in the AED groups and while losartan could significantly attenuate these changes of AED, it was still not comparable with that of the control groups., Conclusions: Our results indicated that administration of losartan not merely restored erectile function, but also significantly prevented corporal apoptosis and oxidative stress in AED by suppressing the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways., (© 2020 American Society of Andrology and European Academy of Andrology.)

Background: Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated., Objectives: The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats., Materials and Methods: A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus-induced erectile dysfunction (streptozotocin-injected), and diabetes mellitus-induced erectile dysfunction + simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus-induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy-related genes and the AMPK-SKP2-CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy., Results: Autophagy-related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus-induced erectile dysfunction rats for 8 weeks, demonstrating that erectile function was improved for 80.5% (P < .05) of rats. Corpus cavernosum fibrosis was alleviated (P < .05), and autophagy was further enhanced (P < .05); these results might be partially caused by AMPK-SKP2-CARM1 pathway activation (P < .05)., Discussion and Conclusion: Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats., (© 2020 American Society of Andrology and European Academy of Andrology.)

Aims: The aim of this study was to evaluate the contribution of small and large fibre neuropathy to erectile dysfunction (ED) in men with type 2 diabetes (T2D)., Methods: Measures of small and large fibre neuropathy were evaluated in 49 participants with T2D and 20 age-matched controls., Results: ED was present in 59% of participants with T2D. There was no difference in age, duration of diabetes, blood pressure, lipid profile, vibration perception threshold (V) (14.3 ± 7.8 vs 11.2 ± 6.6, P = .429), peroneal (41.4 ± 8.2 vs 44.8 ± 4.4, P = .10) and sural (45.4 ± 5.6 vs 47.1 ± 5.8) nerve conduction velocities (m/s), cold (25.1 ± 3.8 vs 26.2 ± 2.9, P = .815) and warm (43.2 ± 4.0 vs 41.0 ± 3.8) perception thresholds (°C), and deep breathing heart rate variability (18 ± 8 vs 18 ± 8) between participants with and without ED. However, intraepidermal nerve fibre density (no./mm 2 ) (4.6 ± 2.8 vs 13.7 ± 2.7, P < .001), corneal nerve fibre density (no./mm 2 ) (23.5 ± 6.8 vs 31.3 ± 8.2, P < .001), corneal nerve fibre branch density (no./mm 2 ) (55.4 ± 35.3 vs 97.7 ± 46.4, P = .004), corneal nerve fibre length (mm/mm 2 ) (17.6 ± 6.8 vs 27.3 ± 6.8, P < .001), and sural (7.7 ± 6.1 vs 14.6 ± 6.7, P = .003) and peroneal (2.5 ± 2.0 vs 4.7 ± 2.0, P = .003) nerve amplitudes were significantly lower in participants with ED compared with those without ED., Conclusion: ED affects almost 2/3 of men with T2D and is associated with small nerve fibre damage but preserved nerve conduction and cardiac autonomic function. Corneal confocal microscopy may serve as a useful non-invasive imaging method to identify small fibre damage in patients with T2D and ED., (© 2019 John Wiley & Sons Ltd.)

Background: Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM) that severely affects the patients' quality of life. However, the effectiveness of oral phosphodiesterase type 5 inhibitors in these patients is poor. Sphingosine-1-phosphate (S1P) and S1P receptor 2 (S1PR2) are important factors regulating the Rho-kinase pathway, and understanding these factors may provide ideas for new therapeutic strategies for ED., Objectives: To investigate whether the S1PR2 receptor antagonist JTE-013 could improve DM-induced ED (DMED) in rats and to explore the potential mechanisms., Materials and Methods: We used 50 male Sprague Dawley rats (8 weeks old) for this experiment. Type Ⅰ DM was induced in forty-two rats via streptozotocin administration; the rest of the rats served as controls. Eight weeks after DM induction, rats with ED were selected via an apomorphine test. Eight of them were injected intraperitoneally with JTE-013 each day for 4 weeks. The rest were fed under the same conditions for 4 weeks. Erectile function was measured by cavernous nerve electrostimulation. The expression levels of related signaling pathways were evaluated using Western blotting, real-time PCR, and immunohistochemistry., Results: Erectile function was significantly impaired in the DMED group compared with the control group and was partially improved in the DMED + JTE-013 group. The expression of S1PR2 and the activity of the RhoA/ROCK/phospho-myosin phosphatase target subunit 1 (p-MYPT1) pathway proteins were higher in the DMED group than in the other two groups, and JTE-013 treatment significantly reduced the expression/activity of these proteins. Furthermore, the DMED group showed severe corporal fibrosis, a higher apoptotic index and increased activity in the TGF-β1/LIMK2/Cofilin pathway compared with the control group. JTE-013 supplementation significantly ameliorated these pathological changes., Discussion and Conclusion: JTE-013 supplementation partially improved erectile function in rats with DMED, likely by inhibiting smooth muscle contraction, corporal fibrosis, and apoptosis., (© 2019 American Society of Andrology and European Academy of Andrology.)

Background: Concerns exist about the effect of delaying treatment for prostate cancer (PCa) regarding both oncological and functional outcomes after radical prostatectomy (RP)., Objective: To assess the impact of time from diagnosis to RP on post-operative erectile function (EF) outcomes., Materials and Methods: We analyzed data for 827 patients treated with RP at a single center from 2002 to 2017. The International Index of Erectile Function-EF (IIEF-EF) was compiled by every patient (EF recovery equal to IIEF-EF ≥ 22). Time from diagnosis to treatment was defined as the interval between biopsy and RP. Cox regression analysis was used to test the impact of time to surgery on the probability of EF recovery. Kaplan-Meier analysis compared the cumulative incidence of EF recovery according to time from diagnosis to surgery. The impact of time to RP on EF was tested also in a sub-cohort of patients eligible for active surveillance (AS)., Results: Overall, low-, intermediate-, and high-risk PCa was found in 306 (37%), 422 (51%), and 99 (12%) patients. Of them, 148 (17.9%) would have been eligible for AS. A total of 152 (18%) and 22 (2.7%) patients were treated after 6 and 12 months from diagnosis. The overall probability of EF recovery was 32% (95% CI: 29-36) at 24 months. Cox regression analysis showed that time from biopsy to surgery was not associated with a different chance of EF recovery (HR: 1.01; 95% CI: 0.97-1.05; p = 0.7). At Kaplan-Meier analysis, the cumulative incidence of EF recovery did not differ between patients treated within 6 months, from 6 to 12 months and after 12 months from diagnosis. Similar findings were obtained for patients eligible for AS., Discussion: Patients may be reassured regarding their chance of post-operative EF recovery in the case of a delayed surgical treatment., Conclusions: Delaying surgery after PCa diagnosis does not affect post-operative EF recovery outcomes regardless of oncological risk., (© 2019 American Society of Andrology and European Academy of Andrology.)