Oral l‐Citrulline Supplementation Improves Erectile Function in Rats with Acute Arteriogenic Erectile Dysfunction

IntroductionOral l‐citrulline supplementation increases serum l‐arginine levels more efficiently than l‐arginine itself and increases nitric oxide (NO) production.AimTo investigate whether oral l‐citrulline supplementation improves erectile function in rats with acute arteriogenic erectile dysfunction (ED).MethodsWe divided 8‐week‐old male Wistar‐ST rats into 3 groups: sham‐operated rats (control group), arteriogenic ED rats who underwent ligation of both internal iliac arteries (ligation group), and arteriogenic ED rats receiving oral 2% l‐citrulline water supplementation (citrulline group). Citrulline water was given to arteriogenic ED rats for 3 weeks from 1 week after surgery. Erectile function was evaluated by maximum intracavernous pressure/mean arterial pressure (ICP/MAP) ratios via cavernous nerve stimulation at 4 weeks after surgery. Then, the penises were resected, stained with Masson's trichrome, and observed microscopically. Serum nitrogen oxides (NOx) levels were measured by high‐performance liquid chromatography. Bonferroni's multiple t‐test was used for statistical analysis.Main Outcome MeasuresThe main outcome measures were changes in ICP/MAP, smooth muscle (SM)/collagen ratios, and NOx levels following l‐citrulline supplementation.ResultsThe ICP/MAP ratio in the ligation group was significantly lower than that in the control group (P < 0.05), denoting ED. The ICP/MAP ratio of the citrulline group was significantly higher than that of the ligation group (P < 0.05), indicating ED amelioration. Levels of NOx in the ligation group were significantly lower than in the control group (P < 0.05), while those in the citrulline group were significantly higher than in the ligation group (P < 0.05). SM/collagen ratios in the ligation group were significantly lower than in the control group (P < 0.05), while ratios in the citrulline group were significantly higher than those in the ligation group (P < 0.05).ConclusionsOral l‐citrulline supplementation improved ICP/MAP and SM/collagen ratios and increased NOx. Therefore, oral l‐citrulline supplementation might be a useful novel therapy for acute arteriogenic ED. Shiota A, Hotta Y, Kataoka T, Morita M, Maeda Y, and Kimura K. Oral l‐citrulline supplementation improves erectile function in rats with acute arteriogenic erectile dysfunction. J Sex Med 2013;10:2423–2429.     

Involvement of Rho‐Kinase/LIM Kinase/Cofilin Signaling Pathway in Corporal Fibrosis after Cavernous Nerve Injury in Male Rats

IntroductionThe molecular mechanism of corporal fibrosis leading to erectile dysfunction (ED) following cavernous nerve (CN) injury is poorly understood.AimTo determine whether the LIMK2/cofilin pathway, the downstream effectors of ROCK1, was involved in ED and corporal fibrosis following bilateral CN injury in male rats.MethodsForty‐eight 10‐week‐old male Sprague‐Dawley rats were equally divided into three groups: sham surgery (S); bilateral CN crush injury (I); and bilateral CN resection (R). Within each groups, two subgroups were analyzed at 1 and 4 weeks postoperatively.Main Outcome MeasuresElectrostimulation was performed to assess erectile function by the ratio of maximal intracavernous pressure to mean arterial pressure (ICP/MAP) and areas under the ICP curve to MAP (AUC/MAP). Penile tissue was processed for Masson's trichrome staining, Western blot (ROCK1, total LIMK2, phospho‐LIMK2, total cofilin, phospho‐cofilin), immunohistochemistry (alpha‐SM actin [α‐SMA]), and double immunofluorescent staining (ROCK1, phospho‐LIMK2, vimentin).ResultsAt each time point, both I and R groups showed a significantly lower percent of ICP/MAP and AUC, and decreased SM cell/collagen ratio and expression of α‐SMA than S group. Densitometry revealed a significantly higher expression of ROCK1 in I and R groups compared with S group at all time points. The LIMK2 phosphorylation in I and R groups significantly increased at 1 week, but not at 4 weeks. The cofilin phosphorylation in R group significantly increased to that in S group starting at 1 week, while that in I group was increased significantly at 4 weeks. The double immunofluorescent staining noted that coexpression of vimentin with ROCK1 or phospho‐LIMK2 in I and R groups was significantly increased mainly in the subtunical area at 1 week but not at 4 weeks.ConclusionsThe ROCK1/LIMK2/cofilin pathway may be involved in ED related to corporal fibrosis, and it appears to be functional particularly in the early period after CN injury. Song SH, Park K, Kim SW, Paick J‐S, and Cho MC. Involvement of Rho‐kinase/LIM kinase/cofilin signaling pathway in corporal fibrosis after cavernous nerve injury in male rats. J Sex Med 2015;12:1522–1532.     

Comprehensive Analysis of lncRNA Expression Pattern and lncRNA–miRNA–mRNA Network in a Rat Model With Cavernous Nerve Injury Erectile Dysfunction

BackgroundLong noncoding RNAs (lncRNAs) are differentially expressed in erectile dysfunction (ED) associated with aging and diabetes mellitus; however, the lncRNA expression profile in cavernous nerve (CN) injury–related ED (CNI-ED) is unknown.AimTo investigate the dysregulated lncRNAs, microRNAs (miRNAs), and mRNA expression in CNI-ED and construct a potential lncRNA–miRNA–mRNA network.Methods22 male Sprague–Dawley (SD) rats were divided into bilateral CN crush (BCNC) and Sham groups. Using second-generation high-throughput sequencing technology, we analyzed the expression profiles of lncRNA, miRNA, and mRNA of the 2 groups. 17 differentially expressed lncRNAs were selected and further validated by quantitative real-time polymerase chain reaction (RT-qPCR). The lncRNA–miRNA–mRNA network, Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using Cytoscape.OutcomesIntra-cavernosal pressure, mean arterial pressure, smooth muscle content, and the expression of miRNA, mRNA, and lncRNA were measured.ResultsThe BCNC group showed decreased intra-cavernosal/mean arterial pressure as well as decreased smooth muscle/collagen ratios compared with the Sham group. The RNA sequencing results revealed dysregulated expressions of 65 lncRNA, 14 miRNA, and 750 mRNA in the BCNC group based on the following criteria: fold change >2 and P < .05. Among the 17 lncRNAs further selected based on mean count number >4 in both groups, 3 lncRNAs (TCONS_00028173, TCONS_00049985, and TCONS_00058429) were further validated for differential expression by RT-qPCR. GO analysis suggests that these 3 lncRNAs could regulate various processes such as myotube differentiation and muscle cell differentiation. Furthermore, the KEGG pathway analysis showed that the mRNAs in the competing endogenous RNA (ceRNA) network are involved in pathways, including axon guidance and vascular endothelial growth factor signaling pathway.Clinical TranslationOur findings may provide new information on molecular pathophysiology of CNI-ED and suggest further research to find a more effective therapy for CNI-ED.Strengths & LimitationsThis study is the first to identify the lncRNA expression pattern and propose a ceRNA network in a rat model with cavernous nerve injury–related erectile dysfunction. However, analogous studies are needed to confirm these findings in humans. In addition, we constructed the network by only confirming the lncRNA.ConclusionOur study reveals differential expression profiles of lncRNAs, miRNAs, and mRNAs between the BCNC and Sham groups and suggests that these differentially expressed lncRNAs may play critical roles in CNI-ED by regulating apoptosis and fibrosis in the corpus cavernosum via targeting mRNAs or miRNAs.Cong R, Wang Y, Wang Y. Comprehensive Analysis of lncRNA Expression Pattern and lncRNA–miRNA–mRNA Network in a Rat Model With Cavernous Nerve Injury Erectile Dysfunction. J Sex Med 2020;17:1603–1617.     

The Neuroprotective Effect of Platelet‐rich Plasma on Erectile Function in Bilateral Cavernous Nerve Injury Rat Model

IntroductionNeurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet‐rich plasma (PRP) on the nerve‐injured site has shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated.AimTo assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury.MethodsMale Sprague‐Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology.Main Outcome MeasuresIntracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase‐3 and transforming growth factor‐β1 (TGF‐β1) in the corpus cavernosum.ResultsFour weeks after surgery, in the vehicle‐only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle‐only group (P < 0.05). Histologically, the PRP‐treated group had a significant preservation of myelinated axons of CNs compared with the vehicle‐only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF‐β1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle‐only group (P < 0.05).ConclusionsPRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model. Wu C‐C, Wu Y‐N, Ho H‐O, Chen K‐C, Sheu M‐T, and Chiang H‐S. The neuroprotective effect of platelet‐rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med 2012;9:2838–2848.     

Erectile Dysfunction Precedes Coronary Artery Endothelial Dysfunction in Rats Fed a High‐Fat,High‐Sucrose,Western Pattern Diet

IntroductionIt is suggested that erectile dysfunction (ED) may be an early risk factor for cardiovascular disease.AimThe goal of this study was to determine whether development of ED precedes the onset of coronary artery endothelial dysfunction in response to a Western diet (WD), thereby establishing whether the WD differentially impacts the endothelium in a time‐dependent manner. Additionally, a goal was to determine if diet‐induced ED is reversible with intracavernosal sepiapterin treatment.MethodsMale Sprague‐Dawley rats were fed a WD for 4, 8, or 12 weeks, or a control diet for 8 weeks. Erectile function was evaluated by measuring the mean arterial pressure (MAP) and intracavernosal pressure (ICP) in response to electrical field stimulation of the cavernosal nerve near the major pelvic ganglion, in the absence and presence of sepiapterin. Coronary artery endothelial function was evaluated ex vivo with cumulative doses of acetylcholine (ACh) applied to segments of the left anterior descending coronary artery preconstricted with serotonin.Main Outcome MeasuresErectile function was assessed as the ICP response to electrical field stimulation (EFS), normalized to MAP. Coronary artery endothelial function was assessed as the effective concentration producing 50% of a maximal response (EC₅₀) of the ACh response.ResultsThe ICP/MAP response to EFS was significantly attenuated following both 8 and 12 weeks of the WD compared with the control diet (P < 0.05). Sepiapterin treatment augmented the ICP/MAP response in all WD groups (P < 0.05). The coronary artery EC₅₀ of the ACh response was not different from control following 4 or 8 weeks but was significantly elevated following 12 weeks of the WD (P < 0.01).ConclusionsThese data suggest that erectile function is reduced prior to coronary artery endothelial function in response to the WD. Improvement of erectile function with sepiapterin in WD rats indicates that nitric oxide synthase uncoupling is a key mechanism in diet‐induced ED. La Favor JD, Anderson EJ, Hickner RC, and Wingard CJ. Erectile dysfunction precedes coronary artery endothelial dysfunction in rats fed a high‐fat, high‐sucrose, Western pattern diet. J Sex Med 2013;10:694–703.     

Factors Influencing Distress Toward Erectile Dysfunction and Attitude Toward Erectile Dysfunction Drugs Among Middle‐Aged and Elderly Chinese Women and Men in Hong Kong

AimThis study aims to explain distress toward erectile dysfunction (ED), attitude toward ED drugs, and experiences with ED drug use in terms of sexual attitudes, relationship satisfaction, and sociodemographic factors among the middle‐aged and elderly Chinese population. Studies show that a significant number of middle‐aged and elderly men in Asia suffer from ED. However, people's attitudes toward ED drugs are not positive. Few studies have sought to reveal the influencing factors of this negative attitude.MethodsNine hundred forty‐six Hong Kong women and men aged 36–80 with stable partners were administered a structured questionnaire through face‐to‐face street‐intercept survey. Self‐reporting on single‐item questions using a five‐point Likert scale was adopted for most of the variables, including attitude toward sex, relationship satisfaction, distress toward ED, and attitude toward ED drugs. Perceived importance of sex in an intimate relationship and attitude toward sex were assessed through three items. Respondents were asked to report whether they had taken ED drugs or bought ED drugs for their partners.ResultsWhile perceived importance of sex in an intimate relationship and distress toward ED both contributed to the estimation of attitudes toward ED drugs for both genders, relationship satisfaction was only associated with men's attitude, while women's attitude was related to two other factors: relationship status and income level. Both age and attitude toward ED drugs influenced experiences with ED drug use for women and men. Men's experience with ED drug use was further related to the perceived importance of sex and to men's self‐esteem and relationship status.ConclusionResults of this study could help identify people who are disturbed by ED but reluctant to seek treatment. Clinicians and public health policy makers could make use of the findings to encourage proper understanding of ED. Liong CCM. Factors influencing distress toward erectile dysfunction and attitude toward erectile dysfunction drugs among middle‐aged and elderly Chinese women and men in Hong Kong. J Sex Med 2013;10:782–790.     

TNF‐α, Erectile Dysfunction,and NADPH Oxidase‐Mediated ROS Generation in Corpus Cavernosum in High‐Fat Diet/Streptozotocin‐Induced Diabetic Rats

IntroductionPatients with diabetes‐associated erectile dysfunction (ED) are characterized by an increase in circulating tumor necrosis factor‐alpha (TNF‐α). However, no study has indicated whether and how TNF‐α plays a role in the pathogenesis of ED associated with diabetes.AimWe examined the effects and potential mechanism of infliximab (INF), a chimeric monoclonal antibody to TNF‐α, on reactive oxygen species (ROS) generation in corpus cavernosum and ED in diabetic rats.MethodsFour groups of male rats were used: age‐matched normal controls; diabetic rats induced by a high‐fat diet (HFD) combined with a single streptozotocin (STZ) injection (35 mg/kg body weight, intraperitoneal [i.p.]); nondiabetic rats receiving INF (5 mg/kg body weight/week, i.p.), and diabetic rats receiving INF. Erectile function was assessed with electrical stimulation of the cavernous nerve after 8 weeks. The blood and penile tissues were harvested for plasma biochemical determinations, serum TNF‐α measurement, penile ROS detection, and molecular assays of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, endothelial nitric oxide synthase (eNOS), phospho‐eNOS, and neural nitric oxide synthase (nNOS) in the penis.Main Outcome MeasuresThe effect of INF on HFD/STZ‐induced diabetic ED and NADPH oxidase‐mediated ROS generation was studied in diabetic corpus cavernosum.ResultsUntreated diabetic rats displayed significantly decreased erectile parameters, and increased plasma TNF‐α levels, penile ROS production, p47^phox and gp91^phox expression compared with nondiabetic controls. INF neutralized TNF‐α and significantly reduced ED in diabetic rats, in which marked decreases in p47^phox and gp91^phox expression and ROS generation in corpus cavernosum were noted. The ratio of phospho‐eNOS to eNOS and expression of nNOS in the penis were significantly increased in INF‐treated vs. untreated diabetic rats.ConclusionsIncreased TNF‐α expression associated with diabetes contributes to ED by promoting NAPDH oxidase‐mediated ROS generation in corpus cavernosum. INF protects against diabetic ED by neutralizing TNF‐α. Long T, Liu G, Wang Y, Chen Y, Zhang Y, and Qin D. TNF‐α, erectile dysfunction, and NADPH oxidase‐mediated ROS generation in corpus cavernosum in high‐fat diet/streptozotocin‐induced diabetic rats. J Sex Med 2012;9:1818–1831.     

Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro

Background

Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking.

Penile Duplex Ultrasonography in Men with Peyronie's Disease: Is it Veno‐Occlusive Dysfunction or Poor Cavernosal Arterial Inflow that Contributes to Erectile Dysfunction?

IntroductionAt least 20% of men with Peyronie's disease (PD) suffer from erectile dysfunction (ED). The fundamental mechanism is thought to arise from the progression of penile fibrosis, which was initially limited to the PD plaque within the tunica albuginea. However, recent studies have highlighted the possibility of fibrosis of the cavernosal vessel media wall leading to impairment of arterial inflow.AimTo evaluate the penile duplex ultrasonographic findings in PD of impotent men and to determine whether early features of PD might predict clinical progression.Main Outcome MeasuresPatient demographic, comorbidities, International Index of Erectile Function‐5 scores, surgical intervention, and physical findings were documented. Penile curvature, plaque size, and peak systolic velocity (PSV) and end‐diastolic velocity (EDV) on color duplex ultrasonography (CDU) were recorded.MethodsWe performed a retrospective review of all men presenting with penile curvature and length loss who underwent penile CDU between January 2001 and January 2010.ResultsA total of 1,120 men underwent penile CDU during the 10‐year period. Complete information was obtained in 810 men; 250 men complained of decreased penile rigidity, while 150 men were unable to sustain erection. Comorbidities were similar between men with PD with and without ED. Tunical thickening (65%) was the most common CDU feature, and mean cumulative calcifications was 24.2 mm² (1–360 mm², standard deviation 76). The PSV and EDV on the right cavernosal artery were 14.2 cm/second and 3.5 cm/second, while the left cavernosal artery measurements were 15.1 cm/second and 3.2 cm/second. Multivariate logistic regression model showed strong correlation between plaque size and development of ED. Both veno‐occlusive dysfunction and impaired cavernosal arterial inflow were associated with ED.ConclusionsVeno‐occlusive dysfunction and impaired cavernosal arterial inflow contributed to the development of ED, and larger plaque size is a strong predictor of surgical intervention. Chung E, De Young L, and Brock GB. Penile duplex ultrasonography in men with Peyronie's disease: Is it veno‐occlusive dysfunction or poor cavernosal arterial inflow that contributes to erectile dysfunction? J Sex Med **;**:**–**.     

Surgical Management of Penile Fracture and Long‐Term Outcome on Erectile Function and Voiding

IntroductionPenile fracture is an emergency in urology. Surgical management is recommended, but objective data of postoperative long‐term effects, especially regarding voiding and erectile function, vary.AimTo assess long‐term results of patients undergoing surgical therapy for penile fracture.MethodsPatients presenting with suspicion of penile fracture were included in this study. Diagnosis of penile fracture was made by clinical assessment and surgery performed thereafter. The defect of the tunica albuginea was closed by absorbable suture. In case of concomitant urethral lesion, the defect was repaired simultaneously. Voiding and erectile function were evaluated at long‐term follow‐up by mail. Patients' status before penile fracture was assessed retroactively.Main Outcome MeasuresErectile function was assessed by the International Index of Erectile Function questionnaire and voiding function by the International Prostate Symptom Score questionnaire.ResultsN = 34 patients were included. Penile fracture was suspected in 28/34 (82.4%) patients. Twenty‐six of the 28 (92.9%) patients underwent surgery. Only less than half of confirmed fracture patients presented with the classical triad of an audible crack, detumescense, and hematoma. Fourteen of the 26 (53.8%) patients after surgery were available for follow‐up. Mean follow‐up was 45.6 months (range: 3.6–128.4). In 13/14 (92.9%) patients, penile fracture was confirmed by surgery. At follow‐up, 7/13 (53.8%) patients had impaired erectile function, with 3/13 (23.1%) patients needing medical treatment. Four of the 13 (30.8%) patients showed deterioration of voiding including occurrence of urethral fistula.ConclusionsPenile fracture is an emergency for which surgery should be offered. Clinical suspicion of fracture should be high even with hematoma alone. Concomitant urethral injury is common, particularly with bilateral corporal rupture and/or initial hematuria. Preoperative counseling should include discussion of long‐term erectile and voiding dysfunction, penile deformity, and urethral fistula both with and without surgery. Close patient follow‐up is required.     

PDEI‐5 for Erectile Dysfunction: A Potential Role in Seizure Susceptibility

IntroductionThere is a high prevalence of erectile dysfunction (ED) in men with epilepsy; however, few studies have been conducted concerning the treatment of ED in this neurological group.AimThe main purpose of this review is to highlight the influence of phosphodiesterase type 5 inhibitor (PDEI‐5) for ED on seizure susceptibility.MethodsAll available online articles with information pertaining to PDEI‐5 and seizure susceptibility were included in this review.Main Outcome MeasuresThe main outcome assessed demonstrated the intriguing role of PDEI‐5 and its metabolites on seizure susceptibility.ResultsCase reports in men without epilepsy described seizure occurrence and electrophysiological changes following sildenafil, tadalafil, or vardenafil treatment. Consistent with these findings, preclinical studies suggested a proconvulsant effect of PDEI‐5 on models of seizure induction.ConclusionsEvidence suggests an influence of PDEI‐5 on seizure susceptibility in humans. In addition, preclinical studies have demonstrated the role of nitric oxide metabolites in the facilitation of paroxysmal phenomenon. Although there are many causes of seizures, medical professionals should be aware of the possible influence of PDEI‐5 on seizure susceptibility. Further investigation by physicians and scientists is required to improve our understanding of this important topic. Matos G, Scorza FA, Cavalheiro EA, Tufik S, and Andersen ML. PDEI‐5 for erectile dysfunction: A potential role in seizure susceptibility. J Sex Med 2012;9:2111–2121.     

Rapamycin Supplementation May Ameliorate Erectile Function in Rats With Streptozotocin–Induced Type 1 Diabetes by Inducing Autophagy and Inhibiting Apoptosis,Endothelial Dysfunction,and Corporal Fibrosis

Introduction

Erectile dysfunction (ED), which is common in patients with diabetes mellitus (DM), seriously affects quality of life. Previous studies on the treatment of DM–induced ED (DMED) involve autophagy, but the specific effect and mechanism of treatment are not yet clear.

Association Between Viral Hepatitis and Erectile Dysfunction: A Population‐Based Case‐Control Analysis

IntroductionChronic liver diseases are often accompanied by hypogonadism, testicular atrophy, and a reduction in libido, all of which are factors that may contribute to the development of erectile dysfunction (ED). However, large‐scaled studies investigating the association between ED and viral hepatitis are still sparse.AimThis study aimed to estimate the association between ED and a prior diagnosis of viral hepatitis using a population‐based dataset with a case‐control design in Taiwan.MethodsWe identified 6,429 patients with ED as cases and randomly selected 32,145 subjects as controls. We used conditional logistic regression to compute the odds ratio (OR) for having previously received a diagnosis of viral hepatitis between cases and controls.Main Outcome MeasureThe prevalence and odds of having been previously diagnosed with hepatitis B, hepatitis C, a coinfection with hepatitis B and C, and viral hepatitis of other etiology were calculated between cases and controls.ResultsOf the 38,574 sampled subjects, 3,930 (10.2%) had viral hepatitis before the index date; viral hepatitis was found in 900 (14.0%) cases and in 3,030 (9.4%) controls. After adjusting for monthly income, geographic location, hypertension, diabetes, hyperlipidemia, hepatic steatosis, coronary heart disease, obesity, and alcohol abuse/alcohol dependence syndrome, cases were found to be more likely to have prior viral hepatitis than controls (OR = 1.51, 95% confidence interval [CI] = 1.39–1.64, P < 0.001). A much higher proportion of coinfection with viral hepatitis B and C was additionally found among cases (OR = 1.84, 95% CI = 1.72–1.97) than controls.ConclusionsWe conclude that ED was associated with prior viral hepatitis, especially with a coinfection of hepatitis B and C, after adjusting for potential confounders. Chung S‐D, Keller JJ, Liang YC, and Lin HC. Association between viral hepatitis and erectile dysfunction: A population‐based case‐control analysis. J Sex Med 2012;9:1295–1302.     

Superoxide Anion Production by NADPH Oxidase Plays a Major Role in Erectile Dysfunction in Middle‐Aged Rats: Prevention by Antioxidant Therapy

Introduction.Prevalence of erectile dysfunction (ED) increases progressively with aging, but the ED pathophysiology at its early stages is still poorly investigated.Aim.This study aimed to evaluate the functional and molecular alterations of erectile function at middle age, focusing on the contribution of oxidative stress in erectile tissue for the ED.Methods.Young (3.5‐month) and middle‐aged (10‐month) male Wistar rats were used. Rat corpus cavernosum (RCC) was dissected free and mounted in 10‐mL organ baths containing Krebs solution. Intracavernosal pressure (ICP) in anesthetized rats was evaluated.Main Outcome Measures.Concentration–response curves to endothelium‐dependent and endothelium‐independent agents, as well as to electrical field stimulation (EFS), were obtained in RCC strips. Measurement of cyclic guanosine monophosphate (cGMP) and expressions of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS), gp91^phox and superoxide dismutase‐1 (SOD‐1) expressions in RCC were evaluated.Results.ICP was significantly reduced in middle‐aged compared with young rats. RCC relaxations to acetylcholine (10^?8 to 10^?2 M), sodium nitroprusside (10^?8 to 10^?2 M), sildenafil (10^?9 to 10^?5 M), BAY 41‐2272 (10^?9 to 10^?5 M), and EFS (4–32 Hz) were decreased in middle‐aged group, which were nearly normalized by apocynin (NADPH oxidase inhibitor; 10^?4 M) or SOD (75 U/mL). Prolonged treatment with apocynin (85 mg/rat/day, 4 weeks) also restored the impaired relaxations in middle‐aged rats. Relaxations to 8‐bromoguanosine 3′,5′‐cyclic monophosphate sodium salt (8‐Br‐cGMP; 10^?8 to 3 × 10^?4 M) remained unchanged between groups. Basal and stimulated cGMP production were lower in middle‐aged group, an effect fully restored by apocynin and SOD. Protein expression of nNOS and phosphorylated eNOS (p‐eNOS) (Ser‐1177) reduced, whereas gp^91phox mRNA expression increased in RCC from middle‐aged rats.Conclusions.ED in middle‐aged rats is associated with decreased NO bioavailability in erectile tissue due to upregulation of NADPH oxidase subunit gp91^phox and downregulation of nNOS/p‐eNOS. Antioxidant therapies may be a good pharmacological approach to prevent ED at its early stages.     

Interplay Between Premature Ejaculation and Erectile Dysfunction: A Systematic Review and Meta‐Analysis

IntroductionThe specific determinants and underlying factors linking erectile dysfunction (ED) and premature ejaculation (PE) have yet to be clearly identified.AimThe aim of this study was to review and meta‐analyze all available data regarding the link between ED and PE.MethodsAn extensive Medline Embase and Cochrane search was performed including the following words: “premature ejaculation” and “erectile dysfunction”.Main Outcome MeasuresAll observational trials comparing the risk of ED in relation to PE were included. Data extraction was performed independently by two of the authors (G.R, G.C.), and conflicts resolved by the third investigator (M.M.).ResultsOut of 474 retrieved articles, 18 were included in the study for a total of 57,229 patients, of which 12,144 (21.2%) had PE. The presence of PE, however defined, was associated with a significant increase in ED risk (odds ratio: 3.68[2.61;5.18]; P < 0.0001). Meta‐regression analysis showed that the risk of ED in PE subjects was higher in older individuals as well as in those with a lower level of education and in those who reported a stable relationship less frequently. In addition, subjects with PE and ED more often reported anxiety and depressive symptoms and a lower prevalence of organic associated morbidities, including diabetes mellitus, hypertension and dyslipidemia. All the latter associations were confirmed even after adjustment for age. Finally the risk of PE‐related ED increased with the increased proportion of acquired ejaculatory problems (adj r = 0.414; P < 0.0001 after the adjustment for age).ConclusionsIn conclusion, the present data showed that ED and PE are not distinctly separate entities, but should be considered from a dimensional point of view. Understanding this dimensional perspective might help sexual health care professionals in providing the most appropriate therapeutic approach to realistically increase patient related outcomes in sexual medicine. Corona G, Rastrelli G, Limoncin E, Sforza A, Jannini EA, and Maggi M. The interplay between premature ejaculation and erectile dysfunction: A systematic review and meta‐analysis. J Sex Med 2015;12:2291–2300.     

Therapeutic Effect of Adipose‐Derived Stem Cells and BDNF‐immobilized PLGA Membrane in a Rat Model of Cavernous Nerve Injury

IntroductionCavernous nerve injury is the main reason for post‐prostatectomy erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising therapeutic strategy for ED.AimTo evaluate the therapeutic efficacy of adipose‐derived stem cells (ADSCs) and brain‐derived neurotrophic factor (BDNF) immobilized Poly‐Lactic‐Co‐Glycolic (PLGA) membrane on the cavernous nerve in a rat model of post‐prostatectomy ED.MethodsRats were randomly divided into five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group, ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF‐membrane (BCNI group with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF‐membrane (BCNI group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF was controlled‐released for a period of 4 weeks in a BDNF/PLGA porous membrane system.Main Outcome MeasuresFour weeks after the operation, erectile function was assessed by detecting the ratio of intra‐cavernous pressure (ICP)/mean arterial pressure (MAP). Smooth muscle and collagen content were determined by Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. Phospho‐endothelial nitric oxide synthase (eNOS) protein expression and cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by Western blotting and cGMP assay, respectively.ResultsIn the ADSC/BDNF‐membrane group, erectile function was significantly elevated, compared with the BCNI and other treated groups. ADSC/BDNF‐membrane treatment significantly increased smooth muscle/collagen ratio, nNOS content, phospho‐eNOS protein expression, and cGMP level, compared with the BCNI and other treated groups.ConclusionsADSCs with BDNF‐membrane on the cavernous nerve can improve erectile function in a rat model of post‐prostatectomy ED, which may be used as a novel therapy for post‐prostatectomy ED. Piao S, Kim IG, Lee JY, Hong SH, Kim SW, Hwang T‐K., Heang S, Lee JH, Ra JC, and Lee JY. Therapeutic effect of adipose‐derived stem cells and BDNF‐immobilized PLGA membrane in a rat model of cavernous nerve injury. J Sex Med 2012;9:1968–1979.     

Nerve‐Sparing Approach Reduces Sexual Dysfunction in Patients Undergoing Laparoscopic Radical Hysterectomy

IntroductionAlthough growing evidence suggests the beneficial effects of a nerve‐sparing (NS) approach to surgery in cervical cancer patients, only limited data on NS laparoscopic radical hysterectomy (LRH) are available, and no studies have investigated the effects of NS‐LRH on sexual function.AimThis study aims to determine whether the implementation of NS‐LRH impacts on sexual function in cervical cancer patients.MethodsSexually active cervical cancer patients undergoing type C (class III) LRH between 2004 and 2013 were enrolled in this prospective study.Main Outcome MeasuresPreoperative and postoperative sexual function were assessed using a validated questionnaire, the Female Sexual Function Index (FSFI). The FSFI evaluates desire, arousal, lubrication, orgasm, satisfaction, and pain.ResultsForty patients undergoing radical hysterectomy (20 conventional LRH vs. 20 NS‐LRH) represented the study group. Baseline characteristics were similar between groups (P > 0.05). No differences in preoperative FSFI scores were recorded (P > 0.05). We observed that both LRH and NS‐LRH worsened postoperative FSFI scores (P < 0.001). However, patients undergoing NS‐LRH had higher postoperative FSFI scores than patients undergoing LRH (21.3 ± 9.4 vs. 14.2 ± 12.5; P = 0.04). Considering postoperative domain scores, we observed that desire, arousal, orgasm, and pain scores were similar between groups (P > 0.05), while patients undergoing NS‐LRH experienced higher lubrication (3.4 ± 2.3 vs. 1.7 ± 2.2; P = 0.02) and satisfaction (4.6 ± 3.9 vs. 2.8 ± 2.2; P = 0.004) scores in comparison with patients undergoing conventional LRH. No between‐group differences in survival outcomes were found.ConclusionsBoth conventional LRH and NS‐LRH impact negatively on patients' sexual function. However, the NS approach impairs sexual function less, minimizing the effects of radical surgery. Bogani G, Serati M, Nappi R, Cromi A, di Naro E, and Ghezzi F. Nerve-sparing approach reduces sexual dysfunction in patients undergoing laparoscopic radical hysterectomy. J Sex Med 2014;11:3012–3020.