Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset hypogonadism.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 µM H2O2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

[Comparative analysis of two assaysin detection of sperm DNA fragmentation index, flow cytometry and AI-based fluorescence microscopy, based on AO staining: A multicentre study].

OBJECTIVE: To study the correlation, consistency, and variations between two assays of DNA fragmentation index based on acridine orange (AO) staining via AI-based fluorescence microscopy(AI-DFI), and flow cytometry (FCM-DFI) across multiple centers. METHODS: We selected 421 male patients from Nanjing Drum Tower hospital ( Hospital G) (226 cases), Eastern Theatre General Hospital (Hospital J) (89 cases) and Jiangsu Province Hospital (Hospital S) (106 cases) . Semen samples from each patient were analyzed for routine semen parameters and for DFI using both AI fluorescence microscopy and flow cytometry. We studied the two methods' stability as well as the correlation, consistency, and variation between the two methods' results in various centers. RESULTS: The two replicate studies' results of AI-DFI and the three centers' FCM-DFI for linear regression analysis indicated strong stability (R2>0.9).Overall(Group A), the AI-DFI results demonstrated good correlation and consistency with the FCM-DFI results of three centers (r>0.85；ICC>0.9).The semen specimens were categorized into two groups: normal specimen group (group B) and abnormal specimen group (group C) (including asthenozoospermia, oligospermia, and semen samples with high impurities).Group C's results showed a decline in correlation and consistency when compared to group A and group B, whereas group B's results showed a little rise in correlation and consistency when compared to group A. Although the consistency and correlation between the results of the two DFI testing methods in the three centers were good, there was still a significant difference between Groups A and C (P<0.05), and in Group B there was a significant difference between the two DFI testing methods only in Hospital G (p＝0.02), with no significant difference in Hospitals J and S (P> 0.05). CONCLUSION: The two detection methods exhibit good stability and correlation. However, significant differences are observed in the DFI detection methods in samples with abnormal semen parameters and high complexity. The main reason for these significant differences may lie in the variations in detection principles. Each detection method has its own advantages, allowing clinical or research settings to choose between them based on laboratory conditions or specific requirements.

The Diagnostic Role of Neurophysiological Tests for Premature Ejaculation: A Prospective Multicenter Study.

PURPOSE: Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Local anesthetics (LAs) and dapoxetine are frequently used to treat PE; however, previous studies show variable efficacy. This study aims to determine the efficacy of LAs and dapoxetine using a novel classification based on neurophysiological tests. MATERIALS AND METHODS: This multicenter cohort study enrolled adult men (568) with an intravaginal ejaculatory latency time (IELT) ≤2 minutes. Patients were divided into 4 groups according to the results of neurophysiological tests and assigned different treatments for 12 weeks: 1) penile sensory hyperexcitability type (Sens)-LAs; 2) penile sympathetic hyperexcitability type (Symp)-dapoxetine; 3) mixed type (Mixed)-both LAs and dapoxetine; 4) normal type (Norm)-both LAs and dapoxetine. Self-estimated IELT and patient-reported outcomes were recorded. RESULTS: The total percentage of men achieving IELT >2 minutes and ≥5 minutes after treatment were 82.7% and 76.7%, respectively. For men with abnormal results of neurophysiological tests, 401 (86.6%) had improved IELT >2 minutes after the 12-week treatment course, in which 375 (81.0%) achieved IELT ≥5 minutes. All patient-reported outcome measures improved in each group after 12 weeks of treatment, with greater improvements among those with abnormal neurophysiological tests. CONCLUSIONS: The efficacy of LAs and dapoxetine increased in PE patients with abnormal results of neurophysiological tests. This novel classification of PE using neurophysiological tests could help guide and improve efficacy of PE therapies.

The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial.

BACKGROUND: A recent sham-controlled clinical study has shown that low-intensity pulsed ultrasound twice per week can safely and effectively treat patients with mild-to-moderate erectile dysfunction (ED). However, large-scale clinical trials are needed to verify its efficacy and safety and determine a reasonable treatment interval. AIM: To study whether low-intensity pulsed ultrasound therapy thrice per week is non-inferior to twice per week in patients with mild-to-moderate ED. METHODS: A randomized, open-label, parallel-group, non-inferiority clinical trial was conducted in 7 hospitals in China. A total of 323 patients with mild-to-moderate ED were randomized (1:1) into thrice per week (3/W) and twice per week (2/W) groups. Low-intensity pulsed ultrasound was applied on each side of the penis for 16 sessions. OUTCOMES: The primary outcome was response rate using the minimal clinically important difference in the International Index of Erectile Function (IIEF-EF) score at week 12. Secondary outcomes included Erection Hardness Score (EHS), Sexual Encounter Profile, Global Assessment Question, and Self Esteem and Relationship Questionnaire. RESULTS: Response rates in 3/W and 2/W groups were 62.0% and 62.5%, respectively. Treatment effect in the 3/W group was noninferior to that of the 2/W group, with rate difference lower bound of -0.01% [95% confidence interval -0.11 to 0.10%] within the acceptable margin (-14.0%). No significant difference was found among secondary outcomes. IIEF-EF score showed a significant increase from baseline in the 3/W group (16.8 to 20.7) and 2/W group (17.8 to 21.7), and the percentage of patients with EHS ≥3 increased in the 3/W (54.9% to 84.0%) and 2/W (59.5% to 83.5%) groups. There was no significant difference in response rate between the 2 groups after controlling for strata factors and homogeneous tests. No treatment-related adverse events were reported. CLINICAL IMPLICATIONS: Low-intensity pulsed ultrasound therapy displays similar efficacy and safety for mild-to-moderate ED when administered thrice or twice per week for 16 sessions. This study provides two options to suit patients' needs. STRENGTHS & LIMITATIONS: This is a large-sample, randomized, controlled, noninferiority trial study. Short-term follow-up and mostly younger patients are the main limitations. CONCLUSION: Low-intensity pulsed ultrasound therapy thrice and twice per week showed equivalent therapeutic effects and safety for mild-to-moderate ED in a young and generally healthy population. This therapy warrants further investigation of its potential value in rehabilitation of ED. Chen, H., Li Z., Li X., et al. The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial. J Sex Med 2022;19:1536-1545.

Application of dual-energy CT angiography in diagnosis of arterial erectile dysfunction: new scanning technology, new scanning area.

OBJECTIVES: To explore the value of dual-energy computed tomography (DE-CT) angiography in diagnosis of arteriogenic erectile dysfunction (ED) patients and feasibility of new scanning area that excludes the testis. MATERIALS AND METHODS: Ninety-three patients suspected of suffering arterial ED and 40 health volunteers underwent penile duplex Doppler ultrasound and DE-CT angiography (DE-CTA). The scanning range of DE-CTA covered whole arterial system of pelvis and testis was excluded. Two blinded investigators independently evaluated the arterial system that supplies the penis. RESULTS: Finally, 1596 segments were evaluated and 470 segments were judged to be abnormal. The distribution was: 2 (0.4%) in common iliac artery, 7 (1.5%) in internal iliac artery, 82 (17.5%) in internal pudendal artery, 89 (18.9%) in penile artery, 120 (25.5%) in dorsal artery, and 170 (36.2%) in cavernosal artery. The specificity, sensitivity, positive predictive value, and negative predictive value of DE-CTA in diagnostic were 86.02%, 87.50%, 94.12%, and 72.92%. Besides, the new scan area allowed for effective evaluation of the arteries while excluding the testis. CONCLUSION: DE-CTA can provide unbiased, safe evaluation of the vascular status of the penile bed in patients with ED.

Serum Vitamin D Level and Erectile Dysfunction in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

INTRODUCTION: A few studies involved the relationship between vitamin D and diabetes mellitus (DM) with erectile dysfunction (ED), and no meta-analysis was conducted to pool these data. The main purpose of our study was to examine the changes in serum vitamin D levels in patients with DM combined with ED. METHODS: An extensive search was performed, including the following words: "erectile dysfunction," "diabetes," and "vitamin D." Databases, including Cochrane Library, PubMed, and Web of Science, were retrieved to identify studies published up to September 30, 2021. Four studies were eligible for our meta-analysis. RESULTS: The weighted mean difference and their corresponding 95% confidence intervals were calculated to the data we selected. The results showed that the level of vitamin D in DM with ED was significantly lower (12.5 nmol/mL) than patients with diabetes alone (p = 0.002). CONCLUSION: Our novel meta-analysis suggests that vitamin D may be a risk factor for DM with ED, which can provide a new idea for the treatment and prevention of DM with ED.

Comparison of fluoxetine with other selective serotonin reuptake inhibitors in the treatment of premature ejaculation: A systematic review and meta-analysis.

The primary goal of this systematic review and meta-analysis was to compare the efficacy and safety of fluoxetine with other oral pharmaceuticals in the treatment of premature ejaculation (PE). We searched through databases including CNKI, PubMed, EMBASE and Cochrane to find research published up to 31 March 2022. PROSPERO was used to pre-register this meta-analysis (registration number CRD42022315459). Two separate writers extracted relevant details from all of the papers included in the study. To analyse the quality of literature publishing, we used the Cochrane risk of bias tool. The severity of premature ejaculation was determined using intravaginal ejaculatory latency time (IELT), and the effectiveness and safety of pharmacological interventions were determined using standardized mean difference (SMD) and risk ratio (RR) values with matching 95% confidence level intervals (95% CIs). Our meta-analysis includes a total of ten trials to investigate into the differences in treatment efficacy and safety between fluoxetine and other medicines. The findings revealed that fluoxetine was more effective than placebo in treating PE, whereas sertraline and paroxetine were more effective than fluoxetine (p < 0.05). The side effects of the medications were not significantly different, and they were all acceptable. The results of the sensitivity analysis were unaffected by the removal of any of the articles. There was no evidence of bias in the media. This meta-analysis examined the differences in efficacy and safety between fluoxetine and other oral medications and can be used by clinicians in the treatment of PE.

Effect of varicocele on sperm DNA damage: A systematic review and meta-analysis.

The updated meta-analysis was conducted to further verify the effect of varicocele on sperm DNA damage, supplying clinicians and researchers with high-grade evidence. The sperm DNA damage was evaluated by DNA fragmentation index (DFI), associated with the male fertility capability tightly. PubMed, Web of Science and Cochrane Library were searched extensively for eligible studies with the search terms: varicocele, sperm DNA and sperm DNA damage. Finally, a total of 12 studies were included in our meta-analysis with a total of 845 patients diagnosed with varicocele and 2,377 healthy controls. A statistical difference of DFI between varicocele patients and healthy controls was found after pooling the data ((Standardised mean difference) SMD: 1.40, 95%CI: 0.83-1.98, p < .0001), using the random effect model. We conducted subgroup analysis according to study region (Brazil and Other countries), detection methods of DFI (TUNEL, Comet, and SCSA), sample size (<50 and >50) and age (<30 and >30 years), based on substantial heterogeneity among eligible studies. The stability of pooled results was verified by sensitivity analysis. All these statistical analyses were conducted using Stata version 16.0. In conclusion, patients diagnosed with clinical varicocele had higher DFI than healthy controls, which means varicocele could impair sperm DNA, consequently the fertility potential of affected men.

The association between uric acid and erectile dysfunction: A systematic review and Meta-analysis.

The main purpose of this systematic review and meta-analysis was to explore the association between uric acid (UA) and erectile dysfunction (ED). Databases including PubMed, Cochrane Library and Web of Science were retrieved to identify studies published in English up to 31 June 2021. We preregistered this meta-analysis in the PROSPERO (registration number CRD42021267035). Two independent authors extracted the relevant data from all enrolled articles. We evaluated the quality of enrolled studies using the Newcastle-Ottawa Scale (NOS). The standardized mean difference (SMD), as well as the corresponding 95% confidence intervals (95% CIs), was used to assess the difference between ED patients and healthy subjects. A total of five studies were enrolled for our meta-analysis to explore the association of UA with ED. The pooled SMD of the UA level difference between ED patients and healthy subjects was 0.42 (95% CI:0.09, 0.74, p < 0.001). There were no individual data that significantly influenced the pooled SMDs in the sensitivity analysis. There was no evidence of publication bias. This novel meta-analysis confirmed that UA was an independent risk factor for ED, which suggested that the erectile function of patients with elevated uric acid should be evaluated by clinicians.

A systematic review and meta-analysis of the relationship between erectile dysfunction and the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios.

Several studies were conducted to explore the association between haematological parameters and erectile dysfunction (ED), but the conclusions were contradictory with small sample size. The extensively search was conducted in PubMed, Cochrane Library and Web of science from inception to August 2021. Studies comparing the haematological parameter (at least NLR, PLR) between ED patients and healthy controls were eligible for the present meta-analysis. The differences in NLR and PLR between ED patients and healthy controls were assessed by calculating the standardised mean difference (SMD) and 95% confidence interval (95% CI). Eventually, 7 studies were remained for our meta-analysis, with a total of 929 ED patients and 737 healthy controls. For the methodological quality based on NOS, 5 studies were of high quality, scored 7, and 8. 2 studies were of moderate quality, scored 6. There were statistically significant differences in NLR values between ED patients and healthy controls, based on the pooled results (SMD: 0.53, 95% CI: 0.24-0.82). Pooled results from the 6 studies revealed that ED patients had higher PLR values than healthy controls (SMD: 0.70, 95%CI: 0.12-1.28). Our meta-analysis solidly confirmed the association between NLR, PLR and ED. Increased NLR and PLR should be independent risk factors for ED.

Endogenous Deficiency of Brain-Derived Neurotrophic Factor Induces the Downregulation of Tryptophan Hydroxylase-2 Expression in Raphe Nuclei of Rapid Ejaculator Rats.

BACKGROUND: Premature ejaculation (PE) is one of the most common ejaculatory disorders. Recent studies have suggested a close relationship between the serotonin (5-hydroxytryptamine [5-HT]) system and brain-derived neurotrophic factor (BDNF), raising the question of whether BDNF plays a role in ejaculation regulation. To our knowledge, no previous studies have explored BDNF level of the central nervous system in ejaculatory disorders. At the same time, the interaction of central BDNF and 5-HT systems has not been undertaken in ejaculation regulation field. AIM: The aim of this study was to investigate the interaction between BDNF and 5-HT levels in raphe nuclei which contains the serotonergic neurons in a rat animal model with different ejaculatory behavior. METHODS: Eighteen male rats were selected and classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. BDNF and 5-HT levels were determined by enzyme-linked immunosorbent assay (ELISA). Real-Time Quantitative PCR and Western blot analyses were used to measure the mRNA level of Tryptophan Hydroxylase-2 (TPH2) gene and the expression of TPH2 protein (the rate-limiting enzyme in central 5-HT synthesis) in raphe nuclei, respectively. OUTCOMES: Male rat sexual behavior, the levels of BDNF and 5-HT in raphe nuclei of rats with different ejaculatory behavior, the mRNA level of gene encoding TPH2 and the expression of TPH2 protein in raphe nuclei. RESULTS: The primary finding of our study was that BDNF concentration was significantly decreased in raphe nuclei of rapid ejaculators. There was a strong positive correlation between the levels of BDNF and 5-HT (r = 0.944, P < .001). Further results showed that decreased TPH2 gene expression accompanied by TPH2 protein was shown in rapid ejaculators with lower BDNF level. CLINICAL IMPLICATIONS: With refinement of current knowledge, BDNF may eventually serve as a promising biomarker in patients with PE. STRENGTHS & LIMITATIONS: There are no previous studies examining the interaction of the brain BDNF and 5-HT in ejaculation regulation field. The main limitation is the limited sample size. CONCLUSION: BDNF may act via increasing the synthesis of central 5-HT in the process of ejaculation regulation. Our results suggest lack of endogenous BDNF induces the downregulation of TPH2 gene expression and the decrease of 5-HT synthesis in raphe nuclei of rapid ejaculator rats. Huang Y, Peng D, Geng H, et al. Endogenous Deficiency of Brain-Derived Neurotrophic Factor Induces the Downregulation of Tryptophan Hydroxylase-2 Expression in Raphe Nuclei of Rapid Ejaculator Rats. J Sex Med 2021;18:1491-1499.

Temperament-Character Traits and Attitudes Toward Premature Ejaculation in 4 Types of Premature Ejaculation.

BACKGROUND: Although temperament-character traits and attitudes toward premature ejaculation (PE) are known to be associated with PE, it is of great significance to study them in PE. Moreover, few studies have evaluated these traits and attitudes in the new classification of 4 subtypes of PE. AIM: We investigated the temperament-character traits and attitudes toward PE in 4 types of PE and their associations with PE. METHODS: Between December 2018 and December 2019, we conducted a survey in our hospital, and enrolled 350 men who complained of PE and 252 men without any complaint of PE. Temperament-character traits and attitudes toward PE were independently assessed by the Temperament and Character Inventory-Revised and several targeted questions, respectively. The Index of Premature Ejaculation (IPE) was used to evaluate ejaculation control, sexual life satisfaction, and distress caused by PE. OUTCOMES: The outcomes included differences of temperament-character traits and attitudes toward PE among 2 groups and their associations with PE. RESULTS: Of the 2 groups, men with PE complaints had lower novelty seeking/self-transcendence (NS/ST) scores and higher harm avoidance (HA) scores vs men without any complaints of PE. Among the 4 types of PE, men with variable PE had the highest score of HA and lowest score of NS; the lowest score of ST was recorded in men with lifelong PE. Additionally, the total and subdomain scores of IPE in men with subjective PE were higher than the other subtypes of PE. After adjusting for age, positive correlations were observed in HA score and total and subdomain scores of IPE, whereas the inverse was true corresponding to NS and ST. CLINICAL IMPLICATIONS: The current study has provided a new perspective for understanding the impact of psychological factors on PE. STRENGTHS & LIMITATIONS: This is the first study to systematically assess the effects of personality traits and attitudes on PE, especially among the 4 types of PE. The main drawback is that the generalizability of this study may be limited by the fact that it was conducted in a single cultural/societal background. CONCLUSION: Men who complained of PE tended to react with indifference or rejection to novelty, tended to feel unsatisfied, cannot effectively adapt to changes in the surrounding environment, and tended to avoid situations involving risk. These characteristics could lead to their becoming disheartened when faced with PE. Furthermore, the attitude of men with PE reflects the needs of the patient during treatment from one aspect. Gao P, Gao J Wang Y, et al. Temperament-Character Traits and Attitudes Toward Premature Ejaculation in 4 Types of Premature Ejaculation. J Sex Med 2021;18:72-82.

Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation.

BACKGROUND: Although some recent neuroimaging studies have indicated the abnormal brain structure or function in patients with lifelong premature ejaculation (LPE), whether and how the abnormal thalamic function participates in processing sexual behavioral information are still unclear in patients with LPE. AIM: The aim of this study was to assess the changes in the thalamus metabolism and structural integrity in patients with LPE. METHODS: We performed a multimodal magnetic resonance approach in a 3.0 T system, including proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging, and volumetric analysis to detect the differences in thalamic metabolism and structure between 20 patients with LPE and 15 healthy controls. OUTCOMES: We analyzed and correlated the clinical symptoms of the subjects with significant 1H-MRS-based features. Peak areas of N-acetylaspartate, choline, creatine (Cr), and glutamate/glutamine (Glu) were calculated with the LCModel software. RESULTS: Diffusion tensor imaging and volumetric analysis of thalami showed no differences between the 2 groups. On the contrary, 1H-MRS study disclosed that both Glu concentrations and Glu/Cr ratio values in the thalami of patients with LPE were remarkably increased when compared with healthy controls (P < .01 for both variables). In addition, both the intravaginal ejaculatory latency time score and Chinese Index of Sexual Function for Premature Ejaculation-5 score were negatively related to increased Glu concentrations and Glu/Cr ratio values. CLINICAL IMPLICATIONS: Glutamatergic activity changes of thalamus may be an underlying indicator for evaluating sensory conduction efficiency in patients with LPE. STRENGTHS & LIMITATIONS: The present study first found the abnormal thalamic metabolism in patients with LPE and contributed to a better understanding of the LPE etiology. Limitations include a cross-sectional study design with small samples and no examination of other brain areas. CONCLUSION: Our findings show that the increase in glutamatergic activity of thalamus is related to LPE, suggesting that the increased Glu neurotransmission in the thalamus may contribute to the development of premature ejaculation. Xia J-D, Chen F, Zhang Q-J, et al. Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation. J Sex Med 2021;18:275-283.

Expression of brain-derived neurotrophic factor in rapid ejaculator rats: A further study.

Limited evidence has indicated that brain-derived neurotrophic factor (BDNF) may be involved in the neurobiology of premature ejaculation (PE). This study aimed to investigate BDNF levels in the central and peripheral nervous systems of a rapid ejaculation model. Eighteen male rats were selected and classified as 'sluggish', 'normal' and 'rapid' ejaculators on the basis of ejaculation frequency during copulatory behavioural tests. BDNF levels in specific brain regions, spinal cord and serum were determined by enzyme-linked immunosorbent assay (ELISA). Consistent with the results in PE patients, the concentration of serum BDNF decreased significantly from the sluggish rats to normal and rapid rats. Besides, in both brain regions and spinal cord, the sluggish group had the highest BDNF levels, while the rapid group had the lowest BDNF levels. Regression analyses of the expression of BDNF presented positive correlations between serum and brain (r = 0.958, p < .001), and between serum and spinal cord (r = 0.967, p < .001) respectively. Our findings suggested insufficient BDNF in the nervous system and serum may lead to rapid ejaculation. The current study adds to the evidence that BDNF is involved in the regulation of ejaculation.

A comprehensive assessment of genetic variation in serotonin transporter gene (5-HTTLPR+rs25531) and the response to dapoxetine in Chinese patients with premature ejaculation.

This study was to explore whether serotonin transporter gene-linked polymorphic region polymorphisms (5-HTTLPR+rs25531) influence the response to dapoxetine treatment in a Chinese population with premature ejaculation (PE). 112 patients with PE re-enrolled from our previous study received dapoxetine monotherapy. At the endpoint, patients with S'S' had a significant increased risk of nonresponse compared with L' carriers (p < .001). The improvement in S'S' genotype was significantly lower in premature ejaculation profile (PEP) items of 'control over ejaculation' (p = .035) and 'distress related to ejaculation' (p = .017) than that in L' carriers. As to clinical global impression of change (CGIC), results in S'S' subjects showed significantly lower scores (p = .008) and a less satisfaction rate reporting at least 'better' (p = .020) compared with L' carriers. Moreover, our findings suggested that patients with S'S' were more likely to develop adverse effects (AEs) compared with L' carriers (p = .040). This study suggests that PE patients bearing the S'S' genotype have an inferior comprehensive efficacy and safety of dapoxetine treatment, which consist of poorer response in IELTs, less improvement in patient-reported outcome (PRO) measures and greater incidence of AEs, than L' carriers. Variants of triallelic 5-HTTLPR may play a major role as a predictor of treatment response to dapoxetine.

Cavernous artery intima-media thickness predicts the response to sildenafil in erectile dysfunction patients as a morphological parameter.

While the intima-media thickness (IMT) of the cavernous artery was used for diagnosis for vascular erectile dysfunction (ED) with more accuracy than the peak systolic velocity, the role of the IMT in predicting treatment responses remained unexamined. A total of 136 patients with ED were enrolled. The baseline clinical and laboratory characteristics were collected. Penile Doppler ultrasonography (PDU) was performed on all patients by a blinded sonographer. Sildenafil was administrated to all patients with an adjusted dose of 50 or 100 mg on demand over a period of 3 months. A follow-up was conducted on all patients using the Erectile Hardness Score (EHS) questionnaire along with the visual and tactile version of the standardised EHS tool. The peak systolic velocity (PSV) and IMT were compared between sildenafil responders and sildenafil nonresponders, while receiver operator characteristic (ROC) curves were used to calculate the cut-off values and compare the test power respectively. There was no statistical difference from the baseline characteristics. The IMT of cavernous artery was more accurate than PSV to predict the sildenafil response (AUC = 0.809, 0.626 respectively). IMT could predict sildenafil responders more accurately than PSV, and the cut-off value of the IMT of the cavernous artery was less than 0.22 mm.

Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study.

INTRODUCTION: Premature ejaculation (PE) is a highly prevalent male sexual dysfunction. Previous studies have found abnormal activity in the sympathetic nervous system and penile sensory pathway of PE. Few studies have investigated the neural mechanisms underlying PE. AIM: The aim of this study was to examine whether the altered cortico-subcortical network topological properties of the brain white matter structural network could be used to differentiate patients with PE from healthy control (HC) subjects. METHODS: Diffusion tensor images data were collected from 32 patients with PE and 35 HC participants. Then, brain white matter structural networks were reconstructed from image acquisition. MAIN OUTCOME MEASURE: Furthermore, nodal measures were calculated and hub regions were identified using the graph-theoretical methods. RESULTS: For cortical brain regions, increased strength, global efficiency, and decreased shortest path length were found in the right superior frontal gyrus (medial), and superior frontal gyrus (medial orbital) were found in patients with PE. In addition, patients with PE also showed decreased strength in the right rolandic operculum and decreased shortest path length, and increased global efficiency in the right inferior frontal gyrus (triangular part). For subcortical brain structures, patients with PE were associated with decreased shortest path length and increased global efficiency in the left insula and right caudate nucleus. Finally, the results showed that 9 PE-specific hub regions were identified in patients compared with HCs, including 7 cortical regions and 2 subcortical regions. CLINICAL IMPLICATIONS: Our results provide new understanding about the pathology of PE and enhances the understanding of PE pathology. STRENGTH & LIMITATIONS: Our results offer biological markers for understanding the physiopathology of PE. However, our study is a cross-sectional design, longitudinal design studies need to explore the causal relationships between aberrant topological characteristics and PE. CONCLUSION: Our results provide new insights into the neural mechanism of PE involving cortico-subcortical network changes, which could serve as a potential biomarker to differentiate individuals with PE from HCs. Chen J, Yang J, Huang X, et al. Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study. J Sex Med 2020;17:48-59.

Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats.

BACKGROUND: Although abnormal sympathetic nerve system (SNS) activity has been demonstrated in the pathogenesis of ejaculation disorders, few data are available on its underlying mechanism. AIM: To investigate whether differences in ejaculatory behavior of rats were associated with the state of SNS activity and gamma-aminobutyric (GABA) receptor expressions in the paraventricular nucleus (PVN) of the hypothalamus and the effects of GABA receptors in the PVN on ejaculatory behavior. METHODS: Based on ejaculatory performance, Sprague-Dawley rats were divided into "sluggish," "normal," and "rapid" ejaculators. PVN microinjection was performed to evaluate the role of GABA receptors on sexual behavior. OUTCOMES: The outcomes include differences in expression and distribution of GABA receptors and norepinephrine level among the 3 groups and changes in copulation behavior parameters after PVN microinjection. RESULTS: Compared with "normal" rats, the "rapid" group ejaculated more times with shorter latency (P < .001, P < .001) and had lower expression and distribution of both GABA-A and GABA-B receptors, while the opposed results appeared in the "sluggish" group. The norepinephrine level was successively increased among "sluggish," "normal," and "rapid" rats (P < .001) and correlated with ejaculation frequency (r = 0.896, P < .001) and ejaculation latency (r = -0.835, P < .001). In addition, bilateral microinjection of the GABA-A and GABA-B receptor agonist (isoguvacine and baclofen) into the PVN both significantly prolonged the intromission latency and inhibited ejaculation, which could be blocked by antagonist gabazine and CGP-35348, respectively. Vigabatrin, the GABA-transaminase inhibitor, caused a significantly reduced ejaculation frequency and extended ejaculation latency in rats, which could be offset by simultaneous injections of gabazine and CGP-35348. CLINICAL IMPLICATIONS: Our findings provide new understanding about GABA receptors in the PVN on sexual behavior and enhance the comprehension of neurobiological mechanisms involved in premature ejaculation. STRENGTHS & LIMITATIONS: Our results have indicated that GABA receptors in the PVN may inhibit ejaculation through restraining the activity of SNS. However, our study did not analyze the changes of GABA receptors in other brain areas, which needs further study. CONCLUSION: Ejaculation behaviors in male rats are associated with SNS activity and could be regulated by GABA receptors in the PVN, which may be of assistance in the treatment of ejaculation disorders in the future. Zhang QJ, Yang BB, Yang J, et al. Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats. J Sex Med 2020;17:614-622.

[PDE-5i combined with RigiScan-based audiovisual sexual stimulation test versus nocturnal penile tumescence test in evaluation of erectile function].

OBJECTIVE: To explore the clinical value of phosphodiesterase type-5 inhibitors (PDE-5i) combined with RigiScan-based audiovisual sexual stimulation (AVSS) test in comparison with that of nocturnal penile tumescence (NPT) test in evaluation of erectile function. METHODS: A total of 166 ED patients, aged 21－63 (mean 31) years, with a disease course of 3 months to 10 years (mean 14 months), underwent NPT test or PDE-5i + RigiScan-based AVSS test from 2017 to 2018. We compared the results of the diagnostic strategies. Normal NPT patterns were presumed to indicate psychogenic and abnormal ones to indicate organic ED. RESULTS: Compared with the results of NPT test, no statistically significant difference was observed in the accuracy rate between Viagra + AVSS test and Cialis + AVSS test (P > 0.05). PDE-5i + RigiScan-based AVSS test achieved a sensitivity of 78.9% and a specificity of 90.7% in the diagnosis of psychogenic ED and an overall accuracy rate of 81.9%. According to the results of PDE-5i + RigiScan-based AVSS test, the patients fell into a normal and an abnormal erection group, with significant differences between the two groups in age, disease course, IIEF-5 score and maintenance time of penile tip rigidity ≥60% (P < 0.05). ROC curve analysis indicated that PDE-5i + RigiScan-based AVSS test accurately manifested the erectile function of the patients. CONCLUSIONS: Compared with NPT test, PDE -5i combined with RigiScan-based AVSS test is simple, inexpensive, practical and with a high sensitivity and specificity, and therefore can be used as the first-choice strategy for etiological diagnosis of ED.

Dopamine D2 receptors in the basolateral amygdala modulate erectile function in a rat model of nonorganic erectile dysfunction.

Nonorganic erectile dysfunction is a problem with unknown central mechanisms. Changes in brain activity in the amygdala have been observed in human patients. This study aimed to investigate the dopamine system in the basolateral amygdala of male rats with nonorganic erectile dysfunction. We applied chronic mild stress to induce nonorganic erectile dysfunction. After exposure to chronic mild stress, the sucrose consumption test, sexual behaviour test and apomorphine test were used to select depression-like rats with erectile dysfunction as nonorganic erectile dysfunction model rats. The sexual behaviour of these rats after central infusion of a dopamine D1/D2 receptor agonist/antagonist was observed. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the basolateral amygdala were also measured. The result of the sucrose consumption test, sexual behaviour test and apomorphine test indicated a successful nonorganic erectile dysfunction model. Central infusion of a dopamine D2 receptor agonist increased intromission ratio in model rats. Lower expression levels of tyrosine hydroxylase and the dopamine D2 receptor in the basolateral amygdala were observed in rats with nonorganic erectile dysfunction. These results suggest that impairment of the dopamine D2 receptor pathway in the basolateral amygdala may contribute to the development of nonorganic erectile dysfunction.