Premature ejaculation: an update on definition and pathophysiology Mohammed Abu El-Hamd, Ramadan Saleh, Ahmad Majzoub Asian Journal of Andrology 2019 21(5):425-432 Premature ejaculation (PE) is the most common male sexual dysfunction, which represents a diagnostic as well as a therapeutic challenge for physicians. However, no universally accepted definition is currently available for PE. As a result, physicians continue to diagnose patients with PE according to major guidelines set by the professional societies. These guidelines either recommend the use of validated questionnaires or patient-reported outcomes. Recent efforts directed toward classifying PE may help provide a better understanding of the prevalence and risk factors of this disorder. While the exact etiology of PE has not been clearly elucidated, several risk factors have been strongly reported in the literature. Clearly, to understand the revised definition of PE, its etiology and pathophysiology is necessary to improve the clinical management of this medical condition and form the basis of future research in this regard. In this review, we highlight the past and current definitions of PE and present an appraisal on the classifications and theories suggested for the etiopathogenesis of PE.

Role of tumor-associated immune cells in prostate cancer: angel or devil? Shui-Qing Wu, Hao Su, Yin-Huai Wang, Xiao-Kun Zhao Asian Journal of Andrology 2019 21(5):433-437 Prostate cancer is the most common malignancy in the reproductive system of older males. Androgen deprivation therapy (ADT) is an important treatment for prostate cancer patients. However, almost all prostate cancer patients unavoidably progress to the castration-resistant stage after ADT treatment. Recent studies have shown that tumor-associated immune cells play major roles in the initiation, progression, and metastasis of prostate cancer. Various phenotypes of tumor-associated immune cells have tumor-promoting or antitumor functions mediated by interacting with tumor cells. Here, we review the current knowledge of tumor-associated immune cells in prostate cancer.

Critical evaluation of two models of flow cytometers for the assessment of sperm DNA fragmentation: an appeal for performance verification Rakesh Sharma, Sajal Gupta, Ralf Henkel, Ashok Agarwal Asian Journal of Andrology 2019 21(5):438-444 Lack of standardized, reproducible protocols and reference values is among the challenges faced when using new or upgraded versions of instruments in reproductive laboratories and flow cytometry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay combined with flow cytometry routinely used for diagnostic measurement of sperm DNA fragmentation (SDF) is a unique example. Any change in the setting of the standard instrument, including upgrades of hardware or software, can lead to different results and may affect clinicians' decision for treatment. Therefore, we compared TUNEL results of SDF obtained from a standard (C6) flow cytometer with a newer version of the same instrument (C6 Plus) and examined the cutoff, sensitivity, and specificity without calibration (adjustment) and after adjustment. Identical sperm preparation and matched acquisition settings were used to examine the performance of two flow cytometers. The strength of agreement of the results between the two observers was also assessed. After adjustment of the settings, overall concordance became high and the two cytometers showed 100% positive and negative predictive value with 100% area under the curve. The overall correlation coefficient observed between C6 and C6 Plus was highly significant (P < 0.0001; r = 0.992; 95% confidence interval [CI]: 0.982–0.997). After adjustment, the two cytometers showed very high precision of 98% and accuracy of >99%. The interobserver agreement on C6 flow cytometer for the two observers was 0.801 ± 0.062 and 0.746 ± 0.044 for C6 Plus. We demonstrated a strong agreement between the samples tested on the two flow cytometers after calibration and established the robustness of both instruments.

Bilateral versus unilateral cryptorchidism in nonobstructive azoospermia: Testicular sperm extraction outcomes Anne-Laure Barbotin, Anaïs Dauvergne, Agathe Dumont, Nassima Ramdane, Valérie Mitchell, Jean-Marc Rigot, Florence Boitrelle, Geoffroy Robin Asian Journal of Andrology 2019 21(5):445-451 Cryptorchidism is one of the most frequent causes of nonobstructive azoospermia (NOA) in adulthood. Although it is well known that spermatogenesis is more impaired in bilateral than in unilateral cryptorchidism, previous studies have only described small cohorts or inhomogeneous population. Consequently, we analyzed a cohort of 225 men with only a history of cryptorchidism as sole etiopathogenetic factor for NOA, and compared testicular sperm extraction (TESE) outcomes between men with bilateral versus unilateral cryptorchidism. Our results show no difference in follicle-stimulating hormone (FSH) levels and testicular volumes between men with a history of bilateral cryptorchidism compared to unilateral cryptorchidism (median: 21.3 IU l−1 vs 19.3 IU l−1, P = 0.306; and 7.2 ml vs 7.9 ml, P = 0.543, respectively). In addition, sperm retrieval rates were similar (66.2% vs 60.0%, P = 0.353). Using multivariate analysis, we have found that only a low inhibin B level (above the assay's detection limit) was positively associated with successful sperm retrieval (P < 0.05). Regarding intracytoplasmic sperm injection outcomes, we found that cumulative pregnancy rate and live birth rate per cycle were not statistically different between the two groups (17.4% vs 27.8%, P = 0.070; and 16.1% vs 26.4%, P = 0.067, respectively). Unexpectedly, there was no significant difference in hormonal profiles (FSH, luteinizing hormone [LH], testosterone, and inhibin B levels) and TESE outcomes between unilateral versus bilateral cryptorchidism. This suggests that a history of unilateral cryptorchidism could reflect a bilateral testicular impairment. Interestingly, inhibin B level might be a predictor of successful TESE.

Losartan improves erectile function through suppression of corporal apoptosis and oxidative stress in rats with cavernous nerve injury Yi Wang, Xiang-Hu Meng, Qi-Jie Zhang, Ya-Min Wang, Chen Chen, Yi-Chun Wang, Xiang Zhou, Cheng-Jian Ji, Ning-Hong Song Asian Journal of Andrology 2019 21(5):452-459 This study aimed to investigate the functional and morphological changes in the corpus cavernosum after cavernous nerve (CN) injury or neurectomy and then reveal whether treatment with the angiotensin II Type 1 receptor antagonist losartan would improve erectile function as well as its potential mechanisms. A total of 48 10-week-old Sprague–Dawley male rats, weighing 300–350 g, were randomly divided into the following four groups (n = 12 per group): sham operation (Sham) group, bilateral cavernous nerve injury (BCNI) group, losartan-treated BCNI (BCNI + Losartan) group, and bilateral cavernous neurectomy (Neurectomy) group. Losartan was administered once daily by oral gavage at a dose of 30 mg kg−1 day−1 for 4 weeks starting on the day of surgery. The BCNI and the Neurectomy groups exhibited decreases in erectile response and increases in apoptosis and oxidative stress, compared with the Sham group. Treatment with losartan could have a modest effect on erectile function and significantly prevent corporal apoptosis and oxidative stress. The phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were substantially lower, while the Bcl-2-associated X protein (Bax)/Bcl-2 ratio, nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1), transforming growth factor-β 1 (TGF-β 1) and heme oxygenase-1 (HO-1) levels, and caspase-3 activity were higher in the BCNI and Neurectomy groups than in the Sham group. After 4 weeks of daily administration with losartan, these expression levels were remarkably attenuated compared with the BCNI group. Taken together, our results suggested that early administration of losartan after CN injury could slightly improve erectile function and significantly reduce corporal apoptosis and oxidative stress by inhibiting the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.

The transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines Octavio Orellana-Serradell, Daniela Herrera, Enrique A Castellón, Héctor R Contreras Asian Journal of Andrology 2019 21(5):460-467 One of the factors promoting tumoral progress is the abnormal activation of the epithelial–mesenchymal transition (EMT) program which has been associated with chemoresistance in tumoral cells. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), a key EMT activator, has recently been related to docetaxel resistance, the main chemotherapeutic used in advanced prostate cancer treatment. The mechanisms involved in this protective effect are still unclear. In a previous work, we demonstrated that ZEB1 expression induced an EMT-like phenotype in prostate cancer cell lines. In this work, we used prostate cancer cell lines 22Rv1 and DU145 to study the effect of ZEB1 modulation on docetaxel resistance and its possible mechanisms. The results showed that ZEB1 overexpression conferred to 22Rv1 cell resistance to docetaxel while its silencing made DU145 cells more sensitive to it. Analysis of resistance markers showed no presence of ATP-binding cassette subfamily B member 1 (MDR1) and no changes in breast cancer resistance protein (BCRP) or ATP-binding cassette subfamily C member 10 (MRP7). However, a correlation between ZEB1, multidrug resistance-associated protein 1 (MRP1), and ATP-binding cassette subfamily C member 4 (MRP4) expression was observed. MRP4 inhibition, using MK571, resensitized cells with ZEB1 overexpression to docetaxel treatment. In addition, modulation of ZEB1 and subsequent change in MRP4 expression correlated with a lower apoptotic response to docetaxel, characterized by lower B-cell lymphoma 2 (Bcl2), high BCL2-associated X protein (Bax), and high active caspase 3 expression. The response to docetaxel in our model seems to be mediated mainly by activation of the apoptotic death program. Our results showed that modulation of MRP4 could be a mediator of ZEB1-related resistance to docetaxel in prostate cancer, making it a possible marker for chemotherapy response in patients who do not express MDR1.

Transurethral resection of prostate for acute urinary retention is linked to shorter survival in younger men Jeremy Yuen-Chun Teoh, Chi-Kwok Chan, Maggie Haitian Wang, Chi-Ho Leung, Eddie Shu-Yin Chan, Peter Ka-Fung Chiu, Chi-Hang Yee, Hon-Ming Wong, Simon See-Ming Hou, Chi-Fai Ng Asian Journal of Andrology 2019 21(5):468-472 It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan–Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11–2.09, P = 0.010) and 70–80 years (adjusted HR: 1.39, 95% CI: 1.15–1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70–80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70–80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.

Success rates of in vitro fertilization versus intracytoplasmic sperm injection in men with serum anti-sperm antibodies: a consecutive cohort study Shao-Ming Lu, Xiao Li, Shi-Li Wang, Xiao-Li Yang, Yan-Zhen Xu, Ling-Ling Huang, Jiao-Long Liu, Fei-Fei Cai, Zi-Jiang Chen Asian Journal of Andrology 2019 21(5):473-477 Antisperm antibodies (ASAs) are assumed to be a possible causative factor for male infertility, with ASAs detected in 5%–15% of infertile men but in only 1%–2% of fertile ones. It remains unclear whether ASAs have an adverse effect on the outcome of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). This study investigated differences in the rates of fertilization, pregnancy, and live births associated with serum ASA-positive and ASA-negative men following IVF or ICSI. Five hundred and fifty-four consecutive infertile couples undergoing IVF (n = 399) or ICSI (n = 155) were included. The two-sample two-sided t-test and Chi-square or Fisher's exact test was used for statistical analysis. Lower rates of fertilization (41.7% vs 54.8%, P = 0.03), good embryos (18.9% vs 35.2%, P = 0.00), pregnancy (38.5% vs 59.4%, P = 0.00), and live births (25.8% vs 42.5%, P = 0.00) were observed in men of the IVF group with a positive serum ASA than in those with a negative ASA. ASA positivity/negativity correlated with pregnancy rates (P = 0.021, odds ratio [OR]: 0.630, 95% confidence interval [CI]: 0.425–0.932) and live birth rates (P = 0.010, OR: 1.409, 95% CI: 1.084–1.831) after controlling for the female serum follicle-stimulating hormone level and the couple's ages at IVF. Women coupled with ASA-positive men had lower live birth rates with IVF than with ICSI (25.8% and 47.4%, respectively; P = 0.07). Women coupled with ASA-positive men had lower rates of pregnancy and live births following IVF than those coupled with ASA-negative men but had a similar outcome with ICSI.

Heavy cigarette smoking and alcohol consumption are associated with impaired sperm parameters in primary infertile men Luca Boeri, Paolo Capogrosso, Eugenio Ventimiglia, Filippo Pederzoli, Walter Cazzaniga, Francesco Chierigo, Federico Dehò, Emanuele Montanari, Francesco Montorsi, Andrea Salonia Asian Journal of Andrology 2019 21(5):478-485 We assessed the concomitant impact of cigarette smoking and alcohol consumption in men presenting for primary couple's infertility. Data from 189 infertile men were analyzed. Semen analysis, serum hormones, and sperm DNA fragmentation (SDF) were obtained. Smoking status was categorized as follows: current nonsmoker (−S), moderate smoker (+MS), and heavy smoker (+HS). Alcohol consumption was categorized as follows: abstainer (−D), moderate drinker (+MD), and heavy drinker (+HD). Descriptive statistics and logistic regression models were applied. Among all the participants, 132 (69.8%), 30 (15.9%), and 27 (14.3%) patients were −S, +MS, and +HS, respectively. In addition, 67 (35.4%), 77 (40.7%) and 45 (23.8%) men were -D, +MD and +HD, respectively. Regarding concomitant habits, 52 (27.5%) patients were nonsmokers and abstainers (−S/−D: Group 1), 91 (48.1%) had at least one recreational habit (−S/+D or +S/−D: Group 2), and 46 (24.3%) were both smokers and drinkers (+S/+D: Group 3). Sperm concentration and progressive motility were lower in +HS and +HD, compared with −S and −D (all P < 0.05), respectively. Similarly, both parameters were significantly lower in Group 3 than Groups 1 and 2 (all P < 0.05). SDF values were higher in Group 3 than Groups 1 and 2 (both P < 0.05). In multivariate analysis, follicle-stimulating hormone (FSH) levels and concomitant +S/+D status were independent predictors of impaired sperm concentration and progressive motility (all P < 0.05). Heavy smoking and heavy drinking were associated with worse seminal parameters than moderate smoking/drinking and nonsmoking/abstaining. When concomitant, +S/+D status has an even greater detrimental effect on semen parameters.

Development and validation of a clinical nomogram predicting bladder outlet obstruction via routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms Young Ju Lee, Jung Keun Lee, Jung Jun Kim, Hak Min Lee, Jong Jin Oh, Sangchul Lee, Sang Wook Lee, Jeong Hyun Kim, Seong Jin Jeong Asian Journal of Andrology 2019 21(5):486-492 We aimed to develop and validate a clinical nomogram predicting bladder outlet obstruction (BOO) solely using routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms (LUTS). A total of 750 eligible patients ≥50 years of age who had previously not responded (International Prostate Symptom Score [IPSS] improvement <4 points) to at least three different kinds of LUTS medications (including a-blocker) for the last 6 months were evaluated as subcohorts for nomogram development (n = 570) and for split-sample validation (n = 180). BOO was defined as Abrams–Griffiths number ≥40, or 20–39.9 with a slope of linear passive urethral resistance ratio >2 cmH2O ml−1 s−1. A stepwise multivariable logistic regression analysis was conducted to determine the predictors of BOO, and b-coefficients of the final model were selected to create a clinical nomogram. The final multivariable logistic regression model showed that age, IPSS, maximum urinary flow rate, postvoid residual volume, total prostate volume, and transitional zone index were significant for predicting BOO; these candidates were used to develop the final nomogram. The discrimination performance of the nomogram was 88.3% (95% CI: 82.7%–93.0%, P < 0.001), and the nomogram was reasonably well-fitted to the ideal line of the calibration plot. Independent split-sample validation revealed 80.9% (95% CI: 75.5%–84.4%, P < 0.001) accuracy. The proposed BOO nomogram based solely on routine clinical parameters was accurate and validated properly. This nomogram may be useful in determining further treatment, primarily focused on prostatic surgery for BOO, without impeding the detection of possible BOO in men with LUTS that is refractory to empirical medications.