Aerobic exercise improves ejaculatory behaviors and complements dapoxetine treatment by upregulating the BDNF-5-HT duo: a pilot study in rats.

Accumulating evidence has revealed many clues that regular aerobic exercise benefits brain health and behaviors. The aims of this study were to explore the effect of aerobic exercise on ejaculatory behaviors, as well as to make a preliminary assessment of aerobic exercise as a complementary strategy to dapoxetine treatment in rapid ejaculators. Copulatory tests of rats and a treadmill training protocol were performed in this study. In total, 12 rapid ejaculators were selected on the basis of ejaculation distribution theory and randomly assigned to 4 groups: control (Ctrol) group, aerobic exercise (Ex) group, dapoxetine (Dapo) group, and Ex+Dapo group. We evaluated the changes in ejaculatory parameters in the 4 groups. Variations in biological markers, including serum corticosterone, serotonin (5-HT), and brain-derived neurotrophic factor (BDNF) of the raphe nucleus, were determined by enzyme-linked immunosorbent assay (ELISA). The primary finding of our study was that both aerobic exercise and acute dapoxetine could enhance ejaculation control and prolong ejaculation latency in rapid ejaculator rats. The ejaculation delay effect of aerobic exercise was nearly equivalent to that of acute dapoxetine. In addition, both aerobic exercise and dapoxetine treatment could lead to increased expression of BDNF and 5-HT in the raphe nucleus of rapid ejaculators. Moreover, the two interventions, when applied together, may further upregulate the expression of BDNF-5-HT duo in a complementary manner. This study highlights the positive effects of aerobic exercise on ejaculation control. Regular aerobic exercise might be a promising complementary treatment to dapoxetine in rats.

Poor Sleep Quality is an Independent Risk Factor for Acquired Premature Ejaculation.

PURPOSE: To determine the role of poor sleep quality as a risk factor for acquired premature ejaculation (APE) after considering the various risk factors, such as ages, lower urinary tract symptoms (LUTS), anxiety, depression, and erectile dysfunction. METHODS: This study presents a multivariate analysis to identify risk factors for PE, including the covariate of age, International Prostate Symptom Score (IPSS), General Anxiety Disorder-7 (GAD-7) score, Patient Health Questionnaire-9 (PHQ-9) score, International Index of Erectile Function (IIEF) score, and Pittsburgh Sleep Quality Index (PSQI). Acquired PE was defined as self-reported intravaginal ejaculation latency time ≤3 minutes, and poor sleep quality was diagnosed using the Pittsburgh Sleep Quality Index tool. RESULTS: A total of 349 men were enrolled in the study after completing the questionnaires and the medical history survey. Among 349 men, 203 individuals (58.17%) suffered from acquired PE. The IIEF-5 score, IPSS, GAD-7 score, PHQ-9 score, and PSQI score of the population with PE were significantly different from the non-PE group. Further multivariate analysis showed that erectile dysfunction, depression, severe prostatitis-like symptoms, and poor sleep quality were high-risk factors of APE. Additionally, our study showed that premature ejaculation diagnostic tool (PEDT) score was associated with IPSS/GAD-7/PHQ-9/PSQI scores positively and associated with IIEF-5 scores negatively. The stratified analysis of sleep quality showed that APE patients with different sleep qualities have different prevalence rates of anxiety, depression, prostatitis-like symptoms, and erectile function. CONCLUSION: In general, sleep quality may be a potential risk factor for patients with acquired premature ejaculation. Our research revealed the impact of sleep quality on premature ejaculation and provided new viewpoints for further understanding and perfecting the pathogenesis of premature ejaculation.

Incidence and Risk Factors of Post-Operative Depression in Patients Undergoing Transurethral Resection of Prostate for Benign Prostatic Hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a frequent-occurring disease in middle-aged and elderly men. This work is a prospective study and aims at exploring the incidence of post-operative depression and the potential risk factors of depression in a cohort of patients with BPH in China. METHODS: In this survey, 611 men who underwent transurethral resection of the prostate (TURP) were strictly selected at our institution from January 2016 to August 2019. Zung Self-rating Depression Scale was used for evaluation of depressive symptoms. Sociodemographic, clinical and other data were also collected. RESULTS: We found that 152/611 (24.9%) patients suffered from different degree of depression at 6 months after TURP, including mild symptoms (20.9%) and moderate/severe symptoms (3.9%). A total of 421 (68.9%) patients developed post-TURP erectile dysfunction (ED). The occurrence of depression was closely associated with marital status, education level, cigarette smoking, alcohol consumption, severity of lower urinary tract symptoms (LUTS), duration of BPH, erectile function, and comorbidities (such as diabetes, dyslipidaemia and bladder stone). The risk factors related to the severity of depression included widowed or single marital status, frequent alcohol consumption, moderate or severe LUTS, longer duration (> 5 years) of BPH, ED, urinary continence, and comorbidities such as diabetes and bladder stone. CONCLUSION: Many risk factors are related to the occurrence of depression in patients undergoing TURP. Widowed or single marital status, frequent alcohol consumption, moderate or severe LUTS, longer duration of BPH, ED, urinary incontinence and comorbidities such as diabetes and bladder stone are connected with the increase odds of moderate or severe depressive symptom.

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.

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.

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.

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.

The relationship between vascular endothelial growth factor and spermatogenesis disturbance in an experimentally-induced unilateral cryptorchidism murine model.

This study is to explore the relationship between vascular endothelial growth factor (VEGF) and pathological changes in cryptorchidism by using murine model of intraperitoneal cryptorchidism with surgical operation. To investigate the relationship between the changes of VEGF expression and heat stress inducing germ cell damage in testicular tissue. Six-week-old ICR male mice were operated to make unilateral cryptorchidism mouse model. Here in our study, a remarkable damaged of germ cells are seen in murine model of unilateral cryptorchidism. And the expression of VEGF was significantly changed in a time dependent way and consistent with the pathological changes of testis, this leading us to conclude that there was a negative correlation between VEGF levels and germ cell damage in unilateral cryptorchidism mouse model. We propose that there is a time dependent decrease of VEGF expression in cryptorchidism and confirm that VEGF is essential in spermatogenesis disorder caused by cryptorchidism and non-obstructive azoospermia.

Changes in sexual performance and biochemical characterisation of functional neural regions: A study in serotonin transporter knockout male rats.

To explore the correlation between SERT expression and sexual activities and seek the possible mechanism of SERT in regulating ejaculations, we analysed the sexual activities and biochemical characteristics of five measured neural regions in three rat genotypes (SERT-/- , SERT+/- and SERT+/+ ). The results showed the SERT-/- group showed fewer ejaculations and a longer ejaculation latency than the SERT+/+ group, while the SERT+/- group did not differ significantly from the SERT+/+ group in sexual performance. In addition, the SERT-/- group showed an almost complete absence of SERT mRNA and protein expression in all measured regions. In the SERT+/- group, the SERT mRNA and SERT protein expressions were downregulated by approximately 50% and 35%, respectively, compared to the SERT+/+ group. The SERT-/- group had the highest 5-HT levels, and the 5-HT level in the SERT+/- group was between the other two groups. Besides, the 5-HT levels differed in almost all measured regions of the three groups. Therefore, our study confirmed that SERT played a key role in sexual performance. A certain amount of SERT protein may be critical to normal sexual performance. Hence, Polymorphisms of the SERT gene should still be highlighted for ejaculation regulation research.

[Correlation between the phenotypic domains of the UPOINT system and sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome].

OBJECTIVE: To investigate the correlation of the six phenotypic domains of the UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, and tenderness) system with premature ejaculation (PE) and ED in male patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We collected the clinical data on 453 cases of CP/CPPS from December 2016 to December 2017, including the general information, CP symptoms, sexual life history, intravaginal ejaculatory latency time (IELT), NIH-CPSI, and IIEF-5 scores. We classified the patients according to the UPOINT system. RESULTS: The CP/CPPS patients were aged 32.75 ± 6.85 years, of whom 45.03% (204/453) were diagnosed with ED and 43.27% (196/453) with PE. The positive rates of the six phenotypic domains of the UPOINT system were 68.78% (U), 60.21% (P), 77.45% (O), 20.34% (I), 46.83% (N), and 65.12% (T), respectively. Multivariate logistic regression analysis showed psychosocial (P) abnormality to be an independent risk factor for PE (OR = 4.55, 95% CI: 2.75－8.06, P < 0.05) and ED (OR = 3.35, 95% CI: 2.02－6.25, P < 0.05). CONCLUSIONS: The psychosocial (P) factor in the UPOINT system plays an important role in the pathogenesis of PE and ED in patients with CP/CPPS.

miR-34c disrupts spermatogonial stem cell homeostasis in cryptorchid testes by targeting Nanos2.

BACKGROUND: Cryptorchidism as a common genitourinary malformation with the serious complication of male infertility draws widespread attention. With several reported miRNAs playing critical roles in spermatogonial stem cells (SSCs), we aimed to explore the fundamental function of the highly conserved miR-34c in cryptorchidism. METHODS: To explore whether miR-34c participates in spermatogenesis by regulating Nanos2, we examined the effect of overexpression and inhibition for miR-34c on Nanos2 expression in GC-1 cells. Moreover, the expression levels of miR-34c and Nanos2 with cryptorchidism in humans and mice were examined. Furthermore, the homeostasis of SSCs was evaluated through counting the number of promyelocytic leukemia zinc finger (PLZF) positive spermatogonia in murine cryptorchid testes. RESULTS: In the present study, we show that miR-34c could inhibit the expression of Nanos2 in GC-1 cells. Meanwhile, miR-34c significantly decreased in both the testicular tissues of patients with cryptorchidism and surgery-induced murine model of cryptorchidism. Western blot revealed that the protein level of Nanos2 was up-regulated and showed to be negatively correlated to the expression of miR-34c in our model. The abnormal expression of miR-34c/Nanos2 disrupted the balance between SSC self-renewal and differentiation, eventually damaging the spermatogenesis of cryptorchid testes. CONCLUSIONS: The miR-34c/Nanos2 pathway provides new insight into the mechanism of male infertility caused by cryptorchidism. Our results indicate that miR-34c may serve as a biological marker for treatment of infertility caused by cryptorchidism.

Altered miRNA profile in testis of post-cryptorchidopexy patients with non-obstructive azoospermia.

BACKGROUND: Cryptorchidism is one of the most common causes of non-obstructive azoospermia (NOA) leading to male infertility. Despite various medical approaches been utilised, many patients still suffer from infertility. MicroRNAs (miRNAs) play vital roles in the progress of spermatogenesis; however, little is known about the miRNA expression profile in the testes. Therefore, the miRNA profile was assessed in the testis of post-cryptorchidopexy patients. METHODS: Three post-cryptorchidopexy testicular tissue samples from patients aged 23, 26 and 28 years old and three testis tissues from patients with obstructive azoospermia (controls) aged 24, 25 and 36 years old were used in this study. Next-generation sequencing (NGS) was used to perform the miRNA expression profiling. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assays were subsequently used to confirm the results of several randomly-selected and annotated miRNAs. RESULTS: A series of miRNAs were found to be altered between post-cryptorchidopexy testicular tissues and control tissues, including 297 downregulated and 152 upregulated miRNAs. In the subsequent qRT-PCR assays, the expression levels of most of the selected miRNAs (9/12, P < 0.05) were consistent with the results of NGS technology. Furthermore, signal transduction, adaptive immune response and biological regulation were associated with the putative target genes of the differentially-expressed miRNAs via GO analysis. In addition, oxidative phosphorylation, Parkinson's disease and ribosomal pathways were shown to be enriched using KEGG pathway analysis of the differentially-expressed genes. CONCLUSIONS: This study provides a global view of the miRNAs involved in post-cryptorchidopexy testicular tissues as well as the altered expression of miRNAs compared to control tissues, thus confirming the vital role of miRNAs in cryptorchidism.

Validity of premature ejaculation diagnostic tool and its association with International Index of Erectile Function-15 in Chinese men with evidence-based-defined premature ejaculation.

The premature ejaculation diagnostic tool (PEDT) is a brief diagnostic measure to assess premature ejaculation (PE). However, there is insufficient evidence regarding its validity in the new evidence-based-defined PE. This study was performed to evaluate the validity of PEDT and its association with IIEF-15 in different types of evidence-based-defined PE. From June 2015 to January 2016, a total of 260 men complaining of PE and defined as lifelong PE (LPE)/acquired PE (APE) according to the evidence-based definition from Andrology Clinic of the First Affiliated Hospital of Anhui Medical University, along with 104 male healthy controls without PE from a medical examination center, were enrolled in this study. All individuals completed questionnaires including demographics, medical and sexual history, as well as PEDT and IIEF-15. After statistical analysis, it was found that men with PE reported higher PEDT scores (14.28 ± 3.05) and lower IIEF-15 (41.26 ± 8.20) than men without PE (PEDT: 5.32 ± 3.42, IIEF-15: 52.66 ± 6.86, P < 0.001 for both). It was suggested that a score of ≥9 indicated PE in both LPE and APE by sensitivity and specificity analyses (sensitivity: 0.875, 0.913; specificity: 0.865, 0.865, respectively). In addition, IIEF-15 were higher in men with LPE (42.64 ± 8.11) than APE (39.43 ± 7.84, P < 0.001). After adjusting for age, IIEF-15 was negatively related to PEDT in men with LPE (adjust r = -0.225, P < 0.001) and APE (adjust r = -0.378, P < 0.001). In this study, we concluded that PEDT was valid in the diagnosis of evidenced-based-defined PE. Furthermore, IIEF-15 was negatively related to PEDT in men with different types of PE.

Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model.

RNA binding protein polypyrimidine tract binding protein 2 (Ptbp2) as a key alternative splicing regulator for male germ cell development is well established. However, its expression levels and role in cryptorchidism testes tissues has not been explored. Additionally, the molecular mechanism of heat stress impacts the correct proliferation and differentiation of germ cells is unclear. To investigate whether changes in Ptbp2 expression are correlated with heat stress-induced germ cell injury in testicular tissue, we used a murine model of intraperitoneal cryptorchidism with surgical operation. Here we present compelling evidence that germ cells are severely damaged in mice with unilateral cryptorchidism, with non-obstructive azoospermia. And the Ptbp2 and Pgk2 mRNA levels were significantly decreased in parallel, leading us to conclude that the negative correlation between Ptbp2 levels and germ cell injury in unilateral cryptorchidism murine model. We hypothesize that Ptbp2 is susceptible to heat stress and its disruption has resulted in stability decline of germ cell transcripts Pgk2 mRNA, which consequently lead to germ cell injury in cryptorchidism testes. Thus, we confirm that Ptbp2 is an essential factor in heat stress-induced sperm cell injury and non-obstructive azoospermia.

Prevalence and Associated Factors of Premature Ejaculation in the Anhui Male Population in China: Evidence-Based Unified Definition of Lifelong and Acquired Premature Ejaculation.

INTRODUCTION: In 2014, new evidence-based definitions of lifelong premature ejaculation (LPE) and acquired premature ejaculation (APE) were proposed by the International Society for Sexual Medicine. Based on the new PE definitions, the prevalence of and factors associated with LPE and APE have not been investigated in China. AIM: To evaluate the prevalence of and factors associated with LPE and APE in men with the complaint of PE in China. METHODS: From December 2011 to December 2015, a cross-sectional field survey was conducted in five cities in the Anhui province of China. Questionnaire data of 3,579 men were collected in our database. The questionnaire included subjects' demographic information and medical and sexual histories. Men who were not satisfied with their time to ejaculate were accepted as having the complaint of PE. Men with the complaint of PE who met the new definition of PE were diagnosed as having LPE or APE. MAIN OUTCOME MEASURES: New definition of LPE and APE. RESULTS: Of 3,579 men who completed the questionnaire, 34.62% complained of PE. Mean age, body mass index, and self-estimated intravaginal ejaculatory latency time for all subjects were 34.97 ± 9.02 years, 23.33 ± 3.56 kg/m2, and 3.09 ± 1.36 minutes, respectively. The prevalences of LPE and APE in men with the complaint of PE were 10.98% and 21.39%, respectively. LPE and APE were associated with age, body mass index, and smoking and exercise rates (P < .001 for all comparisons). Men with APE reported more comorbidities than men with LPE, especially in the presence of hypertension, diabetes mellitus, and heart disease (P < .001 for all comparisons). CONCLUSION: In this study, the prevalences of LPE and APE in men with the complaint of PE were 10.98% and 21.39%, respectively. Patients with APE were older and more likely to smoke, had more comorbidities, and had a higher body mass index than patients with LPE.

Association of STin2 VNTR Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects.

BACKGROUND The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). MATERIAL AND METHODS We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31-0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. CONCLUSIONS Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers.