OBJECTIVE: To investigate whether serum hormone (testosterone, prolactin, gonadotropins, and thyroid hormones) and vitamin (vitamin B12, folic acid, and vitamin D) levels are associated with premature ejaculation (PE).
METHODS: This prospective case-control study included 126 patients with PE (lifelong PE [LPE] in 94 and acquired PE [APE] in 32) who presented to the urology outpatient clinic between April 2016 and January 2023 and 92 healthy men as a control group. The diagnosis of PE was based on the criteria defined by the International Society for Sexual Medicine. Serum total testosterone (TT), free and bioavailable testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone, free triiodothyronine, thyroxine (fT4), vitamin B12, folic acid, and vitamin D levels were measured.
RESULTS: Serum TT, fT4, and vitamin D levels were significantly higher in patients with PE than in the control group (p=0.022, p=0.002, and p=0.044, respectively). However, the serum vitamin B12 level was significantly lower in the PE group (p=0.021). In the multivariate logistic regression analysis, only vitamin B12 was found to be an independent risk factor for PE, with an estimated odds ratio of 0.997 (95% confidence interval 0.994-0.999, p=0.036).
CONCLUSIONS: This study demonstrated that lower vitamin B12 levels are associated with the presence of PE. Therefore, we believe that it would be beneficial to consider vitamin B12 levels in the evaluation of patients with PE.

BACKGROUND: Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders.
OBJECTIVE: In this study we sought to evaluate the genetic association between the rs6296 polymorphism of the 5-HT1b receptor and intravaginal ejaculation latency times (IELTs) in men with LPE compared with men in a control group.
METHODS: This study was a prospective observational genetic case-control association study. The LPE definition of the International Society for Sexual Medicine (ISSM) 2013 was used. Patients were recruited in 2005-2009 while attending the department of Neurosexology, HagaZiekenhuis, the Netherlands. We obtained IELTs with the stopwatch method. Polymerase chain reaction (PCR) was used for genotyping rs6296. A randomly selected group of European Caucasian men from the 1000GENOMES project was used as a control group.
RESULTS: Study outcomes included results of comparisons of analysis of variance (ANOVA) tests between genotypes and IELTs in study participants, genotypes of cases and controls determined with the chi-square test, and expressions of allelotype- and genotype-specific risks for LPE determined with odds ratios.
RESULTS: In total, 67 men with LPE were included in this study. The geometric mean (SD) IELT was 32.0 (27.4) seconds and was non-normally distributed. Genotype frequencies consisted of 29 (43.3%) GG, 31 (46.3%) GC, and 7(10.4%) CC individuals in the LPE group. Log-transformed IELTs were not statistically significant (per ANOVA tests) in men with GG, GC, or CC genotypes (P = .54). Genotype frequencies consisted of 16 (6.6%) GG; 93 (38.8%) GC, and 131 (54.6%) CC individuals in the control group (n = 240). Significant differences were found when comparing allele (P = 1.02e-17) and genotype (P = 3.22e-16) frequencies in cases and controls using a chi-square test. A statistically significant increased risk for LPE was found for carriers of the G allele (OR 5.62; 95% CI 4.13-9.42). Statistically significant risks were also found for the CG genotype (OR 6.24; 95% CI 2.63-14.77) and the GG genotype (OR 33.92; 95% CI 12.79-89.93).
CONCLUSIONS: By investigating polymorphisms in target genes the neuro-pathophysiology of LPE could be further elaborated, potentially leading to more effective treatment.
UNASSIGNED: This is to our knowledge the first study investigating rs6296 with regard to LPE. By using a strict definition for LPE (ISSM 2013) and using the stopwatch method for measuring IELTs, bias in selection of true LPE patients will be relatively low. This study is limited by a relatively small study population and the lack of IELT data in the control group.
CONCLUSIONS: This study shows a genetic association in rs6296 in men with LPE compared with healthy controls. This result warrants attempted replication in future studies.

Premature ejaculation (PE) is a common male sexual dysfunction disorder, and is considered to have the genetic predisposition. However, the internal regulation mechanisms is still unclear. Hence, this study intended to explore the effects of genetic polymorphisms of CYP24A1 on the risk of PE. This case-control study genotyped three SNPs of CYP24A1 (rs2762934, rs1570669 and rs6068816) from 139 PE patients and 372 healthy men using Agena MassARRAY platform. Collected data was then processed in SPSS 18.0. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression analysis to evaluate the associations between CYP24A1 polymorphisms and the PE risk. The results suggested that allele A of rs1570669 was significantly associated with the increased PE risk (OR=1.38, 95% CI=1.04-1.84, P=0.026). Meanwhile, we also identified rs1570669 as a risk factor of PE under the additive model (OR=1.47, 95% CI=1.02-2.11, P=0.039) by comparing the genotypic distributions between cases and controls, and genotype AA of rs1570669 was detected to be significantly related with an increased risk of PE under the codominant model (OR=2.26, 95% CI=1.06-4.83, P=0.036). This study is the first to proved that the genetic variants of CYP24A1 played essential role in affecting the susceptibility to PE in Chinese Han.

We aimed to determine the level of miRNAs 16 and 135a in lifelong premature ejaculation (LPE) patients versus controls. Moreover, we evaluated the potential interplay between the studied miRNAs and fluoxetine in these patients after utilizing fluoxetine daily for 3 months. The study involved 60 consecutive LPE patients and 20 healthy age matched individuals as controls. The median miRNA16 was significantly higher in the controls (1.02) compared to the patients (0.31) (p < 0.001). Moreover, the median miRNA-135a was significantly higher in the controls compared to the patients 1.02 and 0.35, p < 0.001, respectively. In addition, the median pre-treatment miRNA16 in the responders was 0.29 that significantly increased to 0.66 (p < 0.001). The median pre-treatment miRNA-135a in the responders was 0.27 that significantly increased to 0.65 (p < 0.001). Furthermore, considering EXP(β) for the odds ratio evaluation, with a 95% degree of confidence, a 1 fold increase in pre-treatment miRNA 135a fold change decreases the odds for being responsive to SSRI by 0.028. Meanwhile, there was non-significant association between fluoxetine responsiveness and age, pre-treatment miRNA 16, pre-treatment PEDT and pre-treatment IELT. The current study had shown that a lower pre-treatment miRNA 135a was significantly associated with response to fluoxetine.

Previous studies on the association between serotonin transporter linked polymorphic region (5-HTTLPR) polymorphism and premature ejaculation (PE) have led to inconsistent results. The purpose of the present meta-analysis was to examine whether 5-HTTLPR polymorphism is associated with PE susceptibility.All eligible studies were searched and acquired from PubMed, Embase, Science Direct, CNKI, and Wanfang databases according to inclusion and exclusion criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed to assess the strength of the association between 5-HTTLPR polymorphism and PE. In addition, heterogeneity test, publication bias and sensitivity analysis were also conducted.Firstly, the association were observed in 8 studies (L vs S: OR = 0.74, 95% CI = 0.63-0.87; LL vs SS: OR = 0.61, 95% CI = 0.44-0.83; SL vs SS: OR = 0.73, 95% CI = 0.55-0.96; LL + SL vs SS: OR = 0.67, 95% CI = 0.52-0.86; LL vs SL + SS: OR = 0.72, 95% CI = 0.55-0.92). When the 2 studies not in Hardy-Weinberg equilibrium (HWE) were omitted, a positive association could only be observed between the 5-HTTLPR polymorphism and PE in allele contrast model (L vs S: OR = 0.81, 95% CI = 0.67-0.98). In the stratified analysis by subgroup, significantly associations were also found between PE and 5-HTTLPR polymorphism in Caucasians but not Asians (L vs S: OR = 0.79, 95% CI = 0.63-0.98; LL + SL vs SS: OR = 0.67, 95% CI = 0.46-0.96).Our meta-analysis demonstrated that the 5-HTTLPR polymorphism was associated with the susceptibility to PE in the Caucasian population. Compared with S allele, L allele is likely to be less susceptible to PE.

Over-the-counter (OTC) opioid abuse, including codeine, has been a growing problem around the world. Although the majority of the abusers use it for recreational purposes, many become dependent on it after having used it a medication for pain or cough. We present a case of codeine dependence where the initial prescribed use had been as a cough medication, but the subsequent abuse of it occurred the following self-medication for premature ejaculation. There is growing need for awareness among doctors and pharmacists of OTC abuse of opioids and for preventive interventions such as restricting supply, audit of pharmacies, training pharmacists, and counter staff and dispensing knowledge about proper use of opioid-containing medications to patients.

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.

The aim of this study was to investigate whether vitamin B12 levels are associated with premature ejaculation (PE). A total of 109 subjects (56 PE and 53 controls) were included in this study. PE was defined as self-reported intravaginal ejaculatory latency time (IELT) based on the Diagnostic and Statistical Manual of Mental Disorders IV criteria and those who had had an IELT of <2 min was considered as PE. All participants were evaluated using premature ejaculation diagnostic tool (PEDT), International Index of Erectile Function (IIEF) and Beck Depression Inventory (BDI). The vitamin 12 levels were measured in all subjects. The mean age between the PE and controls was comparable (p = .084). Mean IIEF and BDI scores between the two groups did not statistically differ. The mean IELT values in the PE group were significantly lower than in the control group (p < .0001). PE patients reported significantly lower vitamin B12 levels compared with the controls (213.14 vs. 265.89 ng ml-1 ; p < .001). The ROC analysis showed a significant correlation between the diagnosis of PE and lower vitamin B12 levels. This study has demonstrated that lower vitamin B12 levels are associated with the presence of PE. This work also shows a strong correlation between vitamin B12 levels and the PEDT scores as well as the IELT values.

BACKGROUND This study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications. MATERIAL AND METHODS A total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L\'L\' genotype (OR=0.37; 95%CI=0.15-0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes. CONCLUSIONS Contrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies.

Premature ejaculation (PE) is considered to be the most common form of male sexual dysfunction. Given that acute oral administration of d-isomer of modafinil (d-modafinil) can extend the latency to ejaculation in rats without suppressing sexual behaviour, the effects of on-demand d-modafinil treatment were examined on a 30-year-old male patient with lifelong PE. The patient was instructed to take d-modafinil 100 mg 3 h prior to the sexual relation for four times and was invited for a control visit. The patient was re-evaluated 2 weeks later. He reported that his IELT increased to 15 min. He reported heartburn and insomnia when he used d-modafinil for the first time; however, these symptoms were transient and did not recur after the initial dose. Overall, he reported considerable improvement and noted that he feels much better with the treatment. Based on this limited data, on-demand d-modafinil seems to be an effective treatment for men with lifelong PE. The side effects were transient and mild in the reported case. Further randomised clinical trials are necessary to elucidate the therapeutic concept of this drug in patients with lifelong PE.