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Urology Feb 2024
Topics: Male; Humans; Ejaculation; Premature Ejaculation
PubMed: 38123435
DOI: 10.1016/j.urology.2023.09.069 -
Urology Feb 2024
Topics: Humans; Male; Premature Ejaculation
PubMed: 38123434
DOI: 10.1016/j.urology.2023.09.070 -
Basic and Clinical Andrology Dec 2023
PubMed: 38110891
DOI: 10.1186/s12610-023-00216-9 -
Effects of CYP2D6 *10 and *41 Variants in Healthy Chinese Men on the Pharmacokinetics of Dapoxetine.Journal of Clinical Pharmacology May 2024Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and...
Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and flavin-containing monooxygenase 1. The purpose of the study was to evaluate the effect of CYP2D6 polymorphism on the pharmacokinetics of dapoxetine in healthy Chinese men. Thirty-nine subjects who received a single oral dose of 30 mg dapoxetine hydrochloride were classified based on their CYP2D6 genotype: *1/*1 (n = 9), *1/*41 (n = 1), *1/*10 (n = 12), *10/*41 (n = 3), or *10/*10 (n = 14). The difference in pharmacokinetic parameters between different genotype groups was analyzed and then scored according to the activity score system. Compared with the wild-type subjects of CYP2D6 *1/*1, the peak plasma concentration (C) and the area under the plasma drug concentration-time curve (AUC) of dapoxetine in the *10/*10 and *10/*41 groups were notably increased (P ≤ .05). Significant differences in C, AUC, volume of distribution/bioavailability (V/F) and clearance/bioavailability (CL/F) were observed among dapoxetine activity score groups (P ≤ .05). The AUC was increased significantly (154% and 89.73%, P ≤ .05) and the C was increased significantly (73.45% and 42.67%, P ≤ .05) in CYP2D6 *10/*41 subjects, compared with CYP2D6 *1/*1 and *1/*10 subjects. The results obtained indicated that CYP2D6 *10 and *41 polymorphisms have significant effects on the pharmacokinetic properties of dapoxetine.
Topics: Humans; Male; Cytochrome P-450 CYP2D6; Benzylamines; Naphthalenes; Adult; Selective Serotonin Reuptake Inhibitors; Asian People; Young Adult; Genotype; Polymorphism, Genetic; Area Under Curve; Healthy Volunteers; East Asian People
PubMed: 38059315
DOI: 10.1002/jcph.2391 -
The Journal of Sexual Medicine Jan 2024Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders. (Observational Study)
Observational Study
BACKGROUND
Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders.
AIM
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.
OUTCOMES
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).
CLINICAL IMPLICATIONS
By investigating polymorphisms in target genes the neuro-pathophysiology of LPE could be further elaborated, potentially leading to more effective treatment.
STRENGTHS AND LIMITATIONS
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.
Topics: Humans; Male; Case-Control Studies; Polymorphism, Genetic; Premature Ejaculation; Receptor, Serotonin, 5-HT1B
PubMed: 38050328
DOI: 10.1093/jsxmed/qdad159 -
Basic and Clinical Andrology Dec 2023Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried...
BACKGROUND
Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE).
RESULTS
The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all).
CONCLUSION
Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it's efficacy and superiority.
PubMed: 38049720
DOI: 10.1186/s12610-023-00210-1 -
Sexual Medicine Oct 2023Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with...
BACKGROUND
Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with multiple psychological disorders, such as depression and anxiety. However, the correlation between PE and TDP remains unknown.
AIM
The study sought to investigate the relationships between depressive symptoms, TDP, and PE.
METHODS
Adult males in Taiwan who were 20 to 40 years of age and who had sexual intercourse in the past 6 months were recruited to complete online questionnaires composed of general demographics, the Premature Ejaculation Diagnostic Tool (PEDT), 5-item International Index of Erectile Function (IIEF-5), Type D Scale-14, and Depression and Somatic Symptom Scale (DSSS). Chi-square test and independent Student's test were used to compare the parameters between the TDP and non-TDP groups. Univariate and multivariate logistic regression analyses were conducted to evaluate factors related to PE.
OUTCOMES
Outcomes were the prevalence of PE and TDP in young Taiwanese men, the associations between depressive symptoms and PE and TDP, and the predictive factors of PE.
RESULTS
In total, 2558 men with a mean age of 31.3 ± 5.3 years were included in the present study. Among them, 315 (12.3%) and 767 (30.1%) participants were classified as having PE and moderate-to-severe erectile dysfunction (ED), respectively. In total, 1249 (48.8%) participants met the criteria for TDP. The PEDT, IIEF-5, and DSSS, including the total scores and depression and somatic subscales, were significantly higher in men with TDP (all < .001). PE prevalence was significantly greater in men with TDP than in those without TDP (16.2% vs 8.6%; < .001). Most parameters, including age, moderate-to-severe ED, the Type D Scale-14 subscales, and the DSSS somatic and depressive subscales, were significantly associated with PE in the univariate analysis. Only the depressive subscale of the DSSS and moderate-to-severe ED (IIEF-5 ≤16) were the independent predictors of PE in the multivariate analysis.
CLINICAL IMPLICATIONS
The results suggest that it is important to consider the psychological effects of PE in young men, and the study has provided a biopsychosocial aspect to manage patients with PE.
STRENGTHS AND LIMITATIONS
This is the first study to evaluate the association between PE, TDP, and depression in a large population of young adult males. However, the cross-sectional design may have limited the investigation of causality, and selection bias may be present.
CONCLUSION
Men with TDP tended to have higher PEDT scores and a prevalence of PE and ED. Moderate-to-severe ED and depressive symptoms are the independent predictive factors of PE.
PubMed: 38028734
DOI: 10.1093/sexmed/qfad055 -
International Journal of Pharmaceutics Jan 2024Sildenafil citrate is an approved drug used for the treatment of erectile dysfunction and premature ejaculation. Despite a widespread application, sildenafil citrate...
Sildenafil citrate is an approved drug used for the treatment of erectile dysfunction and premature ejaculation. Despite a widespread application, sildenafil citrate shows numerous adverse cardiovascular effects in high-risk patients. Local transdermal drug delivery of this drug is therefore being explored as an interesting and noninvasive alternative administration method that avoids adverse effects arised from peak plasma drug concentrations. Although human and animal skin represents the most reliable models to perform penetration studies, they involve a series of ethical issues and restrictions. For these reasons new in vitro approaches based on artificially reconstructed human skin or "human skin equivalents" are being developed as possible alternatives for transdermal testing. There is little information, however, on the efficiency of such new in vitro methods on cutaneous penetration of active ingredients. The objective of the current study was to investigate the sildenafil citrate loaded in three commercial transdermal vehicles using 3D full-thickness skin equivalent and compare the results with the permeability experiments using porcine skin. Our results demonstrated that, while the formulation plays an imperative role in an appropriate dermal uptake of sildenafil citrate, the D coefficient results obtained by using the 3D skin equivalent are comparable to those obtained by using the porcine skin when a simple drug suspension is applied (1.17 × 10 ± 0.92 × 10 cm/s vs 3.5 × 10 ± 3.3 × 10 cm/s), suggesting that in such case, this 3D skin model can be a valid alternative for ex-vivo skin absorption experiments.
Topics: Male; Animals; Swine; Humans; Sildenafil Citrate; Foreskin; Skin; Skin Absorption; Administration, Cutaneous
PubMed: 37992980
DOI: 10.1016/j.ijpharm.2023.123612 -
Translational Andrology and Urology Oct 2023Premature ejaculation (PE) is a common sexual disorder among male adults and negatively impacts a man's sexual life. Currently, the mainstay treatment of PE is still... (Review)
Review
BACKGROUND AND OBJECTIVE
Premature ejaculation (PE) is a common sexual disorder among male adults and negatively impacts a man's sexual life. Currently, the mainstay treatment of PE is still medical therapy which has drawbacks among patients as a consequence of side effects. Despite the new definitions, the evolution of medical therapy, and the consensus for the management of PE, it remains challenging to treat for many clinicians especially when medical treatment fails. However, the International Society for Sexual Medicine (ISSM) and the American Urological Association (AUA) guidelines ignored surgical therapy due to conflicting medical reports and doubts about the safety of surgical management. This article discusses the surgical management of PE based on recent guidelines, reviews, and evolving techniques.
METHODS
We reviewed the literature using PubMed and searched for the following keywords: premature ejaculation, selective dorsal neurectomy, hyaluronic acid, dorsal nerve neuromodulation, cryo-ablation of the dorsal nerve and inner condom technique until May 2023. Seventeen studies were found.
KEY CONTENT AND FINDINGS
Even though the widespread use of many surgical modalities in Asia such as glans penis augmentation (GPA) using hyaluronic acid (HA) selective dorsal neurectomy (SDN), cryo-ablation of the dorsal nerve, neuromodulation of the dorsal nerve (NMDN), and circumcision are still considered as controversial for the guidelines.
CONCLUSIONS
The mainstay treatment of PE is still pharmaceutical. However, the current body of evidence on surgical treatments for PE is limited. Men considering surgical therapy for PE should be counseled well for the risks and benefits as there may be chronic disabilities. Further, well-designed trials are needed to establish safety and efficacy for the surgical treatment.
PubMed: 37969778
DOI: 10.21037/tau-23-240 -
Sexual & Reproductive Healthcare :... Dec 2023A mixed-methods study was conducted to investigate sexual function among infertile patients undergoing medically assisted procreation for the first time. The study...
A mixed-methods study was conducted to investigate sexual function among infertile patients undergoing medically assisted procreation for the first time. The study employed an interview and content analysis approach, involving 45 infertile patients prior to their medically assisted procreation procedures. The findings revealed that infertile patients are a group at risk for sexual distress. Furthermore, patients with sexual dysfunctions exhibited lower levels of sexual activity, potentially diminishing their chances of achieving pregnancy. Participants faced challenges in openly discussing their sexual problems and demonstrated limited knowledge of sexual functioning. Among infertile women with sexual dysfunctions, the most frequently reported issues were sexual interest/arousal disorders, with a majority also experiencing pain during sexual activity and associated genital-pelvic pain disorders. In contrast, delayed ejaculation and erectile disorder seem to be more common in infertile men, while sexual desire and excitement disorders and premature ejaculation disorders appeared to be as common as in the general population. While the relationship between infertility and sexuality is complex, our study suggests that sexual dysfunctions or the absence of sexual activity may explain infertility. Therefore, it is imperative for clinicians to evaluate the sexual functioning of both men and women undergoing medically assisted procreation treatment, to increase their chances of procreation and offer them sexological support if needed. Future studies should expand their scope to include a larger sample size and delve into the potential etiological factors associated with sexual dysfunctions.
Topics: Male; Pregnancy; Humans; Female; Infertility, Female; Sexual Behavior; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Sexuality
PubMed: 37951081
DOI: 10.1016/j.srhc.2023.100922