Is bulbospongiosus muscle botox injection safe and effective in treating lifelong premature ejaculation? Randomized controlled study.

PURPOSE: To evaluate the safety and efficacy of botulinum-A toxin injections into the bulbospongiosus muscle for cases of lifelong drug-resistant premature ejaculation (PE). METHODS: Ninety-eight outpatients diagnosed with lifelong PE were randomly assigned to two groups: the botulinum-A toxin group comprising forty-nine patients and the placebo (saline) group also consisting of forty-nine patients. A 100 U botulinum-A toxin was diluted into 10 cc of saline, with 5 cc injected into one side of the muscle (botulinum-A toxin group) guided by ultrasound to distribute across most muscle fibers. The same technique was applied using the same volume of saline injected into the bulbospongiosus muscle. Intravaginal ejaculatory latency time (IELT), scores from the premature ejaculation profile (PEP), Premature Ejaculation Diagnostic Tool (PEDT), International Index of Erectile Function (IIEF), and recording of any complications were obtained. Follow-ups occurred at 1-, 3-, and 6-month post-procedure. RESULTS: Cases receiving injections of botulinum-A toxin into the bulbospongiosus muscle showed notably extended intravaginal ejaculatory latency times compared to their initial performance after treatment. In addition, there were enhancements in PEP scores, and notably, no significant complications were reported. Conversely, the bilateral injection of saline into the bulbospongiosus muscle did not demonstrate any impact on ejaculation latencies. CONCLUSION: Our study demonstrated that the injection of botulinum-A toxin into the bulbospongiosus muscle can serve as a safe and effective option for treating PE. Nonetheless, its clinical application warrants further studies involving larger sample sizes and longer follow-up periods.

Effect of Serum Vitamin B12 Levels on Premature Ejaculation.

OBJECTIVE: To assess the impact of vitamin B12 levels in the failure of the dapoxetine used in premature ejaculation (PE) treatment. STUDY DESIGN: Experimental study. Place and Duration of the Study: Andrology Clinic, between May and December 2020. METHODOLOGY: Patients with premature ejaculation complaints completed the Premature Ejaculation Diagnostic Tool (PEDT) questionnaire. Patients were also asked to fill in the Premature Ejaculation Profile (PEP) surveys. Intravaginal ejaculation latency time (IELT) were recorded based on the estimates of patients. Serum vitamin B12 levels were evaluated based on blood samples. All patients were advised to use dapoxetine 30 mg, 1-3 hours prior to intercourse. After four weeks, patients were asked to complete the PEP questionnaire again. IELT times were recorded. RESULTS: A total of 62 patients were included in the study. A total of 39 patients (62.90%) were satisfied with the treatment of the dapoxetine. In comparison to patients who benefited from dapoxetine treatment and those who did not, vitamin B12 levels of patients who did not benefit from dapoxetine were found to be significantly lower (p=0.005). CONCLUSION: Vitamin B12 deficiency can reduce the effectiveness of dapoxetine treatment in patients with PE. It is important to evaluate serum vitamin B12 levels for the evaluation of patients with PE. KEY WORDS: Premature ejaculation, Dapoxetine, Vitamin B12, Serotonin, Treatment.

From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

Effects of physical exercise interventions on ejaculation control.

INTRODUCTION: Premature ejaculation is a prevalent male sexual dysfunction that causes significant distress for men and their partners on a global scale. Despite its widespread impact, effective treatment options without undesirable side effects remain limited. OBJECTIVES: The present review aimed to provide an overview of experimental studies that analyzed the effects of physical exercise interventions on premature ejaculation. METHODS: The inclusion criteria for the review included: Population: Adult men. Intervention: An intervention designed to increase physical exercise was delivered in the study. Comparison: Before versus after intervention with or without a comparison group receiving a drug treatment or an active or no control intervention. Outcomes: Self-reported or clinician-rated premature ejaculation or its symptoms. Study type: Experimental designs. We conducted the search process in 9 databases: APA PsycNET, PubMed, Scopus, SPORTDiscus, JSTOR, ScienceDirect, Web of Science, Embase, and CAB Direct. This review included six intervention studies that included 433 participants (307 men with premature ejaculation) ranging from 18 to 50 years of age. All participants had a stable female sexual partner and had not any other physical or mental problems. RESULTS: The synthesized results indicated that yoga, running, and high-intensity interval training alleviate premature ejaculation symptoms in men with premature ejaculation after varying intervention duration times. The effectiveness of physical exercise for premature ejaculation symptoms was similar to that of drug treatments. CONCLUSION: Physical exercise can be one of the potential treatment modalities for premature ejaculation. The intensity of physical exercise and the effort of participants during exercise are key factors affecting improvements in ejaculation control. A potential limitation was that the review did not include any literature written in non-English languages.

Traditional, Complementary and Alternative Medicines in the Treatment of Ejaculatory Disorders: A Systematic Review.

Background and Objectives: Ejaculatory dysfunction (EjD) is a common male sexual disorder that includes premature ejaculation, delayed ejaculation, retrograde ejaculation, and anejaculation. Although psychological and pharmacological treatments are available, traditional, complementary, and alternative medicine (TCAM) is reportedly used. However, the clinical evidence for TCAM in EjD remains unclear. Therefore, this study aims to systematically review human clinical trials investigating the use of TCAM to treat EjD. Materials and Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted by searching Scopus and PubMed databases. Controlled clinical trials investigating a cohort of male patients diagnosed primarily with EjD and undergoing any TCAM intervention compared to any comparison group were included. Quality of the studies was assessed using the Cochrane Risk of Bias tool for randomized controlled trials. Results: Following article screening, 22 articles were included. Of these, 21 investigated TCAM in premature ejaculation, and only 1 investigated TCAM in retrograde ejaculation. Different TCAM categories included studies that investigated lifestyle, exercise and/or physical activities (n = 7); herbal medicine supplements (n = 5); topical herbal applications (n = 4); acupuncture or electroacupuncture (n = 3); vitamin, mineral and/or nutraceutical supplements (n = 1); hyaluronic acid penile injection (n = 1); and music therapy (n = 1). Only 31.8% (n = 7) of the included studies were found to have a low risk of bias. The available studies were widely heterogenous in the TCAM intervention investigated and comparison groups used. However, the included studies generally showed improved outcomes intra-group and when compared to placebo. Conclusions: Different TCAM interventions may have an important role particularly in the management of PE. However, more studies using standardized interventions are needed.

Management of erectile dysfunction and premature ejaculation: The perspective of Spanish urologists. Results of the PANDORA Project (Part II) / Manejo de la disfunción eréctil y la eyaculación precoz: la perspectiva de los urólogos españoles. Resultados del Proyecto PANDORA (Parte II)

Introduction: ED and PE are the most common male sexual dysfunctions, although they remain underdiagnosed and undertreated. Aim: To ascertain how a group of Spanish urologists currently address ED and PE. Methods: Descriptive study based on a self-designed questionnaire about the clinical practice in ED and PE upon diagnosis, treatment and monitoring, patient–physician relationship and the role of the patient's partner. Results: The survey was completed by 188 experienced urologists. Most patients went to the urologist's office without a previous diagnosis (92% of the urologists found <10 PE-diagnosed patients in public settings). The diagnosis of ED and/or PE was mainly carried out by the current urologist and not by another professional, particularly in private centres as opposed to public centres (78.8% vs 57.0% for ED; 82.0% vs 62.6% for PE). Most urologists believed that these disorders are underdiagnosed and deemed them as general health issues. 38% of urologists acknowledged using validated questionnaires to diagnose ED. PE was considered a subjective problem rather than a true disease and the use of PRO-based diagnosis of PE was not generally accepted (14%). Treatment options of both disorders were chosen as expected. Referral to the andrologist is usually scheduled in moderate-to-severe PE or severe ED. The cohort seemed to be mostly neutral (50%–75% for ED and 40%–55% for PE) regarding patient reluctancy to talk about their sexual problem. Patients’ partners play an important role in helping men seeking treatment. (AU)

Introducción: A pesar de que, la DE y la EP son las disfunciones sexuales masculinas más frecuentes, siguen estando infradiagnosticadas e infratratadas. Objetivo: Conocer cómo es el abordaje actual de la DE y la EP, a partir de un grupo de urólogos españoles. Método: Estudio descriptivo, mediante un cuestionario predefinido, con relación a la práctica clínica de la DE y la EP, incluyendo su diagnóstico, su tratamiento y su seguimiento, la relación médico-paciente y el papel de la pareja. Resultados: Ciento ochenta y ocho urólogos expertos dieron respuesta al cuestionario predefinido. La mayoría de los pacientes acudieron a la consulta del urólogo sin un diagnóstico previo (el 92% de los urólogos hallaron <10 pacientes diagnosticados de PE en el ámbito público). El diagnóstico de la DE y/o la EP fue realizado mayoritariamente por el urólogo, y no por otro profesional, especialmente en el ámbito privado frente al público (78,8 frente al 57,0% para la DE; 82,0 frente al 62,6% para la EP). La gran mayoría de los urólogos señalaron que ambas disfunciones estaban siendo infradiagnosticadas y, por tanto, las consideraron como un problema de salud general. El 38% de los urólogos indicó utilizar cuestionarios validados para el diagnóstico de la DE. La EP se percibió como un problema subjetivo más que como una verdadera enfermedad, y el uso de PRO en el diagnóstico de la EP no fue generalmente aceptado (14%). La elección de las opciones de tratamiento de ambas disfunciones aconteció según lo esperado. Se consideró la derivación a andrología en los casos de la EP moderada-grave o en los casos de la DE grave. En cuanto a la reticencia de los pacientes a hablar de su problema sexual, la respuesta fue mayoritariamente neutra (50-75% para la DE y 40-55% para la EP). Las parejas de los pacientes desempeñan un papel importante en el momento que estos buscan opciones de tratamiento. (AU)

Safety and Pharmacokinetics of PSD502 in Healthy Chinese Male and Female Volunteers: Two Randomized, Double-Blind, Placebo-Controlled, Phase I Trials.

BACKGROUND AND OBJECTIVE: PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. METHODS: Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. RESULTS: Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. CONCLUSIONS: PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

Retrospective evaluation of the efficacy of daily paroxetine/tadalafil combination in patients with premature ejaculation and erectile dysfunction.

OBJECTIVE: Premature ejaculation (PE) and erectile dysfunction (ED) are sexual dysfunction diseases affecting males. The phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are used to treat ED whereas selective serotonin reuptake inhibitors (SSRIs) are preferred for PE. Most of the patients with ED also suffer from PE simultaneously. The combined drug therapies are commonly preferred as they favor elevated intra-vaginal ejaculation latency time (IELT) scores and improved sexual function. The study aimed to evaluate the efficacy and safety of daily paroxetine and tadalafil combination therapy in patients with PE and ED. PATIENTS AND METHODS: A total of 81 PE patients with ED were enrolled in the study. Patients were treated with daily paroxetine 20 mg and tadalafil 5 mg for 4 weeks. Pre- and post-treatment IELT, premature ejaculation profile (PEP), and International Index of Erectile Function-Erectile Function (IIEF-EF) scores of the patients were analyzed. RESULTS: The mean IELT and PEP index scores, and mean IIEF-EF values improved after combination therapy (p<0.001 for each). When lifelong and acquired PE+ED patients were compared, significant improvements were observed in IELT, PEP, and IIEF-EF scores in both groups (p<0.001). CONCLUSIONS: Even though the treatment methods are different, combined therapies to treat simultaneous PE and ED presence are effective compared to monotherapies. However, there is still no definitive treatment that can cure all subtypes of PE or ED.

Hyaluronic acid injection to coronal sulcus of the penis for the treatment of premature ejaculation: a retrospective observational study.

BACKGROUND: Hyaluronic acid (HA) injection has become a burgeoning method to treat premature ejaculation (PE) due to its high biocompatibility and structural properties. PURPOSE: In this study, we proposed a modified technique: injecting hyaluronic acid around coronal sulcus to treat PE, aiming to decrease the complications of hyaluronic acid injection in penis while achieving similar effects. METHOD: A total of 85 patients who had HA injection from January 2018 to December 2019 were analyzed retrospectively in our study. 31 patients received injection at glans penis and 54 patients received injection around coronal sulcus. Intravaginal ejaculation latency time (IELT) was mainly measured to estimate the efficacy and the severity of complications was assessed between two groups. RESULTS: The mean IELT was 123.0 ± 37.28 s of all patients, 124.7 ± 39.01 s of patients injecting at glans penis and 121.9 ± 36.58 s of patients injecting around coronal sulcus. IELT of all patients increased to 482.1 ± 121.7 s at 1 month, 331.2 ± 81.2 s at 3 month and 280 ± 80.4 s at 6 month. In the group of injecting at glans penis, the incidence of complications is 25.8% and it is 1.9% in the group of injecting around coronal sulcus. No severe complication was reported in both groups. CONCLUSION: The modified technique of injecting around coronal sulcus decreases complications and it has the potential to become a new injectable technique for treating premature ejaculation.

Clinical Safety of a Pharmaceutical Formulation Containing an Extract of Acmella oleracea (L.) in Patients With Premature Ejaculation: A Pilot Study.

Acmella oleracea (L.) R. K. Jansen (Asteraceae) is a plant species widely used in traditional Amazonian medicine to treat sexual dysfunction. The use of this plant has gained popularity because of its sensory properties, such as a tingling sensation. In this study on patients with premature ejaculation, we evaluated the clinical action of a nano-formulation containing an ethanolic extract of A. oleracea inflorescences. Major constituents in the extracts were identified based on gas chromatographic analysis. Participants used a spray preparation based on the A. oleracea extract for 12 weeks, during which they were instructed to apply the product 5 min prior to sexual intercourse. To assess therapeutic efficacy, participants were required to record the mean intravaginal latency time for ejaculation (IELT). During the period of spray treatment, the nano-formulation of A. oleracea increased participant IELT values (M = 293 s) compared with the baseline values (193 s). This nano-formulation reported clinical action in patients with premature ejaculation. It is accordingly considered to have potential application as a therapeutic alternative with benefits for both patients and their partners. Given the small number of participants in this study, further multicenter studies involving a larger number of participants are needed to confirm these observations.

Podcast POEMs (BVS APS): Inibidores Seletivos da Recaptação da Serotonina e o tratamento da ejaculação precoce

Neste episódio vou apresentar outra revisão sistemática da Biblioteca Cochrane, avaliando os efeitos dos Inibidores Seletivos da Recaptação da Serotonina no tratamento da ejaculação precoce e suas condições associadas. Também vou comentar sobre diferenças entre ensaios clínicos paralelos e cruzados.

A novel on-demand therapy for lifelong premature ejaculation using a miniature transperineal electrical stimulator-the vPatch: an as-treated analysis.

BACKGROUND: While premature ejaculation (PE) is a common and disturbing sexual dysfunction in men, current available treatment modalities have limited efficacy and low treatment adherence. AIM: To assess the feasibility, safety, and efficacy of the vPatch, a miniaturized on-demand perineal transcutaneous electrical stimulation device for treating PE. METHODS: This prospective bicenter international first-in-human clinical study consisted of 2 arms, was sham controlled, and had a randomized double-blind design. In terms of statistical power calculation, 59 patients aged 21 to 56 years (mean ± SD, 39.8 ± 9.28) with lifelong PE were included. During the initial visit, intravaginal ejaculatory latency time (IELT) was measured over a 2-week run-in period. Eligibility was confirmed in visit 2, based on IELT values, medical and sexual history, and patients' individualized sensory and motor activation thresholds during perineal stimulation with the vPatch. Patients were randomized to the active (vPatch) and sham device groups in a 2:1 ratio, respectively. The vPatch device's safety profile was determined by comparing the incidence of treatment-emergent adverse events. During visit 3, IELTs, Clinical Global Impression of Change scores, and Premature Ejaculation Profile questionnaire outcomes were recorded. Primary end points assessed vPatch device efficacy as mean change in geometric mean IELT; each person was compared with himself, with and without the device, and the sham group was compared with the active group. OUTCOMES: Outcomes included changes in IELT and Premature Ejaculation Profile before and after treatment, last visit Clinical Global Impression of Change scores, and vPatch safety profile. RESULTS: Of 59 patients, 51 completed the study: 34 in the active group and 17 in the sham group. The baseline geometric mean IELT significantly increased from 67 to 123 seconds (P < .01) in the active group, as compared with an insignificant increase from 63 to 81 seconds (P = .17) in the sham group. The increase in mean IELT in the active group was significantly higher than in the sham group (56 vs 18 seconds, P = .01). IELT significantly increased by 3.1 times in the active vs sham group. The mean ratio of fold change (active:sham) was 1.4, significantly different from 1.0 (P = .02). No serious adverse events were reported. CLINICAL IMPLICATIONS: Therapeutic use of the vPatch during coitus may become an on-demand, noninvasive, and drug-free treatment for PE. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first rigorous study investigating whether transcutaneous electrical stimulation during coitus could improve the symptoms of men with lifelong PE. The study is limited by the small number of patients, the exclusion of patients with acquired PE, the short-term follow up, and the use of a device based on a theoretic mechanism of action. CONCLUSION: We demonstrated the possibility to treat lifelong PE by prolonging coitus on demand, using electric stimulation of ejaculation muscles with the vPatch.Clinical trial registration: NCT03942367 (ClinicalTrials.gov).

The role of tyrosine hydroxylase within dapoxetine-assisted therapy against premature ejaculation.

BACKGROUND: There are several investigations that have revealed that cerebral dopamine (DA) plays a pivotal role in the occurrence of premature ejaculation (PE). Although tyrosine hydroxylase (TH) is an essential enzyme for the synthesis of DA, only few investigations have described the role of TH in regulation mechanisms for ejaculation till now. To investigate whether there is a correlation between TH expression level in the brain and different ejaculation behavior in rats. Then explore whether the TH expression in the brain will change after acute dapoxetine treatment in rats with Rapid ejaculation. METHODS AND RESULTS: Rats (male, S-D rats, 6-8 weeks) were separated into three groups based on their ejaculation frequency: Rapid, Normal, and Sluggish. Expression level of DA in the brain was determined by enzyme-linked immune sorbent assay (ELISA) kit, TH expression level in the brain was determined by immunohistochemistry and Western Blot (WB) techniques. Among the three groups, DA and TH expression level were the highest in the Rapid ejaculation group, while the lowest was the Sluggish ejaculation group. The results also showed that TH level was positively associated with ejaculation frequency (r = 0.8038, P < 0.001) and negatively associated with ejaculation latency (r=-0.6199, P = 0.018). Furthermore, acute dapoxetine therapy in rats with Rapid ejaculation downregulated TH level in the brain. CONCLUSION: Changes in ejaculation behavior were significantly linked with TH level. Upregulated TH in selected brain regions related with ejaculation could cause rapid ejaculation. The effect of dapoxetine in prolonging ejaculation could be related to TH downregulation within the brain.

Vital function of DRD4 in dapoxetine medicated premature ejaculation treatment.

BACKGROUND: Recently, dapoxetine has been widely accepted to treat premature ejaculation by fast-inhibiting 5-hydroxytryptamine reuptake. However, dapoxetine is not suitable for all premature ejaculation patients in clinical treatment. We need to investigate and reveal the mechanism deeply to solve this problem. OBJECTIVES: To investigate and reveal the function of dopamine D4 receptor in dapoxetine medicated premature ejaculation treatment. MATERIALS AND METHODS: A rat model was used to screen rapid ejaculators. The molecular mechanisms of histone serotonylation-mediated regulation of dopamine D4 receptor were demonstrated by chromatin immunoprecipitation, DNA pull-down, mass spectrometry analysis, and coimmunoprecipitation experiments. The biological function of dopamine D4 receptor was investigated through in vivo experiments by intrathecal injection of shDRD4 to knockdown dopamine D4 receptor. RESULTS: In this study, we found that dapoxetine increased expression of 5-hydroxytryptamine and dopamine D4 receptor. We demonstrated that dapoxetine increased levels of 5-hydroxytryptamine, which promoted histone serotonylation (H3K4me3Q5ser) and transcription factor myeloid zinc-finger 1 complex binding on the dopamine D4 receptor promoter, upregulated the expression of dopamine D4 receptor and thus delayed ejaculation. DISCUSSION: In this study, we demonstrated that dapoxetine increased the levels of 5-hydroxytryptamine, which promoted histone serotonylation and myeloid zinc-finger 1 complex binding to the dopamine D4 receptor promoter and upregulated the expression of dopamine D4 receptor, thus delaying ejaculation. CONCLUSION: It is a novel mechanism that dapoxetine take effect of premature ejaculation treatment through upregulating the dopamine D4 receptor, which indicated that upregulated dopamine D4 receptor would enhance the dapoxetine effect in premature ejaculation treatment. This may lead to the development of novel therapeutic interventions for premature ejaculation.

Prilocaine/lidocaine spray for the treatment of premature ejaculation: a dose- and time-finding study for clinical practice use.

A eutectic mixture of prilocaine/lidocaine spray (Fortacin™, Recordati, Milan, Italy) has been approved for the management of patients affected by life-long premature ejaculation (PE), but to date, there is a lack of dose- or time-finding studies in the literature that indicate the best method of intake to optimize treatment outcomes. In this multicentre, randomized, two-phase study, we aimed to compare, in terms of treatment effectiveness (primary objective) and safety (secondary objective), different treatment regimens (various doses and times of drug delivery) of Fortacin™ in 91 patients affected with lifelong PE who were recruited at four different centres and randomized (1:1:1 ratio) into three different groups. The study included two phases: during the first phase (focused on time-finding), the same drug dose (three sprays) was taken at different intervals before intercourse (5, 15, 30 min). In the second phase (focused on dose finding), different drug doses (1, 3, 5 sprays) were taken at the same interval before intercourse (5 min). The main outcome measure instruments were self-measured intravaginal ejaculation latency time (sm-IELT), the premature ejaculation diagnostic tool (PEDT), and the International Index of Erectile Function-5 (IIEF-5). Furthermore, patients were asked to report any side effects that appeared during the study period. Our main study findings showed that the treatment regimen with three sprays of Fortacin™ administered 5 min before sexual intercourse showed the best results in terms of ejaculation time and control (Phase I, IELT 221 ± 3.4, PEDT 7.7 ± 0.3; Phase II, IELT 213 ± 4.9, PEDT 7.8 ± 0.4) with a safety profile that was identical to other treatment regimens. Based on these data, patients who are prescribed Fortacin™ should stick to this regimen to optimize treatment results.

His452Tyr 5-HT2A polymorphism and intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.

Lifelong premature ejaculation (LPE) may have heritable components. Selective serotonin reuptake inhibitors have been proven effective in prolonging intravaginal ejaculation latency time (IELT). Given that serotonergic pathways are involved in the ejaculation mechanism, we aimed to investigate whether His452Tyr, also known as the C1354T (RS6314) polymorphism of the 5-HT2A receptor, contributes to LPE pathogenesis and IELT differences among patients with LPE. Dutch Caucasian men with LPE (n = 65) attending the Outpatient Department of Neurosexology, HagaZiekenhuis for drug treatment for LPE in 2009 were selected and included in this case-control study. IELT during coitus was measured using a stopwatch, and all men were genotyped for the His452Tyr polymorphism. Analysis of variance (ANOVA) was performed to determine the association between the genotypes and IELTs. Mean IELTs with standard deviations were 29.7 (±20.9), 31.5 (±14.7), and 26.0 s, and the frequencies were 83.1%, 15.4%, and 1.5% for the CC, CT, and TT groups, respectively, with an average IELT of 29.9 s. No difference in mean IELT was observed between these groups. In the affected group, the frequencies of alleles C and T were 90.8% and 9.2%, respectively; whereas those among randomly selected European Caucasian male controls (n = 503) from the CEPH database were of 92.0% and 8.0%, respectively. No significant difference was observed between the groups. Therefore, no correlation was found between the His452Tyr polymorphism and IELT distribution in patients with LPE.

Majority of men with premature ejaculation do not receive pharmacotherapy.

Premature ejaculation is the most common male sexual dysfunction, with therapies including selective serotonin reuptake inhibitors, clomipramine, topical anesthetics, dapoxetine and tramadol. However, it is currently unknown how many men are receiving pharmacotherapy for premature ejaculation. Using the TriNetX Research network, a large multicenter database containing over 75 million patient records from hospitals across the United States, we evaluated prescribing patterns for treatment of premature ejaculation and assessed variations in prescription patterns among patients from 2015-2021. In addition, we examined if the prescription patterns for tramadol changed with the establishment of Prescription Drug Monitoring Programs. We found that most men (51.7%) were not receiving any pharmacotherapy for premature ejaculation. However, men with mental health disorders, were more likely (56.0%), to have been treated than those without (44.4%). On further analysis, men with mental health diagnoses were significantly more likely to be treated with Selective Serotonin Reuptake Inhibitors (45.0 vs 32.2%) and Tramadol (5.1% vs 3.5%). While the pharmacotherapy for premature ejaculation has been well researched, our findings revealed that most patients diagnosed with premature ejaculation do not receive pharmacotherapy and that patients are more likely to be prescribed premature ejaculation medications if they have a pre-existing mental health diagnosis.

Selective serotonin reuptake inhibitors combined with traditional Chinese medicine for premature ejaculation: A systematic review and meta-analysis.

BACKGROUND: Premature ejaculation (PE) is still a tough problem in drug treatment. Many clinical trials have proven that traditional Chinese medicine (TCM) has a significant effect in the treatment of PE. This article aims to provide the latest evidence for the efficacy and safety of TCM combined with selective serotonin reuptake inhibitors (SSRIs) in the treatment of PE. METHODS: We looked for randomized controlled trials (RCTs) from China National Knowledge Infrastructure, Wanfang, VIP Database, MEDLINE, PubMed, Web of Science, EMBASE, and Cochrane Library until June 30, 2022. STATA 15.1 software was used to analyze all data for this article. The quality of the included articles was evaluated using the Cochrane Reviewer's Handbook 5.3. RESULTS: Finally, we selected 16 high-quality RCTs in our meta-analysis, which containing 889 patients. Meta-analysis suggested that, compared with SSRIs alone, combination of TCM with SSRIs increased significantly intravaginal ejaculation latencv time and the scores of ejaculation control ability, sexual life satisfaction, PE-related distress, and communication difficulties between partners related to PE. Also, there was no significant difference in adverse effects between the two groups. In addition, the results of publication bias test showed that no significant bias occurred. CONCLUSION: The combined use of TCM and SSRIs has significant effect in the treatment of PE compared with SSRIs monotherapy and was generally well tolerated. Due to the small sample size, multicenter and large sample RCT is still needed in the future to further confirm the effectiveness and safety of TCM combined with SSRIs in the treatment of PE.

[Research progress of combination therapy in the treatment of erectile dysfunction and premature ejaculation comorbidity].

There is a close relationship between male erectile dysfunction (ED) and premature ejaculation (PE) on the pathogenesis, leading a high comorbidity rate and a need of simultaneous treatment in clinical practice. Phosphodiesterase 5 inhibitors (PDE5i) and selective serotonin reuptake inhibitor (SSRI) Dapoxetine are first-line oral drugs for ED and PE, respectively. In recent years, multi-country clinical guidelines have provided suggestions and guidance for the combination of these two drugs, with the safety and effectiveness being further explored and verified. This review summarized the status of ED and PE comorbidity, treatment principles, and research progress on the safety and effectiveness of Dapoxetine combined with PDE5i, in order to provide reference for the combination therapy of ED and PE comorbidity.