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Normal male sexual response compared with premature ejaculation. Figure adapted from Kirby 2014 (11).
Source publication
Premature ejaculation (PE) is a common complaint of male sexual dysfunction affecting men and their partners and consequently causing significant personal and interpersonal distress. Increased sensitivity of the glans penis and abnormalities of the afferent-efferent reflex pathway within the ejaculatory process are involved in the occurrence of PE....
Context in source publication
Context 1
... male sexual-response cycle consists of four phases: desire, arousal (erection), orgasm (ejaculation), and resolution ( Fig. 1) (11). The process of ejaculation is classified by two dis- tinct phases, "emission" and "expulsion". Sympathetic, para- sympathetic, and somatic nervous systems are involved in the Normal male sexual response compared with premature ejacu- lation. Figure adapted from Kirby 2014 (11). ejaculatory response and are coordinated by the ...
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Objective To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women.
Data Sources We conducted a search on the PubMed, Embase, Scopus, Web of Science, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allie...
Citations
... В основі фармакотерапії ПЕ лежить використання селективних інгібіторів зворотного захоплення серотоніну (СІЗЗС), місцевих анестетиків, трамадолу та інгібіторів ФДЕ-5 як в монотерапії, так і їхній комбінації, що обґрунтовано в численних дослідженнях [28][29][30][31]. ...
Sexual health is an integral part of the quality of life of every person, as it is of great importance for the physical and mental well-being of individuals, couples, families, and, accordingly, for the social and economic development of communities and countries. The objective: to assess the impact of premature ejaculation (PE) on the quality of life of men depending on the degree of clinical manifestations. Materials and methods. 89 men who had premature ejaculation were under observation. The average age of the patients was 32.6±4.2 years. The average duration of the disease was 4.6±2.4 years. 22 (24.7%) patients had secondary (acquired) premature ejaculation against the background of chronic prostatitis or prostatic vesiculitis. Other 67 (75.3%) men had a primary (congenital) form of premature ejaculation, which began with the beginning of sexual life. The premature ejaculation diagnostic tool (PEDT) was used to determine the severity of premature ejaculation. Quality of life was assessed on the basis of Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF) (). Hospital Anxiety and Depression Scale (HADS) was used for screening detection of anxiety and depression. Study of medical and social characteristics based on the developed program was performed and the sensitivity of the penis was also assessed using biotensiometry. Results. It was established that men with premature ejaculation have a low satisfaction with life (76.4%), against the background of complete (55.1%) or partial (44.9%) dissatisfaction with their sexual life. Premature ejaculation has a negative impact on their daily life, as it leads to negative experiences (92.1%), reduced work capacity (41.6%), deterioration of relations with a wife or partner (48.3%), a feeling of exhaustion and fatigue (32.6%). When evaluating the results of the PEDT diagnostic test, according to the severity of the manifestations, men had a mild (50.5%), medium (31.5%) or severe (18%) degree. A clear correlation between the decline in men’s quality of life and the severity of premature ejaculation was noted (Spearman’s r = –0.938; p<0.01). The data of anxiety and depression scales indicated their high level, which also depended on the degree of severity of premature ejaculation manifestations (Spearman’s r = 0.790; p<0.01) and negatively affected the quality of life (Spearman’s r = –0.760; p<0,01). According to the data of biotensiometry, hypersensitivity of the head of the penis was noted in men with premature ejaculation, in comparison with the data in the control group of men who did not have sexual disorders: 4.2±1.6 W and 12.4±2.6 W respectively (p<0.05). More pronounced indicators of penile hypersensitivity were observed in men with severe PE with a statistically significant difference compared to the indicators in the group of men with mild manifestations of PE (p<0.05) and without a significant difference compared to the indicators in the group of men with average by the degree of PE (p>0.05). Somewhat more pronounced indicators of penile hypersensitivity were observed in men with PE under the age of 30. Conclusions. Premature ejaculation is characteristic of men of young working age, which is accompanied by a negative impact on various areas of their life, and the development of anxiety and depression, as well as a decrease in the quality of life. This requires improving the organization of providing medical and psychological assistance to such patients.
... 2 Several treatments have been considered for the management of PE. 5 Dapoxetine, a shortacting selective serotonin reuptake inhibitor (SSRI) derived from fluoxetine, 6,7 is the gold standard of medical treatment for lifelong and acquired PE. 5,[8][9][10] In cases of acquired PE, treatment of the underlying contributing factor, when identifiable, is the priority (eg, by treating thyrotoxicosis or prostate inflammation). [10][11][12][13] Local anesthetics have also been considered a possible alternative for lifelong PE. 14,15 Although such medications have proven effective to a large extent, several factors contribute to their limited success in clinical practice, such as their side effects, high sale price, and limited support given to manage patients' expectations. [16][17][18][19] In a meta-analysis, treatments based on traditional Chinese medicine (TCM) theory were shown to be effective in improving PE. 20 Acupuncture is an important treatment method based on the theory of TCM and is applied in the treatment of many diseases. ...
Background
Although acupuncture is widely used to treat premature ejaculation (PE), its effectiveness remains highly controversial.
Aim
To evaluate the efficacy and safety of acupuncture on PE.
Methods
According to the relevant keywords, 11 major English and Chinese databases were searched for randomized controlled trials (RCTs) of acupuncture alone or in combination with other treatments for PE. The quality of evidence across studies was assessed by the GRADEpro tool.
Outcomes
Study outcome measures included the intravaginal ejaculation latency time (IELT), the Premature Ejaculation Diagnostic Tool (PEDT), the Chinese Index of Premature Ejaculation–5 (CIPE-5), treatment success rate, and adverse events.
Results
Seven trials were included in this review for a total of 603 participants. A low quality of evidence suggests that it is not possible to determine whether acupuncture, as compared with a selective serotonin reuptake inhibitor, has an advantage in improving the IELT (standardized mean difference [SMD], −1.75; 95% CI, −6.12 to 2.63; P = .43, I2 = 98%), PEDT scores (SMD, 0.32; 95% CI, −0.68 to 1.32; P = .53, I2 = 85%), and treatment success rate (risk ratio, 0.69; 95% CI, 0.41-1.14; P = .15). However, participants receiving acupuncture had a lower CIPE-5 (SMD, −1.06; 95% CI, −1.68 to −0.44; P < .01). As compared with sham acupuncture, acupuncture significantly improved the IELT (SMD, 1.47; 95% CI, 1.01-1.92; P < .01, I2 = 0%) and PEDT scores (SMD, −1.23; 95% CI, −1.78 to −0.67; P < .01, I2 = 37%). When compared with other treatments alone, a combined treatment with acupuncture can significantly improve the IELT (SMD, 7.06; 95% CI, 2.53-11.59; P < .01, I2 = 97%), CIPE-5 (SMD, 0.84; 95% CI, 0.45-1.22; P < .01, I2 = 0%), and treatment success rate (SMD, 1.60; 95% CI, 1.18-2.16; P < .01, I2 = 53).
Clinical Implications
The results suggest a significant effect of acupuncture in the treatment of certain important indicators of PE; however, this finding needs to be treated with caution because of the quality of the RCTs included.
Strengths and Limitations
Comprehensive inclusion of available RCTs has been performed. However, limitations include a low number of studies and a lack of detailed information to allow subgroup analysis.
Conclusion
The present systematic review and meta-analysis show that acupuncture has a significant effect on several subjective PE parameters, such as improving the feeling of control over ejaculation and distress, particularly when used in an integrated way. However, due to the low quality of evidence, acupuncture still needs larger well-designed RCTs to be confirmed.
... However, its use is limited by the attenuated sensation and enjoyment of intercourse in the patient, and in the partner where there is vaginal absorption of the local anaesthetic (if a condom is not used). 139 The lidocaine/prilocaine metered dose spray (Fortacin) containing a pure mixture of lidocaine 150 mg/ml and prilocaine 50 mg/ml is the only EMA-approved topical anaesthetic agent approved for use in PE. 142 However, these topical agents should be avoided in couples wishing to conceive as they may have direct toxic effects on spermatozoa. 144 A proposed management algorithm for PE is shown in Figure 3. ...
Introduction:
Diabetes mellitus (DM) is a rapidly rising metabolic disorder with important systemic complications. Global figures have demonstrated the prevalence of DM has almost quadrupled from 108 million in 1980 to 422 million in 2014, with a current prevalence of over 525 million. Of the male sexual dysfunction resulting from DM, significant focus is afforded to erectile dysfunction (ED). Nevertheless, ejaculatory dysfunction (EjD) constitutes important sexual sequelae in diabetic men, with up to 35-50% of men with DM suffering from EjD. Despite this, aspects of its pathophysiology and treatment are less well understood than ED. The main disorders of ejaculation include premature ejaculation (PE), delayed ejaculation (DE), anejaculation (AE) and retrograde ejaculation (RE).
Background:
Although EjD in DM can have complex multifactorial aetiology, understanding the pathophysiological mechanisms caused by DM has facilitated the development of therapies in the management of EjD. Most of our understanding of its pathophysiology is derived from diabetic animal models, however observational studies in humans have also provided useful information in elucidating important associative factors potentially contributing to EjD in diabetic men. These have provided the potential for more tailored treatment regimens in patients depending on the ejaculatory disorder, other co-existing sequelae of DM, specific metabolic factors as well as the need for fertility treatment. However, the evidence for treatment of EjD, especially DE and RE, is based on low-level evidence comprising small sample-size series and retrospective or cross-sectional studies. Whilst promising findings from large randomised controlled trials (RCTs) have provided strong evidence for the licensed treatment of PE, similar robust studies are needed to accurately elucidate factors predicting EjD in DM, as well as for the development of pharmacotherapies for DE and RE. Similarly, more contemporary robust data is required for fertility outcomes in these patients, including methods of sperm retrieval and assisted reproductive techniques (ART) in RE. This article is protected by copyright. All rights reserved.
... Ejaculation consists of two phases: emission and expulsion [13,16,43,44]. ...
... Expulsion follows emission, where semen is pushed out as the consequence of the rhythmic contractions of the striated muscles of the pelvis and the ischiocavernosus, bulbospongiosus, and perineal muscles [43]. Electromyographic [EMG] studies of the bulbocavernosus or bulbospongiosus have reported evidence of ejaculation or expulsion in animals following electrical or mechanical stimulation of genital structures or of the dorsal nerve of the penis [32,50], which is controlled by lumbar spinothalamic cells. ...
... Factors include anxiety, depression, guilt, stress, history of sexual suppression, lack of poor body image, sexual abuse, problems in understanding among partners, and early sexual experience [43,48,[69][70][71][72]. Anxiety is considered the primary cause of rapid ejaculation. ...
Simple Summary
Sexual dysfunctions are rarely discussed in our current society. Males experience different sexual dysfunctions, including erectile, infertility, and ejaculatory dysfunctions. In this review only the ejaculatory dysfunction will be discussed. Ejaculation is defined as the ejection of contents collectively from the vas deferens, seminal vesicle, prostate and Cowper’s glands. It is completely controlled by a population of neurons present in the lumbar spinal cord. The presence of lesion in these neurons ceases the ejaculatory behavior in males. This population of neurons was first identified in rats; however, recently it was confirmed that these neurons are present in human males as well. The issues are known as ejaculatory dysfunction. The following are the different types of ejaculatory dysfunctions: early ejaculation, ejaculation into the urinary bladder, late ejaculation and no ejaculation.
Abstract
Ejaculation is a reflex and the last stage of intercourse in male mammals. It consists of two coordinated phases, emission and expulsion. The emission phase consists of secretions from the vas deferens, seminal vesicle, prostate, and Cowper’s gland. Once these contents reach the posterior urethra, movement of the contents becomes inevitable, followed by the expulsion phase. The urogenital organs are synchronized during this complete event. The L3–L4 (lumbar) segment, the spinal cord region responsible for ejaculation, nerve cell bodies, also called lumbar spinothalamic (LSt) cells, which are denoted as spinal ejaculation generators or lumbar spinothalamic cells [Lst]. Lst cells activation causes ejaculation. These Lst cells coordinate with [autonomic] parasympathetic and sympathetic assistance in ejaculation. The presence of a spinal ejaculatory generator has recently been confirmed in humans. Different types of ejaculatory dysfunction in humans include premature ejaculation (PE), retrograde ejaculation (RE), delayed ejaculation (DE), and anejaculation (AE). The most common form of ejaculatory dysfunction studied is premature ejaculation. The least common forms of ejaculation studied are delayed ejaculation and anejaculation. Despite the confirmation of Lst in humans, there is insufficient research on animals mimicking human ejaculatory dysfunction.
... More recently, FORTACIN™ has been approved as the first officially topical therapy for lifelong PE [7]. In this context, Prost et al. found that FORTACIN™ increased ejaculatory latency, control and sexual satisfaction, demonstrating the significant benefits for both patients and their partners when using the drug [28]. Likewise, other groups confirmed the after mentioned findings making local anaesthetic a viable alternative for lifelong and acquired PE [10,29]. ...
Topical anaesthetics are considered a first-line therapy option in men with premature ejaculation (PE). A cross-sectional retrospective analysis was performed to evaluate the real-life use of the eutectic mixture of prilocaine/lidocaine spray (FORTACIN™) in a cohort of 198 white-European men who had been consecutively and prospectively seen at a single tertiary-referral andrology centre for self-reported PE and naive for previous PE treatments. Descriptive statistics was used to describe the whole cohort and the paired t-test was applied to investigate potential differences throughout a 12-month follow-up (baseline, 1, 3, 6 and 12 months). Overall, mean (SD) age was 37 (6.5) years. Of all, lifelong, acquired and subjective PE were reported in 101 (51%), 59 (29.8%) and 38 (19.2%) patients at baseline, respectively. FORTACIN™ use increased up to 6 months, with 184 (92.9%) and 128 (66.4%) men who had tried and regularly used the compound, respectively. At 12-month follow-up, 53 (26.8%) men reported a regular use of the compound. Mean Premature Ejaculation Diagnostic Tool score significantly decreased at 6 and 12 months compared to baseline (all p < 0.05). Conversely, mean IELT significantly improved at 6-month follow-up compared to baseline (all p ≤ 0.04). Overall, FORTACIN™ emerged to be a safe and effective treatment option in PE patients of various types, with almost one fourth of patients still under treatment after 12 months. Timing and dosing of the drug can deserve to be adjusted according to patient’s needs and their sexual ecology.
... When compared to PE treatments, topical agents are appealing since they are easy to use and can be applied on-demand. Moreover, local anesthetic agents do not cause systemic side effects [12,19,20]. Conversely, a downside of the application of a desensitizing substance to the glans is the potential for some degree of penile hypoesthesia. ...
... An original prescription information leaflet suggests using the compound as follows: One dose, namely three sprays, to be applied on the glans penis at least five minutes before sexual attempts [34]. Prost et al. found that Fortacin™ increased ejaculatory latency, control, and sexual satisfaction in men with primary PE, demonstrating the significant benefits for both patients and their partners when using the drug [20]. Likewise, other groups confirmed the above mentioned findings making local anesthetics a viable alternative for lifelong and acquired PE [13,15,29]. ...
... Atan et al. assessed the effect of combination therapy with sildenafil and EMLA-cream vs. monotherapy and placebo in 84 men with PE. They found that combination treatment had a higher efficacy (86.4%) compared to placebo (40%) and to either monotherapy (sildenafil 50 mg: 55%; EMLA: 77.3%) [20]. In another study, including 78 men with primary PE, the efficacy of lidocaine spray 10 g/100 mL, tadalafil 5 mg daily and tadalafil 5 mg daily plus lidocaine spray was investigated over 3 months [37]. ...
Topical anesthetics are one of the first line therapeutical options for men with premature ejaculation (PE). Real-life PE management often involves a range of interventions including systemic drug treatments (such as off-label and on-label selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, phosphodiesterase-5 inhibitors (PDE5Is)), topical anesthetic creams and sprays, and behavioral approaches. Among them, on-demand dapoxetine and lidocaine/prilocaine spray formulations are the only approved treatment options for lifelong PE. The earliest strategy to treat PE was based on the use of topical anesthetic agents. The rationale behind the use of anesthetics is that by reducing the glans penis sensitivity, the spinal and cerebral input of sexual arousal impulses may also be reduced. Oral SSRI proved to be effective to treat PE, but their high rate of side effects limit treatment adherence and both short and long term follow up data are lacking. Conversely, topical anesthetics have proved to increase ejaculatory latency, control, and sexual satisfaction in couple affected by PE with limited rates of adverse events. In this context, we aimed to perform a narrative review to summarize the most recent findings regarding the use of topical treatments for PE.
... Dapoxetine previous studies reported significant improvement in the stopwatch-measured intravaginal ejaculation latency time (IELT) (as main outcome) and increased PE profile self-reported outcome measure by patients [41,43,44]. A metered-dose aerosol topical spray called Fortacin TM induces local anesthesia at the glans area of the penis [45]. Even though the FDA did not approve it, the EMA officially approved its treatment use for lifelong PE. ...
The incidence of premature ejaculation (PE) has been on the rise over the years. Thus, significant research efforts have been directed toward understanding the pathogenesis and hence treatment of PE. Here, we performed a comprehensive analysis of the worldwide trends in research outputs in the field of PE. This study investigated the universal findings of previous PE studies and the trending issues surrounding the condition. We employed the Web of Science Core Collection for data collection. The Excel (2016) and CiteSpace IV were used for information analysis. The information was categorized using journal names, institutions, research frontiers, citation reports, regions/countries, and authors. A sum of 886 publications concerning PE between 2008 and 2018 were identified as of July 6, 2019. The highest number of publications was identified in the Journal of Sexual Medicine published. The United States of America (USA) had the highest number of publications and H-index value. The highest co-citations were from Waldinger MD. The most common keyword was ‘drug treatment’. A steady pattern was observed for PE publications done between the period of 2008–2018. Thus, the USA is at the forefront of research on PE research. The interesting advanced research frontiers were drug treatment, circumcision, and sertraline.
... 2 PE involves a complex sensory pathway which can be targeted at two main sites: in the central nervous system by delaying in the transmission of ejaculation processing neural stimuli, and at the level of penile sensory receptors, by reducing penile sensitivity. 3 Currently, pharmacotherapy represents the first-line treatment for lifelong PE. 1 Oral treatment with selective serotonin re-uptake inhibitors (SSRIs) and/or Phosphodiesterase type 5 inhibitors (PDE5is) are strongly recommended. 1 Topical anesthetic agents are considered a viable alternative to oral treatments. 1 For many years topical anesthetic agents have been prescribed as off-label treatments. More recently, Fortacin™ (Lidocaine/Prilocaine, Recordati) has been approved as the first officially topical therapy for primary PE. 1 It was officially approved for use in the European Union in 2013 and finally launched in the UK in November 2016. 4 Before beginning treatment, it is essential that an appropriate assessment of the PE patient is carried out and that there is a thorough discussion about expectations. ...
... With regard to the route of administration, most experts declared that their patients prefer the topical one. The use of topical anesthetics represents the oldest form of pharmacotherapy in PE and dates back to 1943. 5 These agents are currently considered a viable alternative to oral treatments. 1 These agents can be applied directly to the glans penis in order to produce some degree of penile desensitization and are directed to the hypersensitivity aspect of PE. 3 Advantages of topical treatments include on-demand dosing with minimal systemic effects. Indeed, as emerged from the panel discussion, the better toxicity profile associated with topical agents is perceived as more adequate to control a subjective symptom. ...
... First generation topical anesthetics had dosing difficulties with the potential of either over or under-dosing, with subsequent risk of penile hypoesthesia, erectile dysfunction and/or transvaginal transmission resulting in vaginal numbness and anorgasmia or lack of efficacy, respectively. 3 Their ease of application and tolerability was further limited by the presence of a number of excipients in the formulation of the majority of creams and topical products causing difficulties in applying the correct measured dose. 3,18 In addition, difficulties in applying the cream were reported. ...
Introduction
Premature ejaculation (PE) represents the most prevalent male sexual issue. Before beginning treatment, it is essential to discuss the patient’s expectations thoroughly.
Methods
Herein, we report the results of an expert panel discussion about perceptions, expectations, preferences, and attitudes towards PE, its diagnosis and treatment. The panel took place in October 2019 and involved 30 Italian urologists experienced in the management of male sexual dysfunction. It aimed at investigating physicians’ points of view about selected aspects of PE management which emerged during the counselling of PE patients over the previous two years. Treatment-related questions were mainly focused on topical treatment with Fortacin™.
Results
Overall, 83.3% of those interviewed declared that most of their patients perceive PE as a bother rather than a disease. The percentage of urologists interviewed perceived that improved subjective control over ejaculation and prolonged intravaginal ejaculatory latency time (IELT) as the main benefit expected by the majority of their patients was 56.5% and 10%, respectively. Eighty percent of urologists reported on-demand regimen as the dosage modality preferred by the majority of their patients and half of them reported the topical route to be the way of administration preferred in most cases. Moreover, 73.3% of urologists reported that adherence to treatment was higher in patients undergoing topical treatment. Finally, 80% of urologists perceived Fortacin to be efficacious in patients with acquired PE and 70% of them perceived its efficacy to be independent from IELT.
Discussion
Most patients perceive PE as a bother rather than a disease and mainly advocate an improved control over ejaculation. Fortacin is perceived as efficacious in patients with acquired PE, and independent from IELT.
... Although dapoxetine had weak ejaculation delaying effect, on-demand use of 30 mg dapoxetine is the first registered oral drug for the treatment of LPE (9). Fortacin topical Spray has been the second registered drug for the treatment of LPE (41). Moreover, there are also many Off-label drugs to treat LPE, especially the selective serotonin reuptake inhibitors (42). ...
The relationship between 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) gene and lifelong premature ejaculation (LPE) risk was discussed widely for the last few years, which was still controversial and remained to be explored. We performed the meta-analysis with 8 reliable research, which were searched in the following databases: PubMed, Embase and Cochrane Library. We also performed random and fixed effects models to evaluate the odds ratios (ORs) and 95% confidence intervals respectively. By pooling all included studies, we found that SS genotype of 5-HTTLPR polymorphism was linked with significantly higher PE risk in Caucasian population (OR =0.635, 95% CI: 0.417-0.958, I2=0.311, P=0.035), and S-allele of 5-HTTLPR polymorphism increased the risk of LPE significantly in Asian population (OR =0.656, 95% CI: 0.539-0.799, I2=0.435, P<0.001). However, no significant was observed between 5-HTTLPR gene polymorphism and LPE risk in overall studies. Further studies were anticipated to be done.
... EMLA V R cream still is the most widely used topical anesthetic. In the same line, an aerosol-delivery form containing lidocaine-prilocaine eutectic-like mixture (Fortacin TM ) was approved to be used for treatment of premature ejaculation in the European Union in 2016 (Porst and Burri 2017). ...
Solvents play key roles in designing drug delivery systems (DDSs). They are used as the reaction media in the preparation of DDSs and as vehicles for delivery of problematic drugs. The number of pharmaceutically acceptable solvents is limited and developing new green ones is of a great of interest. A deep eutectic solvent (DES) is a room temperature liquid composed of a mixture of hydrogen bond acceptor and hydrogen bond donor. DESs exhibit interesting physical and chemical characteristics such as low vapor pressure, non-inflammability, chemically tailorable, solvency power for a wide range of solutes, and water non-reactivity. Furthermore, they can be easily prepared from low toxicity, readily available, and inexpensive constituents. Due to these properties, DESs have attracted growing attention as green solvents in different areas of science from chemistry to material engineering and biology. In this review, after a brief introduction about DESs, we provide an overview about current advances made over the last decade in utilizing of DESs for solubilization of water insoluble drugs, transdermal drug delivery, inorganic nanoparticle synthesis, and designing polymeric and self-assembled drug carriers. This paper also discusses main challenges and limitations of DESs that should be considered before using of DESs.
