Pathophysiology Of Premature Ejaculation Research Articles

MOLECULAR APPROACH TO PREMATURE EJACULATION: A PILOT STUDY ON S1P SERUM LEVELS AND S1PR1, S1PR2, S1PR3 POLYMORPHISMS

Objective: Sphingosine-1-phosphate (S1P) and its receptors are involved in various sexual functions, particularly in smooth muscle regulation and vascular responses. However, the role of S1P and its receptors in premature ejaculation (PE) remains unclear. This study investigates the relationship between single nucleotide polymorphisms (SNPs) in the S1PR1, S1PR2, and S1PR3 genes and plasma S1P levels in individuals with PE. Materials and Methods: The study included 100 individuals with PE and 100 healthy controls recruited from urology and psychiatry clinics. DNA was isolated from blood samples, and PCR was used to identify SNPs in the S1PR1 (rs2038366), S1PR2 (rs56357614), and S1PR3 (rs7022797) genes. Plasma S1P levels were measured using ELISA. Results: A significant association was observed between the heterozygous GT genotype of the S1PR1 gene and an increased risk of PE (OR 2.25, 95% CI 1.215–4.168, p = 0.0099). No significant associations were found between S1PR2 or S1PR3 polymorphisms and PE. Plasma S1P levels were significantly lower in the PE group (median 253.25 ng/L) compared to the control group (median 430.82 ng/L) (p < 0.001). Conclusion: S1PR1 gene polymorphism and reduced plasma S1P levels may be linked to the pathophysiology of PE. In contrast, S1PR2 and S1PR3 do not appear to be associated. Further research with larger samples is needed to confirm these findings.

Assessing the nitric oxide and asymmetric dimethylarginine levels in lifelong premature ejaculation: A prospective study

ObjectiveTo evaluate nitric oxide (NO) and asymmetric dimethylarginine (ADMA) levels in men with premature ejaculation (PE), which is a common condition that adversely affects quality of life. Material and methodOf the 20–50-year old men presenting to the urology clinic, who were married or had regular sexual intercourse, 40 that were diagnosed with lifelong PE according to the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) measured by a stopwatch were included in the study. The results of the PE group were compared to those of the control group formed with 40 healthy hospital personnel. Venous blood samples were centrifuged and stored at −80°C. The NO and ADMA values were compared between the individuals with and without PE. ResultsThere was no statistically significant difference between the groups in terms of age, body mass index (BMI), and The International Erectile Dysfunction Index-5 (IIEF-5) questionnaire scores. The NO and ADMA values were significantly lower in the PE group than in the control group (29.76±13.26μmol/L vs. 48.27±22.71μmol/L; p<0.001 and 1.01±0.49nmol/ml vs. 1.83±1.06nmol/ml; p<0.001, respectively). There was a significant correlation between IELT and NO levels (r=0.407, p=0.001). ConclusionOur study can contribute to the explanation of the pathophysiology of PE having unclear etiology and treatment. Further studies on these molecules with larger case series are required for the diagnosis and treatment of PE.

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Higher inter-hemispheric homotopic connectivity in lifelong premature ejaculation patients: a pilot resting-state fMRI study.

Lifelong premature ejaculation (PE) is one common male sexual dysfunction and is implicated in widespread structural and functional abnormalities of bilateral hemispheres. However, whether the inter-hemisphere functional connectivity (FC) of lifelong PE patients was altered still remain unclear. Thirty-four lifelong PE patients and 30 healthy controls (HCs) were enrolled in this study and all underwent T1-weighted and resting-state functional MRI (fMRI) scan. The voxel-mirrored homotopic connectivity (VMHC) measure and independent sample t-test were applied to examine the alterations of VMHC values in the patients relative to HCs with the significant threshold at P<0.05, false discovery rates corrected. Correlation analysis was adopted to calculate the relationships between the imaging results and clinical characteristics of patients (P<0.05, Bonferroni corrected). Receiver operating characteristic (ROC) curve analysis was performed to investigate the possible biomarkers for distinguishing the patients from the HCs using the VMHC values of inter-group differences. The results revealed that compared with HCs, lifelong PE patients had higher VMHC values in the precentral gyrus (PG), primary somatosensory cortex (S1), supplementary motor area (SMA), precuneus, middle temporal cortex (MTC), superior temporal pole (STP), thalamus, caudate and middle cingulate cortex (MCC). Correlation analysis showed that the mean VMHC values in the S1 negatively correlated with intravaginal ejaculation latency time (IELT) in the patient group. Furthermore, the caudate revealed the well classification power from the ROC analysis. The present study showed the abnormal inter-hemisphere interaction and integration of information involved in ejaculation inhibitory control, sensorimotor mediation and self-reference processing including the thalamus, caudate, MCC, widespread parietal cortex and temporal cortex in lifelong PE patients compared with HCs. Correlation analysis and ROC analysis revealed the importance of S1 and caudate in lifelong PE. Notably, the ROC result of caudate might show the core roles of caudate played in the pathophysiology of lifelong PE.

Aberrant default mode network and auditory network underlying the sympathetic skin response of the penis (PSSR) of patients with premature ejaculation: A resting‐state fMRI study

Hyperactivity of the sympathetic nervous system is considered as an important component involved in the pathological mechanisms of premature ejaculation (PE). However, the neural mechanisms of PE with high sympathetic activity are still not well understood. The activity of the sympathetic innervations in the penis was evaluated by the sympathetic skin response of the penis (PSSR) with an electromyograph and evoked potential equipment. Resting-state functional magnetic resonance imaging (fMRI) data were acquired from 18 PE patients with high sympathetic activity (sPE), 17 PE patients with normal sympathetic activity (nsPE), and 24 healthy controls (HC). We investigated the neural basis of sPE based on the measure of regional homogeneity (ReHo). Moreover, the correlations between brain regions with altered ReHo and PEDT scores and PSSR latencies in the patient group were explored. Altered ReHo values among three groups were found in the temporal, cingulated, and parietal cortex in the default mode network (DMN), as well as the temporal cortex in the auditory network (AUD). Compared with HC, Patients with sPE had increased ReHo values of brain regions in DMN, AUD, and decreased ReHo values of brain regions in DMN. In addition, increased ReHo values were found in DMN of patients with nsPE, while decreased ReHo values were found in DMN and the attention network (AN). Moreover, sPE patients had increased ReHo values in AUD and decreased ReHo values in DMN when compared with nsPE patients. Finally, altered ReHo values of brain regions in DMN and AUD were associated with PEDT scores and PSSR latencies in the patient group. Our results suggested that PE patients had abnormal ReHo values in DMN, AUD, and AN. Patients with sPE were characterized by increased neuronal activity in AUD and decreased activity in DMN. This highlighted the significances of DMN, AUD, and AN in the pathophysiology of PE and also provided potential neuroimaging biomarkers for distinguishing sPE from nsPE and HC.

Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS).

Premature ejaculation (PE) is the most prevalent male sexual dysfunction, and the most recently defined. PE is often mistakenly considered a purely psychosexological symptom by patients: the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients' side, making PE the most underdiagnosed sexual complaint. However, an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE. In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), we propose 33 recommendations concerning the definition, pathophysiology, treatment and management of PE aimed to improve patient care. These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions, such as prostate inflammation, endocrine disorders, and other sexual dysfunctions, and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach. New therapeutic options, as well as combination and off-label treatments, are also described.

Premature Ejaculation: 2020 Update

Premature ejaculation (PE) is one of the most common forms of male sexual disorder. There are still different opinions and point of view regarding its definition, classification, prevalence, pathophysiology and treatment alternatives. For these reasons, we aim to recap the recently accumulated data on definition, classification, pathophysiology and treatment alternatives of PE. The literature pertaining to PE has been reviewed by the authors. All the related articles were critically analyzed and examined. Levels of evidence (Les) and grades of recommendation (Grs) are provided based on a thorough analysis of the literature and consensus. After the initial evidence-based definition developed for lifelong PE, the International Society for Sexual Medicine (ISSM) advertised another unified definition for lifelong and acquired PE and confirmed the time criterion for the diagnosis of PE. The ISSM has also acknowledged the presence of the two more PE subtypes (variable and subjective PE) underlining the fact that more research is required to develop an evidence-based definition of these sexual problems. Although the pathophysiology of these four PE syndromes has not been completely elucidated yet, pharmacotherapy must be considered the treatment of choice for lifelong PE patients whereas treating the underlying pathology must be the initial goal for patients with acquired PE. To treat PE, we can use daily or on-demand use of SSRIs, on-demand use of topical anaesthetics, on-demand tramadol or phosphodiesterase type-5 inhibitors. Psychotherapy can be offered to patients who describe variable and subjective PE. Despite the recent progress reached in the field of PE, there are on-going debates regarding the definition, classification, pathophysiology and treatment of this common problem. Future clinical trials must be performed to understand the actual aetiology of the four PE syndromes and develop more effective and safe treatment alternatives.

Current and emerging therapies in premature ejaculation: Where we are coming from, where we are going.

Premature ejaculation is the most common form of sexual dysfunction among men. The pathophysiology of premature ejaculation appears to be multifactorial, implicating the need for multimodal therapeutic regimens to successfully treat premature ejaculation. Multiple treatment regimens have been shown to be effective in extending the time between penetration and ejaculation. These treatment modalities include everything from behavioral modifications and medications to diet alterations and major surgery. The goal of the present article was to review the commonly used treatment regimens used in the treatment of premature ejaculation, as well as to introduce and discuss the newest treatment routines under study for the treatment of premature ejaculation.

The pathophysiology of lifelong premature ejaculation.

For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of stopwatch research, clinically inexperienced investigators and inclusion of anonymous men in a study performed by the Internet endanger the continuation of objective research of lifelong PE.

The epidemiology of premature ejaculation

Vast advances have occurred over the past decade with regards to understanding the epidemiology, pathophysiology and management of premature ejaculation (PE); however, we still have much to learn about this common sexual problem. As a standardized evidence-based definition of PE has only recently been established, the reported prevalence rates of PE prior to this definition have been difficult to interpret. As a result, a large range of conflicting prevalence rates have been reported. In addition to the lack of a standardized definition and operational criteria, the method of recruitment for study participation and method of data collection have obviously contributed to the broad range of reported prevalence rates. The new criteria and classification of PE will allow for continued research into the diverse phenomenology, etiology and pathogenesis of the disease to be conducted. While the absolute pathophysiology and true prevalence of PE remains unclear, developing a better understanding of the true prevalence of the disease will allow for the completion of more accurate analysis and treatment of the disease.

The characterization, current medications, and promising therapeutics targets for premature ejaculation.

Premature ejaculation (PE) is the most prevalent male sexual dysfunction. This is associated with negative personal and interpersonal psychological outcomes. The pharmacologic treatment of PE includes the use of antidepressants, local anesthetic agents, and phosphodiesterase type 5 inhibitors. While numerous treatments can control PE, only antidepressants and topical anesthetic creams and sprays have recently been shown to be more effective. This review focuses on the physiology and pharmacology of ejaculation, the pathophysiology of PE and the most effective pharmacological treatment of PE. Pharmacotherapy of PE with off-label short-acting selective serotonin reuptake inhibitors (SSRIs) is common, effective, and safe. Dapoxetine, a SSRI with a short half-life, has been recently evaluated for the treatment of PE by several countries and results are promising. In clinical practice, follow-up side effects are an important part of the management strategy for PE. The understanding of etiology, pathophysiology, and treatment modalities of PE would be beneficial to clinician in helping patients with this disappointing sexual problem.

FLOUXETINE IMPROVED INTRAVAGINAL EJACULATORY LATENCY TIME THROUGH DECREASED LEVELS OF INTERFERON-GAMMA AND INCREASED LEVELS OF SEROTONIN IN PATIENT WITH PREMATURE EJACULATION

Pathophysiology of premature ejaculation (PE) is very complex because it is associated with many factors, which can be grouped into biological factors and psychological factors. Various diseases have been found correlate between psychological factors and biological factors through cytokines, one of which is IFN-y (IFN-g). IFN-y affect indolamine dioxygenase enzyme (IDO) and decrease levels of serotonin. Low levels of serotonin leads to PE. The purpose of this study was to prove the relationship of serotonin and IFN-y in pathophysiology of PE.This study was designed as a pretest-posttest double-blind cross-over control group design. Patients with PE were divided into 2 groups: control group and treatment group. Treatment group received flouxetine 20 mg for 30 days. Then the control and treatment groups were crossed after passing a 14-days washout period. Previously as a control group to treatment group and received flouxetine 20 mg per day for 30 days. Before and after treatment in each group was examined the levels of serotonin and IFN-y.Of the 26 subjects, each group there was 13 subjects. Flouxetine 20 mg per day for 30 days increased serotonin levels were significantly (p &lt; 0.05), and decreased levels of IFN-y were significantly (p &lt; 0.05). Increased levels of serotonin and decreased levels of IFN-y was significantly associated with improvements (intravaginal ejaculatory latency time) ejaculation in PE patient.From these results it can be concluded that PE occurs because decreased levels of serotonin. Decreased levels of serotonin are associated with increased levels of IFN-y.Â

Pathophysiology of Premature Ejaculation

Although the characteristics of premature ejaculation (PE) are established, the exact aetiology is largely unknown. Genetic, neurobiological, pharmacological, psychological, urological and endocrine factors have all been proposed. In addition PE and erectile dysfunction are often co-morbid. This article provides an overview of the proposed biological and psychological aetiologies of PE. Review of the literature. Current data on the pathophysiology of PE. This review shows that most of the proposed biological and psychological aetiologies of PE are not evidence-based and/or that attempts to confirm them have given conflicting results. There are good data to support roles for genetic and psychological factors, either causal, or secondary to PE for the latter, in lifelong PE. Conversely, more evidence-based data support the responsibility of opioid substance withdrawal, prostatic inflammation or hyperthyroidism in some cases of acquired PE, in addition to a probable role of psychological factors. The determinants of PE are certainly complex and multifactorial, while each partner's reaction to the frustration caused by the sexual dysfunction may exacerbate or perpetuate it. It is important to understand, as far as possible, the aetiology in the individual patient to ensure appropriate assessment and treatment. It should be noted that identification of an aetiological factor does not necessarily mean the cause of the PE has been completely explained, and the patient may require a combination of treatment approaches.

ORIGINAL RESEARCH—PSYCHOLOGY: A New Combination Treatment for Premature Ejaculation: A Sex Therapist’s Perspective

ABSTRACT This article describes the diagnosis and treatment of premature ejaculation (PE) from a sex therapist’s perspective and proposes that combination therapy integrating sex therapy and sexual pharmaceuticals is frequently the best treatment approach. Failure to appreciate the multimodal etiology and pathophysiology of PE makes the condition more difficult to diagnose and treat. Many physicians have tried pharmacologic approaches, but are limited to providing topical anesthetics or suggesting off-label uses of antidepressant and erectile dysfunction medications, because no medication is currently indicated specifically for PE. Furthermore, patients frequently relapse after discontinuation of the pharmaceutical. Sex therapists appreciate the multidimensional nature of PE for the patient and partner, but few patients seek out this approach, which is labor-intensive and often lacking long-term follow-up success. Most men with PE are not receiving treatment, secondary to their embarrassment about discussing their condition and a lack of clinician inquiry about sexual dysfunction. Even for those who do engage in discussion, diagnoses may be inconsistent, because a universally accepted definition of the condition and diagnostic criteria are nonexistent. Men with PE experience anxiety and lack sexual self-confidence; subsequently, their sexual and overall relationship frequently suffer. Because PE involves psychosocial and physiologic factors, treatment that addresses both should yield the best balance of function. There is interest in new agents designed specifically for PE to provide an improved pharmacotherapeutic opportunity. Yet, a combination treatment integrating pharmaceuticals and sex therapy would provide an optimized approach. Besides increasing coital latency directly, sexual pharmaceuticals could be used to provide greater opportunity for men to recognize their premonitory sensations to ejaculation more readily, facilitating a “choice point”, which is key to facilitating behavioral change and learning. Such a combination approach would result in prolonged ejaculatory latency, improved treatment satisfaction, and superior long-term outcome.

Etiology of Ejaculation and Pathophysiology of Premature Ejaculation

Ejaculation is comprised of three stages of the male sexual response cycle, namely emission, ejection, and orgasm; however, in comparison with erection, which is a well-understood component of male sexual response, the pathophysiology of ejaculation has yet to be fully delineated. Premature ejaculation (PE), the most common sexual disorder in men, while believed to have a multifactorial etiology, is even less well understood. This article reviews the physiology of ejaculation, and the multifactorial pathophysiology of PE. The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24-26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives. Data were obtained by extensive examination of published peer-reviewed literature. Evidence supports that biologic mechanisms associated with neurotransmitters such as norepinephrine, serotonin, oxytocin, Gamma-amino-butyric acid, and nitric oxide (NO) as well as the hormone estrogen play central roles in ejaculation, and subsequently may mediate PE. There is also emerging evidence to show that hyperthyroidism may be a causal factor in PE. Recent data also suggest that psychogenic factors include high level of any experience by some men with PE. The pathophysiology of both lifelong and acquired PE appears to be both neurobiogenic and psychogenic. While psychogenic factors appear to be contributory to PE, pharmacologic intervention of PE can modify intravaginal ejaculatory latency time (IELT), which suggests that IELT is a biological variable, and is likely biologically dependent upon neurotransmitters and hormones.