Pathophysiology of Lifelong Premature Ejaculation

Abstract

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.

An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)

“…Serefoglu et al were the first to report prevalence rates for the four PE subtypes [ 40 , 58 , 59 ] as described by Waldinger and Schweitzer [ 10 , 15 , 23 ] A 2010 study reported the distribution of PE subtypes in PE patients admitted to a urology outpatient clinic in Turkey, while a subsequent 2011 study reported the prevalence of PE subtypes in the general male population in Turkey randomly selected by a proportional sampling method according to postal code [ 40 , 58 ]. This research design was replicated by Zhang et al [ 53 ] and Gao et al [ 50 ] in a Chinese population.…”

Assessing satisfaction in men with premature ejaculation after dapoxetine treatment in real-world practice

“…Of the 286 patients treated with dapoxetine, 142 (49.7%) patients had at least one follow‐up visit and 37 (12.9%) patients had at least two follow‐up visits. The mean of initial prescription was 1.5 ± 0.7 packs (3 tablets/pack), and the refill rate of dapoxetine at 2nd visit was 73.9% (105/142). A total of 712 packs of dapoxetine were purchased during this study, with an average of 2.5 ± 2.5 packs per person.…”

“…The diagnosis and classification of PE followed the guidelines of the ISSM . Based on the SHIM score, the severity of ED was classified as: severe ED , moderate ED , mild‐to‐moderate ED , mild ED , and no ED .…”

“…In the past, psychological or interpersonal factors were believed to be the underlying cause of PE and behaviour therapy was the main treatment for it. In the last two decades, evidence‐based research supported that neurobiological factor, diminished serotonin neurotransmission or a hypersensitivity of 5‐HT 1A receptors in the central nervous system, or a genetic polymorphism was attributed to a short intravaginal ejaculatory latency time (IELT) in lifelong PE . It is important to diagnose the underlying primary cause of PE and any associated comorbidities, such as hyperthyroidism and prostatitis , because they should be treated first or at the same time as PE .…”

The heart rate recovery is impaired in participants with premature ejaculation

“…The International Society for Sexual Medicine describes the lifelong PE (LPE) as the ejaculations occurring prior to or within the first minute of vaginal penetration almost every time and associated with concerns such as inconvenience, frustration, avoidance of intimacy and/or emotional pain (Serefoglu et al, 2014). Ejaculation has a complex mechanism that occurs under the influence of central nervous system, peripheral nervous system and endocrine system (El‐Hamd, Saleh, & Majzoub, 2019; Waldinger, 2016). The exact mechanism of PE is not yet fully understood.…”