Ejaculatio praecox, erectio praecox, and detumescentia praecox as symptoms of a hypertonic state in lifelong premature ejaculation: A new hypothesis

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Abstract

In the last two decades, in vivo animal research and human neurobiological, genetic and pharmacological research of lifelong premature ejaculation (PE) have much contributed to a better understanding of the role of the central and peripheral nervous systems in mediating ejaculation. Research of genetic polymorphisms in men with lifelong PE and clinical research of the validity of the classification into four PE subtypes have provided a better insight into lifelong PE and its distinction from the three other PE subtypes. Nevertheless, a number of symptoms of lifelong PE and its treatment by SSRIs are still not well understood. In the current article, it will be argued that lifelong PE is characterized not only by early ejaculations (ejaculatio praecox), a diminished control over ejaculation, and negative personal consequences, but also by early erections (erectio praecox) and an immediately occurring detumescence of the penis after ejaculation (detumescentia praecox) as symptoms of an (sub)acute hypertonic or hypererotic physical state when making love. Based on animal research it is postulated that the facilitated erection, facilitated ejaculation and facilitated penile detumescence are associated with centrally and peripherally increased oxytocin release. In addition, it is postulated that mechano- and thermosensory activity of transient receptor potential (TRP) ion channels, located in skin receptors of the glans penis, are associated with lifelong PE. Research into the three characteristics of the (sub)acute hypererotic state will presumably contribute to a better phenomenological description of and better neurobiological understanding of lifelong PE and its delineation to the three other PE subtypes.

Introduction

The introduction of selective serotonin reuptake inhibitors (SSRIs) and their application to delay ejaculation in men with premature ejaculation (PE) has stimulated pharmacological, neuroanatomical and neurophysiological research into ejaculation in laboratory animals and pharmacological research in men with lifelong PE (Argiolas et al., 1986, Argiolas et al., 1989, Olivier et al., 1998, Olivier et al., 2011, Veening and Coolen, 1998, Pfaus, 1999, Truitt and Coolen, 2002, Hull et al., 2002, Hull and Dominguez, 2007, Pattij et al., 2005, Waldinger, 2007, de Jong et al., 2007, Chan et al., 2010, Chan et al., 2011, Giuliano et al., 2010). As a result, groundbreaking progress has been made through the attention given to the diagnosis and drug treatment of PE (Waldinger et al., 2004, Waldinger, 2007). In addition, evidence based research has given way to a neurobiological, genetic, and medical view of lifelong and acquired PE. It has also led to the formulation of two additional PE subtypes (Variable PE and Subjective PE) and two new definitions of PE (the ISSM definition of lifelong PE and the DSM-5 definition of PE) both of which now include a cutoff point of about 1 min for the ejaculation time (Waldinger, 2008, Waldinger, 2011, Waldinger and Schweitzer, 2008, McMahon et al., 2008, American Psychiatric Association, 2013). However, in spite of these important developments a number of symptoms of lifelong PE and its treatment by SSRIs are still not well understood.

Lifelong PE (Waldinger, 2013a, Waldinger et al., 1998a) is characterized by the following symptoms: 1) early ejaculation exists from the (nearly) first sexual experiences, usually starting in puberty or adolescence; 2) it occurs with (nearly) every female partner in more than 80–90% of events of intercourse; 3) there is little change in the IELT as men age, or it aggravates in 25–30% of the patients at around the age of 30–35 years; 4) it occurs within 30–60 s after vaginal penetration with nearly every coitus in the majority, i.e., > 90%, of men affected by the dysfunction, whereas about 10–20% of men complaining of lifelong PE ejaculate within 1–2 min; and 5) these symptoms lead to irritability, annoyance and other mental symptoms of embarrassment. The aforementioned features are characteristic of lifelong PE, but there is no such detailed description in the ISSM definition of lifelong PE (McMahon et al., 2008) and the DSM-5 definition of PE (American Psychiatric Association, 2013), as in general a definition of a disorder cannot encompass all the detailed features of the disorder. Lifelong PE may also affect homosexual men, but hardly any clinical research has been conducted in these men.

Treatment by selective serotonin reuptake inhibitors (SSRIs) has led to a paradigm shift in the understanding and treatment of PE (Waldinger et al., 2004). It was shown that all SSRIs exert ejaculation delaying effects (Waldinger et al., 2004). However, and interestingly, considering the similar mechanism of action of the SSRIs, the extent to which SSRIs induce ejaculation delay differs between the SSRIs (Waldinger et al., 1998b, Waldinger et al., 2004). Of all SSRIs, daily use of 20 mg paroxetine exerts the strongest ejaculation delay whereas 100 mg fluvoxamine exerts the smallest ejaculation delay both in in-vivo laboratory animal studies (Waldinger et al., 2002), as in mentally healthy men with lifelong PE (Waldinger et al., 1998b), and as in patients with a depressive and/or anxiety disorder (Serretti and Chiesa, 2009). In 2007, de Jong et al. hypothesized that the different extents of ejaculation delay induced by fluvoxamine and citalopram on the one hand, and paroxetine and fluoxetine on the other hand are related to gradual desensitization of 5-HT1A receptors on oxytocin neurons (de Jong et al., 2007). Their serotonin–oxytocin hypothesis is based on various studies indicating that the neuropeptide oxytocin plays an important role in both the SSRI-induced delayed ejaculation and in the functional differences between the SSRIs (de Jong et al., 2007).

Section snippets

Neurobiological and genetic hypothesis

Based on in-vivo animal research of the 1980s (Ahlenius et al., 1981, Berendsen and Broekkamp, 1987, Foreman et al., 1988), Waldinger et al. (1998c) postulated in 1998 that lifelong PE in terms of an intravaginal ejaculation latency time (IELT) of less than 1 min is related to genetic factors and to diminished central 5-HT neurotransmission and/or dysfunctional 5-HT1A and 5-HT2C receptors. Notably, due to an absence of selective 5-HT1A and 5-HT2C receptor ligands for safe human usage, it has not

Classification by Schapiro

In 1943, Schapiro (1943) was the first to classify PE into two types. He called the first type “the sexually hypertonic or hypererotic type” or “type B” (Schapiro, 1943). In 1989, this type was called lifelong PE (Godpodinoff, 1989). The other type “the hypotonic type” or “type A” was later called “acquired PE” (Schapiro, 1943, Godpodinoff, 1989).

Classification by Waldinger

With the increase in knowledge about the IELT duration in men with lifelong and acquired PE, and epidemiological stopwatch research on the IELT in the

Inadequate description of the “phenotype” lifelong PE

Recently, I argued that the clinical “phenotype” lifelong PE has only been partly described (Waldinger, 2013c). For many years, the focus of attention has mainly been concentrated on its early ejaculations (ejaculatio praecox), diminished control over ejaculation, and negative personal consequences. This is understandable as the early ejaculation and its lack of control are the most disturbing symptom of PE. However, in my clinical work with men with lifelong PE I have noted some clinically

Men with lifelong PE often report better ejaculation delay during masturbation compared to during intravaginal contact. Transient receptor potential (TRP) ion channels have so far not been related to PE. However, as TRP ion channels, which are located in (penile) skin receptors, sense the environment (Damann et al., 2008) their activity might play a role in lifelong PE. TRPs in the glans penis act as mechano- and thermosensors that registrate penile movements, and touch, temperature and

For many years it has been thought that lifelong PE is only characterized by complaints of persistent early ejaculations and/or diminished control of ejaculation leading to negative personal consequences. However, the phenomenology of lifelong PE seems to be more complex. A (so far not yet known) number of these men have not only a premature ejaculation, but also a premature erection and, as argued in the current article, a premature penile detumescence, as part of an acute hypererotic state

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      The differences between these studies in terms of case selection, research methodology, and statistics are also shown (Tables 1–4). It has been postulated that the IELT of <1 minute in men with LPE is associated with disturbed central serotonin (5-HT) neurotransmission, hypersensitivity of 5-HT1A receptors, and/or hypofunction of 5-HT2C receptors.35,36 For these reasons, 6 studies37,38,54,56 have attempted to investigate the question of whether the frequency of different genetic susceptibility alleles of serotonin receptors (HTR1A, HTR2A, HTR1B, and HTR2C) in men with PE differs from those in a control group.

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