Marcel Waldinger

Drexel University College of Medicine · Department of Pharmacology & Physiology

Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT 1A receptors in rats facilitate ejaculatory behavior. However, the relative contribution of 5-HT 1A somatodendritic autoreceptors and heteroreceptors in this pro-sexual behavior is unclear. Moreover, it is unclear...

Men with Subjective premature ejaculation (PE) have complaints of PE but have normal intravaginal ejaculation latency time (IELT) durations. We found two previously published large epidemiological stopwatch-mediated IELT studies to encompass IELT details of men with Subjective PE, albeit this term was not mentioned in both studies or in reviews of...

Recently it was shown that a stopwatch-measured IELT distribution can be transformed to a mathematical formula of a specific mathematical type distribution. The IELT distribution of men in the general population is a Lognormal distribution whereas that of Caucasian men with lifelong premature ejaculation (PE) is a Gumbel Max distribution. In this a...

Recently, the ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS, 2018 Version) has been published with a new definition of premature ejaculation (PE), including a third PE subtype. This definition differs from Diagnostic and Statistical Manual of Mental Disorders (DSM-5) definition of PE. We hereby address the similarities and differences b...

As lifelong premature ejaculation (PE) and subjective PE are two different PE subtypes, the measurement of their characteristic features requires different objective measures. In this article, we address the differences between lifelong PE and subjective PE, in terms of the extent of variation of sexual performance and propose a new objective measu...

The widespread serotonergic system in the central nervous system and spinal cord is equipped with one neurotransmitter, 14 different serotonin receptors, and a transporter. The serotonergic system is involved in practically all behavioral and physiological functions, including sexual behavior. Serotonin (5-hydroxytryptamine (5-HT)) plays a modulato...

Introduction: Various drugs are available for lifelong and acquired premature ejaculation (PE), but only dapoxetine and FortacinTM have been officially registered. On the other hand, all sorts of pharmacologically not-investigated over-the-counter-products (OTCs) are used by men with complaints of PE with normal ejaculation time durations (subjecti...

Tramadol is an effective pharmacological intervention in human premature ejaculation (PE). To investigate whether the inhibitory action of tramadol is primarily caused by its selective serotonin reuptake inhibitory (SSRI) effects we tested the dose–response effects of tramadol on sexual behavior in serotonin transporter wild type (SERT+/+), heteroz...

Kernpunten van het hoofdstuk • Veel psychiatrische stoornissen gaan gepaard met veranderingen van het seksueel functioneren. Het is in het kader van diagnostiek en behandeling van belang hier actief aandacht aan te geven. • Kennis van de invloed van psychiatrische stoornissen op seksueel functioneren kan effectief in de behandeling worden ingepast....

A case is described of a 40 year old woman with persistent spontaneous orgasms after use of Cannabis and five hour hard pounding sexual activity. She presented with severe anxiety in particular to suffer from Restless Genital Syndrome (ReGS). However, she did not fulfill to any of the five criteria of ReGS. It was concluded that her spontaneous org...

Premature ejaculation (PE) has given rise to various and sometimes highly contrasting theories, approaches, and treatments. PE was believed to be mainly a psychological disorder for the first half of the twentieth century and regarded as a symptom of a neurosis that had to be treated by psychoanalysis in order to solve the unconscious conflicts tha...

Oral drug treatment for PE has been available since 1932 when Bernard Schapiro developed Präjaculin for the treatment of lifelong PE, which was even more than a decade before the first review article on PE was published by Schapiro in 1943 and long before behavioral treatments were advocated as the first choice of treatment. However, it was only af...

Ejaculation consists of emission and expulsion. Both phases are synchronized by close co-ordination of a group of highly specialized neurons in the lumbar spinal cord, e.g., the spinal generator of ejaculation (SGE), and various brain areas. By parasympathetic activation the seminal vesicles excrete seminal fluid. However, by sympathetic activation...

Introduction: Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definitions of sexual dysfunction do not identify all sexual problems experienced clinically by women and are not necessarily applicable for biologic or biopsychosocial management of female sexual dysfunction. A unified nomenclature system enables cl...

Tramadol is a well-known and effective analgesic. Recently it was shown that tramadol is also effective in human premature ejaculation. The inhibitory effect of tramadol on the ejaculation latency is probably due to its mechanism of action as a μ-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake inhibitor. In order to test this sp...

In dit hoofdstuk wordt vroegtijdige zaadlozing beschreven als combinatie van snelle zaadlozing (korte interavaginale ejaculatielatentietijd), geen controle erover, met lijdensdruk als gevolg. Er bestaan vier subtypen. Vanwege schaamte zoeken weinig patiënten hulp. De huisarts moet serieus op de klacht ingaan, niet bagatelliseren, een luisterende op...

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 fr...

Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or masturbation. Two subtypes are distinguished: Primary and secondary POIS. It also occurs before or after a man has been sterilized. POIS is an invalidating most probably auto-immune disease lea...

Introduction: Tramadol exhibits an effect profile similar to that of opioid agonists, and tramadol abuse seems to be a problem for a number of countries. The relationship between tramadol and sexual function appears to be controversial. Men with premature ejaculation (PE) may benefit from taking tramadol off label; however, these patients live "on...

Purpose To find the most accurate mathematical description of the intravaginal ejaculation latency time (IELT) distribution in the general male population. Materials and Methods We compared the fitness of various well-known mathematical distributions with the IELT distribution of two previously published stopwatch studies of the Caucasian general...

Sexual problems are highly prevalent among patients with psychiatric disorders. They may be caused by the psychopathology of the psychiatric disorder but also by its pharmacotherapy. Both positive symptoms (e.g., psychosis, hallucinations) as well as negative symptoms (e.g., anhedonia) of schizophrenia may negatively interfere with interpersonal an...

Introduction In the last two decades much progress has been made in the neurobiological, pharmacological and neuro-imaging research of sexual dysfunctions. Objectives to present an overview of current treatment options Aims to provide better understanding of underlying (neuro)biological mechanisms Methods use of evidence-based research articles...

Treatment of paroxetine-induced penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) by Low-power Laser Irradiation (LPLI) is unknown in medical literature. The aim of the current article is to report partial efficacy of LPLI for paroxetine-induced persistent penile anesthesia. We report on a male patient who presented with a history of reversi...

Purpose of review: As there are various drugs and different treatment strategies to delay ejaculation, a review of the current drug treatments for premature ejaculation is relevant for daily clinical practice. Recent findings: There are four premature ejaculation subtypes: lifelong premature ejaculation, acquired premature ejaculation, variable...

Purpose Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. Materials and Methods Five males with lifelong PE who were k...

It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE...

Oxytocin (OT) is a nonapeptide with an impressive variety of physiological functions. Among them, the 'prosocial' effects have been discussed in several recent reviews, but the direct effects on male and female sexual behavior did receive much less attention so far. As our contribution to honor the lifelong interest of Berend Olivier in the control...

Purpose: To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE). Materials and Methods: This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation...

IntroductionThe International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE.AimThe ai...

IntroductionThe International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE.AimThe ai...

Introduction: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychologica...

IntroductionAlfred Kinsey (1894–1956) was the first pioneer of scientific sexology after World War II with his surveys on human sexuality in the male (1948) and the female (1953), which underwent worldwide translations and also had a major impact in Europe.AimTo clarify the role of the journalist Oswalt Kolle (1928–2010) as the promoter of sex educ...

To analyze a recently published meta-analysis of six studies on 5-HTTLPR polymorphism and lifelong premature ejaculation (PE). Calculation of fraction observed and expected genotype frequencies and Hardy Weinberg equilibrium (HWE) of cases and controls. LL,SL and SS genotype frequencies of patients were subtracted from genotype frequencies of an id...

To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE). This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measure...

Seksueel gedrag is een complex fenomeen dat beïnvloed wordt door veel verschillende factoren en sterk gereguleerd wordt door neurobiologische processen. Deze bijdrage geeft, aan de hand van een aantal actuele voorbeelden, een beeld van de translationele waarde van onderzoek bij ratten voor het bestuderen van de neurobiologische regulatie van seksue...

Op basis van farmacologisch in vivo dieronderzoek, en humaan klinisch en genetisch onderzoek is een neurobiologische visie ontwikkeld op lifelong premature ejaculatie (PE). Een aantal symptomen van lifelong PE wordt echter nog steeds niet begrepen. In dit artikel wordt beargumenteerd dat lifelong PE niet alleen gekenmerkt wordt door vroegtijdige ej...

Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT1A receptor hyperfunction and 5-HT2C hypofunction. To investigate the relationship between 5-HT1A...

In the last two decades, in vivo animal research and human neurobiological, genetic and pharmacological research of lifelong premature ejaculation (PE) has much contributed to a better understanding of the role of the central and peripheral nervous system in mediating ejaculation. Research of genetic polymorphisms in men with lifelong PE and clinic...

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducability of our standardized test procedure that asses...

The central serotonergic system remains the most important system that can be manipulated to delay ejaculation. Based on animal research, combination of an SSRI with a 5-HT1A antagonist may lead to an acute strong ejaculation delay. This may form the basis for the development of new powerful on-demand drugs to treat lifelong PE. Currently available...

Since their introduction in the 1990s, selective serotonin re-uptake inhibitors (SSRIs) have become well-known for their ejaculation delaying effects. But although not approved by the Food and Drug Administration (FDA), off-label use of the SSRIs to treat premature ejaculation (PE) has become popular and also recommended as one of the treatment opt...

Introduction Spontaneous orgasm triggered from inside the foot has so far not been reported in medical literature. Aims The study aims to report orgasmic feelings in the left foot of a woman. Methods A woman presented with complaints of undesired orgasmic sensations originating in her left foot. In‐depth interview, physical examination, sensory t...

Introduction Restless Genital Syndrome (RGS) refers to the experience of excessive and persistent sensations of genital arousal, with either restless legs and/or complaints of overactive bladder, in absence of conscious feelings of sexual desire. RGS is caused by a small fiber sensory neuropathy of the dorsal nerve of the clitoris, an endbranch of...

Restless Genital Syndrome (RGS) refers to the uncommon experience of excessive and persistent sensations of genital and clitoral arousal, with either restless legs or symptoms of an overactive bladder, in the absence of conscious feelings of sexual desire. RGS is caused by a small fiber sensory neuropathy of the dorsal nerve of the clitoris. To dat...

In 2010 the International Society of Sexual Medicine published its practice guideline for the diagnosis and treatment of premature ejaculation. This guideline was translated and adapted on a number of points by a committee consisting of members of two Dutch sexological societies, the 'WVSD' and the 'NVVS'. The most important subjects in this guidel...

Introduction: Ejaculatory/orgasmic disorders are common male sexual dysfunctions and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. Aim: To provide recommendations and guidelines of the current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men as...

In the last two decades an increasing number of sexual behavioral studies in laboratory animals has contributed to a better understanding of the neural basis of ejaculatory functioning. In addition, these studies, which mainly involved male and female Wistar rats, elucidated basic mechanisms that underly the psychopharmacology of SSRI-induced ejacu...

Introduction. Selective serotonin reuptake inhibitors (SSRIs) cause sexual dysfunctions in humans. However, because SSRIs are used to treat depression, it is unclear whether the problems are caused by the drug, by the depression itself, or an interaction between both. Aim. The present study investigated the effects of chronic paroxetine treatment o...

Hypoactive sexual desire disorder (HSDD) is a common problem in women and may have a negative impact on quality of life. A recent clinical study shows an increase in sexual drive of HSDD women after cotreatment of testosterone and vardenafil (phosphodiesterase type 5 inhibitor). In this study, we investigated the effect of testosterone and vardenaf...

Postorgasmic illness syndrome (POIS) is a combination of local allergic symptoms and transient flu-like illness. In this study, the investigators propose five preliminary criteria to establish the diagnosis. To describe the clinical details in 45 males being suspected of having POIS and to test an immunogenic hypothesis as the underlying mechanism...

Postorgasmic illness syndrome (POIS) is a post-ejaculatory complex of local and/or systemic symptoms that nearly always occurs within seconds, minutes, or hours post-masturbation, coitus, or spontaneous ejaculation. Recent data suggest an autoimmunogenic/allergic underlying mechanism. To treat males with POIS by hyposensitization with their own sem...

Serotonin plays an important role in both male and female sexual behaviour. In general, reduction of 5-HT function facilitates, whereas enhancement inhibits sexual behaviour. Most fundamental research on the involvement of 5-HT in sex has been performed in rats. Selective serotonin reuptake inhibitors (SSRIs) have comparable effects on male and fem...

Female sexual dysfunction (FSD) affects 33-48% of women. Female rats with low sexual activity might model FSD. In this study, we have investigated whether in a population of normal female rats, subpopulations of rats exist with different levels of sexual behavior. Sexually experienced, intact, estradiol-primed female rats were placed in an empty co...

Recently, four premature ejaculation (PE) subtypes have been distinguished on the basis of the duration of the intravaginal ejaculation latency time (IELT). These four PE subtypes have different etiologies and pathogeneses. Genetic research on PE should consider the existence of these PE subtypes and the accurate measurement of the IELT with a stop...

Serotonin (5-HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels. To investigate the putative role of the SERT in male sexual behavior. After extensive sexual training...

In the last two decades enormous progress has been made in the characterization of premature ejaculation (PE). Although lifelong (primary) PE and acquired (secondary) PE has been known since the 1980s, a new classification of PE has been proposed in 2006 by Waldinger et al., who distinguished two other PE subtypes, e.g., premature-like ejaculatory...

This unit describes the testing of sexual behaviors of male Wistar rats. The described test enables the detection of stimulatory and inhibitory profiles of compounds. The test includes four training sessions to reach a stable sexual performance, followed by acute and/or chronic administration of drugs. The main quantifiable sexual behaviors are num...

Restless genital syndrome (ReGS) is characterized by unwanted, unpleasant genital sensations, restless legs, and/or overactive bladder, as well as neuropathy of the dorsal nerve of the clitoris. So far, ReGS has only been reported in females. To report the occurrence of ReGS in two males. Two males with unwanted genital sensations presented in our...

Introduction Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder,...

Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the...

Introduction. Ejaculatory/orgasmic disorders are common male sexual dysfunctions, and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. Aim. To provide recommendations and guidelines concerning current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men....

Serotonin plays a key role in sexual behavior. In serotonin transporter (SERT) knockout rats (-/-), basal extracellular 5-HT levels are considerably increased, indicating a serotonergic disturbance. Heterozygous SERT(+/-) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SERT promoter (5...

Introduction: Females despairing of restless genital syndrome (ReGS) may request clitoridectomy for treatment of unwanted genital sensations. Aim. The aim of this study was to report persistence of ReGS despite clitoridectomy. Methods: Following a clitoridectomy for spontaneous orgasms, a 77-year-old woman was referred to our clinic for persiste...

INTRODUCTION: Serotonin plays a key role in sexual behavior. In serotonin transporter (SERT) knockout rats (-/-), basal extracellular 5-HT levels are considerably increased, indicating a serotonergic disturbance. Heterozygous SERT(+/-) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SE...

Currently, efficacious treatment of restless genital syndrome (ReGS) is not available. This study aimed to report the results of transcutaneous electrical nerve stimulation (TENS) for ReGS, being a combination of genital dysesthesias, imminent and/or spontaneous orgasms, and/or restless legs, and/or overactive bladder. Two women with ReGS were refe...