Vous êtes sur la page 1sur 6

european urology supplements 6 (2007) 762767

available at www.sciencedirect.com
journal homepage: www.europeanurology.com

Evolution of the Understanding of Premature Ejaculation:


Historical Perspectives
Marcel D. Waldinger a,b,*
a

Department of Psychiatry and Neurosexology, Haga Hospital Leyenburg, The Hague, The Netherlands
Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences,
Utrecht University, Utrecht, The Netherlands

Article info

Abstract

Keywords:
Premature ejaculation
IELT
Definition
Serotonin
Psychoanalysis

The perception of lifelong premature ejaculation (PE) has evolved from


that of a relatively obscure complaint to one of a relatively common
syndrome with a neurobiological component. During the last century,
four historical periods, each about 30 yr in duration, can be distinguished. In these periods PE was regarded according to the major prevailing viewpoint of mental disorders, that is, from phenomenological,
psychoanalytic, behavioral, and neurobiological points of view.
Although the influences of these different periods on the medical
approach to PE are still present today, recent scientific evidence suggests
that lifelong PE is related to an imbalance in central serotonin neurotransmission. A basic premise for further research remains an evidencebased definition of PE. Such an evidence-based definition is essential to
ensure accurate and reproducible clinical outcomes.
# 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Department of Psychiatry and Neurosexology, Haga Hospital Leyenburg, Leyweg 275,
2545 CH The Hague, The Netherlands. Tel. +31 70 3592086; Fax: +31 70 3594902.
E-mail address: md@waldinger.demon.nl.

1.

Introduction

Scientific and medical perspectives on premature


ejaculation (PE) have evolved throughout the last
century. Although PE was considered as nothing
more than a peculiar anomaly until about 1917, it
was believed to be mainly a psychological disorder
for the first half of the 20th century [1,2]. During the
1960s, the perspective shifted to the view that PE
was not a symptom of a neurosis but a manifestation of self-learned behavior. Today, in contrast,
individuals who have experienced PE from the time
of their first sexual encounter as well as many of

those who develop PE after a period of normal


ejaculatory function are considered to have lifelong
and acquired PE, respectively [3]. However, although
lifelong PE is regarded to be highly neurobiologically
determined, and acquired PE may have both a
medical and a psychological basis [4], the etiologies
of both types of PE are still not completely understood.
Our current understanding of the neurobiological
basis of PE was reached primarily through animal
studies and, particularly in the 1990s, through an
increasing number of drug treatment studies with
selective serotonin reuptake inhibitors (SSRIs) and

1569-9056/$ see front matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.

doi:10.1016/j.eursup.2007.04.009

european urology supplements 6 (2007) 762767

clomipramine [57]. These studies have demonstrated a key role of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT
receptor subtypes in regulating ejaculation [4,8].
For many years there have been two separate and
rather contrasting approaches to PE: the medical
approach favoring drug treatment and the psychological approach focusing on behavioral therapy of
PE. A current challenge in PE treatment is to combine
psychological and neurobiological insights into an
evidence-based definition of PE. This review will
focus on the historical viewpoints and the current
neurobiological approach of PE.

2.
Historical perspectives of premature
ejaculation
2.1.

The first period: phenomenological

After the first report of PE in the medical literature in


1887 [9], a period of 30 yr ensued in which PE was
regarded as only a rather disturbing symptom and
for which no etiology was suggested.
2.2.

The second period: psychoanalytic

The psychoanalytic period began in 1917 when Karl


Abraham, a psychoanalyst, ascribed PE to a neurosis, that is, as the symptom of unsolved unconscious conflicts, and advocated treatment by
classical psychoanalysis [10]. His purely psychological explanation was later challenged by Bernard
Schapiro, a German psychiatrist, who in 1943
postulated that PE was not a neurotic but a
psychosomatic disorder [11]. He argued that both
biological and psychological factors contributed to
rapid ejaculatory performances. Years ahead of his
time, Schapiro advocated drug treatment in the
form of anesthetic ointments to delay ejaculation. In
addition, he is credited with identifying the two
types of PE recognized today as primary (lifelong)
and secondary (acquired) PE [11]. Because he was the
first clinician to use a medical approach to PE,
Bernard Schapiro is regarded as a pioneer in
researching this condition.
The accurate differential diagnosis and biologic
components of Schapiros arguments were ignored
in his time. Psychoanalytic treatment, mainly
conducted by psychiatrists, prevailed throughout
the 1940s and 1950s. Records of the course and
results of these psychoanalytic treatments could
have provided insights into how this medical
condition affects unconscious processes and its
unconscious impact on neurotic adaptations to daily

763

life. For example, considered from a classical


Freudian perspective, it may be relevant whether
individuals cope differently with lifelong PE dependent on more anal, oral, or oedipal period neurotic
fixations [12]. Unfortunately, very little of this
information is documented in the literature.
2.3.

The third period: behavioristic

In the mid-1960s, concurrent with a rejection of


psychoanalysis and an increasing popularity of
behaviorism in academic psychology, the approach
and treatment of sexual disorders began to evolve.
Although originally borne out of psychiatry and
handled mainly by psychiatrists, sexology now
became the field of psychologists and sexologists
who, particularly in those years of antipsychiatry,
demonstrated an overt aversion to psychoanalysis,
and the medical and drug treatment approach of
mental and sexual disorders. The rejection of the
medical and psychoanalytic roots of sexual dysfunctions contributed to the separation and isolation of sexology from psychiatry and ultimately also
from academic medicine, a separation that still
exists today. It is with this background that one has
to consider the third period of PE, the behavioristic
period. This perspective started in 1970 when
Masters and Johnson [13] published their book in
which they argued that PE was the result of a selflearned behavior, meaning that PE became acquired
by hurried intercourse during initial sexual experiences. Masters and Johnson stated that PE could
be cured through behavioral therapy in the form of
the squeeze technique, a masturbation technique
that resembled the older stop-start method of
Semans [13,14]. Their ideas on PE prevailed until
very recently, despite the lack of evidence-based
studies to support their theories of etiology and
treatment effectiveness. For a period of 2030 yr,
with little exception [15], authors did not criticize the
lack of evidence for the theories of Masters and
Johnson. Moreover, various sexologists, competing
to improve upon their theory, proposed shortening
the duration of the behavioral treatment as proposed by Masters and Johnson. In this way it was
proposed to have only limited sessions and/or
limited telephone contacts with the patient because
it was assumed that solely practicing the masturbation exercises would automatically ameliorate the
problem [16,17]. A failure of behavioral therapy to
delay ejaculation was often ascribed to the patient
not practicing the exercises in the appropriate
manner. This early approach of sexologists to
diminish the frequency of face-to-face contacts
with men with PE highly contrasts with the current

764

european urology supplements 6 (2007) 762767

view. Today, many sexologists insist on talking


with the couple and emphasize the inadequacies of
using medication exclusively to delay ejaculation.
During the period of behavioral treatment, case
reports and placebo-controlled studies described
the efficacy of the tricyclic antidepressant clomipramine in delaying ejaculation [1820]. These
studies, although often not conducted according
to current standards of evidence-based medicine,
paved the way for the increasing popularity of oral
drug treatment of PE.
2.4.

The fourth period: neurobiological

In the mid-1990s the introduction of the selective


serotonin reuptake inhibitors (SSRIs) brought about
a revolutionary change in the understanding
and treatment of PE. Their efficacy in delaying
ejaculation together with the increasing interest of
neuroscientists, like Sven Ahlenius [5,21], in investigating sexual behavior in laboratory rats led to
the end of the supremacy of the behavioristic
approach of PE and marked the beginning of the
neurobiological view. Animal studies and the use of
stopwatch assessment of the intravaginal ejaculatory latency time (IELT) [22] both during the baseline
period and during drug treatment led to a more
evidence-based approach of drug treatment trials
[23,24].
2.4.1.

The role of serotonin in ejaculatory motor control

Experimental studies demonstrated that serotonin


and serotonin receptors modulate motor control of
ejaculation in animals [5,8]. In addition, animal
studies have shown that a diminished serotonin
neurotransmission and activation of 5-HT1A receptors lead to faster ejaculation, whereas activation
of 5-HT2C and 5-HT1B receptors delays ejaculation
[5,8,25]. Although the efficacy of SSRIs in the treatment of PE argues for a similar role in humans, there
is no evidence to date that these specific 5-HT
receptors are involved in human ejaculation [1].
2.4.2.

Definition of PE

There is accumulating evidence for a neurobiological basis of lifelong PE, despite the contrasting and
conflicting medical and psychological approaches
to PE that prevailed until the mid-1990s. However,
an official evidence-based definition of PE is still
lacking. The definition of PE as formulated in the
Diagnostic and Statistical Manual, Fourth Edition, Text
Revision (DSM-IV-TR) issued by the American Psychiatric Association (APA) is persistent or recurrent
ejaculation with minimal sexual stimulation before,
on, or shortly after penetration and before the

person wishes it [26]. The DSM requires that the


disturbance causes marked distress or interpersonal
difficulty [26]. This definition is vague because it
fails to operationalize marked distress and
marked interpersonal difficulty. The definition
issued by the American Urological Association
(AUA) Guideline on the Management of Premature
Ejaculation, ejaculation that occurs sooner than
desired, either before or shortly after penetration,
causing distress to either one or both partners, is
similarly vague as it is nearly an exact copy of the
DSM definition [27,28]. Both the definitions offered
by the APA and the AUA are not based on controlled
studies, but the result of expert (authority) consensus [29,30]. Recently, however, and based on
controlled studies, Waldinger and Schweitzer [29,30]
proposed a new syndromal instead of subjective
complaint approach to define PE in the pending
DSM-V and ICD-11 editions.
2.4.3.

Intravaginal ejaculation latency time

An important issue in neurobiological research is


the reproducibility of quantified data by the use of
operationally defined measures and reliable instruments. To address this need in PE research,
Waldinger et al [22] emphasized the clinical and
scientific importance of the ejaculation time and
introduced the measurement of IELT, which is
defined as the time between vaginal intromission
and intravaginal ejaculation. Waldinger et al [8]
further postulated that the IELT is neurobiologically
determined and variably distributed both in the
general male population and in men with lifelong
PE. Indeed, such a continuum of the IELT was found
in a clinical cohort of 110 men with complaints of
lifelong PE. In this population, the IELT was 30 s in
80%, between 40 and 60 s in approximately 10%, and
between 1 and 2 min in the remaining 10% [31].
2.4.4.

Defining abnormal IELTs

To determine the distribution of IELTs in the general


male population, Waldinger et al [32] conducted a
stopwatch study in a random cohort of 491 men
among five nations (the Netherlands, United Kingdom, Spain, Turkey, and the United States). To
ensure a random cohort of men enrolled in the
study, they did not apply inclusion and exclusion
criteria. Because the distribution of IELTs did not fall
on a bell-shaped curve, analysis using percentiles
was used. Currently accepted statistical methods
use cut-offs of 0.52.5 percentiles to define abnormal
values in skewed populations such as this one [33].
Men who were below the 0.5 percentile reported
IELTs <1 min, and those in the range of 0.52.5
percentiles reported IELTs between 1.0 and 1.5 min

european urology supplements 6 (2007) 762767

[34]. On the basis of these IELTs, Waldinger et al [34]


proposed that definite PE be defined by an IELT
<1 min and probable PE by an IELT between 1.0
and 1.5 min, indicating that the risk to develop
complaints of PE becomes higher when the IELT gets
shorter. Within those categories, the severity of PE
was further classified on a four-point scale of
none, mild, moderate, or severe as determined by psychological and sexual distress. The
1-min cut-off IELT is consistent with data from a
clinical study by Waldinger et al [31], in which 90% of
men actively complaining of PE ejaculated within
1 min.
2.4.5.

Treatment with SSRIs

The first double-blind placebo-controlled study on


the efficacy of paroxetine to delay ejaculation in
men with PE was published in 1994 [22]. Subsequent
studies have shown that daily treatment with
paroxetine [35,36] and sertraline [3638] can significantly prolong IELT in patients with PE. Also,
fluoxetine [36,39,40] has been proven efficacious
with continuous dosing as has the tricyclic antidepressant clomipramine [41]. However, the ondemand use of these SSRIs [4246] has resulted in
contrasting results that presumably are due to
methodological insufficiencies [45]. To date, none
of these agents has received US Food and Drug
Administration approval for treatment of PE.
Although daily treatment with SSRIs clinically
relevantly delays ejaculation, the requirement for
continuous use of SSRIs, particularly for men with
lifelong PE, may hamper patient compliance in the
long term. Moreover, evidence suggests that acute
effects of SSRI treatments may be limited by
inherent neurotransmission feedback mechanisms
[8]. Therefore, continuous research is being encouraged to develop and investigate new drugs to treat
PE.

3.

Conclusion

Although PE has been an identified male sexual


complaint for many centuries, it was described in
the medical literature for the first time in 1887. Since
then, four distinct areas of PE have evolved on the
basis of the prevailing theories of mental and/or
sexual disorders of each period. The current view of
PE is in accordance with the present day understanding of the physiological basis of mental
disorders. This Neurobiological Period started in
the mid 1990s after the introduction of the SSRIs and
has led to an expanding body of knowledge about
the factors underlying PE.

765

The historical perspectives taken from earlier


periods have contributed to our current understanding of PE. However, few well-controlled studies
were performed during the psychoanalytic and
behavioral periods. Documentation of how lifelong
PE affects the unconscious minds of men affected by
this dysfunction and placebocontrolled, comparative studies using IELT measurements to assess the
efficacy of behavioral treatments would be valuable
in determining the value of these modalities in
treating patients with PE. In the current area of
neurobiology, neuroscientific and psychopharmacological research has contributed highly to the
availability of effective drugs to treat PE. Still,
continuous research is encouraged and needed to
develop and investigate new drugs for the treatment
of PE. However, as we move forward with the
research and treatment of PE, a basic condition for
any further research remains an evidence-based
definition of PE. Such an evidence-based definition,
as has recently been proposed in terms of a
syndromal PE approach, is essential to ensure
accurate and reproducible clinical outcomes.

Conflicts of interest
The author has nothing to disclose.

References
[1] Waldinger MD. The neurobiological approach to premature ejaculation. J Urol 2002;168:235967.
[2] Waldinger MD. Lifelong premature ejaculation: from
authority-based to evidence-based medicine. BJU Int
2004;93:2017.
[3] Waldinger MD. Emerging drugs for premature ejaculation.
Expert Opin Emerg Drugs 2006;11:99109.
[4] Olivier B, van Oorschot R, Waldinger MD. Serotonin,
serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Int Clin Psychopharmacol
1998;13(Suppl 6):S914.
[5] Ahlenius S, Larsson K. Failure to antagonize the 8hydroxy-2-di-n-propylaminotetralin-induced facilitation
of male rat sexual behavior by the administration of 5-HT
receptor antagonists. Eur J Pharmacol 1984;99:27986.
[6] Bitran D, Hull EM. Pharmacological analysis of male
rat sexual behavior. Neurosci Biobehav Rev 1987;11:
36589.
[7] Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B.
Relevance of methodological design for the interpretation
of efficacy of drug treatment of premature ejaculation: a
systematic review and meta-analysis. Int J Impot Res
2004;16:36981.
[8] Waldinger MD, Berendsen HHG, Blok BFM, Olivier B,
Holstege G. Premature ejaculation and serotonergic anti-

766

[9]
[10]
[11]
[12]

[13]

[14]
[15]
[16]

[17]

[18]
[19]

[20]
[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

european urology supplements 6 (2007) 762767

depressants-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res 1998;
92:1118.
Gross S. Practical treatise on impotence and sterility.
Edinburgh: YJ Pentland; 1887.
Abraham K. Ueber ejaculatio praecox, Zeitschr. Aerztl
Psychoanal 1917;4:17186.
Schapiro B. Premature ejaculation: a review of 1130 cases.
J Urol 1943;50:3749.
Waldinger MD. The need for a revival of psychoanalytic
investigations into premature ejaculation. J Mens Health
Gender 2006;3:3906.
Masters W, Johnson V. Premature ejaculation. In: Masters
W, Johnson V, editors. Human sexual inadequacy. Boston:
Little, Brown; 1970. p. 92115.
Semans JH. Premature ejaculation: a new approach. South
Med J 1956;49:3537.
Zilbergeld B, Evans M. The inadequacy of Masters and
Johnson. Psychology Today 1980;14:2934.
Clement U, Schmidt G. The outcome of couple therapy for
sexual dysfunctions using three different formats. J Sex
Marital Ther 1983;9:6778.
Trudel G, Proulx S. Treatment of premature ejaculation by
bibliotherapy: an experimental study. Sex Marital Ther
1987;2:1637.
Eaton H. Clomipramine in the treatment of premature
ejaculation. J Int Med Res 1973;1:4324.
Porto R. Essai en double aveugle de la clomipramine
dans lejaculation prematuree. Med Hygiene 1981;39:
124953.
Assalian P. Clomipramine in the treatment of premature
ejaculation. J Sex Res 1988;24:2135.
Ahlenius S, Larsson K. Evidence for an involvement of
5-HT1B receptors in the inhibition of male rat ejaculatory
behavior produced by 5-HTP. Psychopharmacology (Berl)
1998;137:37482.
Waldinger MD, Hengeveld MW, Zwinderman AH. Paroxetine treatment of premature ejaculation: a double-blind,
randomized, placebo-controlled study. Am J Psychiatry
1994;151:13779.
Pattij T, de Jong T, Uitterdijk A, et al. Individual differences in male rat ejaculatory behavior: searching for
models to study ejaculation disorders. Eur J Neurosci
2005;22:72434.
Waldinger MD. Towards evidence-based drug treatment
research on premature ejaculation: a critical evaluation of
methodology. Int J Impot Res 2003;15:30913.
Giuliano F, Clement P. Serotonin and premature ejaculation: from physiology to patient management. Eur Urol
2006;50:45466.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th edition, text revision) (DSM-IV-TR). Washington, American Psychiatric
Association; 2000.
Montague DK, Jarow J, Broderick GA, et al. AUA guideline
on the pharmacologic management of premature ejaculation. J Urol 2004;172:2904.
Waldinger MD. Overview of premature and retarded ejaculation. Eur Urol Today 2005;17:202.

[29] Waldinger MD, Schweitzer DH. Changing paradigms from


a historical DSM-III and DSM-IV view toward an evidencebased definition of premature ejaculation. Part Ivalidity
of DSM-IV-TR. J Sex Med 2006;3:68292.
[30] Waldinger MD, Schweitzer DH. Changing paradigms
from a historical DSM-III and DSM-IV view toward an
evidence-based definition of premature ejaculation. Part
IIproposals for DSM-V and ICD-11. J Sex Med 2006;3:
693705.
[31] Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier
B. An empirical operationalization study of DSM-IV diagnostic criteria for premature ejaculation. Int J Psychiatry
Clin Pract 1998;2:28793.
[32] Waldinger MD, Quinn P, Dilleen M, Mundayat R, Schweitzer DH, Boolell M. A multi-national population survey of
intravaginal ejaculation latency time. J Sex Med 2005;2:
4927.
[33] Obuchowski NA, editor. Statistical methods in diagnostic
medicine. Wiley series in probability and statistics. New
York: Wiley-Interscience; 2002.
[34] Waldinger MD, Zwinderman AH, Olivier B, Schweitzer
DH. Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data. J Sex
Med 2005;2:498507.
[35] Waldinger MD, Hengeveld MW, Zwinderman AH. Ejaculation-retarding properties of paroxetine in patients
with primary premature ejaculation: a double-blind,
randomized, dose-response study. Br J Urol 1997;79:
5925.
[36] Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier
B. Effect of SSRI antidepressants on ejaculation: a doubleblind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol 1998;18:27481.
[37] Mendels J, Camera A, Sikes C. Sertraline treatment
for premature ejaculation. J Clin Psychopharmacol 1995;
15:3416.
[38] Balbay MD, Yildiz M, Salvarci A, Ozsar O, Ozbek E. Treatment of premature ejaculation with sertralin. Int Urol
Nephrol 1998;30:813.
[39] Kara H, Aydin S, Yucel M, Aqarqun MY, Odabas O, Yilmaz
Y. The efficacy of fluoxetine in the treatment of premature ejaculation: a double-blind placebo controlled study.
J Urol 1996;156:16312.
[40] Lee HS, Song DH, Kim CH, Choi HK. An open clinical trial
of fluoxetine in the treatment of premature ejaculation.
J Clin Psychopharmacol 1996;16:37982.
[41] Kim SC, Seo KK. Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with premature ejaculation: a double-blind, placebo controlled study. J Urol
1998;159:4257.
[42] McMahon CG, Touma K. Treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 singleblind placebo controlled crossover studies. J Urol 1999;
161:182630.
[43] Murat Basar MA, Atan A, Yildiz M, Baykam M, Aydoganli L.
Comparison of sertraline to fluoxetine with regard to their
efficacy and side effects in the treatment of premature
ejaculation. Arch Esp Urol 1999;52:100811.

european urology supplements 6 (2007) 762767

[44] Kim SW, Paick JS. Short-term analysis of the effects of as


needed use of sertraline at 5 PM for the treatment of
premature ejaculation. Urology 1999;54:5447.
[45] Waldinger MD, Zwinderman AH, Olivier B. On-demand
treatment of premature ejaculation with clomipramine

767

and paroxetine: a randomized, double-blind fixed-dose


study with stopwatch assessment. Eur Urol 2004;46:5106.
[46] Rivera P, Gonzalez R, Gonzalez F, Storme O. Use of paroxetine on-demand in premature ejaculation [in Spanish]. Actas Urol Esp 2005;29:38791.