Introduction Into the Diagnostics and Treatment of Premature Ejaculation SUMMARY

MEDICINE
REVIEW ARTICLE
Introduction Into the Diagnostics
and Treatment of Premature
Ejaculation
Michael J. Mathers, Jan Schmitges, Theodor Klotz, Frank Sommer
SUMMARY
Introduction: Premature ejaculation (PE) is a subjective experience characterized by a short
intravaginal ejaculatory latency time and decreased ejaculatory control. The prevalence of
premature ejaculation is approximately 25%. The etiology is unknown and there is no causal
treatment. The significant role of serotonin during ejaculation is currently being widely discussed.
Besides behavioural treatments, specific serotonin reuptake inhibitors (SSRIs) as well as
phosphodiesterase 5 inhibitors are being used with success. Methods: Selective literature review
using PubMed with the keywords premature ejaculation, prevalence, etiology, diagnostics,
therapy. Results: A thorough sexual history is mandatory in order to evaluate the potential causes
of PE. Although the exact etiology of PE is not fully understood it is becoming increasingly clear
that this condition has a neurophysiological, psychogenic, and psychological element, with
probable serotonin involvement. Effective treatment requires a thorough understanding of the
underlying pathophysiology. Besides psychotherapy there are effective treatments, which can
significantly improve the patient's sexual quality of life. Dtsch Arztebl 2007; 104(50): A 3475–80
Key words: sexual medicine, premature ejaculation, ejaculation control, treatment, serotonin,
psychotherapy
P
remature ejaculation is the most common problem affecting sexual function in men
(1–3) and is insufficiently understood. It is subject to cultural and socioeconomic
influences, which makes an exact definition difficult. Difficulties with the definition and
divergent study designs hamper the collection of prevalence data and are the cause for the
wide spread in the literature (1–3). Often, premature ejaculation is regarded as a primarily
psychoreactive problem. Neurobiological components and optional drug treatment are
often not being considered.
Objectives and methods
This article presents an overview of the diagnostic and therapeutic options for premature
ejaculation. Particular attention has been paid to the difficulty of finding a definition and to
prevalence, etiology, risk factors, diagnostics, and therapy. The literature search was
performed on PubMed in March 2007, without a time limit and using the search terms
premature ejaculation, prevalence, etiology, diagnostics, therapy. Because of the large
number of publications, systematic reviews and – where available – meta-analyses of randomized controlled studies were selected. These were identified and subsequently linked
by content related criteria. If a minimum of 3 authors found an article relevant it was
included in the review.
Definition
In addition to quantifiable and reproducible traits, such as the ejaculatory latency time and
the personal mental trauma of one or both partners should be taken into consideration.
Premature ejaculation is mostly defined as a deviation from the normal length of intravaginal
ejaculatory latency time (IELT). This is the time from penetration to ejaculation. According
to Masters and Johnson, who formulated one of the first definitions in the 1970s, premature
ejaculation is the inability to delay the moment of ejaculation long enough so that the women
reaches orgasm in 50% of sexual encounters (3). Control over the moment of ejaculation
Urologische Gemeinschaftspraxis Remscheid, Kooperationspraxis der Klinik für Urologie und Kinderurologie, Klinikum Wuppertal,
Universität Witten/Herdecke: Dr. med. Mathers, FEBU; Institut für Männergesundheit – Klinik und Poliklinik für Urologie, Universitäts-Klinikum, Hamburg-Eppendorf: Dr. med. Schmitges, Prof. Dr. med. Sommer; Klinik für Urologie, Andrologie und Kinderurologie am Klinikum Weiden: Prof. Dr. med. Klotz, MPH
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TABLE 1
Definition der Ejaculatio praecox*
Source
Definition
DSM-IV
Persistent or repeated ejaculation with minimal sexual
stimulation before or shortly after penetration and before the
person desired this. This state of affairs must cause noticeable
mental trauma or interpersonal difficulties.
ICD-10
An inability to control ejaculation sufficiently, so that both
partners enjoy the sexual act, because ejaculation occurs
before or very shortly after starting intercourse (if a time limit
is required, within 15 s) or because ejaculation occurs
in the absence of an erection sufficient for intercourse.
The problem is not due to prolonged sexual abstinence.
EAU guidelines
An inability to control ejaculation for a sufficient time span
before vaginal penetration. This does not result in impaired
fertility if intravaginal ejaculation occurs.
AUA guidelines
Ejaculation that occurs earlier than desired, either before or
shortly after penetration, and which results in mental trauma
for one or both partners.
* From (4, 5, 6, e2); AUA, American Urological Association;
EAU, European Association of Urology
TABLE 2
Estimated intravaginal ejaculatory latency time (IELT) of women and men
in different countries
Country (n = m/w)
USA (606/300)
Estimated IELT
for men (mins)
Estimated IELT
for women (mins)
13.6
11.2
United Kingdom (315/222)
9.9
8.5
France (301/203)
9.3
8.4
Germany (328/201)
6.9
7.4
Italy (304/206)
9.6
8.6
and sexual satisfaction of the man and woman are possible components and are included in
the standard classification systems and guidelines of large urological organizations (4, 5).
Definitions of premature ejaculation in the Diagnostic and Statistical Manual of Mental
Disorders, 4th edition (DSM-IV), International Classification of Diseases (ICD-10), and
others generally mention 3 central aspects (e1, e2):
> Shortened intravaginal ejaculatory latency time
> Loss of deliberate control of ejaculation
> Mental trauma in man or woman.
The suffering of the partner is mentioned only in DSM-IV and the guidelines of the
American Urological Association (AUA) (table 1).
The sensation of what is "normal" varies and is highly subjective. The average time from
penetration to ejaculation perceived as normal is 7 to 14 min and shows geographical
variations. Women mostly estimate the time as slightly shorter (table 2) (6).
Waldinger et al. found a median IELT of 5.4 min (diagram 1) in 491 men from 4 European
countries and the United States (7). Analyzed by country, age, circumcision status, and use
of condoms, the IELT was significantly shorter in older men (>51 years) and in men of
Turkish origin; sexual intercourse took place a median of 8 times per month in all subgroups
(7). If the 0.5th and 2.5th percentile are chosen to define the disorder, the resulting range is
0.9 to 1.3 min. Questionnaires can be used as an instrument for standardized psychometric
recording. Validated questionnaires are the IPE (index of premature ejaculation) (8) and the
Arab IPE (e3). The IPE comprises 10 items to describe sexual satisfaction, ejaculatory control,
and mental trauma. The partner's sexual satisfaction is not included. In combination with
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the time measurements of the IELT, two tools are therefore available to capture the pathology
of premature ejaculation. Questionnaire and time measurements do not reflect real
conditions – in practice, personal mental trauma is crucial.
In the Second International Consultation on Erectile and Sexual Dysfunction (e4), "early
ejaculation" or "rapid ejaculation" are suggested as replacement terms for "premature
ejaculation." Another possible term might be "premature orgasm", because ejaculation is
not impaired; the problem is that the orgasm reflex is triggered too early. In addition to the
exclusively premature orgasm, another type of orgasm could be differentiated that is
associated with erectile dysfunction. The secondary form occurs as a result of erectile
dysfunction or reduction in sexual appetence.
Prevalence
In the Global Study of Sexual Attitudes and Behaviours (GSSAB) (1, 2), the frequency of
premature ejaculation was investigated. This study included 27 500 men and women aged
40 to 80 worldwide. It is regarded as the largest epidemiological study of sexuality and its
dysfunctions. The GSSAB reported prevalence rates of up to 30%. Geographical differences
should be considered in the sociocultural context of the different countries. In selected
patients, prevalence rates of far higher than 50% were found (e5, e6).
Geographical and regional differences
In the GSSAB, premature ejaculation is the most common sexual dysfunction; its prevalence
is highest in Asia, Central America, and South America (diagram 2) (2). The explanation
for the high prevalence rates is the importance placed on female sexuality in these societies
(9, 10). In spite of patriarchal social structures and low described sexual activity (9), East
Asia has the Tantric and Taoist philosophies as its cultural or ideological foundation. In
their sexual traditions, the female organism is their central element (10). Coupled with this
is the perception among men that ejaculation that happens too early is a problem. The
coexistence of premature ejaculation and female anorgasmia supports this observation
(diagram 2).
Other factors
Erectile dysfunction can be regarded as a comorbidity, cause, or effect or premature ejaculation.
An association of premature ejaculation with low educational attainment has also been
described (2). Men without academic qualifications in Central America and South America
and in the Middle East are at doubly the risk of developing premature ejaculation. In the
Middle East, a difficult financial situation seems to have a negative influence (2). Irregular
sexual intercourse can lead to premature ejaculation, as is confirmed by the GSSAB.
Etiology and risk factors
Psychogenic and organic components can have a role in the etiology of premature ejaculation.
Anxiety disorders can have a key role in its development (11). A causal connection between
fear and male sexual dysfunction has not been confirmed to date. Whether anxiety disorders
are the sequelae or cause of premature ejaculation is not clear (12). The fear of premature
orgasm can reduce a couple's sexual pleasure (3, 8, 9). There are further psychological risk
factors that are associated with premature ejaculation. The most commonly named is sexual
inexperience, scarce sexual activity, and fearfulness (3). Organ related risk factors include
urinary tract infections and diabetes mellitus (e7). The side effects of some medical drugs –
for example, opiates and sympathomimetics – can result in premature ejaculation (e8). The
most common comorbidity, at up to 30%, is erectile dysfunction (13, 14). This should be
treated as a priority.
The role of serotonin in the ejaculatory process
In addition to hormones, several neurotransmitters influence sexual activity and the ejaculatory
process. A raised serotonin concentration in the brain in humans and rats raises the threshold
to ejaculation (e9). The impairment of male sexuality was ascribed to serotonergic neurons
of the medial raphe nuclei, whose inhibitory function is also responsible for the refractory
period between ejaculations (e10). Non-selective activation of serotonin receptors results
in dose dependent prolongation of the ejaculatory latency period up to anejaculation (15).
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DIAGRAM 1
Distribution of
average ejaculatory
latency time on 491
couples in Europe
and the United
States. Adapted
from: Waldinger et
al.: A multinational
population survey of
intravaginal ejaculation latency time;
adapted to (7)
DIAGRAM 2
Prevalence of
premature ejaculation in 7 regions.
Participants were
asked whether in
the preceding 12
months, orgasm
had been reached
too rapidly for at
least 2 months.
Adapted from:
Laumann et al.:
Sexual problems
among women and
men aged 40–80 y:
prevalence and
correlates identified
in the Global Study
of Sexual Attitudes
and Behaviors
adapted to (2)
Diagnostics
Diagnosis is problematic. For clinical practice, qualitative and quantitative features have
been developed, which are not fully established. Only some men with premature ejaculation
receive medical help (16). Most men with sexual disorders would welcome talking to a doctor,
but only a small proportion is willing to initiate the conversation themselves (16, e11).
The GSSAB study showed that only 18% of men with a sexual problem had received
medical advice (1). According to another study, only 1% of men aged above 40 years
reported having received medical advice about their premature ejaculation, although they
had told the treating physician about their problem (1). Similar results emerged from a large,
anonymous, multinational internet study (17). It may be assumed that fewer patients receive
advice for premature ejaculation than for erectile dysfunction (18). A detailed sexual
history is of the utmost importance; this should include questions about sexual experiences,
sexual development, and avoidance strategies already deployed. The extent to which the
fear of premature orgasm impairs sexual pleasure should also be investigated (16). The
history is part of the therapeutic conception because it provides a setting in which it is safe
to admit whether the orgasm is associated with negative emotions.
If the time between insertion of the penis and ejaculation is less than 2 min as a rule, the
definition of the pathology premature ejaculation is met (7). In clinical practice, premature
ejaculation is diagnosed especially when the deliberate control of ejaculation fails and the
relationship suffers as a result.
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BOX 1
Therapy
> Strengthen the man's physical sensitivity
– Stop-start method
– Squeeze method
> Psychotherapy/sexual therapy
> Drug treatment
– Local: lidocaine, prilocaine
– Systemic: antidepressants: clomipramine, selective
serotonin reuptake inhibitors (fluoxetine, sertraline,
paroxetine, and dapoxetine) and phosphodiesterase-5
inhibitors (sildenafil, vardenafil, tadalafil)
DIAGRAM 3
Squeeze technique:
the ejaculatory
reflex is interrupted
by applying pressure
in the frenulum area
with the tip of the
thumb. The figure
shows the use of
the squeeze
technique with the
help of a partner
Therapy
Among underlying physical causes for premature ejaculation, psychoreactive elements
play a central part. Drug treatment targets the symptoms. Psychotherapeutically,
established behavioral therapies should be used (3, e11, e13). If possible, the partner
should be included.
For couple therapy, it is helpful if the patient is in a steady relationship, if the sexual
problems are experienced as a central obstacle to a satisfying relationship, and if both
partners are interested in the treatment. Approaching the problem together can even be
enough to bring about the desired result in some cases and supports all subsequent measures.
This may help reduce the pressure for success – for example, by recommending sexual
activity without actual intercourse as a first step.
Controlled studies exist for all forms of therapy (box 1). The different study designs,
however, hinder the interpretation of drug treatments that are given in accordance with the
AUA guidelines of 2004 (e15). An exception is dapoxetine, as controlled studies have been
published only since 2004 and have a higher level of evidence; only very few studies cover
vardenafil and tadalafil.
For some men, a preceding orgasm is helpful in delaying ejaculation. In some cases, sex
therapy is an option to increase a man's sensitivity to the moment of ejaculation. The men
affected can learn through different techniques to experience as well as influence the
process up to the point that they perceive as inevitable. The stop-start method (e13) and the
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squeeze method recommended by Masters and Johnson (3) have proved successful in
treatment, but even these are not uncontroversial.
In the literature, most studies of premature ejaculation are neither prospective, randomized,
controlled, blinded, nor quantified by IELT measurement and therefore do not meet the
strict criteria of evidence based studies (e14). Small cohort studies of patients without long
term follow-up exist (e14). An AUA committee complied guidelines in 2004, which were
accepted by a consensus (e15).
Stop-start method
This method aims to teach men to experience their own sexual arousal more clearly and
control it. In a first step, the man masturbates and then stops masturbating shortly before the
critical threshold, the point of no return. Further stimulation is avoided (stop signal) until
the patient has returned to a notably lower level of arousal. The then sexual stimulus is
renewed. The patient repeats the stop-and-start steps until he manages a certain degree of
control over his arousal (e13).
Squeeze method
The squeeze method is a modified stop-start exercise and aims to teach the man to experience
his arousal consciously by means of sensuality training. Afterwards he learns to realize the
moment at which ejaculation is imminent more precisely and in a further step, he learns to
influence this. By applying pressure with the tip of the thumb to the frenulum area, the
ejaculatory reflex is interrupted (diagram 3) (3). In optimal circumstances, the exercises
should be used in a relaxed atmosphere in the setting of couple therapy.
Masters and Johnson (3) in 1970 reported on 186 men who were treated with different
behavioral approaches, including the squeeze technique. The success rate immediately
after therapy was 90%. Other working groups did not achieve such high rates (e12).
Hawton et al (e12) reported success rates of 64% immediately after behavioral therapies.
All long term reports confirm, however, that after therapy has concluded the problem of
premature ejaculation has a tendency to resurface (19).
Drug therapy
In cases where psychotherapy has been insufficiently successful or not had any success at
all, several drugs can be administered.
Local anesthetics (such as lidocaine or prilocaine) are applied to the glans and reduce the
excitability of the penis (e16). The effect usually sets in after about 20 min, but during
BOX 2
Summary
> Premature ejaculation is the most common problem in
sexual function in men and is subject to strong cultural
influences.
> Premature ejaculation is defined as a shortened
intravaginal ejaculatory latency time, the loss of
deliberate ejaculation control, and it is characterized by
personal mental trauma of those affected.
> Diagnostics include a thorough sexual history, eliciting
the extent of suffering mental trauma, and if required
the couple's dynamic and importance of sexuality.
> Psychotherapeutically, established therapies with
different approaches from the armamentarium of sexual
therapies are used – the stop-start method and the
squeeze method after Masters and Johnson.
> Drug treatments include local anesthetics, antidepressants
such as clomipramine and SSRIs, and PDE-5 inhibitors.
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Short case report
A 67 year old, married, successful businessman, whose hypertension has been
well controlled for years, reports having experienced premature ejaculation.
Recently, sexual intercourse has been possible at most once a month, in a
"quickie" fashion, if his partner stimulates him maximally; he then ejaculates in
seconds. The wife has been sympathetic and does not think that sex is the most
important thing in life.
Relevant findings
No findings on abdominal, genital, and rectal examination on physical examination,
international index for erectile function (IIEF): 15 points (normal >25 points),
RR 140/95 mm Hg, testosterone, prolactin, full blood count, thyroid stimulating
hormone, and blood glucose all in the normal range.
Medication
AT1 blocker
Methods
Sexual therapy for the couple was recommended so that both partners learnt to
express their desires. In parallel, a controlled attempt was made with PDE-5
inhibitors at a medium dosage because of suspected secondary premature
ejaculation. The cost problems were discussed with the patient.
Verlauf
Sex therapy over 3 months improved both partners' ability to articulate their sexual
desires. Erections improved in quality thanks to PDE-5 inhibitor treatment, and the
medication is required only occasionally. The premature ejaculation improved
throughout the couple therapy, so that the patient does not experience a related
mental trauma.
intercourse, the partner's sensations may also become impaired. In double blinded, randomized,
placebo controlled studies, IELT of longer than 5 min have been reported, as has greatly
improved patient satisfaction (20, e17, e18). All oral drug therapies are off label, and the
dosages differ from those given in licensed indications.
Psychopharmaceuticals such as clomipramine and selective serotonin reuptake inhibitors
(SSRIs)-such as fluoxetine, sertraline, or paroxetine – should be taken several hours before
sexual intercourse, so as to delay the time to ejaculation. Paroxetine is most efficacious
(21). According to a prospective, double blinded, randomized, crossover study, all drugs
mentioned prolong the IELT significantly (22). These drugs and the local anesthetics
mentioned earlier were therefore included as therapeutic options in US guidelines (e15).
Dapoxetine is still going through the licensing process; its effect onset is rapid and its half
life is short (23).
In men who took the drug as needed, ejaculation was delayed significantly, by 3 min, in a
randomized, double blinded, placebo controlled, phase 3 study (23). The study included
2614 men who took either 30 mg or 60 mg dapoxetine in the treatment group.
Since 2001, studies have become available that investigated treatment for premature
ejaculation with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, and more recently
also vardenafil and tadalafil), either alone or in combination with SSRIs. Most of these
studies are, however, not double blinded and placebo controlled, and often the IELT was
not measured (24). This limits the study conclusions with regard to efficacy and
comparability. Salonia et al, in a prospective study, compared the efficacy of paroxetine
alone or in combination with sildenafil in 80 potent patients with premature ejaculation
(25). The combination of paroxetine and sildenafil improved the IELT significant to more
than 5 min, compared with paroxetine alone (25). Results from other studies are equally
encouraging (22, 23, 24). The AUA guidelines mention only sildenafil (5). Individual
studies of vardenafil and tadalafil were published only after these guidelines in 2004.
Because of their low side effect profile and the fact that they can be taken when needed,
PDE-5 inhibitors may be used to treat premature ejaculation, especially if the patient also
has erectile dysfunction.
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Drug treatment cannot cure premature ejaculation; the problem continues to exist after
the drugs have been stopped. Because of possible negative side effects, they should therefore
be used only as a measure of last resort.
Conclusions
Premature ejaculation is the commonest sexual disorder in men. Patients do not address
their problem often enough in the setting of a medical consultation. In clinical practice, a
diagnosis can be made by taking a targeted sexual history. Currently, no causal treatment is
known. Some therapies are promising. In addition to psychotherapeutic and behavioral
measures, antidepressants such as SSRIs, and phosphodiesterase-5 inhibitors have been
used successfully (box 2). Suitable treatment improves the patient's quality of life and often
has a positive effect on the relationship (short case report).
Conflict of Interest Statement
Dr Schmitges receives financial support from Bayer-Schering. Professor Sommer receives financial support from Bayer-Schering
and Pfizer. Dr Mathers and Professor Klotz declare that no conflict of interest exists according to the Guidelines of the International
Committee of Medical Journal Editors.
Manuscript received on 9 March 2007, revised version accepted on 22 October 2007.
Translated from the original German by Dr Birte Twisselmann.
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Corresponding author
Dr. med. Michael J. Mathers, FEBU
Fastenrathstr. 1
42853 Remscheid, Germany
[email protected]
Dtsch Arztebl 2007; 104(50): A 3475–80 ⏐ www.aerzteblatt.de
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