EPIDEMIOLOGY
There is limited information concerning the extent of PE in the general population. In a random survey of 1511 men in the USA, about one third considered that they had ejaculated prematurely over the past year [1]. However, the proportion that perceived their condition as problematic was not stated. Data from the National Health and Social Life Survey have revealed a prevalence of 21% in men ages 18 to 59 in the United States [12]. In general, however, the prevalence of PE is reported as being between 22–38% of adult male population [1,13]. In 1943 Schapiro noted that men with PE seemed to have family members with similar complaints [14]. Waldinger [15] reported that odds of family occurrence is much higher
than the suggested population prevalence rate of 4% to 39% and suggested that premature ejaculation is also genetically determined. In addition the psychiatric literature on the prevalence of such disorders is suggestive of family or genetic origins [16].

PATHOPHYSIOLOGY
The ejaculatory response is triggered by genital and cortical stimulation. The glans penis has tactile receptors that are connected via the dorsal penile and pudendal nerve to the sacral spinal cord. The sympathetic nerves involved in
emission originate from the intermediolateral columns of the spinal cord (T10–L2) and travel via the sympathetic chain and hypogastric nerve to the pelvic plexus and from there via the cavernous nerve to the vas deferentia. Sympathetic impulses produce smooth muscle contractions of the epididymis and vas deferens that move sperm to the posterior urethra.
Seminal vesicles and prostatic glands contract expelling and mixing their fluids with sperm. Eventually this mixture in turn intermixes with fluid from the bulbourethral glands making semen. Semen causes pressure in the wall of the ampullae urethra that culminates to afferent impulses, which reach the spinal cord (S2–4) through the pudendal and pelvic nerves. Expulsion is mediated by motor neurons in the nucleus of Onuf that via the pudendal nerve provide coordinated contractions of the bulbo- cavernosus and
ischio-cavernosus muscles of the pelvic floor. Idiopathic primary premature ejaculators may have lower penile sensory thresholds [17] and/or greater cortical penile representation [18] than their normal counterparts. Animal
and sexual psychopharmacological human studies [19] attributed a serotonergic genesis [20-22] and possible genetic etiology [23] to the neurobiological view of PE. The inhibitory effect of serotonin on libido, ejaculation and orgasms is well documented and has been attributed to a
serotonin-induced decrease in dopamine (a neurotransmitter enhancing sexual function) level in the central nervous system. [24,25] Therefore, tricyclic antidepressants (clomipramine) and selective serotonin reuptake inhibitors (SSRIs); (paroxetine, fluoxetine, sertraline) have merged as safe and effective new treatments for patients with PE. In addition, selective
noradrenaline reuptake inhibitors nortriptyline and protriptyline have been found to be associated with delayed ejaculation [26]. Among the different subtypes of 5-hydroxytryptamine (5-HT) receptors, the most important ones on ejaculation are 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT2C receptors [27]. Because the rapid onset of postponement of ejaculation by some of the SSRIs has a similar time course as their synaptic effect on 5-HT, it is suggested that the effect on ejaculation is mediated by acute enhancement of 5-HT
neurotransmission or by differential activation of different 5- HT receptor populations, notably 5-HT1A and 5-HT2C receptors [28,29]. Activation of the 5-HT1B/1D receptors also inhibit 5-HT release and male rat ejaculatory behavior [30]. The total absence of ejaculation delay in men who took
nefazodone was attributed to its 5-HT2C and 5-HT2A receptor-blocking properties [31]. Organic (e.g. PE secondary to neurological disease, diabetes, pelvic injury, vascular disease, prostatic hypertrophy, chronic prostatitis, hypogonadotrophic hypogonadism, pelvic surgery, radical prostatectomy) psychological, behavioral, and biogenic causes have been implicated [32-34]. Both anxiety and depression have been associated with PE [5]
although this may be a consequence of the condition rather than a cause. Others have failed to find such an association [35]. As with other sexual disorders, PE is probably caused by a combination of biological-psychological, psychophysiological, and sociobiological; except in unusual cases when a pure cause can be demonstrated [32,36,37]. For example, Grenier et al. [38] reported that: “It is more likely that PE is the result of a number of factors that interact than the result of a single factor”. Also in another study, Athanasiadis [39] emphasized that: “The hypothesis about a
possible interaction between factors might propose a more satisfactory explanation for PE than a one-dimensional approach”. A number of genetic theories have also been proposed to explain PE. It is possible that some racial groups are more susceptible than others to PE [40], particularly men from the Indian subcontinent who may present with the Dhat syndrome [41]. Some or all of the following features characterizes this syndrome: concern about spontaneous seminal loss, affective illnesses, psychosomatic complaints and PE.

DIAGNOSIS
American Urological Association (AUA) guideline on the pharmacologic management of PE recommended, “Thediagnosis of PE is based on sexual history alone. A detailed sexual history should be obtained from all patients with ejaculatory complaints” [42]. In most cases an apparent organic cause is not evident at diagnosis [43,44]. Limited attempts to provide a consensus and more objective criteria for the diagnosis of PE have not succeeded. The diagnosis based on DSM-IV relies on subjective self-reported symptoms. Parameters that are necessary and/or sufficient to make a diagnosis of PE according to the DSM-IV are unclear. Organic causes such as those previously mentioned should be ruled out. In general, an IELT of less than 2
minutes—probably most accurately determined using stopwatch methodology —is thought to provide adequate sensitivity for diagnosis.

TREATMENT
General Considerations
Medical treatment in PE needs careful interpretation with respect to design and methodology of studies [45,6]. Subjective estimation and questionnaire assessments of ejaculation latency may lead to higher variability in clinical
outcome measures [45], therefore, for the most accurate determination of ejaculation latency the best method is the use of stopwatch. Treatment of PE should primarily attempt to alleviate concern about the condition as well as to increase sexual satisfaction in the patient and partner. The risks and benefits of all treatment options should be discussed with the patient prior to any intervention. Patient and partner satisfaction is the primary target outcome for the treatment of PE. Men with PE secondary to erectile dysfunction, other sexual dysfunction or organic causes should receive
appropriate etiology specific treatment. Simple measures such as education to discuss sexual norms, and facilitation of sexual negotiation between the couple may be useful. Some medications cause sexual dysfunction as a side
effect (Table 1). Use of  some sympathomimetics [47] such as ephedrine sulfate, pseudoephedrine hydrochloride, and phenylpropanolamine hydrochloride and withdrawal from some other drugs, such as trifluoperazine hydrochloride [48], and opiates [49-51] can cause PE. Simply discontinuing an agent that is thought to cause PE in order to eliminate it from the body may be considered if the general health and
physician permit it.

Psychosexual Behavioral Therapy
Historically the cause of PE has been considered to be psychological. The psychoanalytic idea of unconscious conflicts being the cause of PE has never been investigated in a manner that allowed generalization, as only case reports on psychoanalytic therapy have been published. This is also
true for behavioral therapy. These have included psychoanalytical approaches although it is the behavioral and cognitive approaches that have proven most effective. These include the stop–squeeze method [52] developed in 1956 and later adopted by Masters and Johnson in their sex therapy clinic as well as other approaches that have become the gold
standard for treatment of PE [53]. Stop-start and squeeze techniques or the sensate-focus phase are used in therapeutic programs for the treatment of PE. The techniques are performed as effective treatments that delay PE by reducing or removing stimulation, [4,54] but longitudinal follow-up results of treatment for PE are even rarer than controlled outcome investigations, and long-term success rates are disappointing [36]. In addition, the application of the principles of evidence-based medicine shows that there is
little evidence to support the psychological approach and behavioral treatment [6].

Drug Therapy
The primary therapeutic approach to PE is pharmacotherapy. Pharmacological treatment of men with PE may include a variety of approaches. No pharmacological agents are licensed for use for PE. However many centrally and peripherally acting drugs have been proposed to treat
primary PE. These include

1- Selective serotonin reuptake inhibitors (SSRIs)
2- Tricyclic antidepressants
3- Monoamine oxidase inhibitors
4- Topical anesthesia
5- Neuroleptics
6- Sympatholytics
7- Phosphodiestrase inhibitors
In the next paragraphs an overview will be presented of the various drug treatment studies for premature ejaculation that have been published since 1943. Apart from the phosphodiesterase inhibitor studies, all of these drug
treatment studies have previously been categorized in a systematic review and meta-analysis study, published by Waldinger et al. in 2004 [9].

[1]. The World Health Organization (WHO) includes the right to sexual health among its fundamental rights for the individual. There should be “a freedom from organic disorders, disease and deficiencies that interfere with sexual and reproductive freedom”. PE has been associated with erosion in sexual self- confidence

[2] and low sexual satisfaction in men and their female partners

[3]. Before the last decade, the major approach to treating PE was behavioral and psychotherapy, relying on such techniques as the `pause’ and `squeeze’ methods

[4,5]. However, the application of the principles of evidence-based medicine shows that there is little evidence to support the psychological approach and behavioral treatment

[6]. This paper reviews pharmacological agents in treatment of PE. It describes some of the issues for drug development in this indication, reviewing many of the clinical studies that have already been completed.

DEFINITION OF PREMATURE EJACULATION

There are a number of definitions, none of which is wholly satisfactory. Most men with PE readily recognize their problem and there is no lack of self-assessment. Most men who report PE usually ejaculate prior to or within1–2 min after vaginal intromission. A small proportion of men ejaculate prior to intromission. A universally accepted definition of PE has yet to be established. Masters andJohnson proposed one of the earliest definitions that focused on the inability to delay ejaculation long enough for the woman to achieve orgasm 50% of the time, assuming that PE is the sole cause of the female anorgasmia [4]. Kaplan first suggested that PE is primarily a problem of voluntary control over timing of ejaculation [5]. It is obvious that their definition is inadequate because it implies that any partners of a woman who has difficulty in reaching orgasm in half the attempts have PE. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (4th Edition Text Revision) (DSM-IV-TR) [7] defines PE as “persistent or recurrent onset of orgasm and ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it”. Until recently, any scientific basis for the DSM-IV definition was lacking. For instance, the meaning of ‘persistent’, ‘recurrent’, ‘minimal’ and ‘shortly after’ is vague and certainly needs further qualification. Waldinger et

al. [8] attempted to operationalise the DSM-IV criteria for PE. They studied 110 men suffering from life long PE and demonstrated that about 10% of the men ejaculated at 1–2 min but most (90%) ejaculated within 1 min of intromission, and 80% were actually ejaculating within 30 seconds, whereas 60% ejaculated within 15 seconds. They also empirically defined life long PE as an ejaculation of <1 min in >90% of episodes of sexual intercourse, independent of age and duration of relationship. Intravaginal ejaculation latency time (IELT) was measured by methods of verbal estimation, list based, imagined (with clock and without) or by using a stopwatch during intercourse. Most men and partners considered the stopwatch as an accurate measurement of their IELT. The WHO second International Consultation on Sexual Dysfunction proposed a multivariate definition for PE: “Premature ejaculation is persistent or recurrent ejaculation with minimal stimulation before, on, or shortly after penetration, and before the person wishes it, over which the sufferer has little or no voluntary control which causes the sufferer and/or his partner bother or distress.” While the above definitions identify multiple criteria for a PE diagnosis, IELT has been the most commonly used
endpoint in recent PE studies. In general, an IELT of less than 2 minute—probably most accurately determined using stopwatch methodology [9]—is thought to provide appropriate definition for PE [10,11]. PE may be classified into various subtypes based on the developmental history and response characteristics. Primary PE is defined as PE that has always been present and secondary PE as the development of PE after a period of perceived normal ejaculatory functioning.
EPIDEMIOLOGY
There is limited information concerning the extent of PE
in the general population. In a random survey of 1511 men in
the USA, about one third considered that they had ejaculated
prematurely over the past year [1]. However, the proportion
that perceived their condition as problematic was not stated.
Data from the National Health and Social Life Survey have
revealed a prevalence of 21% in men ages 18 to 59 in the
United States [12]. In general, however, the prevalence of PE
is reported as being between 22–38% of adult male
population [1,13].
In 1943 Schapiro noted that men with PE seemed to have
family members with similar complaints [14]. Waldinger
[15] reported that odds of family occurrence is much higher
than the suggested population prevalence rate of 4% to 39%
and suggested that premature ejaculation is also genetically
determined. In addition the psychiatric literature on the
prevalence of such disorders is suggestive of family or
genetic origins [16].
PATHOPHYSIOLOGY
The ejaculatory response is triggered by genital and
cortical stimulation. The glans penis has tactile receptors that
are connected via the dorsal penile and pudendal nerve to the
sacral spinal cord. The sympathetic nerves involved in
emission originate from the intermediolateral columns of the
spinal cord (T10–L2) and travel via the sympathetic chain and
hypogastric nerve to the pelvic plexus and from there via the
cavernous nerve to the vas deferentia. Sympathetic impulses
produce smooth muscle contractions of the epididymis and
vas deferens that move sperm to the posterior urethra.
Seminal vesicles and prostatic glands contract expelling and
mixing their fluids with sperm. Eventually this mixture in
turn intermixes with fluid from the bulbourethral glands
making semen. Semen causes pressure in the wall of the
ampullae urethra that culminates to afferent impulses, which
reach the spinal cord (S2–4) through the pudendal and pelvic
nerves. Expulsion is mediated by motor neurons in the
nucleus of Onuf that via the pudendal nerve provide
coordinated contractions of the bulbo- cavernosus and
ischio-cavernosus muscles of the pelvic floor.
Idiopathic primary premature ejaculators may have lower
penile sensory thresholds [17] and/or greater cortical penile
representation [18] than their normal counterparts. Animal
and sexual psychopharmacological human studies [19]
attributed a serotonergic genesis [20-22] and possible genetic
etiology [23] to the neurobiological view of PE.
The inhibitory effect of serotonin on libido, ejaculation
and orgasms is well documented and has been attributed to a
serotonin-induced decrease in dopamine (a neurotransmitter
enhancing sexual function) level in the central nervous system.
[24,25] Therefore, tricyclic antidepressants (clomipramine)
and selective serotonin reuptake inhibitors (SSRIs); (paroxetine,
fluoxetine, sertraline) have merged as safe and effective
new treatments for patients with PE. In addition, selective
noradrenaline reuptake inhibitors nortriptyline and protriptyline
have been found to be associated with delayed
ejaculation [26]. Among the different subtypes of 5-hydroxytryptamine
(5-HT) receptors, the most important ones on
ejaculation are 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT2C
receptors [27]. Because the rapid onset of postponement of
ejaculation by some of the SSRIs has a similar time course as
their synaptic effect on 5-HT, it is suggested that the effect
on ejaculation is mediated by acute enhancement of 5-HT
neurotransmission or by differential activation of different 5-
HT receptor populations, notably 5-HT1A and 5-HT2C
receptors [28,29]. Activation of the 5-HT1B/1D receptors also
inhibit 5-HT release and male rat ejaculatory behavior [30].
The total absence of ejaculation delay in men who took
nefazodone was attributed to its 5-HT2C and 5-HT2A
receptor-blocking properties [31].
Organic (e.g. PE secondary to neurological disease,
diabetes, pelvic injury, vascular disease, prostatic hypertrophy,
chronic prostatitis, hypogonadotrophic hypogonadism, pelvic
surgery, radical prostatectomy) psychological, behavioral,
and biogenic causes have been implicated [32-34]. Both
anxiety and depression have been associated with PE [5]
although this may be a consequence of the condition rather
than a cause. Others have failed to find such an association
[35]. As with other sexual disorders, PE is probably caused
by a combination of biological-psychological, psychophysiological,
and sociobiological; except in unusual cases
when a pure cause can be demonstrated [32,36,37]. For
example, Grenier et al. [38] reported that: “It is more likely
that PE is the result of a number of factors that interact than
the result of a single factor”. Also in another study,
Athanasiadis [39] emphasized that: “The hypothesis about a
possible interaction between factors might propose a more
satisfactory explanation for PE than a one-dimensional
approach”.
A number of genetic theories have also been proposed to
explain PE. It is possible that some racial groups are more
susceptible than others to PE [40], particularly men from the
Indian subcontinent who may present with the Dhat
syndrome [41]. Some or all of the following features
characterizes this syndrome: concern about spontaneous
seminal loss, affective illnesses, psychosomatic complaints
and PE.
DIAGNOSIS
American Urological Association (AUA) guideline on
the pharmacologic management of PE recommended, “The

diagnosis of PE is based on sexual history alone. A detailed
sexual history should be obtained from all patients with
ejaculatory complaints” [42]. In most cases an apparent
organic cause is not evident at diagnosis [43,44]. Limited
attempts to provide a consensus and more objective criteria
for the diagnosis of PE have not succeeded. The diagnosis
based on DSM-IV relies on subjective self-reported
symptoms. Parameters that are necessary and/or sufficient to
make a diagnosis of PE according to the DSM-IV are
unclear. Organic causes such as those previously mentioned
should be ruled out. In general, an IELT of less than 2
minutes—probably most accurately determined using
stopwatch methodology —is thought to provide adequate
sensitivity for diagnosis.
TREATMENT
General Considerations
Medical treatment in PE needs careful interpretation with
respect to design and methodology of studies [45,6].
Subjective estimation and questionnaire assessments of
ejaculation latency may lead to higher variability in clinical
outcome measures [45], therefore, for the most accurate
determination of ejaculation latency the best method is the
use of stopwatch. Treatment of PE should primarily attempt
to alleviate concern about the condition as well as to increase
sexual satisfaction in the patient and partner. The risks and
benefits of all treatment options should be discussed with the
patient prior to any intervention. Patient and partner
satisfaction is the primary target outcome for the treatment of
PE. Men with PE secondary to erectile dysfunction, other
sexual dysfunction or organic causes should receive
appropriate etiology specific treatment. Simple measures
such as education to discuss sexual norms, and facilitation of
sexual negotiation between the couple may be useful.
Some medications cause sexual dysfunction as a side
effect (Table 1). Use of some sympathomimetics [47] such
as ephedrine sulfate, pseudoephedrine hydrochloride, and
phenylpropanolamine hydrochloride and withdrawal from
some other drugs, such as trifluoperazine hydrochloride [48],
and opiates [49-51] can cause PE. Simply discontinuing an
agent that is thought to cause PE in order to eliminate it from
the body may be considered if the general health and
physician permit it.
Psychosexual Behavioral Therapy
Historically the cause of PE has been considered to be
psychological. The psychoanalytic idea of unconscious
conflicts being the cause of PE has never been investigated
in a manner that allowed generalization, as only case reports
on psychoanalytic therapy have been published. This is also
true for behavioral therapy. These have included psychoanalytical
approaches although it is the behavioral and
cognitive approaches that have proven most effective. These
include the stop–squeeze method [52] developed in 1956 and
later adopted by Masters and Johnson in their sex therapy
clinic as well as other approaches that have become the gold
standard for treatment of PE [53]. Stop-start and squeeze
techniques or the sensate-focus phase are used in therapeutic
programs for the treatment of PE. The techniques are
performed as effective treatments that delay PE by reducing
or removing stimulation, [4,54] but longitudinal follow-up
results of treatment for PE are even rarer than controlled
outcome investigations, and long-term success rates are
disappointing [36]. In addition, the application of the
principles of evidence-based medicine shows that there is
little evidence to support the psychological approach and
behavioral treatment [6].
Drug Therapy
The primary therapeutic approach to PE is pharmacotherapy.
Pharmacological treatment of men with PE may
include a variety of approaches. No pharmacological agents
are licensed for use for PE. However many centrally and
peripherally acting drugs have been proposed to treat
primary PE. These include
1- Selective serotonin reuptake inhibitors (SSRIs)
2- Tricyclic antidepressants
3- Monoamine oxidase inhibitors
4- Topical anesthesia
5- Neuroleptics
6- Sympatholytics
7- Phosphodiestrase inhibitors
In the next paragraphs an overview will be presented of
the various drug treatment studies for premature ejaculation
that have been published since 1943. Apart from the
phosphodiesterase inhibitor studies, all of these drug
treatment studies have previously been categorized in a
systematic review and meta-analysis study, published by
Waldinger et al. in 2004 [9].
Selective Serotonin Reuptake Inhibitors (SSRIs)
Probable mechanism of these drugs is the enhancement
of net serotonergic transmission by blocking the presynaptic
5-hydroxytryptamine (serotonin, 5-HT) uptake site [20,55].
Pre-clinical researches clearly indicate the role of serotonin
in ejaculatory processes. Among the different subtypes of 5-
HT receptors, the most important ones on ejaculation are
HT1A, 5-HT1B, 5-HT1D, and 5-HT2C receptors. Administration
SSRIs, results in active blockade of presynaptic membrane
5-HT transporters, and the resultant higher synaptic cleft
levels of 5-HT activate post-synaptic 5-HT2C and 5-HT1A
receptors and delay ejaculation. 5-HT1A receptor activation
by the selective 5-HT1A receptor agonist 8-OH-DPAT (8-
hydroxy-2-(di-n-propylaminotetralin) or flesinoxan inhibits
the release of 5-HT in the synaptic cleft, shortens the
ejaculation latency time and reduces the number of intermissions
preceding ejaculation in animals. 5-HT2C receptor
agonistsD-LSD (D-lysergic acid diethylamide) and quipazine
cause ejaculation delay [56]. In summary, SSRIs activate the
5-HT2C receptor and therefore switch the threshold to a
higher level, leading to a delay in ejaculation.
There are 2 drug treatment strategies to treat PE with
SSRIs: 1) daily treatment 2) as-needed treatment. Waldinger
et al. reported that, on-demand SSRI treatment has
less ejaculation-delaying effects than daily SSRI treatment
[57]. Acute administration of various SSRIs, such as,

Table 1. Sexual Side Effects of Common Prescription Medications
Type of drug Generic name Sexual side effects
Antihypertensive medications
Diuretics
Spironolactone
Thiazides,
Furosemide
Decreased libido, breast swelling, impotence
Impotence
None
Centrally acting agents
Methyldopa
Clonidine
Reserpine
Decreased libido, impotence
Impotence
Decreased libido, impotence, depression

You can use the “Squeeze” method if the Masters and Johnson does not work for you on its own. You can combine both methods.So, you have learned a little more about how to overcome your premature ejaculation problem.

These two methods are an integral part of the Condensed Method. For some
they are successful after a very long work, however, for a large percentage of
people these two methods are not sufficient.

This means that, to overcome your problem of premature ejaculation, you need
other techniques which will enable you to make more rapid progress, on both
the psychological and the physiological level.

Those who have benefited from the Condensed Method discover and try out
several training techniques which teach them to know their own bodies.
And that is the key to learning, successfully, how to stop the ejaculation reflex,
without disturbing your partner’s increasing pleasure.
Let us not forget that ejaculation is a reflex and it cannot be stopped. Yes,
nobody can stop ejaculation once it has started! Nonetheless, knowing the physiology of your own body will enable you to recognise the start of this reflex, without diminishing your pleasure in making love, on the contrary. You will find several ways in the “Condensed Method”.
To overcome your premature ejaculation problem once and for all.
You will also learn how to make love to your partner in a different way, you
will make love together.
In other words, you will be at one with your partner.

The Master and Johnson method requires a lot of patience and practice, that
why you need the Condensed Method to really brings results.
Follow the instructions described below
You can start by masturbating, get yourself close to the point of orgasm, and
stop. This will enable you to relax before starting again.
The more often you start again, the more you will be able to bring yourself
closer to an orgasm; up to the point where you can no longer control yourself.
A lubricant may help (available in the pharmacy).
Repeating the exercise several times on different occasions will help you to
discover your point of no return.
Once you have reached this point, you should be able to ask your partner to
stimulate you, to complete the exercise to its full with her/his help and
cooperation.
The best way of practising this method is to ask your “lover“to participate,
although, at the beginning you can do this exercise alone.
For this exercise, you should not penetrate your partner (she masturbates you
and you stimulate yourself with fellation) and little by little you reach the point
just before ejaculation.
At this moment you must indicate to your partner to stop stimulation (at this
point you can use the so-called „squeeze“method, see below) and try to
diminish the erection a little. Repeat these stages several times so that you
become comfortable with them.

You should do this exercise for several days before proceeding to penetration.
Once you are ready to go on to the penetration stage, lie on your back and
explain to your partner that she should sit on you so that she herself can control
the penetration of your penis.
Your partner starts the “coming and going” gently and very slowly, as soon as
you feel you have reached the critical point (preferably just before), give her a
pre-arranged stop signal; relax so that you can decrease your erection a little.
Give a signal to start again, and then if you feel the need to ejaculate, she
should bring you to ejaculation, either by hand or mouth.

Introduction
Orgasm and ejaculation constitute the final stage of
the sexual response in men. There are three basic
mechanisms involved in the normal antegrade
ejaculation: emission, ejection and orgasm.1
Ejaculation is a reflex comprising sensory receptors
and areas, afferent pathways, cerebral sensory areas,
spinal motor areas and efferent pathways (Figure 1).
The ejaculation reflex is controlled by a complex
interplay between central serotonergic and dopaminergic
neurons, with a secondary involvement of
cholinergic, adrenergic, nitrergic, oxytocinergic and
GABA (gamma aminobutyric acid)-ergic neurons.2
Seminal emission and ejaculation are integrated into
the complex pattern of copulatory behaviour by
several forebrain and midbrain structures (Figure 1).3
Prevalence of premature ejaculation
Premature ejaculation is one of the most frequently
reported sexual dysfunctions seen in clinical
practice. Varying rates have been estimated from
different populations. A systematic review of 28
studies suggested a prevalence of 15%.4 A large
representative sample of American men, aged
between 18 and 59 years, found that 31% of men
admitted to premature ejaculation occurring for
at least one month over the past 12 months.5
However, a more detailed study in the UK of 5000
16–44-year-old men found that 11.7% said that they
had experienced premature ejaculation for at least
one month in the past year, but only 2.7% hadexperienced the problem for at least six months in
the past year, suggesting that the problem affects
many men some of the time.6 Data from a large
observational study show overlapping distributions
of ejaculation times in men, who subjectively
had premature ejaculation compared with those
who were subjectively normal (Figure 2).7 A
substantial number of men who do not have
premature ejaculation have short ejaculation times
and conversely some men who complain of
premature ejaculation appear to have long ejaculation
times. This suggests that other features of
premature ejaculation have to be considered, as
well as time, i.e. degree of control and distress.
Definition
A universally accepted definition has yet to be
established. Masters and Johnson proposed that
premature ejaculation is the inability of a man to
delay ejaculation long enough for the woman to
reach orgasm 50% of the time.8 Some authors have
defined premature ejaculation as the number of
vaginal thrusts the man makes before ejaculation.
9–11 Clinical studies have used intravaginal
ejaculation times as measured by a stopwatch to
define premature ejaculation. Standardized inventories
may be available in the future, which will
generate individual data on the subjective perception
of lack of control and associated distress. The
DSM IV (American Association of Psychiatrists)
define premature ejaculation as: ‘persistent or
recurrent ejaculation with minimal sexual satisfaction
before, or shortly after penetration and before
the person wishes’.12 The disorder should result in

Aetiology of PE
The reader is referred to a detailed review of this elsewhere (5). However, the main factors are summarised below.
Idiopathic primary premature ejaculators may have lower penile sensory thresholds (6) and/or greater cortical penile representation (7) than their normal counterparts. Other workers contend that men with PE become sexually aroused more rapidly than normals (8).  Both anxiety and depression have been associated with PE(9) although this may be a consequence of the condition rather than a cause.  Others have failed
to find such an association (10).
A number of psychodynamic theories have been proposed to explain PE, as well as psychosocial and relationship factors (5) (e.g. family problems or a recent new baby). It is possible that some racial groups are more susceptible than others to PE (11), particularly men from the Indian subcontinent who may present with the Dhat syndrome (12) (a clinical picture with some or all of the features of concern about spontaneous seminal loss, affective illnesses, psychosomatic complaints and PE).
There are a number of anecdotal reports of PE being associated with neurological disease, diabetes, pelvic injury, vascular disease, prostatic hypertrophy, chronic prostatitis and hypogonadotrophic hypogonadism (5)
Patient Assessment

(i) History
This should include a brief but thorough assessment of whether the problem is primary or secondary in nature, and any associated personal, social or religious correlates, as well as a brief medical and psychiatric history (including alcohol and illicit drug details).  The presence of sexual desire should be documented Finally it is important to ensure that fast detumescence is in fact not caused by erectile problems rather than PE.  An interpreter may be needed to obtain the correct history.
(ii) Clinical examination
An assessment of the penis and other secondary sexual characteristics is mandatory as well as brief general physical and mental state assessments.
(iii) Investigations
No special investigations are routinely necessary to make the diagnosis of PE.
We consider that all new patients merit at least a 30 minute minimal consultation time for their first appointment.
Treatment of PE
General considerations
Treatment of PE should primarily attempt to alleviate concern about the condition as well as to increase sexual satisfaction in the patient and partner (if he has one). Simple measures such as education to discuss sexual norms, and facilitation of sexual negotiation between the couple (e.g. the man clitorally stimulates his partner to orgasm before vaginal penile entry) may be useful.  Formal cognitive behaviour  therapy (CBT) may be usefully incorporated into the specific techniques described below.
Specific Treatments
These therapeutic options include:-
1.  The squeeze/stop-start techniques
2.  Pharmacotherapies
3.  Other therapies
Squeeze/stop-start techniques
Most men learn to achieve ejaculatory control by various self learned techniques e.g.
thought distraction, transient cessation of penile thrusting.  The techniques described below merely attempt to formally train men in ejaculatory control.
In the “squeeze” technique (13) the glans is firmly squeezed between thumb and forefingers, at the frenular level until some detumesence results.  This is usually accomplished using one hand, with the index finger and forefinger being placed dorsally over the glans and distal shaft and the thumb over the ventral subcoronal frenular area. The “squeeze” is usually accompanied by a diminution of sexual arousal. It should take place before the patient has reached the stage that he feels it is inevitable he is going to ejaculate/orgasm.  This point may not be initially discernible to the patient with PE, but he usually learns to recognise it with time.  A partner usually carries out the squeeze but the patient may train himself to control the
PE by undertaking the squeeze himself.
A similar end point is reached by merely ceasing penile stimulation at the “pre-inevitable point” and then restarting penile stimulation when arousal and the erection have subsided.  This is the so-called “stop-start” technique (14). Both these techniques may be incorporated into a sensate focus regime. This is essentially a series of graded massage exercises, in which an initial ban is put on intercourse and the touching of erotic zones in order to relieve any performance anxiety.  There is a gradual reintroduction of erotic massage, vaginal penetration (using the female –superior position) and, lastly penetrative intercourse. These behavioural techniques may take up to 3-6 months to achieve significant changes (5).
Masters and Johnson reported an initial success rate of greater than 95% in the treatment of PE using the squeeze technique (13).  Less biased surveys indicate initial success rates of about 60%.  Most of the initial treatment gains appear to be lost over follow up with time (15)(16)(17)(18).

Pharmacotherapies

Systemic therapies
A number of placebo-controlled studies show that both clomipramine and the SSRI antidepressants (e.g. fluoxetine, paroxetine, sertraline) significantly retard ejaculation (19)(20)(21)(22)(23). However, they may all produce quite marked side effects, particularly in higher dosages e.g. low sexual desire, erectile dysfunction and fatigue. They can be taken on a continuous basis, which is the usual practice, or as required some hours before sex is anticipated (24)  The intermittent therapy can be commenced de novo (20) or after about a month of daily therapy (24) .
The daily dosages used tend to be lower than those used to treat depression e.g. 10mg to 50 mg of clomipramine, 10mg to 20mg per day of fluoxetine, 10mg to 20mg of paroxetine or 50mg of sertraline.  Once begun, medication needs to be continued to retain its beneficial effect.  However it is possible there can be a learning effect while on medication, as in one study two thirds of the patients on continuous sertraline for 7 months maintained their improvement after drug withdrawal (25).

Local therapies
EMLA cream (prilocaine-lidocaine) or lidocaine ointment used on the frenular area of the penis 15-30 minutes before intercourse (but wiped off before sexual contact) can produce useful results in retarding ejaculation (26).  Titrating the area of application against its effects can minimise penile numbness.
Other treatments
Both pelvic floor rehabilitation (27) and dorsal nerve neurotomy (28) have been shown to give good results in the short term but are experimental techniques at present and are not recommended for routine use. References
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