Premature Ejaculation

Premature Ejaculation
Monday, February 15, 2010

Ejaculation Physiology
Ejaculation is a complex reflex that consists of two distinct
phases: emission and expulsion.
The emission phase is characterized by the secretion of

seminal fluids from the accessory sex glands, as well as
closure of the bladder neck to ensure expulsion of semen
from the urethral meatus as opposed to retrograde
transport into the bladder.
During the expulsion phase, stereotypic rhythmic

contractions of the smooth muscle of the urethra, as well
as striated perineal muscles such as the ischiocavernosus
and bulbocavernosus muscles, result in the forceful
expulsion of semen. This response consists of 10 to 15
contractions.

Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV-TR)
American Psychiatric Association (APA)
‘‘persistent or recurrent ejaculation with minimal sexual

stimulation before, on, or shortly after penetration and
before the person wishes it’’.
‘‘The clinician must take into account factors that affect

duration of the excitement phase, such as age, novelty of
the sexual partner or situation, and recent frequency of
sexual activity’’.
PE can only be diagnosed when ‘‘the disturbance causes

marked distress or interpersonal difficulty’’.

The International Classification of
Diseases (ICD-10)
PE is defined as ‘‘the inability to delay ejaculation

sufficiently to enjoy lovemaking, which is manifested by
either an occurrence of ejaculation before or very soon
after the beginning of intercourse (if a time limit is
required: before or within 15 s of the beginning of
intercourse) or ejaculation occurs in the absence of
sufficient erection to make intercourse possible’’

The ISSM Definition of
Constructs that are necessary to
define PE are
• time from penetration to
ejaculation
• inability to delay ejaculation
• negative personal
consequences from PE.

The ISSM Definition of
Lifelong PE is a male sexual dysfunction characterized
by
• ejaculation that always or nearly always occurs prior

to or within about one minute of vaginal
penetration;
• the inability to delay ejaculation on all or nearly all
vaginal penetrations; and
• negative personal consequences such as distress,
bother, frustration, and/or the avoidance of sexual
intimacy.

Types of Premature
Ejaculation
• Lifelong PE
• Acquired PE
• Natural variable PE
• Premature-like ejaculatory dysfunction

Life long PE
• Ejaculation occurs too early nearly every time
intercourse takes place
• With (nearly) every woman
• From about the first sexual encounters onwards
• In the majority of cases (80%) within 30–60 seconds or

between 1 minute and 2 minutes (20%)
• Remains rapid throughout the lifetime of the subject

Acquired PE
• Early ejaculation occurs at some point in a man’s life
• The man had normal ejaculation experiences before
• The onset is either sudden or gradual
• The dysfunction may be a result of urological, neurological,
or thyroid dysfunctions
• The dysfunction may be because of psychological or
relationship problems

Natural Variable PE
• Early ejaculations are inconsistent and occur irregularly
• This type of PE should not be regarded as a symptom a
real pathology but rather a normal variation in sexual
performance
• The ability to delay ejaculation may be diminished or
lacking
• the impression of diminished control of ejaculation, are
accompanied by either a short or normal ejaculation
time
Premature-like ejaculatory
dysfunction
Men with premature-like ejaculatory dysfunction experience or
complain of PE while the ejaculation time is in the normal range
• subjective perception of consistent or inconsistent rapid ejaculation

during intercourse;
• preoccupation with an imagined early ejaculation or lack of control of

ejaculation;
• The actual intravaginal ejaculation latency time is in the normal range

or may even be of longer duration
• Ability to delay ejaculation may be diminished or lacking
• The preoccupation is not better accounted for by another mental

disorder

Prevalence
• Most estimates from general population prevalence studies fall
between 22% and 38%, with ranges from 4% to 39%. The wide
variability in the reported ranges is mirrored in the variability and
lack of standardized definitions for PE.
• In spite of the high prevalence rates, PE is the disorder for which

patients are least likely to seek professional assistance, raising the
distinct possibility that the problem may be more prevalent than
currently estimated.
• It has also been suggested that the prevalence of PE may vary

between racial groups
• The recurrent emerging pattern appears to be that PE is a largely

underdiagnosed condition

Prevalence

Etiology
• Psychogenic causes include anxiety, an unpleasant
introductory or early sexual experience, infrequent sexual
intercourse, poor ejaculatory control techniques, and
evolutionary as well as psychodynamic factors.
• Biogenic causes include penile hypersensitivity,
hyperexcitable ejaculatory reflex, hyperarousability,
endocrinopathy, genetic predisposition, and 5-hydroxy
tryptamine (5-HT)-receptor dysfunction.

Risk factors of lifelong PE
• Genetic predisposition (Race, fi rst-degree
relatives, twins, other factors)
• Psychosomatic disorder
• Behavioral or cognitive disorder from early
experience
• Greater sexual arousal
• Evolutionary natural selection Penile
hypersensitivity & reflex hyperexcitability
• Ejaculation distribution theory with
• dysregulation of 5 HT receptor subtypes
• Oxytocin release theory

5-HT Transporter
• The 5-HTT is a membrane bound
protein transporter that facilitates
serotonin re-uptake from the
synapse
• The 5-HTT protein is encoded for
and its functioning determined by
promoter region of polymorphic 5-
HTT gene (5-HTTLPR)
• 5-HTT gene is located on the long
arm of chromosome 17 (17q11.1)

Serotonergic Basis of
Ejaculation
Male rat studies demonstrate that serotonin and 5-HT
receptors and to a lesser extent oxytocin, are involved in
the ejaculatory process.
Selective serotonin re-uptake inhibitors (SSRIs) block 5-
HT transporters, resulting in higher synaptic cleft levels of
5-HT and delay of ejaculation.
Stimulation of 5-HT2C receptors with non-selective 5-
HT2C agonists delays ejaculation in male rats.
Stimulation of 5-HT1A receptors facilitates ejaculation.

SERT Gene
The 5-HTTLPR gene has two variant alleles: a short (S) and a
long (L) allele.
The genotypes of these alleles are called LL, SS, and SL
The S allele of the 5-HTT genotype reduces transcriptional
efficiency of the 5-HTT gene promoter, resulting in a 50%
reduction 5-HTT protein expression and reduced serotonin
reuptake compared with the L allele
S allele is associated with increased vulnerability for mood
disorders, reduced response to SSRIs and less side-effects
Men with LL genotypes have shorter IELTs than men with SS
and SL genotypes

Risk factors of Aquired
Psychorelational Functional (experiences, education)
Constitutive (psychological constitution)
Stress-induced (acute or chronic)
Psychosexual skill deficit
Neurological Multiple sclerosis
Spina bifida
Spinal cord tumors
Traumatic brain injury
Cerebrovascular accidents

Psychorelational Factors
 Functional (experiences, education)
 Constitutive (psychological constitution)
 Stress-induced (acute or chronic)
 Psychosexual skill deficit
Neurological
 Multiple sclerosis
 Spina bifida
 Spinal cord tumors
 Traumatic brain injury
 Cerebrovascular accidents

Endocrinological and Hyperthyroidism
metabolic Diabetes mellitus?
Metabolic syndrome?
Higher fasting leptin levels
Haemodialysis?
Hypoactive sexual desire
Erectile dysfunction
Relative hypogonadism (respect to non-PE patients)
Hyperprolactinaemia?

Etiology
Urologic causes, including chronic prostatitis, or post.
urethrtis.
Early animal studies revealed that nonselective agonists

of the 5-HT2C receptors delay ejaculation, but selective
5-HT2A agonists do not have a similar effect, and
selective 5-HT1A agonists cause a shorter ejaculatory
latency compared with 5-HT2C agonists. PE may be
secondary to relative hyposensitivity of the 5-HT2C and/
or 5-HT1A hypersensitivity.

Diagnosis: The Sexual History
Frequency and duration of PE
Proportion of sexual attempts with PE
Relationship to specific partners
Frequency and nature of sexual activity
Aggravating or alleviating factors
Impact of PE on sexual activity
Effect on relationships and QoL
Relationship to drug use/abuse
Other considerations
➡ Lifelong vs. acquired
➡ Situational vs. universal/global
➡ Because of psychological or combined psychological/
biological factors
➡ Any links to ED?

PE and Hyperthyroidism
Established link between thyroid hormones, central 5-HT and depression
Chronic treatment with thyroxine (T4) is an effective therapy of depression
The 5-HT2A receptor is up-regulated in the cortex of suicide victims, down-
regulated by antidepressant drugs and seems to be under thyroid hormone
regulation
The majority of patients with thyroid hormone disorders experience sexual
dysfunction
Corona et al. reported a significant correlation between PE and suppressed
TSH values of hyperthyroidism
Carani et al. subsequently reported a PE prevalence of 50% in men with
hyperthyroidism which fell to 15% after treatment with thyroid hormone
normalization
Waldinger et al. failed to demonstrate an increased incidence of thyroid
dysfunction in lifelong PE, consistent with the notion that hyperthyroidism
appears to be a cause of only acquired PE

PE and Chronic Prostatitis
Acute and chronic prostatitis and Chronic Pelvic Pain
Syndrome (CPPS) are associated with painful ejaculation,
ED and PE
In 3700 men with benign prostatic hypertrophy (BPH),

painful ejaculation, ED and PE were reported by 18.6%,
72% and 75% and were all associated with more severe
lower urinary tract symptoms (LUTS)
Several studies report PE as the main sexual disorder

symptom in men with chronic prostatitis or chronic pelvic
pain syndrome with a prevalence of 26-77%.

PE and Chronic Prostatitis
Prostatic inflammation and prostatitis have been reported as
common findings in men with both lifelong and acquired PE
Shamloul and El-Nashaar reported prostatic inflammation
and chronic bacterial prostatitis in 64% and 52% of men
with PE
The exact pathophysiology of the link between chronic
prostatitis, ED and PE is unknown
Although physical and microbiological examination of the
prostate in men with painful ejaculation or LUTS is
mandatory, there is insufficient evidence to support routine
screening of men with PE

Diagnosis: The Sexual History
How well are you enjoying your sex life?
Do you ejaculate too soon or earlier than desired? If so,

can you estimate the amount of time before you
ejaculate?
Do you feel you have control over the timing of your

ejaculation?
Does ejaculating early bother/distress you and/or your

partner?

Medical History and Examination
To rule out an acute or chronic illness or identify injuries or
surgeries that might interfere with healthy sexual functioning.
In particular, the clinician should focus on any physical signs of

neurological impairment, chronic systemic illness, and
endocrine dysfunction.
Infection in the urethra, prostate, or epididymis should also be

ruled out.
Current medications that might influence sexual functioning.
laboratory assessments to identify drug or alcohol use/abuse, as

PE has been reported to result from opiate withdrawal

PE Medical Treatment
Psychotherapy/Behavioural Therapy
Pharmacotherapy
➡ Daily Dosing
SSRI drugs and clomipramine
Daily alpha-adrenoreceptor antagonists
➡ On-demand Dosing
SSRI drugs, dapoxetine and clomipramine
Tramadol
Topical anesthetic sprays or gels
PDE-5 inhibitors

Central Serotonergic Neuron
Multiple 5-HT receptors
Synaptic cleft 5-HT is regulated by

the 5-HT transporter re-uptake
system and several autoreceptors
As 5-HT is released, the

transporter system is activated,
removes 5-HT from the synaptic
cleft, preventing over-stimulation
of postsynaptic 5-HT2C receptors

Effect of SSRIs on Ejaculation
McMahon CG (1998) J Urol 59:1935-8

Selective Serotonin Reuptake
Inhibitors (SSRIs)
Treatment with an SSRI activates the 5-HT2C receptor and delays
ejaculation
The ability of SSRIs to delay ejaculation was first uncovered
during the use of these medications in the treatment of depressed
men in the 1970s. Fluoxetine was next shown to be helpful in the
intentional treatment of PE
SSRIs may cause an increase in latency time as early as 2–3 days
after the initiation of oral therapy. This effect tends to plateau after
3–4 weeks, with a six- to eightfold increase in IELT.
In order of clinical response,Paroxetine is the most effective,
followed by fluoxetine, then sertraline, and lastly fluvoxamine

Pharmacological Treatment
Level 1 evidence to support the efficacy of
SSRIs
citalopram, fluoxetine, fluvoxamine,

paroxetine and sertraline
Serotonergic tricyclic, clomipramine
Meta-analysis of all drug treatment studies has

demonstrated that paroxetine exerts the
strongest ejaculation delay (mean IELT fold
increase of 8.8)

Daily SSRI Treatment
Usually well tolerated
Adverse effects of SSRIs
➡ Fatigue, yawning, mild nausea, loose stools or
perspiration
➡ Start in the first week after intake
➡ Attenuate within 2-3 weeks
➡ Occasionally hypoactive sexual desire and mild
ED
➡ Occasional agitation - avoid in men with history
of bipolar depression
Suspend gradually over 3-4 weeks to avoid
withdrawal symptoms

On-Demand Intervention SSRIs
➡ Dapoxetine, an SSRI structurally related to fluoxetine,
is the first SSRI developed with a short half-life,
convenient for the on-demand treatment of PE
➡ When taken 3 hours prior to intercourse, increased the
IELT 3.0–3.7 times over baseline.
➡ Nausea was the most frequently noted side effect
reported in up to 20.1% of patients on the higher
(60mg) dose of dapoxetine; other commonly observed
side effects in the 30- and 60-mg doses, respectively,
were diarrhea (3.9%, 6.8%), headache (5.9%, 6.8%),
and dizziness (3.0%, 6.2%).

Behavioral Therapy and Psychotherapy
Squeeze technique
Behavioral therapy has long been a
mainstay of treatment for PE and remains,
in the absence of anything better, a
common approach today.
This technique involves withdrawal of the

penis during intercourse and prior to the
moment of ejaculatory inevitability. The
sexual partner is instructed to give a very
sharp and hard squeeze to the glans penis
to abort the ejaculation. However, many
practitioners and patients report that this
technique is unpractical.
Behavioral Therapy and Psychotherapy
The stop–start technique
has been used, with variations, for some three
decades and was particularly popularized by
Kaplan in 1983.
This method requires the man to pause during
sexual stimulation, just prior to impending
ejaculation.
The pause allows the patient to acclimatize to the
sensation and eventually to condition himself to
increased ejaculatory control.

Medical Treatment
Decreasing sensory perception in the penis has been
the goal of most topical agents aimed at treating PE
Prilocaine-lidocaine cream (EMLA, eutectic mixture of

local anesthetics)
Aerosol TEMPE formulation (topical eutectic mixture

for PE)

TEMPE - IELT

Topical Agents - Side effects
Anesthetic creams require a somewhat messy application
within a condom, and the entire shaft is anesthetized.
Aerosol TEMPE formulation, on the other hand, requires a
decreased time for prior application, and only the glans
penis is anesthetized
Significant penile hypoanesthesia and risk of transvaginal

absorption with vaginal numbness, unless a condom is
utilized. Irritating topical reactions, both penile and vaginal,
can occur, and systemic reactions are also possible. Efforts
to wash off the medication prior to intercourse may reduce
the risk of these side effects, but also reduce the spontaneity
of the coital experience

Clomipramine
Clomipramine is a tricyclic antidepressant used in the
treatment of obsessive compulsive disorders.
Although it is not an SSRI, it does inhibit 5-HT transport.
A 25-mg dose has effected delay in ejaculation, when taken as
a one-time treatment 5 hours before intercourse by men with
lifelong PE
Side effects include dry mouth, fatigue, nausea, and dizziness.
Tricyclic antidepressants seem to share with the SSRIs the
risk of increased suicide, when initiated in men under age 24.
At higher doses (75mg for more than 3 months), clomipramine
may have an adverse effect on sperm function

Tramadol
Tramadol, a centrally acting synthetic opioid analgesic
Effective on-demand agent
The ejaculatory-delaying mechanism of tramadol has not
been fully understood
➡ Binds to µ-opioid receptors
➡ Weak GABA, norepinephrine, serotonin re-uptake inhibitors
Occasionally associated with serotonin syndrome especially
when co-administered with SSRI anti-depressant
Dependance occurs but appears minimal

PDE5 Inhibitors
PE may be seen in up to a third of patients with ED
In cases of PE associated with ED, treatment of ED

by using PDE5 inhibitors may have a salutary effect
on ejaculatory dysfunction
PDE5 inhibitors may exert a secondary benefit for

patients with PE when they (i) allow for a sustained
penile erection, even after ejaculation; (ii) facilitate a
second intercourse after the initial ejaculation, which is
often less prone to PE; and/or (iii) help the patient to
overcome performance anxiety, which often
exacerbates PE

Future PE Drugs
5_HT1A receptor antagonists
➡ The superior ejaculatory delay seen with daily SSRIs due
to desensitization of 5-HT1A receptors, increased
activation of postsynaptic 5-HT2C and the resultant
higher increase in synaptic 5-HT neurotransmission can
be achived by blockage of 5-HT1A receptors with c0-
administered 5-HT1A receptor antagonists
Oxytocin receptor antagonists

➡ Plasma oxytocin is elevated during erection and orgasm
➡ Electrical stimulation of the dorsal penile nerve produced
excitation in 1/2 of oxytocin cells in the PVH and SON of
rats

Premature Ejaculation

Încărcat de

Informații document

Descriere originală:

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Premature Ejaculation

Încărcat de

Drepturi de autor:

Formate disponibile

Premature Ejaculation

Monday, February 15, 2010

The emission phase is characterized by the secretion of

During the expulsion phase, stereotypic rhythmic

Monday, February 15, 2010

‘‘persistent or recurrent ejaculation with minimal sexual

‘‘The clinician must take into account factors that affect

PE can only be diagnosed when ‘‘the disturbance causes

Monday, February 15, 2010

PE is defined as ‘‘the inability to delay ejaculation

Monday, February 15, 2010

consequences from PE.

Monday, February 15, 2010

• ejaculation that always or nearly always occurs prior

Monday, February 15, 2010

Monday, February 15, 2010

• With (nearly) every woman

• From about the first sexual encounters onwards

• In the majority of cases (80%) within 30–60 seconds or

• Remains rapid throughout the lifetime of the subject

Monday, February 15, 2010

Monday, February 15, 2010

• subjective perception of consistent or inconsistent rapid ejaculation

• preoccupation with an imagined early ejaculation or lack of control of

• The actual intravaginal ejaculation latency time is in the normal range

• Ability to delay ejaculation may be diminished or lacking

• The preoccupation is not better accounted for by another mental

Monday, February 15, 2010

• In spite of the high prevalence rates, PE is the disorder for which

• It has also been suggested that the prevalence of PE may vary

• The recurrent emerging pattern appears to be that PE is a largely

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

Early animal studies revealed that nonselective agonists

Monday, February 15, 2010

Monday, February 15, 2010

Monday, February 15, 2010

In 3700 men with benign prostatic hypertrophy (BPH),

Several studies report PE as the main sexual disorder

Monday, February 15, 2010

Monday, February 15, 2010

How well are you enjoying your sex life?

Do you ejaculate too soon or earlier than desired? If so,

Do you feel you have control over the timing of your

Does ejaculating early bother/distress you and/or your

Monday, February 15, 2010

In particular, the clinician should focus on any physical signs of

Infection in the urethra, prostate, or epididymis should also be

Current medications that might influence sexual functioning.

laboratory assessments to identify drug or alcohol use/abuse, as

Monday, February 15, 2010

Monday, February 15, 2010

Multiple 5-HT receptors

Synaptic cleft 5-HT is regulated by

As 5-HT is released, the