Ejaculatory disorders

Ege Can Serefoglu  MD FECSM
Ege Can Serefoglu MD FECSMSexual & Reproductive Medicine, Urology Service at Bagcilar Education and Research Hospital um Biruni University
Ege Can Serefoglu, MD, FECSM
Bagcilar Training & Research Hospitaly, Dept. of Urology,
Istanbul
Ejaculatory Disorders
Introduction
Definitions & Classification
Delayed Ejaculation
Premature Ejaculation
Ejaculatory Disorders
Introduction
Definitions & Classification
Delayed Ejaculation
Premature Ejaculation
Introduction
 Ejaculation is the expulsion of semen from the meatus
 Constituted by 2 phases
 Emmision: Ejection of the semen into the posterior urethra
Contraction of testes, epididymes, VD, SV, prostate
 Expulsion: Ejection of sperm from urethra
REFLEX response to the presence of semen in BU
Rhythmic contractions of perineal muscles (BS/IC)
Ejaculatory disorders
Ejaculatory Disorders
Introduction
Definitions & Classification
Definitions & Classification
Premature Ejaculation
Definition & Classification
 Ejaculatory Dysfunction  common MSD
 Premature Ejaculation
 Retrograde Ejaculation
 Delayed Ejaculation
 Painful Ejaculation
 Anejaculation
 Chronological Classification
 Primary (Lifelong): from the very first intercourse and with
almost all couples
 Secondary (Acquired): From a certain point in life
Definition & Classification
 Ejaculatory Dysfunction  common MSD
 Premature Ejaculation
 Retrograde Ejaculation
 Delayed Ejaculation
 Painful Ejaculation
 Anejaculation
 Chronological Classification
 Primary (Lifelong): from the very first intercourse and with
almost all couples
 Secondary (Acquired): From a certain point in life
Ejaculatory disorders
0
10
20
30
40
50
60
70
80
90
100
Percentageofsubjects
Mean IELT(s)
Median IELT of 5.4 minutes
(range, 0.55-44.1 min) in
Netherlands, United
Kingdom, United
States, Spain, and Turkey
Waldinger et al. (2005) J Sex Med 2:492–497
Normative IELT data
Unselected “normal” population of 500 heterosexual couples
Stopwatch timing of the IELT
MEDIAN
5.4 min
TURKEY
3.7 min
Ejaculation Distribution Theory
Premature
Ejaculation
Normal
Ejaculation
Delayed
Ejaculation
Anejaculation
IELT < 1-2 m IELT <4-10 m IELT >20-30m IELT ∞
Waldinger and Schweitzer 2005
Ejaculatory Disorders
Introduction
Definitions & Classification
Delayed Ejaculation
Premature Ejaculation
Definition & Characteristics of DE
 Delayed=Retarded=Inhibited=Inadequate=Difficult
 Least common/studied/understood male SD
 Diminished sexual satisfaction for man and partner
Jannini and Lenzi, 2005; Rowland et al. 2004; Rowland et al. 2005; Segraves 2010
Definition & Characteristics of DE
 DSM-V: Delayed Ejaculation 302.74 (F52.32)
A. Either of the following symptoms must be experienced on almost all or all
occasions (approximately 75-100%) of partnered sexual activity (in identified
situational contexts or, if generalized, in all contexts), and without the individual
desiring delay:
1. marked delay in ejaculation
2. marked infrequency or absence of ejaculation on almost all or all occasions
of partnered sexual activities
B. The symptoms in Criterion A have persisted for a minimum duration of
approximately 6 months
C. The symptoms in Criterion A cause clinically significant distress in the individual
D. The sexual dysfunction is not better explained by a nonsexual mental disorder
or as a consequence of severe relationship distress or other significant stressors
and is not attributable to the effects of a substance/medication or other medical
condition.
 WHO 2nd Consultation on SD
 Persistent or reccurent difficulty, delay in, or absence of attaining orgasm after
sufficient sexual stimulation which causes personal distress
Definition & Characteristics of DE
 DSM-V: Delayed Ejaculation 302.74 (F52.32)
A. Either of the following symptoms must be experienced on almost all or all
occasions (approximately 75-100%) of partnered sexual activity (in identified
situational contexts or, if generalized, in all contexts), and without the individual
desiring delay:
1. marked delay in ejaculation
2. marked infrequency or absence of ejaculation on almost all or all occasions
of partnered sexual activities
B. The symptoms in Criterion A have persisted for a minimum duration of
approximately 6 months
C. The symptoms in Criterion A cause clinically significant distress in the individual
D. The sexual dysfunction is not better explained by a nonsexual mental disorder
or as a consequence of severe relationship distress or other significant stressors
and is not attributable to the effects of a substance/medication or other medical
condition.
 WHO 2nd Consultation on SD
 Persistent or reccurent difficulty, delay in, or absence of attaining orgasm after
sufficient sexual stimulation which causes personal distress
Definition & Characteristics of DE
 These definitions
 Not evidence-based
 Excessively vague
 Lack specific operational criteria
 Severity (e.g. 75% of sexual occasions)
 Duration (e.g. 6 mo)
 IELT (e.g. desired ejaculation lasting???)
 Rely on the subjective judgment of the diagnostician…
Althof. 2012; Rowland et al. 2005; Perelman. 2006; Patrick et al. 2005; Segraves. 2010
Definition & Characteristics of DE
 most sexually functional men ejaculate ≈ 4-10 mins
 A man with DE is expected to:
 have IELT > 20 - 30 mins (21-23 min represents 2SD above the mean)
 cease sexual activity due to exhaustion or irritation
 report relationship distress/frustration/performance anxiety
 seek help for his sexual dissatisfaction (despite good erections!!)
Rowland et al. 2005; Perelman. 2006; Patrick et al. 2005; Segraves. 2010
+
 Impact of DE on the patient and partner is often not fully appreciated
 Some perceive DE to be a positive attribute that allows the man to
“bestow multiple coital orgasms to his partner”
 DE is involuntary and causes distress for both the man and the partner
 Partners believe they are not attractive enough for the patient. They feel
unneeded and rejected.
 Extended coitus causes pain for the patient and partner
 Anejaculation results in a failure to conceive
Definition & Characteristics of DE
Definition & Characteristics of DE
 The prevalence is unclear
 Lack of normative data
 Lack of operational criteria
 0.15 - 5% of sexually active men
 2.5-5% of men with SD
 Increasing --- PDE5 inhibitors restored ED, w/o restoring arousal
 More common among older (>50 years-old)
 neuronal degeneration, dermal atrophy, low penile sensitivity
 loss of pelvic floor muscle tone
 More severe and common (46-75%) with LUTS (independent of age)
Simons et al. 2001; Patrick et al. 2005; Rowland et al. 2004; Corona et al. 2006; Traeen 2011; Perelman and Rowland 2006;
Blanker et al. 2001; Rosen et al. 2003; Nathan et al. 1986; Nazareth et al. 2003; Rosen et al. 2009
Definition & Characteristics of DE
 Classification
 Lifelong (primary) ≈25%
 Acquired (secondary) ≈75%
 Global / Situational / Intermittent
 Genetic influence?
 heme oxygenase-2 gene lacking mice develop DE/anejaculation
 no genetic influence is found on humans
 shared environmental influence detected between twins…
 PET scans  higher activity in the anterior temporal lobe
(centers for vigilance and fear behaviour)
Perelman 2004; Rowland et al. 2004; Kriegsfeld et al. 1999; Jern et al. 2007; Georgiadis and Holstege. 2004
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
Fear/Anxiety
Relationship diff.
Religion/Culture
Insuff. sexual arousal
Masturbation (Autosexuality)
Delayed Ejaculation
Four Diverse Psychological Theories
All Without Empirical Support
Insufficient Stimulation
Failure to achieve sufficient mental
or physical stimulation
Masturbation
High frequency of masturbation
Idiosyncratic masturbatory style
Disparity between fantasy & reality
Outgrowth of Psychic Conflict
Loss of self from loss of semen, fear of harm
from female genitals, fear that ejaculation
may hurt the partner, fear of impregnating
the female, fear of defiling the partner with
semen, hostility toward partner, not willing
to give of oneself, guilt from strict religious
upbringing
Disguised and Subtle Desire
Disorder Masquerading as an
Ejaculatory Dysfunction
Automatic functioning in the absence of
genuine arousal, autosexual
orientation, partner’s touch
inhibiting, penis becomes
insensate, compulsion to satisfy partner
+
Masturbation and DE
 Of 80 men diagnosed with DE
 25% could not achieve ejaculation under any circumstance
 75% could masturbate to orgasm
 Three factors were correlated to DE diagnosis
 Relatively high frequency of masturbation
 over 35% reported masturbating at least every other day or more
 Idiosyncratic style of masturbation
 Idiosyncratic in the speed, pressure, duration and intensity necessary to
produce an orgasm, yet dissimilar to what they experienced with a partner
 Disparity between the reality of sex with the partner and the use of
sexual fantasy during masturbation
Perelman M. (2005) Idiosyncratic Masturbation Patterns: A Key Unexplored Variable in the Treatment of
Retarded Ejaculation by the Practicing Urologist. Journal of Urology. 173(4): supp:340.
DE
Psychogenic
Anatomic.
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
TURP/TIUP/RP
Bladder neck inc.
Imperforated Anus correction
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
Mullerian cyst
Wolfian abnormalities
Prune-belly synd
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
Autonomic neuropathy (DM)
SCI
RP / RT
Proctocolectomy
Bilat. Sympathectomy
Abdominal aortic aneurysmectomy
Para-aortic lymphadenectomy
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
Urethritis
GU tuberculosis
Schistosomiasis
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
64% of hypothyroid men reported DE
26% of men with DE had hypogonadism
Carani et al. 2005; Corona et al 2008
DE
Psychogenic
Anatomic
Congenital
NeurogenicInfective
Endocrine
Medications
Organic/Psychological Causes of DE
Alpha-Methyl DOPA
Thiazide Diuretics
TC/SSRI Antidepressants
Phenothiazide
Alcohol Abuse
Evaluation of DE (History)
Investigate domains related to the psychologic and relationship issues associated with DE
Religious Orthodoxy Performance Anxiety Autosexuality
Perceived Partner
Attractiveness
Review the conditions under which the man is able to ejaculate
During sleep With masturbation
With partner’s hand or
mouth stimulation
With varying coital
positions
Life events / circumstances related to orgasmic cessation must be reviewed
Pharmaceuticals Ilness Life Stressor Trauma
Find potential physical and specific psychologic/learned causes of DE
Any concomitant or contributory organic factors involved?
Evaluation of DE (History)
Investigate domains related to the psychologic and relationship issues associated with DE
Religious Orthodoxy Performance Anxiety Autosexuality
Perceived Partner
Attractiveness
Review the conditions under which the man is able to ejaculate
During sleep With masturbation
With partner’s hand or
mouth stimulation
With varying coital
positions
Life events / circumstances related to orgasmic cessation must be reviewed
Pharmaceuticals Ilness Life Stressor Trauma
Find potential physical and specific psychologic/learned causes of DE
Any concomitant or contributory organic factors involved?
Evaluation of DE (History)
Investigate domains related to the psychologic and relationship issues associated with DE
Religious Orthodoxy Performance Anxiety Autosexuality
Perceived Partner
Attractiveness
Review the conditions under which the man is able to ejaculate
During sleep With masturbation
With partner’s hand or
mouth stimulation
With varying coital
positions
Check life events / circumstances related to orgasmic cessation
Pharmaceuticals Illness Life Stressor Psycho/Trauma
Find potential physical and specific psychologic/learned causes of DE
Any concomitant or contributory organic factors involved?
Evaluation of DE (History)
Investigate domains related to the psychologic and relationship issues associated with DE
Religious Orthodoxy Performance Anxiety Autosexuality
Perceived Partner
Attractiveness
Review the conditions under which the man is able to ejaculate
During sleep With masturbation
With partner’s hand or
mouth stimulation
With varying coital
positions
Check life events / circumstances related to orgasmic cessation
Pharmaceuticals Illness Life Stressor Psycho/Trauma
Find potential physical and specific psychologic/learned causes of DE
Any concomitant or contributory organic factors involved?
Evaluation of DE (History)
Investigate domains related to the psychologic and relationship issues associated with DE
Religious Orthodoxy Performance Anxiety
Masturbation
fq/patterns
Perceived Partner
Attractiveness
Review the conditions under which the man is able to ejaculate
During sleep With masturbation
With partner’s hand or
mouth stimulation
With varying coital
positions
Check life events / circumstances related to orgasmic cessation
Pharmaceuticals Illness Life Stressor Psycho/Trauma
Find potential physical and specific psychologic/learned causes of DE
Any concomitant or contributory organic factors involved?
Evaluation of DE (PE & Lab)
Electrophysiological Evaluation
Pudental Somatosens
Evoked Pot (SEPs)
Pudental Motor
Evoked Pot (MEPs)
Sacral Reflex Arc
Testing
Sympathetic Skin
Responses
Imaging
Testicular US TRUS Cystoscopy Vasography Perineal US
Laboratory
Serum Glucose Testosterone fT3/fT4/TSH PSA
Examine penis, testicles , epididymes, vas deferens (rarely diagnostic)
Identify reversible
urethral, prostatic, epididymal and testicular
infections
Penile irritation/erythema (idiosyncratic
masturbation/prolonged thrusting)
Evaluation of DE (PE & Lab)
Electrophysiological Evaluation
Pudental Somatosens
Evoked Pot (SEPs)
Pudental Motor
Evoked Pot (MEPs)
Sacral Reflex Arc
Testing
Sympathetic Skin
Responses
Imaging
Testicular US TRUS Cystoscopy Vasography Perineal US
Laboratory
Serum Glucose Testosterone fT3/fT4/TSH PSA
Examine penis, testicles , epididymes, vas deferens (rarely diagnostic)
Identify reversible
urethral, prostatic, epididymal and testicular
infections
Penile irritation/erythema (idiosyncratic
masturbation/prolonged thrusting)
Evaluation of DE (PE & Lab)
Electrophysiological Evaluation
Pudental Somatosens
Evoked Pot (SEPs)
Pudental Motor
Evoked Pot (MEPs)
Sacral Reflex Arc
Testing
Sympathetic Skin
Responses
Imaging
Testicular US TRUS Cystoscopy Vasography Perineal US
Laboratory
Serum Glucose Testosterone fT3/fT4/TSH PSA
Examine penis, testicles , epididymes, vas deferens (rarely diagnostic)
Identify reversible
urethral, prostatic, epididymal and testicular
infections
Penile irritation/erythema (idiosyncratic
masturbation/prolonged thrusting)
Evaluation of DE (PE & Lab)
Electrophysiological Evaluation
Pudental Somatosens
Evoked Pot (SEPs)
Pudental Motor
Evoked Pot (MEPs)
Sacral Reflex Arc
Testing
Sympathetic Skin
Responses
Imaging
Testicular US TRUS Cystoscopy Vasography Perineal US
Laboratory
Serum Glucose Testosterone fT3/fT4/TSH PSA
Examine penis, testicles , epididymes, vas deferens (rarely diagnostic)
Identify reversible
urethral, prostatic, epididymal and testicular
infections
Penile irritation/erythema (idiosyncratic
masturbation/prolonged thrusting)
Treatment of DE
Medication
Reduce the
dose
Use antidot
Vascular /
Neuropatic
damage
Irreversible Counselling
GU Infection Culture Antibiotics
Androgen
deficiency
FSH / LH
levels
T
replacement
therapy
Hypothyroid
Tiroid
hormone
Treatment of DE
 Lifestyle changes
 Reduce alcohol consumption
 Making love when not tired
 decreasing the frequency of masturbation
 Psychotherapy
 Pharmacotherapy
Treatment of Primary DE
 Lifestyle changes
 Psycho / Physiotherapy : none has been properly
evaluated
 Sex education/therapy (discontinuation of masturbation)
 Reduction of goal-focused anxiety
 Genitally-focused stimulation (anal, rectal stimulation with
finger or vibrator)
 Role-playing, desensitizing exercises
 Re-alignment of sexual fantasies and arousal strategies
 Pharmacotherapy
Delayed Ejaculation
Case Examples
Insufficient Stimulation
Failure to achieve sufficient mental or
physical stimulation
Masturbation
Outgrowth of Psychic Conflict Disguised and Subtle Desire Disorder
Masquerading as an Ejaculatory
Dysfunction
79 year old married ♂ with a 5 yr history of
being unable to achieve orgasm/ejaculation
under any circumstance. BCG treatment for
same period of time. Good marriage, intercourse
1x/10days, good sexual desire.
61 year old ♂, divorced 1 yr ago had been
married 35 years. Has mild ED and low T (220
ng/dl), able to ejaculate by self. Long distance
relationship with 43 year old ♀ and unable to
ejaculate. Finds her self centered, histrionic, and
demanding.
31 year old healthy married ♂ who
ejaculates with masturbation yet unable to
ejaculate with partner. Couple trying to
conceive. High frequency and idiosyncratic
style of masturbating. Some disparity in
fantasy as well.
38 year old, engaged, healthy♂ unable to
have coital ejaculation. Increasing awareness
of lack of arousal toward partner, wanted to
please her, significant performance anxiety
Delayed Ejaculation
Treatment Based Upon Etiology
Insufficient Stimulation
Failure to achieve sufficient mental or
physical stimulation
Masturbation
High frequency of masturbation
Idiosyncratic masturbatory style
Disparity between fantasy & reality
Outgrowth of Psychic Conflict
Loss of self from loss of semen, fear of harm from female
genitals, fear that ejaculation may hurt the partner, fear of
impregnating the female, fear of defiling the partner with
semen, hostility toward partner, performance
anxiety, unwillingness to give oneself, guilt from strict
religious upbringing
Disguised and Subtle Desire Disorder
Masquerading as an Ejaculatory
Dysfunction
Treatment
Vibrator stimulation
Enhancing mental arousal
Demanding pelvic thrusting
Treatment
Psychotherapy targeting areas of conflict
Sensate Focus
Treatment
Masturbatory retraining
Realignment of sexual fantasies
Treatment
Change orientation from self to partner
Less focus on pleasing partner
Treatment of Primary DE
 Lifestyle changes
 Psychotherapy
 Pharmacotherapy: no placebo-controlled studies
1. Seratonergic Drugs
 Desipramine
 Cyproheptadine
 Buspirone
 Mianserin
 Nefazodone
McCormick et al. 1990; Ashton et al. 1997; Aizenberg et al. 1995; Othemer et al. 1987
Treatment of Primary DE
 Lifestyle changes
 Psychotherapy
 Pharmacotherapy: no plcebo-controlled studies
1. Seratonergic Drugs
2. Dopaminergic Drugs
 L-DOPA
 Amantadine
 Yohimbine
 Bupropion
Ferraz and Santos. 1995; Yells et al. 1995; Balogh et al. 1992; Valevski et al. 1998; Ashton et al. 1997;
Price and Grunhaus. 1990; Jacobsen. 1992; Ashton and Rosen. 1998; Abdel-Hamid and Saleh. 2011
Conclusion DE
 Less common, less studied, and less understood (compared to PE)
 Current authority-based definitions are vague, multi-
interpretable, lack specific operational criteria
 Etiology is multifactorial (organic / psychogenic / pharmacologic)
 Physical examination and lab studies are rarely diagnostic
 If possible, treat the organic cause first
 If not:
 Several pharmacologic agents are reported to treat drug induced DE (not
well-controlled studies)
 The mainstay of treatment is by psychotherapy (strong need for more
controlled research)
 Combining medical and psychological interventions may be
beneficial
Case 1
 62 yo man with DE for 2 years
 Medical History:
 DM (5 years – metformin)
 HT (8 years – thiazide + ACE inhibitor)
 Paroxetine 20 mg/day (4 years)
 Regular alcohol consumption
 Sexual History ?
 He lost his wife 4 years ago – have a relation for 1 year
 Mild ED – tadalafil 5 mg “on-demand”
 IELT > 20 min, sometimes cannot ejaculate
Case 1
 Physical Examination
 Mildly Obese (BMI: 30)
 Urogenital examination OK
 Laboratory Tests?
 FBG: 130
 HbA1c: 7.2
 Testosteron: N
 T3/T4/TSH: N
 PSA: N
Case 1
 Physical Examination
 Mildly Obese (BMI: 30)
 Urogenital examination OK
 Laboratory Tests?
 Imaging?
 Electrophysiologic Studies?
Case 1
 Treatment ?
 Reduce alcohol consumption
 Change Thiazide with another anti - hypertansive
 Reduce the dose of paroxetine / change it with bupropion
Case 2
 26 yo man with the complaint of DE for 2 mo
 Medical History: uneventful
 Sexual History
 Recently married (2 months ago).
 Did not have regular sexual relations before.
 Ejaculates with masturbation, IELT > 25 min
 Female partner complains
 High frequency and idiosyncratic style of masturbating.
 Some disparity in fantasy as well.
Case 2
 What to do next?
 DSM-V: Delayed Ejaculation
 A marked delay in ejaculation, or, A marked infrequency or
absence of ejaculation on almost all or all occasions of
partnered sexual activities
 Minimum duration of approximately 6 months
Case 2
 6 months later
 Physical Examination: N
 Urogenital examination OK
 Laboratory Tests?
 FBG: 92
 HbA1c: 5.2 %
 Testosteron: N
 T3/T4/TSH: N
 PSA: N
Case 2
 Treatment ?
 Sex education/therapy (discontinuation of masturbation)
 Re-alignment of sexual fantasies and arousal strategies
Ejaculatory Disorders
Introduction
Definitions & Classification
Delayed Ejaculation
Premature Ejaculation
Premature Ejaculation
 Affects 3 to 30%, according to definition used
 Cited as“the most common male sexual dysfunction”
 Causes important psychological problems
 Diminished self-esteem
 Anxiety
 Embarrassment
 Relationship problems
ISSM definition of lifelong and acquired PE
1. ejaculation which always or nearly always
occurs before or within about 1 minute of
vaginal penetration from the first sexual
experiences (lifelong PE), or,
a clinically significant and bothersome
reduction in latency time, often to about 3
minutes or less (acquired PE), and;
2. inability to delay ejaculation on all or nearly
all vaginal penetrations, and;
3. negative personal consequences, such as
distress, bother, frustration and/or the
avoidance of sexual intimacy
Serefoglu EC, et al. J Sex Med 2014
Premature ejaculation is a male sexual dysfunction
characterized by:
+
Definition of PE
 The ISSM unified definition of lifelong and acquired
PE represents the first evidence-based definitions for
these conditions.
 These definitions will enable researchers to design
methodologically rigorous studies to improve our
understanding about acquired PE.
Serefoglu EC, et al. J Sex Med 2014
No recommendations could be made for PE patients who do not meet the ISSM criteria.
ejaculation occurs after 3 min of vaginal penetration
sometimes ejaculate prematurely
+
The Four PE Syndromes
 PE as a “complaint” must be
distinguished from PE as a
“syndrome”
 PE Syndromes
1. Lifelong PE
2. Acquired PE
3. Variable PE
4. Subjective PE
Waldinger (2008) Sexologies 17:30–35
+
The Four PE Syndromes
Lifelong SubjectiveVariableAcquired
•Very short IELT
•Neurobiological
genetic
•Medication
•Low prevalence
+
The Four PE Syndromes
Lifelong SubjectiveVariableAcquired
•(Very) short IELT
•Medical/Psychological
•Medication
psychotherapy
•Low prevalence
•Very short IELT
•Neurobiological
genetic
•Medication
•Low prevalence
+
The Four PE Syndromes
Lifelong SubjectiveVariableAcquired
•Normal IELT
•Normal variation
•Reassurance
•High prevalence
•(Very) short IELT
•Medical/Psychological
•Medication
psychotherapy
•Low prevalence
•Very short IELT
•Neurobiological
genetic
•Medication
•Low prevalence
+
The Four PE Syndromes
Lifelong SubjectiveVariableAcquired
•Normal/long IELT
•Psychological
•Psychotherapy
•High prevalence
•Normal IELT
•Normal variation
•Reassurance
•High prevalence
•(Very) short IELT
•Medical/Psychological
•Medication
psychotherapy
•Low prevalence
•Very short IELT
•Neurobiological
genetic
•Medication
•Low prevalence
+
The Four PE Syndromes
Lifelong SubjectiveVariableAcquired
•Normal/long IELT
•Psychological
•Psychotherapy
•High prevalence
•Normal IELT
•Normal variation
•Reassurance
•High prevalence
•(Very) short IELT
•Medical/Psychological
•Medication
psychotherapy
•Low prevalence
•Very short IELT
•Neurobiological
genetic
•Medication
•Low prevalence
Waldinger (2008) Sexologies 17:30–35
+
The distribution of PE patients
according to PE syndromes
63%
16%
15%
7%
In an outpatient clinic2
(n=261)
11%
19%
42%
26%
2%
In the population1
(n=512/2593)
Lifelong PE
Acquired PE
Variable
Subjective
Not classified
1 Serefoglu et al J Sex Med 2012; 2 Serefoglu et al J Sex Med 2010
+
Etiology of PE
Psychogenic
Urologic
NeurologicHormonal
Medication
+
Etiology of PE
Psychogenic • developmental (e.g., sexual abuse, attitudes
toward sex internalized during childhood),
• individual psychological factors (e.g., body
image, depression, performance
anxiety, alexithymia),
• relationship factors (e.g., decreased
intimacy, partner conflict)
+
Etiology of PE
Urologic
• ED and other sexual
comorbidities
• Prostatitis
• chronic pelvic pain
syndrome (CPPS)
+
Etiology of PE
Neurologic
• hypersensitivity of the glans penis
• cortical representation of the
pudendal nerve 
• disturbances in central 5-HT
neurotransmission
• genetics
+
Etiology of PE
Hormonal
• Thyroid disorders
+
Etiology of PE
Medication
• detoxification from
medications
• recreational drugs
+
Etiology of PE
Psychogenic
Urologic
NeurologicHormonal
Medication
Althof S, et al. J Sex Med 2014
+
Diagnosis of PE
Althof S et al J Sex Med 2014
+
Diagnosis of PE
Althof S et al J Sex Med 2014
+
Diagnosis of PE
Althof S et al J Sex Med 2014
+
Diagnosis of PE
Althof S et al J Sex Med 2014
+
Diagnosis of PE
Althof S et al J Sex Med 2014
Pharmacological Treatment
 Over the past 20-30 years, the PE treatment paradigm has shifted from
psychotherapy to drug treatment
 Anti-depressants
(paroxetine, sertraline, citalopram, fluoxetin, clomipramine, dap
oxetine)
 Topical Anesthetics
 Tramodol
 Others
Althof S et al J Sex Med 2014
Pharmacological Treatment
 Dapoxetine
 First compound specifically
developed for the treatment of PE
 fast-acting, short half-life
selective serotonin reuptake
inhibitor (SSRI)
 Level 1A evidence to support the
efficacy and safety of on-demand
dosing of dapoxetine
 Only “approved” medication…
Ejaculatory disorders
To assess both the acceptance and the discontinuation rates of DPX
Single centre, 1-year prospective observational study
n=120, lifelong PE and normal EF (IIEF EF <21) treated with DPX 30-60mg
Mondaini N et al. Urology, 2013
Reasons for treatment non-acceptance and discontinuation
24 patients (20%)
decided not to start
dapoxetine.
90% of the patients
who started therapy
discontinued after 1
year
 “On-Demand” Topical Anesthetics
 Lidocaine, lidocaine/prilocaine (EMLA), TEMPE® spray, Promescent® Spray
 Few controlled studies
 Moderately effective in delaying ejaculation
 Potential risk of penile hypo-anaesthesia, transvaginal absorption, resulting in
vaginal numbness and resultant female anorgasmia
 Level 1A evidence to support the efficacy and safety of on-demand topical
anaesthetics in the treatment of PE
Pharmacological Treatment
Althof S et al J Sex Med 2014
Pharmacological Treatment
 Tramadol
 Oral, centrally acting opioid analgesic indicated for the treatment of
moderate to severe pain
 Its efficacy in the treatment of PE reported
 Mode of action is unclear
 Not recommended (risk of addiction?)
Pharmacological Treatment
 Others
 Modafinil (wake promoting agent and is used for the
treatment of narcolepsy)
 α1-blockers (alfuzosin, terazosin, silodosin)
 Epelsiban (GSK-557,296-B) (oral oxytocin receptor antagonist)
 Botulinum toxin A injection
Conclusions …
 The neurochemical control of ejaculation is complex and incompletely
understood
 Multiple neurotransmitters/neuromodulators and receptors are involved
at multiple levels of the nervous system
 The manipulation of several new pharmacological targets can potentially
delay ejaculation
 Continued basic research will further identify those mechanisms which
control ejaculation and serve to identify new therapeutic targets and
treatment for PE
Case 1
 26 yo man with the complaint of PE since first sexual
encounter
 Medical History: uneventful
 Sexual History
 Recently married (12 months ago).
 Did not have regular sexual relations before.
 IELT < 30 sec
 Female partner complains
 Distressed, frustrated
Case 1
 Physical Examination?
 Advisable but not mandatory
 Laboratory Tests?
 Not necessary
Case 1
 Treatment
 Dapoxetine 60mg on-demand (1–2 hours before intercourse)
 Follow-up?
 1 mo later
Case 1
 1 month later
 The patient experienced improvement in controlling his ejaculations
 IELT = 90 seconds
 Asking how long he is supposed to use this drug
 Wondering about more convenient ($$$) alternatives
 Treatment – 2 ?
 Paroxetine 20 mg/day
 Follow-up?
 1 mo later
Case 1
 1 month later
 The patient experienced improvement in controlling his
ejaculations
 IELT = 4-5 mins
 Nausea and constipation in the first 2 weeks but now OK
 Asking how long he is supposed to use this drug
 Wondering if he can conceive a child
Ejaculatory disorders
Case 1
 1 month later
 The patient experienced improvement in controlling his ejaculations
 IELT = 4-5 mins
 Nausea and constipation in the first 2 weeks but now OK
 Asking how long he is supposed to use this drug
 Wondering if he can conceive a child
 Treatment – 3 ???
 Modafinil?
 Botulinum toxin A?
Thank you…
egecanserefoglu@hotmail.com
1 von 94

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Ejaculatory disorders

  • 1. Ege Can Serefoglu, MD, FECSM Bagcilar Training & Research Hospitaly, Dept. of Urology, Istanbul
  • 2. Ejaculatory Disorders Introduction Definitions & Classification Delayed Ejaculation Premature Ejaculation
  • 3. Ejaculatory Disorders Introduction Definitions & Classification Delayed Ejaculation Premature Ejaculation
  • 4. Introduction  Ejaculation is the expulsion of semen from the meatus  Constituted by 2 phases  Emmision: Ejection of the semen into the posterior urethra Contraction of testes, epididymes, VD, SV, prostate  Expulsion: Ejection of sperm from urethra REFLEX response to the presence of semen in BU Rhythmic contractions of perineal muscles (BS/IC)
  • 6. Ejaculatory Disorders Introduction Definitions & Classification Definitions & Classification Premature Ejaculation
  • 7. Definition & Classification  Ejaculatory Dysfunction  common MSD  Premature Ejaculation  Retrograde Ejaculation  Delayed Ejaculation  Painful Ejaculation  Anejaculation  Chronological Classification  Primary (Lifelong): from the very first intercourse and with almost all couples  Secondary (Acquired): From a certain point in life
  • 8. Definition & Classification  Ejaculatory Dysfunction  common MSD  Premature Ejaculation  Retrograde Ejaculation  Delayed Ejaculation  Painful Ejaculation  Anejaculation  Chronological Classification  Primary (Lifelong): from the very first intercourse and with almost all couples  Secondary (Acquired): From a certain point in life
  • 10. 0 10 20 30 40 50 60 70 80 90 100 Percentageofsubjects Mean IELT(s) Median IELT of 5.4 minutes (range, 0.55-44.1 min) in Netherlands, United Kingdom, United States, Spain, and Turkey Waldinger et al. (2005) J Sex Med 2:492–497 Normative IELT data Unselected “normal” population of 500 heterosexual couples Stopwatch timing of the IELT MEDIAN 5.4 min TURKEY 3.7 min
  • 11. Ejaculation Distribution Theory Premature Ejaculation Normal Ejaculation Delayed Ejaculation Anejaculation IELT < 1-2 m IELT <4-10 m IELT >20-30m IELT ∞ Waldinger and Schweitzer 2005
  • 12. Ejaculatory Disorders Introduction Definitions & Classification Delayed Ejaculation Premature Ejaculation
  • 13. Definition & Characteristics of DE  Delayed=Retarded=Inhibited=Inadequate=Difficult  Least common/studied/understood male SD  Diminished sexual satisfaction for man and partner Jannini and Lenzi, 2005; Rowland et al. 2004; Rowland et al. 2005; Segraves 2010
  • 14. Definition & Characteristics of DE  DSM-V: Delayed Ejaculation 302.74 (F52.32) A. Either of the following symptoms must be experienced on almost all or all occasions (approximately 75-100%) of partnered sexual activity (in identified situational contexts or, if generalized, in all contexts), and without the individual desiring delay: 1. marked delay in ejaculation 2. marked infrequency or absence of ejaculation on almost all or all occasions of partnered sexual activities B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months C. The symptoms in Criterion A cause clinically significant distress in the individual D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or other medical condition.  WHO 2nd Consultation on SD  Persistent or reccurent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation which causes personal distress
  • 15. Definition & Characteristics of DE  DSM-V: Delayed Ejaculation 302.74 (F52.32) A. Either of the following symptoms must be experienced on almost all or all occasions (approximately 75-100%) of partnered sexual activity (in identified situational contexts or, if generalized, in all contexts), and without the individual desiring delay: 1. marked delay in ejaculation 2. marked infrequency or absence of ejaculation on almost all or all occasions of partnered sexual activities B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months C. The symptoms in Criterion A cause clinically significant distress in the individual D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or other medical condition.  WHO 2nd Consultation on SD  Persistent or reccurent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation which causes personal distress
  • 16. Definition & Characteristics of DE  These definitions  Not evidence-based  Excessively vague  Lack specific operational criteria  Severity (e.g. 75% of sexual occasions)  Duration (e.g. 6 mo)  IELT (e.g. desired ejaculation lasting???)  Rely on the subjective judgment of the diagnostician… Althof. 2012; Rowland et al. 2005; Perelman. 2006; Patrick et al. 2005; Segraves. 2010
  • 17. Definition & Characteristics of DE  most sexually functional men ejaculate ≈ 4-10 mins  A man with DE is expected to:  have IELT > 20 - 30 mins (21-23 min represents 2SD above the mean)  cease sexual activity due to exhaustion or irritation  report relationship distress/frustration/performance anxiety  seek help for his sexual dissatisfaction (despite good erections!!) Rowland et al. 2005; Perelman. 2006; Patrick et al. 2005; Segraves. 2010
  • 18. +  Impact of DE on the patient and partner is often not fully appreciated  Some perceive DE to be a positive attribute that allows the man to “bestow multiple coital orgasms to his partner”  DE is involuntary and causes distress for both the man and the partner  Partners believe they are not attractive enough for the patient. They feel unneeded and rejected.  Extended coitus causes pain for the patient and partner  Anejaculation results in a failure to conceive Definition & Characteristics of DE
  • 19. Definition & Characteristics of DE  The prevalence is unclear  Lack of normative data  Lack of operational criteria  0.15 - 5% of sexually active men  2.5-5% of men with SD  Increasing --- PDE5 inhibitors restored ED, w/o restoring arousal  More common among older (>50 years-old)  neuronal degeneration, dermal atrophy, low penile sensitivity  loss of pelvic floor muscle tone  More severe and common (46-75%) with LUTS (independent of age) Simons et al. 2001; Patrick et al. 2005; Rowland et al. 2004; Corona et al. 2006; Traeen 2011; Perelman and Rowland 2006; Blanker et al. 2001; Rosen et al. 2003; Nathan et al. 1986; Nazareth et al. 2003; Rosen et al. 2009
  • 20. Definition & Characteristics of DE  Classification  Lifelong (primary) ≈25%  Acquired (secondary) ≈75%  Global / Situational / Intermittent  Genetic influence?  heme oxygenase-2 gene lacking mice develop DE/anejaculation  no genetic influence is found on humans  shared environmental influence detected between twins…  PET scans  higher activity in the anterior temporal lobe (centers for vigilance and fear behaviour) Perelman 2004; Rowland et al. 2004; Kriegsfeld et al. 1999; Jern et al. 2007; Georgiadis and Holstege. 2004
  • 22. DE Psychogenic Anatomic Congenital NeurogenicInfective Endocrine Medications Organic/Psychological Causes of DE Fear/Anxiety Relationship diff. Religion/Culture Insuff. sexual arousal Masturbation (Autosexuality)
  • 23. Delayed Ejaculation Four Diverse Psychological Theories All Without Empirical Support Insufficient Stimulation Failure to achieve sufficient mental or physical stimulation Masturbation High frequency of masturbation Idiosyncratic masturbatory style Disparity between fantasy & reality Outgrowth of Psychic Conflict Loss of self from loss of semen, fear of harm from female genitals, fear that ejaculation may hurt the partner, fear of impregnating the female, fear of defiling the partner with semen, hostility toward partner, not willing to give of oneself, guilt from strict religious upbringing Disguised and Subtle Desire Disorder Masquerading as an Ejaculatory Dysfunction Automatic functioning in the absence of genuine arousal, autosexual orientation, partner’s touch inhibiting, penis becomes insensate, compulsion to satisfy partner
  • 24. + Masturbation and DE  Of 80 men diagnosed with DE  25% could not achieve ejaculation under any circumstance  75% could masturbate to orgasm  Three factors were correlated to DE diagnosis  Relatively high frequency of masturbation  over 35% reported masturbating at least every other day or more  Idiosyncratic style of masturbation  Idiosyncratic in the speed, pressure, duration and intensity necessary to produce an orgasm, yet dissimilar to what they experienced with a partner  Disparity between the reality of sex with the partner and the use of sexual fantasy during masturbation Perelman M. (2005) Idiosyncratic Masturbation Patterns: A Key Unexplored Variable in the Treatment of Retarded Ejaculation by the Practicing Urologist. Journal of Urology. 173(4): supp:340.
  • 27. DE Psychogenic Anatomic Congenital NeurogenicInfective Endocrine Medications Organic/Psychological Causes of DE Autonomic neuropathy (DM) SCI RP / RT Proctocolectomy Bilat. Sympathectomy Abdominal aortic aneurysmectomy Para-aortic lymphadenectomy
  • 29. DE Psychogenic Anatomic Congenital NeurogenicInfective Endocrine Medications Organic/Psychological Causes of DE 64% of hypothyroid men reported DE 26% of men with DE had hypogonadism Carani et al. 2005; Corona et al 2008
  • 30. DE Psychogenic Anatomic Congenital NeurogenicInfective Endocrine Medications Organic/Psychological Causes of DE Alpha-Methyl DOPA Thiazide Diuretics TC/SSRI Antidepressants Phenothiazide Alcohol Abuse
  • 31. Evaluation of DE (History) Investigate domains related to the psychologic and relationship issues associated with DE Religious Orthodoxy Performance Anxiety Autosexuality Perceived Partner Attractiveness Review the conditions under which the man is able to ejaculate During sleep With masturbation With partner’s hand or mouth stimulation With varying coital positions Life events / circumstances related to orgasmic cessation must be reviewed Pharmaceuticals Ilness Life Stressor Trauma Find potential physical and specific psychologic/learned causes of DE Any concomitant or contributory organic factors involved?
  • 32. Evaluation of DE (History) Investigate domains related to the psychologic and relationship issues associated with DE Religious Orthodoxy Performance Anxiety Autosexuality Perceived Partner Attractiveness Review the conditions under which the man is able to ejaculate During sleep With masturbation With partner’s hand or mouth stimulation With varying coital positions Life events / circumstances related to orgasmic cessation must be reviewed Pharmaceuticals Ilness Life Stressor Trauma Find potential physical and specific psychologic/learned causes of DE Any concomitant or contributory organic factors involved?
  • 33. Evaluation of DE (History) Investigate domains related to the psychologic and relationship issues associated with DE Religious Orthodoxy Performance Anxiety Autosexuality Perceived Partner Attractiveness Review the conditions under which the man is able to ejaculate During sleep With masturbation With partner’s hand or mouth stimulation With varying coital positions Check life events / circumstances related to orgasmic cessation Pharmaceuticals Illness Life Stressor Psycho/Trauma Find potential physical and specific psychologic/learned causes of DE Any concomitant or contributory organic factors involved?
  • 34. Evaluation of DE (History) Investigate domains related to the psychologic and relationship issues associated with DE Religious Orthodoxy Performance Anxiety Autosexuality Perceived Partner Attractiveness Review the conditions under which the man is able to ejaculate During sleep With masturbation With partner’s hand or mouth stimulation With varying coital positions Check life events / circumstances related to orgasmic cessation Pharmaceuticals Illness Life Stressor Psycho/Trauma Find potential physical and specific psychologic/learned causes of DE Any concomitant or contributory organic factors involved?
  • 35. Evaluation of DE (History) Investigate domains related to the psychologic and relationship issues associated with DE Religious Orthodoxy Performance Anxiety Masturbation fq/patterns Perceived Partner Attractiveness Review the conditions under which the man is able to ejaculate During sleep With masturbation With partner’s hand or mouth stimulation With varying coital positions Check life events / circumstances related to orgasmic cessation Pharmaceuticals Illness Life Stressor Psycho/Trauma Find potential physical and specific psychologic/learned causes of DE Any concomitant or contributory organic factors involved?
  • 36. Evaluation of DE (PE & Lab) Electrophysiological Evaluation Pudental Somatosens Evoked Pot (SEPs) Pudental Motor Evoked Pot (MEPs) Sacral Reflex Arc Testing Sympathetic Skin Responses Imaging Testicular US TRUS Cystoscopy Vasography Perineal US Laboratory Serum Glucose Testosterone fT3/fT4/TSH PSA Examine penis, testicles , epididymes, vas deferens (rarely diagnostic) Identify reversible urethral, prostatic, epididymal and testicular infections Penile irritation/erythema (idiosyncratic masturbation/prolonged thrusting)
  • 37. Evaluation of DE (PE & Lab) Electrophysiological Evaluation Pudental Somatosens Evoked Pot (SEPs) Pudental Motor Evoked Pot (MEPs) Sacral Reflex Arc Testing Sympathetic Skin Responses Imaging Testicular US TRUS Cystoscopy Vasography Perineal US Laboratory Serum Glucose Testosterone fT3/fT4/TSH PSA Examine penis, testicles , epididymes, vas deferens (rarely diagnostic) Identify reversible urethral, prostatic, epididymal and testicular infections Penile irritation/erythema (idiosyncratic masturbation/prolonged thrusting)
  • 38. Evaluation of DE (PE & Lab) Electrophysiological Evaluation Pudental Somatosens Evoked Pot (SEPs) Pudental Motor Evoked Pot (MEPs) Sacral Reflex Arc Testing Sympathetic Skin Responses Imaging Testicular US TRUS Cystoscopy Vasography Perineal US Laboratory Serum Glucose Testosterone fT3/fT4/TSH PSA Examine penis, testicles , epididymes, vas deferens (rarely diagnostic) Identify reversible urethral, prostatic, epididymal and testicular infections Penile irritation/erythema (idiosyncratic masturbation/prolonged thrusting)
  • 39. Evaluation of DE (PE & Lab) Electrophysiological Evaluation Pudental Somatosens Evoked Pot (SEPs) Pudental Motor Evoked Pot (MEPs) Sacral Reflex Arc Testing Sympathetic Skin Responses Imaging Testicular US TRUS Cystoscopy Vasography Perineal US Laboratory Serum Glucose Testosterone fT3/fT4/TSH PSA Examine penis, testicles , epididymes, vas deferens (rarely diagnostic) Identify reversible urethral, prostatic, epididymal and testicular infections Penile irritation/erythema (idiosyncratic masturbation/prolonged thrusting)
  • 40. Treatment of DE Medication Reduce the dose Use antidot Vascular / Neuropatic damage Irreversible Counselling GU Infection Culture Antibiotics Androgen deficiency FSH / LH levels T replacement therapy Hypothyroid Tiroid hormone
  • 41. Treatment of DE  Lifestyle changes  Reduce alcohol consumption  Making love when not tired  decreasing the frequency of masturbation  Psychotherapy  Pharmacotherapy
  • 42. Treatment of Primary DE  Lifestyle changes  Psycho / Physiotherapy : none has been properly evaluated  Sex education/therapy (discontinuation of masturbation)  Reduction of goal-focused anxiety  Genitally-focused stimulation (anal, rectal stimulation with finger or vibrator)  Role-playing, desensitizing exercises  Re-alignment of sexual fantasies and arousal strategies  Pharmacotherapy
  • 43. Delayed Ejaculation Case Examples Insufficient Stimulation Failure to achieve sufficient mental or physical stimulation Masturbation Outgrowth of Psychic Conflict Disguised and Subtle Desire Disorder Masquerading as an Ejaculatory Dysfunction 79 year old married ♂ with a 5 yr history of being unable to achieve orgasm/ejaculation under any circumstance. BCG treatment for same period of time. Good marriage, intercourse 1x/10days, good sexual desire. 61 year old ♂, divorced 1 yr ago had been married 35 years. Has mild ED and low T (220 ng/dl), able to ejaculate by self. Long distance relationship with 43 year old ♀ and unable to ejaculate. Finds her self centered, histrionic, and demanding. 31 year old healthy married ♂ who ejaculates with masturbation yet unable to ejaculate with partner. Couple trying to conceive. High frequency and idiosyncratic style of masturbating. Some disparity in fantasy as well. 38 year old, engaged, healthy♂ unable to have coital ejaculation. Increasing awareness of lack of arousal toward partner, wanted to please her, significant performance anxiety
  • 44. Delayed Ejaculation Treatment Based Upon Etiology Insufficient Stimulation Failure to achieve sufficient mental or physical stimulation Masturbation High frequency of masturbation Idiosyncratic masturbatory style Disparity between fantasy & reality Outgrowth of Psychic Conflict Loss of self from loss of semen, fear of harm from female genitals, fear that ejaculation may hurt the partner, fear of impregnating the female, fear of defiling the partner with semen, hostility toward partner, performance anxiety, unwillingness to give oneself, guilt from strict religious upbringing Disguised and Subtle Desire Disorder Masquerading as an Ejaculatory Dysfunction Treatment Vibrator stimulation Enhancing mental arousal Demanding pelvic thrusting Treatment Psychotherapy targeting areas of conflict Sensate Focus Treatment Masturbatory retraining Realignment of sexual fantasies Treatment Change orientation from self to partner Less focus on pleasing partner
  • 45. Treatment of Primary DE  Lifestyle changes  Psychotherapy  Pharmacotherapy: no placebo-controlled studies 1. Seratonergic Drugs  Desipramine  Cyproheptadine  Buspirone  Mianserin  Nefazodone McCormick et al. 1990; Ashton et al. 1997; Aizenberg et al. 1995; Othemer et al. 1987
  • 46. Treatment of Primary DE  Lifestyle changes  Psychotherapy  Pharmacotherapy: no plcebo-controlled studies 1. Seratonergic Drugs 2. Dopaminergic Drugs  L-DOPA  Amantadine  Yohimbine  Bupropion Ferraz and Santos. 1995; Yells et al. 1995; Balogh et al. 1992; Valevski et al. 1998; Ashton et al. 1997; Price and Grunhaus. 1990; Jacobsen. 1992; Ashton and Rosen. 1998; Abdel-Hamid and Saleh. 2011
  • 47. Conclusion DE  Less common, less studied, and less understood (compared to PE)  Current authority-based definitions are vague, multi- interpretable, lack specific operational criteria  Etiology is multifactorial (organic / psychogenic / pharmacologic)  Physical examination and lab studies are rarely diagnostic  If possible, treat the organic cause first  If not:  Several pharmacologic agents are reported to treat drug induced DE (not well-controlled studies)  The mainstay of treatment is by psychotherapy (strong need for more controlled research)  Combining medical and psychological interventions may be beneficial
  • 48. Case 1  62 yo man with DE for 2 years  Medical History:  DM (5 years – metformin)  HT (8 years – thiazide + ACE inhibitor)  Paroxetine 20 mg/day (4 years)  Regular alcohol consumption  Sexual History ?  He lost his wife 4 years ago – have a relation for 1 year  Mild ED – tadalafil 5 mg “on-demand”  IELT > 20 min, sometimes cannot ejaculate
  • 49. Case 1  Physical Examination  Mildly Obese (BMI: 30)  Urogenital examination OK  Laboratory Tests?  FBG: 130  HbA1c: 7.2  Testosteron: N  T3/T4/TSH: N  PSA: N
  • 50. Case 1  Physical Examination  Mildly Obese (BMI: 30)  Urogenital examination OK  Laboratory Tests?  Imaging?  Electrophysiologic Studies?
  • 51. Case 1  Treatment ?  Reduce alcohol consumption  Change Thiazide with another anti - hypertansive  Reduce the dose of paroxetine / change it with bupropion
  • 52. Case 2  26 yo man with the complaint of DE for 2 mo  Medical History: uneventful  Sexual History  Recently married (2 months ago).  Did not have regular sexual relations before.  Ejaculates with masturbation, IELT > 25 min  Female partner complains  High frequency and idiosyncratic style of masturbating.  Some disparity in fantasy as well.
  • 53. Case 2  What to do next?  DSM-V: Delayed Ejaculation  A marked delay in ejaculation, or, A marked infrequency or absence of ejaculation on almost all or all occasions of partnered sexual activities  Minimum duration of approximately 6 months
  • 54. Case 2  6 months later  Physical Examination: N  Urogenital examination OK  Laboratory Tests?  FBG: 92  HbA1c: 5.2 %  Testosteron: N  T3/T4/TSH: N  PSA: N
  • 55. Case 2  Treatment ?  Sex education/therapy (discontinuation of masturbation)  Re-alignment of sexual fantasies and arousal strategies
  • 56. Ejaculatory Disorders Introduction Definitions & Classification Delayed Ejaculation Premature Ejaculation
  • 57. Premature Ejaculation  Affects 3 to 30%, according to definition used  Cited as“the most common male sexual dysfunction”  Causes important psychological problems  Diminished self-esteem  Anxiety  Embarrassment  Relationship problems
  • 58. ISSM definition of lifelong and acquired PE 1. ejaculation which always or nearly always occurs before or within about 1 minute of vaginal penetration from the first sexual experiences (lifelong PE), or, a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE), and; 2. inability to delay ejaculation on all or nearly all vaginal penetrations, and; 3. negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy Serefoglu EC, et al. J Sex Med 2014 Premature ejaculation is a male sexual dysfunction characterized by:
  • 59. + Definition of PE  The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definitions for these conditions.  These definitions will enable researchers to design methodologically rigorous studies to improve our understanding about acquired PE. Serefoglu EC, et al. J Sex Med 2014 No recommendations could be made for PE patients who do not meet the ISSM criteria. ejaculation occurs after 3 min of vaginal penetration sometimes ejaculate prematurely
  • 60. + The Four PE Syndromes  PE as a “complaint” must be distinguished from PE as a “syndrome”  PE Syndromes 1. Lifelong PE 2. Acquired PE 3. Variable PE 4. Subjective PE Waldinger (2008) Sexologies 17:30–35
  • 61. + The Four PE Syndromes Lifelong SubjectiveVariableAcquired •Very short IELT •Neurobiological genetic •Medication •Low prevalence
  • 62. + The Four PE Syndromes Lifelong SubjectiveVariableAcquired •(Very) short IELT •Medical/Psychological •Medication psychotherapy •Low prevalence •Very short IELT •Neurobiological genetic •Medication •Low prevalence
  • 63. + The Four PE Syndromes Lifelong SubjectiveVariableAcquired •Normal IELT •Normal variation •Reassurance •High prevalence •(Very) short IELT •Medical/Psychological •Medication psychotherapy •Low prevalence •Very short IELT •Neurobiological genetic •Medication •Low prevalence
  • 64. + The Four PE Syndromes Lifelong SubjectiveVariableAcquired •Normal/long IELT •Psychological •Psychotherapy •High prevalence •Normal IELT •Normal variation •Reassurance •High prevalence •(Very) short IELT •Medical/Psychological •Medication psychotherapy •Low prevalence •Very short IELT •Neurobiological genetic •Medication •Low prevalence
  • 65. + The Four PE Syndromes Lifelong SubjectiveVariableAcquired •Normal/long IELT •Psychological •Psychotherapy •High prevalence •Normal IELT •Normal variation •Reassurance •High prevalence •(Very) short IELT •Medical/Psychological •Medication psychotherapy •Low prevalence •Very short IELT •Neurobiological genetic •Medication •Low prevalence Waldinger (2008) Sexologies 17:30–35
  • 66. + The distribution of PE patients according to PE syndromes 63% 16% 15% 7% In an outpatient clinic2 (n=261) 11% 19% 42% 26% 2% In the population1 (n=512/2593) Lifelong PE Acquired PE Variable Subjective Not classified 1 Serefoglu et al J Sex Med 2012; 2 Serefoglu et al J Sex Med 2010
  • 68. + Etiology of PE Psychogenic • developmental (e.g., sexual abuse, attitudes toward sex internalized during childhood), • individual psychological factors (e.g., body image, depression, performance anxiety, alexithymia), • relationship factors (e.g., decreased intimacy, partner conflict)
  • 69. + Etiology of PE Urologic • ED and other sexual comorbidities • Prostatitis • chronic pelvic pain syndrome (CPPS)
  • 70. + Etiology of PE Neurologic • hypersensitivity of the glans penis • cortical representation of the pudendal nerve  • disturbances in central 5-HT neurotransmission • genetics
  • 71. + Etiology of PE Hormonal • Thyroid disorders
  • 72. + Etiology of PE Medication • detoxification from medications • recreational drugs
  • 74. + Diagnosis of PE Althof S et al J Sex Med 2014
  • 75. + Diagnosis of PE Althof S et al J Sex Med 2014
  • 76. + Diagnosis of PE Althof S et al J Sex Med 2014
  • 77. + Diagnosis of PE Althof S et al J Sex Med 2014
  • 78. + Diagnosis of PE Althof S et al J Sex Med 2014
  • 79. Pharmacological Treatment  Over the past 20-30 years, the PE treatment paradigm has shifted from psychotherapy to drug treatment  Anti-depressants (paroxetine, sertraline, citalopram, fluoxetin, clomipramine, dap oxetine)  Topical Anesthetics  Tramodol  Others Althof S et al J Sex Med 2014
  • 80. Pharmacological Treatment  Dapoxetine  First compound specifically developed for the treatment of PE  fast-acting, short half-life selective serotonin reuptake inhibitor (SSRI)  Level 1A evidence to support the efficacy and safety of on-demand dosing of dapoxetine  Only “approved” medication…
  • 82. To assess both the acceptance and the discontinuation rates of DPX Single centre, 1-year prospective observational study n=120, lifelong PE and normal EF (IIEF EF <21) treated with DPX 30-60mg Mondaini N et al. Urology, 2013 Reasons for treatment non-acceptance and discontinuation 24 patients (20%) decided not to start dapoxetine. 90% of the patients who started therapy discontinued after 1 year
  • 83.  “On-Demand” Topical Anesthetics  Lidocaine, lidocaine/prilocaine (EMLA), TEMPE® spray, Promescent® Spray  Few controlled studies  Moderately effective in delaying ejaculation  Potential risk of penile hypo-anaesthesia, transvaginal absorption, resulting in vaginal numbness and resultant female anorgasmia  Level 1A evidence to support the efficacy and safety of on-demand topical anaesthetics in the treatment of PE Pharmacological Treatment Althof S et al J Sex Med 2014
  • 84. Pharmacological Treatment  Tramadol  Oral, centrally acting opioid analgesic indicated for the treatment of moderate to severe pain  Its efficacy in the treatment of PE reported  Mode of action is unclear  Not recommended (risk of addiction?)
  • 85. Pharmacological Treatment  Others  Modafinil (wake promoting agent and is used for the treatment of narcolepsy)  α1-blockers (alfuzosin, terazosin, silodosin)  Epelsiban (GSK-557,296-B) (oral oxytocin receptor antagonist)  Botulinum toxin A injection
  • 86. Conclusions …  The neurochemical control of ejaculation is complex and incompletely understood  Multiple neurotransmitters/neuromodulators and receptors are involved at multiple levels of the nervous system  The manipulation of several new pharmacological targets can potentially delay ejaculation  Continued basic research will further identify those mechanisms which control ejaculation and serve to identify new therapeutic targets and treatment for PE
  • 87. Case 1  26 yo man with the complaint of PE since first sexual encounter  Medical History: uneventful  Sexual History  Recently married (12 months ago).  Did not have regular sexual relations before.  IELT < 30 sec  Female partner complains  Distressed, frustrated
  • 88. Case 1  Physical Examination?  Advisable but not mandatory  Laboratory Tests?  Not necessary
  • 89. Case 1  Treatment  Dapoxetine 60mg on-demand (1–2 hours before intercourse)  Follow-up?  1 mo later
  • 90. Case 1  1 month later  The patient experienced improvement in controlling his ejaculations  IELT = 90 seconds  Asking how long he is supposed to use this drug  Wondering about more convenient ($$$) alternatives  Treatment – 2 ?  Paroxetine 20 mg/day  Follow-up?  1 mo later
  • 91. Case 1  1 month later  The patient experienced improvement in controlling his ejaculations  IELT = 4-5 mins  Nausea and constipation in the first 2 weeks but now OK  Asking how long he is supposed to use this drug  Wondering if he can conceive a child
  • 93. Case 1  1 month later  The patient experienced improvement in controlling his ejaculations  IELT = 4-5 mins  Nausea and constipation in the first 2 weeks but now OK  Asking how long he is supposed to use this drug  Wondering if he can conceive a child  Treatment – 3 ???  Modafinil?  Botulinum toxin A?