1. society
2. sex

The challenge of defining acquired PE ‐ where are we now?
Emmanuele A. Jannini, MD School of Sexology ‐ University of L'Aquila, Italy
Classify the symptom: the Taxonomy of PE
•
CAUSE
–
ORGANIC
•
•
•
•
•
–
Functional (experiences, education)
Constitutive (psychological constitution)
Stress‐induced (acute or chronic)
Psychosexual skill deficit
ONSET (Shapiro)
–
–
PRIMARY (lifelong)
ACQUIRED (after a period of normal ejaculatory control)
TIME
–
–
•
–
•
ANTE PORTAS (before penetration)
INTRA MOENIA (during penetration)
TYPE
–
NON‐ORGANIC (idiopathic)
•
•
•
•
•
Genetic
Neurobiological
Urological
Endocrine
Pharmacological
•
ABSOLUTE (irrespective of partners or context, generalized)
RELATIVE (to a partner or a context, situational)
CO‐MORBIDITIES
–
–
SIMPLE (in absence of other sexual symptoms)
COMPLICATED (in presence of other
sexual symptoms)
•
•
With erectile dysfunction
Due to erectile dysfunction
2008: ISSM Ad Hoc Committee of international experts PE is a male sexual dysfunction characterized by – ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and – 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”
McMahon, CG, Althof, SE, Waldinger, MD et al.
J Sex Med 2008; 5(7):15905(7):1590-1606
Evidence to Support the Ejaculatory Latency Criterion <~1minute
100 250
100
90
90
80 200
80
70
70
P e rc e n t a g e o f s u b je c t s
P e rc e n t a g e o f s u b je c t s
60 150
60
No. of subjects
• Several studies suggest that 80‐
90% of men seeking treatment for lifelong PE ejaculate within I minute, with the remaining 10‐
20% ejaculating within 1‐2 minutes • These data are consistent with epidemiological PE risk analysis of normative community IELT data using the 0.5 and 2.5 percentiles as acceptable standards of disease definition IELT
IELTDISTRIBUTION
DISTRIBUTIONININAACONSECUTIVE
CONSECUTIVE
SERIES
OF
TREATMENT
SERIES
OFMEN
MENSEEKING
SEEKING
TREATMENTFOR
FOR
NORMATIVE
IELT DATA
PE
PE(N=989)
(N=989)
(N=500)
50
50
40 100
40
30
30
80-90%
80-90%
80-90%
ejaculate
ejaculatewithin
within
•Median
ejaculate
within
60
60sec
sec IELT
stopwatch
60
sec
is
IELT
ofIELT
5.4 minutes
IELT
isis
distributed
distributed
(range,
0.55in
-inaaa
distributed
in
positively
positively
44.1
min.)
positively
skewed
skewed
pattern
•IELT
is pattern
skewed
pattern
distributed in a
positively
skewed pattern
20 50
20
10
10
0 0
0
0 10
200 4003060040 50
800 1,000701,20080 1,400
1,600110
1,800
2,200150
2,400160
2,600 180
2,800
1202,000
130140
0 20020 400
600 800601,000
1,200 90100
1,400 1,600
1,800
2,000 2,200
2,400 170
2,600 2,800
MeanIELT
IELT (s) (s)
Mean IELT (s)
McMahon
(2002)
IntJ(2005)
JImp
ImpRes
Res
14(Suppl.3):S19
1.1.McMahon
(2002)
14(Suppl.3):S19
1. Waldinger
etInt
al.
J Sex
Med 2:492–
2:492–497
Evidence to Support the Control Criterion
• Patrick et al. reported ratings of "very poor" or "poor" for control over ejaculation in 72% of men with PE compared to 5% in a group of normal controls [1] • Shorter IELTs were associated with lower ratings for control 1. Patrick et al. (2005) J Sex Med 2:3582:358-367
Evidence to Support the Stress Criterion
• PE is been associated with negative psychological outcomes in men and their women partners
• Patrick et al. reported significant differences in men with and without PE in the PRO measures of personal distress (64% versus 4%) suggesting that this personal distress has discriminative validity in diagnosing PE • The personal and/or interpersonal distress, bother, frustration and annoyance that results from PE may affect men’s quality of life and partner relationships, their self‐esteem and self‐confidence, and can act as an obstacle to single men forming new partner relationships
Assalian
Jannini
McMahon
Rowland
Waldinger
Standard Operating Procedures
Level
Level 33 evidence
evidence to
to support
support the
the ISSM
ISSM
definition
definition of
of Lifelong
Lifelong PE
PE and
and its
its universal
universal
acceptance
acceptance as
as the
the basis
basis for
for clinical
clinical trial
trial
design
design and
and the
the office
office management
management
of
of lifelong
lifelong PE
PE
Grade
Grade AA Recommendation
Recommendation
… however
• The figure of “about 1 minute” is not always easy to use in the clinical practice.
• (LL‐)PE is just defined in : – vaginal intercourse – heterosexual couples
• The Committee did not make any recommendations for men who complain of ejaculating prematurely but do not strictly meet the ISSM criteria of LL‐PE
• The panel concluded that there were insufficient data for an evidence‐based definition of A‐PE
• IELT
• MELT
• AELT
• OELT
Challenges to development of an evidence‐based A‐PE definition
–No well designed community observational studies
–Most studies are specific aetiology sub‐
group case series and fail to comply with observational trial design recommendations
Defining A‐PE
• Substantial opportunity exists for gaining additional insight into A‐PE by performing a post‐
hoc analysis of dapoxetine
phase 3 baseline data
• Not an ideal A‐PE study group, but provides preliminary understanding
IELT
Mean (SD) = 1.01 ± 0.49
100%
1%
Mean (SD) = 0.90 ± 0.48
1%
90%
80%
70%
49%
37%
50%
> 2 min
1 - ≤2 min
40%
0 - ≤ 1 min
60%
30%
20%
50%
50%
62%
10%
0%
Acquired
N=1671
Lifelong
N=3161
Includes studies: C-2002-012, US-C-2002-013, PRE-3001, PRE-3003
Control Over Ejaculation and Satisfaction
Control
100%
90%
1%
1%
6%
Satisfaction
1%
1%
5%
80%
70%
47%
42%
3%
10%
28%
3%
13%
29%
60%
50%
40%
30%
20%
46%
44%
39%
16%
16%
Very Good
Good
Fair
Poor
Very Poor
53%
10%
0%
Acquired
Lifelong
N=1948
N=3620
Acquired
Lifelong
N=1948
N=3620
Includes studies: C-2002-012, US-C-2002-013, PRE-3001, PRE-3002, PRE-3003
13/38
SSRIs work better in LL‐ or in A‐PE?
A. Better in LL‐PE
B. Better in A‐PE
C. They have the same efficacy in both subsets of patients
D. ???
No distinction between LL‐ and A‐
PE
Baseline characteristics except
duration of PE were similar in men
with LL- and A-PE. Dapoxetine
treatment improved significantly
mean IELT (arithmetic and
geometric) and PRO responses
(perceived control over ejaculation,
satisfaction with sexual intercourse,
ejaculation related personal distress,
and interpersonal difficulty) for LLand A- subtypes.
PROs under Dapo and LL‐ or A‐PE
Although not perfectly designed for this purpose and not conclusive, so far all published evidences agree that LL‐ and A‐
PE have substantially comparable clinical
characteristics
However, Serefoglu et al (J Sex Med 2011) compared the mean scores obtained from each of PEP measures in the published trials:
‐ A‐PE: Worse scores for “sexual satisfaction”
and “interpersonal difficulty”
‐ LL‐PE: Worse scores for “perceived control”
<<As noted recently by Jannini, clinical trials of
dapoxetine contained men with A-PE as well as men with
LL-PE, and dapoxetine was shown to be effective in both
groups. These trials typically included stopwatchmeasured IELT and validated PRO measures of control
over ejaculation and distress or bother related to PE;
therefore, information from these trials may provide some
insight into the clinical picture of A-PE.>>
CONTROVERSIAL ISSUES
IN DEFINING A‐PE
Anxiety, depression, alexithymia have been frequently found in PE. Is this a demonstration that this is a possible cause of (A‐)PE?
A. No
B. Yes
C. ???
Prostatitis and hyperthyroidism have been frequently found in PE. Is this demonstrating that they are possible causes of (A‐)PE?
A. No
B. Yes
C. ???
EAU-EBU Updates. Series 4: 141-149, 2006
THE FIVE RISK FACTORS FOR
PREMATURE EJACULATION
<<Doc, I ejaculated too fast from the beginning of my sexual life with several girls. Then, at 22, I reached a good control of ejaculation. Now I am 47 and I cannot control my ejaculation again>> How do you label this patient? A.
B.
C.
D.
E.
LL‐PE
A‐PE
LL‐A‐PE
PE
???
Is it always mandatory to determine if PE is LL‐ or A‐?
A. Yes, for therapeutic purposes
B. Yes, for the diagnosis
C. Yes: a patient with LL‐PE is genetically determined and I do not need to go ahead with dignosis
D. No. Basically the answer will non change my clinical behavior
E. ???
Do you agree with this possible Guideline point # 1: All patients with A‐PE should be clinically evaluated for the at‐the‐present known possible risk factors: psychological, neurological, hormonal and urological and for the co‐morbidity with another sexual dysfunction ?
A. Yes
B. No
C. ???
Do you agree with this possible Guideline point # 2: All patients with (A‐)PE should receive a complete physical evaluation (full andrological evaluation) ?
A. Yes
B. No
C. ???
Do you agree that the unique, universal, evidence‐based difference between LL‐ and A‐PE is the onset of the symptom? A. Yes B. No
C. ???
A‐PE is a male sexual dysfunction occurring after a period of normal ejaculatory performance, in which ejaculation occurs within about 1 minute after vaginal penetration, with the feeling of loss of control over ejaculation and induction of PE‐related stress. The inability to delay ejaculation can be either: i) correlated to organic risk factors; ii) correlated to psychological difficulties; iii) a co‐morbidity with other sexual dysfunctions; or iv) idiopathic.
HOW DO YOU LIKE THIS DEFINITION?
A. I like it
B. I like, but some terms should be changed
C. I dislike