Download Ejaculation Prématurée : diagnostic et traitement

Session Francophone d’Initiation à la Médecine Sexuelle
sous la responsabilité de la
Société Francophone de Médecine Sexuelle
Jeudi 15 Décembre 2011
Au cours du
Premier congrès de la Société Africaine de Médecine Sexuelle
Ejaculation prématurée :
diagnostic et traitement
Béatrice Cuzin, Service d’Urologie et de la Transplantation, CH E
Herriot, Lyon, France
Contexte


Contexte culturel (Asie Tao, Tantrisme)
Littérature médicale récente
Contexte: définitions actuelles de l’EP : du
DMS IV à l’ISSM


Definie par un consensus d’experts (DMS, ICD-10)
Basée sur des critères diagnostiques subjectifs et
variables:



Ejaculation survenant avant que le sujet ou sa
partenaire ne le souhaite
Sentiment de ne pas contrôler le temps de
l’éjaculation.
La gêne crée une détresse marquée ou des
difficultés interpersonnelles.
Mac Mahon and al 2008; Waldinger and Schweiter 2008.
Contexte: définitions actuelles de l’EP : du
DMS IV à l’ISSM


Absence de critères objectifs basés sur la recherche
scientifique.
Besoins d’objectiver des criteres diagnostiques:



Temps avant éjaculation
Détresse psychologique
Mac Mahon and al 2008; Waldinger and Schweiter 2008.
Definition ISSM









Groupe Travail international en 2007
Proposé pour la prochaine version du DSM-V
Premier critère diagnostique : temps de latence éjaculatoire
intra-vaginal (IELT)
(IELT) (mesures « stop-watch » mesure par la partenaire et/ou
temps estimé par le patient /partenaire (Waldinger and al
2005)
Etude sur des populations internationales : Hollande, RU,
Espagne, Turquie, USA
Valeur moyenne: 8 minutes
Médiane : 5,4 minutes
Statistiquement « anormal » court: inf to 1 mn
Prevalence de l’EP: entre 5-6% et non , entre 20 et 30%
Perception of Canadian Sexologists about
normal and abnormal IELT





Adequate IELT : 3-7 minutes
Wished IELT : 7-13 minutes
Too short IELT : 1-2 minutes
To long IELT : 10-30 minutes
Corty, Guardini 2008
Women’s partnered orgasm consistency is associated with greater duration of
penile–vaginal intercourse but not of foreplay.
A B ST R A CT
Introduction. It has been asserted that women’s likelihood or consistency of partnered orgasm (her
orgasm as a result of sexual activities with a partner) is determined by duration of foreplay, but not by
duration of penile–vaginal intercourse.
Aims. The objective was to examine the extent to which women’s likelihood or consistency of partnered
orgasm is associated with duration of foreplay, duration of penile–vaginal intercourse, and age.
Methods. In a representative sample of the Czech population, 2,360 women reported their consistency of
orgasm with a partner (from “never” to “almost every time”), and estimates of their typical durations of
foreplay and of penile–vaginal intercourse.
Main Outcome Measures. The association of consistency of partnered orgasm with typical durations of
both foreplay and penile–vaginal intercourse.
Results. In univariate analyses, consistency of partnered orgasm was more associated with penile–vaginal
intercourse duration than with foreplay duration (consistency also correlated negatively with age). In
multivariate analysis,foreplay ceased to be a significant correlate of partnered orgasm consistency (the
exclusion of respondents reporting a penile–vaginal intercourse duration of 1 minute or less did not alter
the results).
Conclusions. When both sexual activity categories are examined in tandem on a population level, women’s
likelihood or consistency of partnered orgasm is associated with penile–vaginal intercourse duration, but
not with foreplay duration. In contrast to the assumptions of many sex therapists and educators, more
attention should be given to to improve the quality and duration of penile–vaginal intercourse rather than
foreplay.
Weiss P, and Brody S. J Sex Med 2009;6:135–141.
Commentaires : la cohorte est importante et théoriquement représentative de la population
féminine tchéque, mais aucune donnée démographique n’est disponible dans l’article.
L’argumentaire de départ est très pertinent pose principalement deux problèmes celui du rôle
du thérapeute dans les concepts sexologiques et celui des variations de la sexualité en
fonction de la culture. En effet, une enquête récente réalisée chez des sexologues canadiens
et Américains, fait apparaître une durée du rapport intra-vaginale qualifiée de trop longue
lorsqu’elle atteint 4 minutes et conseille d’appliquer ce « conseil » lors de la prise en charge
des patients en sexologie . Nous sommes bien devant une des difficultés de notre profession
jusqu’à qu’elle point la médecine doit être « directive », surtout la médecine sexuelle ? Notre
rôle est celui d’écoute, de dépistage des souffrances, de réponses en terme, si possible, de
données obtenues d’autres patients et traitées de manières scientifiques (études
épidémiologiques réalisées chez les patients). Modestement nous devrions être des
« passeurs » au sens noble du terme. La paragraphe discussion de cet article est également
bien étayé, seul bémol, il cite sans l’argumenter le rôle de « l’immaturité » féminine dans
l’absence d’orgasme intra-vaginal. Les découvertes récentes concernant l’anatomie du clitoris
et rendant caduques , l’opposition femme « clitoridienne » et femme « vaginales » auraient pu
faire soulever le rôle de l’éducation sexuelle du couple et des expériences sexuelles, dans les
pratiques sexuelles observées, ainsi que celui du sexologues dans l’information aux femmes de
leur double potentiel. On a donc un peu l’impression que les auteurs se rangent dans le clan
des défenseurs de l’orgasme vaginal, alors que cette problématique est à mon sens,
complètement dépassée.
(1) Corty EW, Guardiani JM. Canadian and American sex therapists’ perceptions of normal and abnormal
ejaculatory latencies: How long should intercourse last? J Sex Med 2008;5:1251–6.
Autres critères

Consequences négative de l’EP: détresse, anxieté,
frustration, et/ou évitement de la sexualité.

Chez l’homme:






Qualité de vie
Relation avec la partenaire
Estime de soi
Difficultées à developper des nouvelles relations
Chez la partenaire
Dans le couple
Rowland et al 2004, Porst et al 2007, Dunn et al 199, Symonds et al 2003, Mc Cabe 1997, Byers et grenier
2003, Riley et Riley 2005, Harmann et al 2005, Brock et al 2007, Althof 2006, Rosen et Althof 2008.
Proposition pour la nouvelle
classification DSM V
Contexte: la physiologie
Pathophysiology





Lien avec anxieté, unsatisfaction, depression
Hypersensibilité du réflexe ejaculatoire ?
Rôle prostatite ?
Genetique ?
Lien avec une diminution neurotransmission centrale de
la serotonine (5HT):




Hyposensibilité des 5-HT2c recepteurs
Hypersensibilité des 5-HT1a recepteurs
SSRI block 5 HT transporteurs
Hypersensibilité ?



PE is better understoos as a « biological and
comportemental » answer under psycho-physiological
control.
Men with PE could intentionally modify their exitation,
but they are not able to change receptors sensibility or
neurotransmettors delivery (Rowland 2005, ESSM)
Opposition: brain adaptable (possible learning)/PE
genetically programmed spinal cord (non adaptable)
En résumé:
Diagnostic
Type d’EP: primaire secondaire
 Presence ou absence d’une autre dysfonction
sexuelle
 Impact de l’EP sur la relation avec la partenaire
 Impact de l’EP sur qualité de vie
 Traitement précédent, réponse
 Examen clinique

Influence sur le couple
Les traitements médicamenteux
Priligy™ (Dapoxetine) Receives First Regulatory Approvals For The
Treatment Of Premature Ejaculation (PE) In Finland And Sweden
17 Feb 2009
Janssen-Cilag EMEA, a division of Janssen Pharmaceutica N. V., announced that
Priligy™(dapoxetine) has received marketing authorisation in Finland and Sweden for the ondemand treatment of premature ejaculation (PE) in men 18 - 64 years of age. These approvals
follow the positive outcome of a decentralised marketing authorisation procedure in seven
European Union countries: Sweden, Austria, Finland, Germany, Spain, Italy and Portugal. The
procedure was finalised in December 2008, and Finland and Sweden are the first countries
worldwide to grant marketing authorisation for this compound. National approvals and licenses
in the other five European countries are expected to follow. Dapoxetine is not approved for
marketing in the United States.
Dapoxetine is a drug specifically developed for the on-demand treatment of PE and is the first
oral medication (tablet) to be approved for this condition. Dapoxetine has been extensively
evaluated in five randomised, placebo-controlled Phase III clinical trials involving more than
6,000 men with PE and their partners. This is the largest and most comprehensive clinical trial
programme to date for a drug therapy to treat PE. Dapoxetine is a unique, short-acting,
selective serotonin reuptake inhibitor (SSRI) designed to be taken only when needed, that is 1-3
hours before sexual intercourse is anticipated, rather than every day. Dapoxetine will be
marketed by Janssen-Cilag, marking another significant advance in the company's commitment
to developing innovative, high quality treatments for unmet medical needs.
Dapoxetine
.
Lancet. 2006 Sep 9;368(9539):929-37.Efficacy and tolerability of dapoxetine in treatment
of premature ejaculation:an integrated analysis of two double-blind, randomised
controlled trials.Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJ, Shabsigh R,
MiloslavskyM, Kell S
BACKGROUND: No drugs are approved for treatment of premature ejaculation. Ouraim was to
determine the efficacy and tolerability of on-demand dapoxetine inpatients with severe premature
ejaculation. METHODS: We determined the efficacy of dapoxetine in a prospectively predefined
integrated analysis of two 12-weekrandomised, double-blind, placebo-controlled, phase III trials of
identicaldesign done independently, in parallel, at 121 sites in the USA. Men withmoderate-to-severe
premature ejaculation in stable, heterosexual relationshipstook placebo (n=870), 30 mg dapoxetine
(874), or 60 mg dapoxetine (870)on-demand (as needed, 1-3 h before anticipated sexual activity). The
primaryendpoint was intravaginal ejaculatory latency time (IELT) measured by stopwatch.Safety and
tolerability were assessed. All analyses were done on anintention-to-treat basis. The trials are
registered at ClinicalTrials.gov,numbers NCT00211107 and NCT00211094. FINDINGS: 672, 676, and
610 patientscompleted in the placebo, 30 mg dapoxetine, and 60 mg dapoxetine groups,respectively.
Dapoxetine significantly prolonged IELT (p<0.0001, all doses vsplacebo). Mean IELT at baseline was
0.90 (SD 0.47) minute, 0.92 (0.50) minute,and 0.91 (0.48) minute, and at study endpoint (week 12 or
final visit) was 1.75(2.21) minutes for placebo, 2.78 (3.48) minutes for 30 mg dapoxetine, and
3.32(3.68) minutes for 60 mg dapoxetine. Both dapoxetine doses were effective on thefirst dose.
Common adverse events (30 mg and 60 mg dapoxetine, respectively)were nausea (8.7%, 20.1%),
diarrhoea (3.9%, 6.8%), headache (5.9%, 6.8%), anddizziness (3.0%, 6.2%). INTERPRETATION: Ondemand dapoxetine is an effective andgenerally well tolerated treatment for men with moderate-tosevere prematureejaculation.
La dapoxétine
La dapoxétine
McMahon C, Kim SW, Park NC, et al. Treatment of premature ejaculation in the Asia-Pacific region: results from a
phase III double-blind, parallel-group study of dapoxetine. J Sex Med 2010 Jan; 7 (1 Pt 1): 256-68
Buvat J, Tesfaye F, Rothman M, et al. Dapoxetine for the treatment of premature ejaculation: results from a randomized,
double-blind, placebo-controlled phase 3 trial in 22 countries. Eur Urol 2009 Apr; 55 (4): 957-68
Pryor JL, Althof SE, Steidle C, et al. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation:
an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006 Sep; 368 (9539): 929-37
Kaufman JM,RosenRC, MudumbiRV, et al.Treatment benefit of dapoxetine for premature ejaculation: results froma placebocontrolled
phase III trial. BJU Int 2009 Mar; 103 (5): 651-8
McMahon C, Althof S, Kaufman J, et al. Efficacy and safety of dapoxetine for premature ejaculation: integrated analysis
of 5 phase 3 trials [abstract no. PD-068]. J Sex Med2009; 6 Suppl. 2: 69-70. Plus oral presentation presented at
the Joint Congress of the European and International Societies for Sexual Medicine; 2008 Dec 7-11; Brussels
Le Tramadol
Salem EA, Wilson SK, Bissada NK, Delk JR II, Hellstrom WJ, and Cleves MA.
Tramadol HCL has promise in on-demand use to treat premature ejaculation.
J SexMed 2008;5:188–193.
Single-blind, placebo-controlled, crossover, stopwatch monitored two-period study was conducted,
on 60 patients with lifelong PE. PE was defined as IELT of < 2 minutes in 80% of intercourse
episodes. A total of 25 mg of Tramadol hydrochloride was given to one group (30) prior to
intercourse and placebo was supplied for the other group (30) for 8 weeks. Drugs were taken 1–2
hours before sexual activity and sexual intercourse was required at least once per week. After the
initial treatment period, the two groups took the alternate medication for another 2 months. The
two 8-week treatment periods were separated by 1 week washout period. IELT was timed by a
stopwatch at each intercourse and was reported by patients or partners. Results. The baseline
(mean± SD) IELT for patients before treatment was 1.17± 0.39 minutes. At the end of the
treatment period utilizing the active drug, the mean IELT was increased significantly in patients on
Tramadol treatment to 7.37 ± 2.53 minutes. The same patients on placebo medication had mean
IELT of only 2.01±0.71 minutes. Patients uniformly reported satisfaction with their resulting
control over ejaculation.
Conclusions.Tramadol, a drug with a proven safety record as an anti-inflammatory agent, shows
promise as a drug for treating rapid ejaculation.
25 MG 2HEURES AVANT
PSD502 For Premature Ejaculation - Positive Outcomes From European
Phase III Pivotal Trial
07 Nov 2008
Plethora Solutions Holdings PLC ("Plethora" or the "Company", AIM: PLE), the
specialist developer of products for the treatment and management of urological
disorders, announces that its European Phase III double-blind placebo controlled
study of PSD502 for the treatment of premature ejaculation (PE) has met its
three co-primary endpoints of Intra-vaginal Ejaculation Latency Time ('IELT') and
Index of Premature Ejaculation ('IPE'; Ejaculatory Control and Sexual Satisfaction
domains).
The successful European study is one of two pivotal Phase III studies running in
parallel with identical protocols. The second Phase III study is being conducted in
North America and is expected to complete in the first half of 2009. Once the
results from the US Phase III study become available, data from the two studies
will be combined for submission for regulatory approval in the USA and Europe.
European and US Phase III Study Details
Each Phase III study is a multi-centre, randomised, double blind, placebocontrolled efficacy study and the programme is expected to recruit a total of 540
patients across the two studies. Patients are treated for a 12 week period with an
optional open label phase of up to 9 months.
The European study was conducted with 300 randomised patients across 32
investigational centres in 4 countries across Europe. Of these, 265 patients also
entered the optional 9 month open label study.
PSD 502/Tempe (Pletora)
Dinsmore WW, Wyllie MG. PS D502 improves ejaculatory latency, control and sexual
satisfaction when applied topically 5 min before intercourse in men with premature
ejaculation: results of a phase III, multicentre, double-blind, placebo-controlled study. BJU
Int. 2009 Apr;103(7):940-9.
RESULTS: In all, 300 men with PE were randomized from 31 centres in Europe. The geometric
mean (range) IELT over the 3-month treatment period increased from a baseline of 0.6 min in
both groups to 3 .8 (0.3-57.8) and 1.1 (0 -15.0) min in the PSD502 and placebo groups,
respectively. Adjusting for treatment-group imbalances, this represents a 6.3-fold and 1.7-fold
increase in adjusted geometric means. There were s ignificantly grea ter increases in the scores for
the IPE domains of ejaculatory control and sexual satisfaction in the PSD502 group than in the
placebo gr oup, with a mean (sem) 7.0 (0.59)-point difference between treatments in change from
baseline in the IPE domain for ejaculatory control and a 5.9 (0.57)- point difference in change
from baseline in the IPE domain for sexual satisfaction (both P < 0.001). This was supported by
improvements in all secondary endpoints. At the end of the treatment period 66% o f patients
rated PSD502 as 'good' or 'excellent'. PSD502 was well tolerated and no systemic adverse events
were reported. Localized treatment-related adverse events were reported by 2.6% and 3.1% of
patients and partners, respectively. CONCLUSION: PSD502 applied topically 5 min before
intercourse improved ejaculatory latency and significantly improved ejaculatory control and
sexual satisfaction, factors relevant for accep tance of a PE treatment by both patient/physician
and regu latory authorities. PSD502 was well tolerated by both patients and partners, with no
systemic side-effects and a low incidence of localized effects, and was rated favourably by most
users. PSD502 therefore appears to offer significant advantages over other therapies in
development for the treatment of PE.
Other studies
Henry R, Morales A, Wyllie MG. TEMPE: Topical eutecticlike mixture for premature ejaculation. Expert
Opin Drug Deliv 2008;5:251–61.
Dinsmore WW, Hackett G, Goldmeier D, Waldinger M, Dean J, Wright P, Calendar M, Wylie K, Novak C,
Keywood C, Heath P,Wyllie M. Topical eutectic mixture for premature ejaculation (TEMPE): A novel
aerosol-delivery form of lidocaine-prilocaine for treating premature ejaculation. BJU Int 2007;99:369-75.
Henry R, Morales A. Topical lidocaine prilocaine spray for the treatment of premature ejaculation: A
proof of concept study. Int J Impot Res 2003;15:277–81.
Dinsmore W, Wyllie M. PSD502 improves ejaculatory latency, control and sexual satisfaction when
applied topically 5 min before intercourse in men with premature ejaculation: Results of a phase III,
multicentre, double-blind, placebocontrolled study. BJU Int 2009;103:940–9.
Vardenafil
Ave rsa A, Pili M, Francomano D, Bruzziches R, S pera E, La Pera G, S pera G.
Effects of va rdenafil administration on intravaginal ejaculatory latency time in men with
lifelong premature ejaculation. Int J Impot Res. 2009 Jul-Aug;21(4):221-7.
Premature ejaculation (PE) is thought to be the most common male sexual dysfunction; however,
the prevalence of lifelong ( LL)-PE is relatively low. The aim of this study was to investigate the
effects of on-demand vardenafil (10 mg) to modify the intravaginal ejaculatory latency time
(IELT) in men with LL-PE without erectile dysfunction. Forty-two men (18-35 years) were
enrolled in a 16-week, double-blind, placebo-controlled, cross-over study. Primary end point was
the modification from baseline of IELT assessed by stopwatch technique; secondary end points
were post-ejaculatory refractory time (PERT) and variations of scores at the Index of Premature
Ejaculation questionnaire. The changes in geo metric mean IELT were superior after taking
vardenafil (0.6+/-0.3 vs 4.5+/-1.1 min, P<0.01), compared with placebo (0.7+/-0.3 vs 0.9+/-1.0
min, ns). PERT dropped significantly after vardenafil (16.7+/-2.0 vs 4.3+/-0.9 min, P<0.001),
compared with placebo (15.3+/-2.2 vs 15.8+/-2.3 min). Patients who took vardenafil (vs placebo)
reported significantly (P<0.01) increased ejaculatory control (6+/-2 vs 16+/-2), improved overall
sexual satisfaction (7+/-2 vs 15+/-1) and distress (4+/-1 vs 8+/-1) scores, respectively. M ultiple
regression analysis (r(2)=0.86) for IELT by the number of attempts at sexual intercourse showed
significant differences between the slopes of lines for placebo and vardenafil (P<0.0001). T he
most common adverse events for vardenafil (vs placebo) were headache (10 vs 3%), flushing (1 2
vs 0%) and dyspepsia (10 vs 0%), which tended to disappear over the time. In conclusion, in our
study, vardenafil increased IE LT and reduced P ERT in men with LL-PE. Besides, improvements
in confidence, perception of ejaculatory control and overall sexual satisfaction were reported.
La psychothérapie
La psychothérapie (revue de la Cochrane)
La psychothérapie en pratique

Approche analytique

Approche sexo-comportementale:



Éducation
Stop and go, muscles périnéaux
« désensibilisation »: retrouver le plaisir d’être ensemble sans
culpabilité
Le suivi
Proposals for DSM V
Conclusions







Depuis le recherche sur les nouveaux traitements:
Nouvelle définition, concept
évolution de la physiopathologie
des outils d’évaluation
évolution de la qualité des études
prochaine commercialisation de produits avec AMM
nécessité de thérapie intégrative