Ejaculation prématurée :

diagnostic et traitement

Béatrice Cuzin, Service d’Urologie et de la Transplantation, CH E Herriot, Lyon, France

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

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 S T R A C T

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 on-demand 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.

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: On-demand dapoxetine is an effective andgenerally well tolerated treatment for men with moderate-to-severe prematureejaculation.

Dapoxetine

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, placebo-controlled 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.

Dinsmore WW, Wyllie MG. 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, 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 acceptance 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.

PSD 502/Tempe (Pletora)

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.

Ave rsa A, Pili M, Francomano D, Bruzziches R, Spera E, La Pera G, Spera G.

Effects of vardenafil 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 geometric 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. Multiple

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 (12

vs 0%) and dyspepsia (10 vs 0%), which tended to disappear over the time. In conclusion, in our

study, vardenafil increased IELT and reduced P ERT in men with LL-PE. Besides, improvements

in confidence, perception of ejaculatory control and overall sexual satisfaction were reported.

Vardenafil

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