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李長茂沙巴談少人啟齒的早洩問題 PREMATURE EJACULATION Dr Clarence Lei Chang Moh MMA Sabah 3rd SABAH GP CONFERENCE Kota Kinabalu 15 May 2011

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  • 1.PREMATURE EJACULATION: the less talked about sexual condition
    • MMA Sabah
  • 3 rdSABAH GP CONFERENCE
  • Kota Kinabalu 15 May 2011
  • CHAIRMAN: Datuk Dr Jayaram Menon
  • Chief Physician, Queen Elizabeth Hospital, KK
  • by Dr Clarence Lei ChangMoh, FRCS Urol
  • Consultant Urologist
  • email: clarencelei@gmail.com
  • kuchingurology.com

2. 48 yrs contractor, M, 6 +2children, (real 12.5.11)

  • Ejaculation within age 18 in Netherlands, UK, Spain, Turkey and US Not selected for ejaculatory status or co-morbidities IELT measured bystop-watchfor 4 weeks ----------------------------------------------------------------------------------------------- RESULTS by Country(Median IELT in minutes) Netherlands UK Spain Turkey US ALL 5.17.65.83.77.05.4 ----------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------- Waldinger MD, Quinn P, Dilleen M et al. J Sex Med 2:492-7, 2005. 9. There is a confusion between PE & ED
    • 65% of Malaysian men believe PE and ED are very similar, and the same medication can treat bothconditions whichin fact they can t

    ISSM Sept 2010 Seoul, Janssen Cilag: Data on file 10. Up to 29% of Malaysian men suffer from PE at some point in their lives China Aust/NZ Taiwan Thailand Korea Hong Kong Malaysia Indonesia Philippines Total

          • Malaysia : 15% self-reported vs 29% objective assessment
    • .

    Champion: koreans !! 11. Prevalence of PE is similar across countries 1.Porst et al, 2007.2. Janssen-Cilag Data On File 2009 PEPA (Premature Ejaculation Perceptions and Attitudes) Study *Men classified as having PEif low / absent control over ejaculation that is viewed as a problem by men or/ their partners ** Men classified as having PE or Probable PE by PEDT diagnosis ** ** * * * * 12. Prevalence of PE is Consistent Across Age Groups

    • PEPA: Premature ejaculation perceptions and attitudes. Porst et al. (2007) Eur Urol 51:816824

    13. Normal Male Sexual Response Time Sexual interest/ stimulation Peniletumescence High arousal / penile erection Plateau Orgasm Ejaculation accompanied by orgasm Peniledetumescence Resolution Adapted fromDonatucci(2006)J Sex Med 3(suppl 4):303308 Excitement Penetration 14. Premature Ejaculation Time Rapid ejaculation and associated orgasm with normal erection Normal response Adapted fromDonatucci(2006)J Sex Med 3(suppl 4):303308 Short plateau phase Steep excitementphase with normal erection PE 15. What percentage of men with PEmight want treatment? Authors Percent Rowland et al( JSexMed 1:225, 2004) 50% Carson et al ( JUrol 169 Suppl 2003) 24% Brock et al ( JUrol 177 Suppl 2007) 38% 16. Current Treatment Options ? 17. Pharmacological Treatment of PE, previous

    • Topical (local) anesthetics eg Emla, Gambir Swak,
    • PDE5 inhibitors
    • Tricyclic antidepressant (clomipramine)
    • Selective Serotonin Reuptake Inhibitors (SSRI s)
    • Tramadol

    18. Topical PE Therapy ?

    • Desensitizing creams use lidocaine (Emla) or lidocaine with prilocaine applied 20-30 minutes prior to sexual activity
      • Lessen penile sensitivity during foreplay and intercourse

    19. New topical penile spray using a combination of lidocaine and prilocaine to treat PE DB PC phase 2 study of 43 men with PE Drug Placebo Number of men 20 23 Baseline IELT (min)1.00.9 Follow-up (min)4.9 1.6 Dinsmore WW et al. BJU International 99:369-375, 2007 (Feb) 20. Efficacy of Sildenafil for Premature Ejaculationand Post-Ejaculatory Refractory Time Double-blind placebo-controlled study157 men with PE ages 18-65 (mean 43 yrs)Compared flexible-dose sildenafil (50-100 mg) to placebo Results: No signficant difference between sildenafil and placebo in IELT Sildenafil-treated men had greater ejaculatory control and sexual satisfaction scores Sildenafil-treated men had decreased post-ejaculatoryrefractory timeMcMahon CG, Stuckey BGA, Andersen M, et al. J Sex Med 2: 368-375, 2005 21. FIG 1 The mechanism ofejaculation 2005 BJU International 95, 1181-1186 ejaculate 22. Neurophysiology of Ejaculation Motor supply to bulbospongiosus muscle Pudendal nerve Sensory inputs from genital areas Supraspinal Centres Spinothalamic cells L3-L4: Coordination of spinal nuclei Hypogastric Plexus~ T12-L1: Emission Spinal ReflexS1-S3:Expulsion afferent efferent Giuliano & Clement (2005) Ann Rev Sex Res16:190216 Higher brain Centres Excitatory & inhibitory control Sympathetic supply to: Epididymis, Vas deferens Seminal Vesicles Prostate Pons: nPGi: Nucleus paragigantocellularisDorsal nerve of penis 23.

    • The following neurotransmitters are involved in the processing of emissionand ejaculation:
      • Serotonin (5-HT)
      • Dopamine (DA)
      • Gamma-aminobutyric acid (GABA)
      • Noradrenaline
      • Serotonin is considered to be the key inhibitory neurotransmitter involved in the processing ofejaculation
        • There are multiple serotonin receptors in the hypothalamus, brainstem and the spinal cord

    Neurotransmitters Involvedin Control of EjaculationMcMahon et al, Disorders of orgasm and ejaculation in men. In Sexual Medicine: Sexual dysfunctions in men and women. 2nd International Consultation on Sexual Dysfunctions, Paris, 2004 24.

    • Nucleus ParaGiganto- cellularis (nPGi) and other centers haveprojections to the lumbosacral spinal cord which are thought to exert tonic inhibition of ejaculation

    Central Serotonin and PE Tonic descendingserotonergic inhibitionof ejaculationfrom NPGi nPGi (brainstem) MPOA (hypothalamus) PVN (hypothalamus) Sympathetic control of ejaculation in the lumbosacral cord Ejaculationreflex mediatedby the L-S cord 25. Lifelong PE:NOTpsychogenic ORGANIC CAUSE OFPREMATURE EJACULATION1

    • Serotonin in the CNS inhibits the ejaculation reflex
    • Withl ow CNS serotonin,ejaculation is not inhibited,setting the ejaculatory threshold at a lower point
    • PE seems to have a neurologic basis in some men

    1 Waldinger MD, Schweitzer DH and Olivier B. J Sex Med 2:121-131, 2005 26. Indirect Evidence for a Genetic Explanation of PE

    • (1) Dutch study in men with lifelong PE with IELT < 1 minute showed
    • an increased familial occurrence of lifelong
    • PE in first degree male relatives 1
    • (2) Finnish male twin questionnaire study showed a moderate genetic
    • influence on PE 2
    • (3) Animal studies showed a subgroup of persistent rapidly ejaculating
    • Wistar rats 3-5
    • 1.Waldinger M, et al. Psychiatr Genet 1998;8:37-40
    • 2.Jern P, et al.J Sex Med 2007;4:1739-49
    • 3.Pattij T, et al Curr Pharm Des 2005;11:4069-77
    • 4.Waldinger M, et al. World J Urol 2005;23:115-8
    • 5.Pattij T, et al. Eur J Neurosci 2005;22:724-34

    27. Dapoxetine (Priligy) A highly potent inhibitor of serotonin reuptake transporterFollowing oraladministration, it is rapidly absorbedAfter reaching T max, serum concentration declines rapidly At 60 mg dose:1 T max = 1.2 hr T initial = 1.5 hr Single dose and multiple dose pharmacokinetics are similar1 No interaction when used with food 2 , alcohol 3or PDE5 inhibitors 4 1 Dresser M, et al. Clin Pharmacol Therap 32:2004. Abstract Pl-113 2 Dresser M, et al. J Sex Med 3 (Suppl 1):25, 2005. Abstract 37.3 Modi N, et al. J Urol 173 (Suppl):239, 2005. Abstract 879.4 Dresser M, et al. J Urol 173 (Suppl):201, 2005. Abstract 739. 28. Dapoxetine

    • Dapoxetine is the first compound specifically developed for the treatment of PE,30-60mg ,1-3 hrs before, on demand, short acting
    • Approved in several EU countries, Mexico, Korea, New Zealand ,Malaysia(1.8.2010)with anticipated approval in other countries
    • Level 1A evidence to support the efficacy and safety of on-demand dosing of dapoxetine [1]

    1 . ICSD Paris 2009 29. Dapoxetine Pharmacokinetics

    • Dapoxetine undergoes rapid absorption (Tmax of 1.0 hours), rapidly achieves peak plasma concentration (Cmax) and hasa mean half-life after a single dose is 1.3 hours
    • Minimal accumulation with plasma concentration rapidly declining to about 5% of Cmax at 24 hours.
    • Dose-dependent pharmacokinetics with plasma concentrations and area under the curve (AUC) which are unaffected by multiple dosing

    30. Dapoxetine Phase III Studies Summary J & J Pharmaceutical Services LLC, 2007 Study number Description Subjects enrolled Sites 012 & 013 12 week phase III trials of dapoxetine in men with moderate to severe premature ejaculation (completed 2004) 2614 121 sites in USA 014 9 month open label extension of studies 012 & 013 (completed 2005) 1774 121 sites in USA 3001 24 week phase III trial of dapoxetine in men with moderate to severe premature ejaculation (completed 2007) 1162 143 sites in Europe, South Mexico, America, Canada, Israel and South Africa 3002 Withdrawal effects of chronic daily and as-needed dosing with dapoxetine in the treatment of PE (completed 2005) 1238 91 sites in USA and Canada 3003 12 week phase III trial of dapoxetine in men with moderate to severe premature ejaculation (completed 2007) 1349 52 sites in Asia and Australia 31. Dapoxetine IELT for

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