Ejaculation and Orgasm: I m confused! Seacourses July 22 August Stacy Elliott, MD

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1 Ejaculation and Orgasm: I m confused! Seacourses July 22 August Stacy Elliott, MD

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Faculty/Presenter Disclosure Relationships with commercial interests in the last 20 years Speaker: Stacy Elliott, MD - Holder of Stocks/Shares none Grants/Research Support : CIHR, Neurotrauma funds, Pfizer ( female SCI) Speakers Bureau/Honoraria/Consulting Fees: Other: Lilly, Pfizer, Bayer, Abbott Employee of Vancouver Hospital and Faculty at the University of British Columbia

4 Disclosure of Commercial Support I have received no direct payment from pharmaceutical companies for this talk. I have received an honoraria for this talk from SeaCourses.

5 MITIGATING POTENTIAL BIAS All the recommendations involving clinical medicine are based on evidence from well-designed clinical trials published in peerreviewed journals. Seacourses has in no way influenced the information in this talk. All medical treatments for ejaculatory disorders currently available in Canada will be discussed in this CME event

6 Objectives To understand how ejaculation occurs To know the difference between ejaculation and orgasm To differentiate functional from organic ejaculatory problems To be aware of the various behavioral and medical treatments for premature ejaculation and delayed orgasm

7 Ejaculation +/- orgasm Orgasmic threshold Sympathetic Parasympathetic Arousal Tumescence Detumescence Refractory period

8 Physiology of Ejaculation Spinal cord reflex involving specific coordination between T10 S4 Central inhibitory control over spinal cord reflex

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10 Ejaculation and Orgasm Ejaculation: - the process of sperm transport from the testes to the urethral meatus ( neurology defined) Orgasm: - the combination of a local, learned reflex and/or the brain s interpretation of it ( neurology unclear) - usually accompanies ejaculation

11 What is orgasm? No good scientific definition Argued about Mystifying to those who have not experienced it Pleasurable sensation felt in the head and pelvic area and/or body and/or abdominal viscera at the point of ejaculation State of euphoria depicted in many art forms Can occur multiple times without ejaculation Can occur without ejaculation, erection or a penis

12 Physiology of Ejaculation Two phases: Seminal emission - sympathetic T10- L1 - some voluntary control Propulsatile ejaculation (expulsion) - parasympathetic and somatic - loss of voluntary control

13 Ejaculatory Inevitability Point of no return Closure of the bladder neck with seminal emission with concomitant closure of the external sphincter increasing intraprostatic pressure Not dependant on ejaculate to trigger

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15 WHEN ASLEEP Ejaculation +/- orgasm Orgasmic threshold Detumescence? Nocturnal erection? Refractory period Nocturnal ejaculations ( emissions )

16 Orgasmic Threshold: genetic variation may be a combination of neurology and endocrine factors and influenced easily ( distractability, SSRI) Afferent and efferent can be genital, brain, or both Intraspinal excitation part of variability and visceral components Brain shuts down ( except brain stem and cerebellum) in order to experience euphoria, satiety MOST orgasmic experiences from genitally induced reflexogenic activity ( this is honed from experience)

17 Involuntary Emissions Nocturnal Emissions: - cerebral ( not peripheral) afferent - normal in young men - usually accompanied by orgasm Spontaneous Emissions: - secondary to neurological disorders - secondary to subtle cord injuries - abnormal - nonsexual and distressing (+/- orgasm)

18 Ejaculation: What can go wrong? Emission & propulsion don t happen Emission failure Propulsatile failure Retrograde ejaculation Obstruction

19 Orgasm: What can go wrong? Feel it, but altered Don t feel it despite ejaculating Pain with orgasm

20 Clinical Evaluation Ejaculatory Disorders Sexual Dissatisfaction - ejaculation latency - pre-ejaculate or semen issues - orgasmic quality Sexual Dysfunction - rapid/premature ejaculation - delayed or inhibited ejaculation - sequelae from neurological disorders

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22 Clinical Evaluation Ejaculatory Disorders Medical Implications - hematospermia - pain with ejaculation Fertility Consequences - anejaculation - lack of seminal emission - retrograde ejaculation - failed vasectomy reversal

23 Non-operative sperm retrieval Vibrostimulation & Electroejaculation

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25 Definitions Anorgasmia and anejaculation are some of the most misunderstood definitions Orgasm present Orgasm absent ( anorgasmia) Ejaculation Present - Normal function - Functional or latency difficulties (PE to DE) -Neurogenic ( SCI,MS) - Anhedonic ejaculation (psych and iatrogenic) Ejaculation Absent or disordered -Retrograde ejaculation -Post radical prostatectomy - RPLND - SCI -Multiorgasmic men -Anejaculation ( failure to have seminal emission and propulsatile ejaculation) - Prostatectomy

26 Anorgasmia Ejaculation Present Neurogenic - spinal cord injury (SCI) Iatrogenic - medications ( despiramine) Psychogenic - anhedonic ejaculation Ejaculation Disordered or interrupted ( rare) Neurogenic -MS with weak propulsatile phase Anatomic - post PCa treatments - ejaculatory duct obstruction Ejaculation absent Neurogenic - SCI anejaculation Iatrogenic - SSRI anejaculation Functional/acquired - severe delayed ejaculation Functional /inherent -Primary anorgasmia

27 Neurologically what is orgasm? Concept of local generated reflex in the animal and human literature Supported by urogential reflex in spinalized rats which display orgasmic facies at ejaculation Theory is there is a neurological trigger ( sympathetic) Oxytocin and dopamine go up at orgasm to trigger things off, followed by increase in prolactin to shut things down Men with spinal cord injuries have taught us that the ejaculation reflex is a predictor but not essential to experience subjective orgasm

28 Spinal Cord Injury Model Most men with complete SCI have anejaculation (90%) and anorgasmia ( 45-50%) Ejaculation induced by sperm retrieval methods occasionally produces first orgasmic experience since injury ( usually incomplete) Subjective experience of orgasm after SCI in men can occur without ejaculation ( but best chance is with ejaculation) Incomplete, low injuries with some genital sensation most likely to experience ejaculation accompanied by orgasm

29 Anorgasmia Ejaculation Present Neurogenic - spinal cord injury (SCI) Iatrogenic - medications ( despiramine) Psychogenic - anhedonic ejaculation Ejaculation Disordered or interrupted ( rare) Neurogenic -MS with weak propulsatile phase Anatomic - post PCa treatments - ejaculatory duct obstruction Ejaculation absent Neurogenic - SCI anejaculation Iatrogenic - SSRI anejaculation Functional/acquired - severe delayed ejaculation Functional /inherent -Primary anorgasmia

30 Ejaculation Occurs, No Orgasm If neurogenic some men with SCI have orgasmic sensation derived from - non-genital sources - morphed pelvic visceral sensations ( i.e. anal /prostatic stimulation even if complete ) - morphed autonomic dysreflexia If iatrogenic switch/stop offending drugs ( desipramine) If anhedonic harder to treat - do rule out reversible causes such as low testosterone, poor pelvic floor awareness - psychiatric diagnosis/treatment

31 Anorgasmia Ejaculation Present Neurogenic - spinal cord injury (SCI) Iatrogenic - medications ( despiramine) Psychogenic - anhedonic ejaculation Ejaculation Disordered or interrupted ( rare) Neurogenic -MS with weak propulsatile phase Anatomic - post PCa treatments - ejaculatory duct obstruction? Ejaculation absent Neurogenic - SCI anejaculation Iatrogenic - SSRI anejaculation Functional/acquired - severe delayed ejaculation Functional /inherent -Primary anorgasmia

32 Ejaculation centers T12 L1 S1-3 L3-4 LSt Cells ( rats) Sympathetic centers (emission) Lumbar Spinothalamic - spinal generator of ejaculation Somatic ( expulsion) Parasympathetic ( secretion)

33 Ejaculation Disordered Can any semblance be reconstructed in order to recruit some recognizable afferents again? MS, Stroke can be helpful to have pelvic floor therapy or sex therapy to pay attention to remaining pelvic floor afferents - learn how to breathe, accentuate pre-orgasmic arousal Post prostatectomy: may regain improved sensation Sex therapy : The greater the anatomical damage, the more psychotherapy facilitates adjustment to the loss rather than restoration of function (Perelman 2014)

34 Anorgasmia Ejaculation Present Neurogenic - spinal cord injury (SCI) Iatrogenic - medications ( despiramine) Psychogenic - anhedonic ejaculation Ejaculation Disordered or interrupted ( rare) Neurogenic -MS with weak propulsatile phase Anatomic - post PCa treatments - ejaculatory duct obstruction? Ejaculation absent Neurogenic - SCI anejaculation Iatrogenic - SSRI anejaculation Endocrinologic Functional/acquired - severe delayed ejaculation Functional /inherent -Primary anorgasmia

35 Neurogenic Anorgasmia/Anejaculation INTERRUPTED cord difficult ( sacral stenosis) INTERRUPTED autonomics contribute ( pelvic surgeries and rectal cancer surgery) Most of these men had normal ejaculation/orgasm prior to surgery so the extent of autonomic preservation ( and anatomy) Congenital anomalies of the Wolffian duct ( incomplete regression of Mullerian duct remnants may affect ejaculation and cause DE) Circumcision?? Use of sex therapy important

36 Neurogenic Anorgasmia/Anejaculation SCI : What can we do to excite the spinal cord enough to trigger the ejaculation reflex? Can sometimes add a sympathomimetic ( but watch AD) Can repetitive action cause neuroplasticity over time such that the subjective sensation of release is realized? INTACT cord good ( i.e. sacral reflex ) because we can alter the amplitude and frequency of vibrostimulation to induce ejaculation

37 Vibrators for men with without SCI Acuvibe Hitachi Magic Wand and others Viberect FDA approved WAHL Pulse Cobra

38 Do orgasmic difficulties distress the partner? 374 men with PE and 377 women with anorgasmai For men, significant predictors of perceived partner distress included self-distress, relationship quality, interest in sex, and arousal difficulty For women, only the level of self-distress significantly predicted perceived partner distress. Rowland and Kolba J Sex Res. 2017

39 Sato et al 2016 J Urology and Int J Urol 2017 Silodosin in acquired premature ejaculation in patients with or without ED highly selective α1a-adrenoceptor antagonist Excellent for LUTS, has strong suppressive effect on ejaculation 4 mg one hour before intercourse intravaginal ejaculation latency times were 1.9, 4.1, and 7.6 min at baseline, control and with silodosin No adverse effects but reduced semen volume ( can be managed by dose reduction)

40 Assessing Orgasmic and Ejaculatory Problems First diagnostic question: Is orgasm possible?

41 Assessing Orgasmic and Ejaculatory Problems Once chief complaint is elicited 1. Duration 2. Situational or generalized 3. Entirety of sexual response 4. Reaction to the problem 5. Effect on the relationship 6. Motivation

42 FIGURE 1 ALGORITHM FOR ASSESSING EJACULATORY AND ORGASMIC CONCERNS Ejaculation/orgasmic concern Orgasm reached? No Not sure Yes Rarely or with Too fast Ejaculate issue Pain with difficulty - volume low ejaculation - blood, etc Differential diagnosis Inhibited ejaculation Inhibited ejaculation Hematospermia Prostatitis Anejaculation Neuro/drug/hormone effect infertility Pelvic dynias Infertility Aging Anhedonic ejaculation Premature ejaculation

43 Fast or Premature Ejaculation Definition: several Ejaculation that proceeds or occurs immediately after vaginal penetration and results in personal distress All accepted criteria have consistent elements of: Short latency time ( less than one minute) Perceived lack of control Negative consequences or impact ( distress)

44 Premature Ejaculation Common : 25-30% prevalence rate through lifetime. 75% of men experience it at least once in their lifetime Lifelong or primary Biological component speculated to be more likely, possibly due to abnormalities in CNS serotonin and/or serotonin receptors Acquired or secondary Psychological component speculated to be more likely, more likely to be associated with erectile dysfunction Rosen RC (2000) Curr Psychiatr Rep 2: Laumann EO et al (1999) JAMA 281: Spector JS and Carey MP (1990) Arch Sex Behav 19: McMahon CG (1998) J.Urol 159: J & J Pharmaceutical Services LLC, 2007

45 Respondents (%) Men Reporting ED or PE by Age Group (M.A.L.E.S) ED sample (n=2912) PE sample (n=233) P<0.001 for trend Age (years) McMahon et al. Eur Urol 2005; Suppl 4: 174. J

46 Circumcision does not have effect on premature ejaculation A systematic review and meta-analysis total of circumcised and uncircumcised men were no significant differences in PE and orgasmic difficulty However, IELT (intravaginal ejaculation latency time), ED and pain during intercourse favoured circumcised group. Wang et al Andrologia Jun 27

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48 PE: Quality of Life Impact In-person interviews with PE sufferers Diminished self-esteem 68% of responders identified erosion of sexual self-confidence and self-esteem as primary concern 50% of responders reported reluctance to start new relationship/distress in not satisfying partner Anxiety 36% reported anxiety associated with PE (cause or effect?) Embarrassment 67% reported embarrassment as barrier to consulting physician Partners claim confusion, isolation, and also question selfesteem/satisfaction Symonds T. Roblin D. Hart K. et al. J Sex Marital Ther. 2003; 29(5) J

49 J Male Sexual Response Sexual Interest/ Stimulation Orgasm Ejaculation accompanied by orgasm Penile Tumescence Penetration Penile Detumescence High arousal/ Penile erection Plateau Resolution Excitement

50 J What s Different in Men With PE? Rapid ejaculation and associated orgasm Short Plateau phase Normal male sexual response Steep Excitement phase PE male sexual PEresponse Etiology of PE remains largely unknown

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52 Etiology: Organic Theories Penile hypersensitivity Reach ejaculatory threshold more rapidly Lower ejaculatory threshold Hyperexcitable ejaculatory reflex Faster emission and/or expulsion phase Faster bulbocavernosus reflex Colpi et al. 1996; Waldinger, et al. 1998; Waldinger J

53 Etiology: Organic Theories Genetic Predisposition Higher incidence of PE in first-degree relatives Central 5-HT receptor sensitivity ( serotonin has inhibitory role ) Lower 5-HT neurotransmission in PE? 5-HT2C receptor hyposensitivity? 5-HT1A receptor hypersensitivity? Colpi et al. 1996; Waldinger, et al. 1998; Waldinger J

54 Current Treatment Options Self-help treatment Behavioral treatment Topical treatment (local anesthetics) PDE 5 inhibitors Use of antidepressants in PE J & J Pharmaceutical Services LLC, 2007

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56 Self-Help Approaches to PE Coping strategies are often used before presentation to physician Multiple condoms to reduce sensitivity Pre-coital masturbation Distraction (mental exercise) during foreplay and/or intercourse Aggressive thrusting to speed partner satisfaction Some exacerbate PE (by deliberately ignoring sexual sensations needed to establish control) Sotomayor M J Sex Med 2005, Suppl 2: I

57 Medical Management of Fast Ejaculation Know your choices 1. Reduce the reflex hyperactivity 2. Raise the orgasmic threshold pharmacologically ( reversible) 3. Dampen the afferent signals ( temporary) Which will help with the etiology verses the symptomatology?

58 I Behavioral Therapy of PE Squeeze technique Masters and Johnson (1970) Withdrawal and squeeze of the glans penis Stop-start technique Semans (1956); Kaplan (1983) Pause sexual stimulation at impending ejaculation Factors influencing success Heightened male awareness of sexual stimulation Decreased emphasis on coitus

59 Rapid Ejaculation: Behavioral methods Consistent exercises ( 3 X week) with well motivated patient ( self or partnered) Stop start or squeeze method Start to recognize high arousal with some control / delay of premonitory signs Success (note: old studies) 60% short term (Clarke & Parry, 1973) 25% long term (De Amicis et al, 1985) Best book: Sy Silverberg s Lasting Longer Clarke M, Parry L (1973) Aust NZ J Psychiatr 7: De Amicis LA et al (1985) Arch Sex Behav

60 PEA ( Premature Ejaculation App) On average Pea users have increased their sexual response time from 2.5 minutes in level 1 to 12 minutes in level 3 (9.5 X)

61 PE:Reduce the Sensation (dampen the afferents of the reflex) Lidocaine/ prilocaine cream SS creams Anesthetic throat spray Condoms (Barrier ) EMLA Asian form. Choraseptic OTC especially those for lasting longer Lidocaine 2.5%, prilocaine 2.5%, mins pre-intercourse Think of the Queen of England

62 Topical Treatment of PE Local anaesthetics Lidocaine or prilocaine cream, gel or spray Diminish sensitivity of glans penis SS cream Made from extracts of nine herbs Some have local anaesthetic properties Applied to glans penis one hour before coitus Washed off immediately prior to intercourse Henry R, Morales A. Int J Impot Res 2003;15(4): Busato W, Galindo CC. BJU Int 2004;93(7): Choi HK, Jung GW, Moon KH, et al. Urol. 2000;55(2): Choi HK, Xin ZE, Choi YD, et al. Int J Impot Res. 1999;11(5): I

63 Summary on Current Therapies for PE Benefits, Risks and Limitations Topical Local Anesthetics Improvements in IELT of 5-10 minutes claimed but some methodological inconsistencies Lidocaine and / or prilocaine creams, with or without fluoxetine (claims 70-80%) SS cream (claims 80-90%) Unwanted effects include penile anaesthesia, erectile dysfunction and partner genital anaesthesia McMahon and Meston (co-chairs) et al. Disorders of Orgasm in Men and Women, Ejaculatory Disorders in Men. I

64 Promescent vs EMLA Promescent FDA approved, nonprescription 3 10 sprays as needed on demand Works in 10 minutes Don t require a condom No significant side effects Some mild irritation of female partner reported EMLA Not FDA approved, used off label ( skin anesthetic) On demand Works in minutes Need condom Some abnormal skin sensation and burning, temp sensation, pale skin,redness or swelling

65 Use of PDE 5 Inhibitors in PE Indicated for ED not PE Role in PE not established Minimal double-blind placebo controlled data available Effect on IVLT questionable; only two studies show increased IVLT while others show no effect on IVLT Some evidence of decrease in refractory period from orgasm to next erection J & J Pharmaceutical Services LLC, 2007 Sommer F, Klotz T, Mather MJ. Treatment of premature ejaculation: a comparative vardenafil and SSRI crossover study. AUA 2005, San Antonio. Abstract 1858 McMahon CG, Stuckey BGA, Andersen M, et al. J Sex Med 2: , 2005 Bar-Yosef Y, et al. J Urol 177 Suppl, AUA 2007 Abstract 1171 Mondaini N et al (2003) IJIR 15: Aversa A et al (2000) Hum Reprod 15: Sommer F et al (2005) J Urol 173 (Supp): 202

66 Antidepressants, Serotonin and Sex Serotonin is broadly associated with mediation of central sexual inhibition Different receptors have different effects - some of them excitatory Animal studies suggest that peripheral serotonergic fibres downregulate penile sensory information, leading to delayed or absent orgasm Enhanced CNS serotonergic activity may lead to reduced dopaminergic activity, elevated prolactin levels and loss of sexual drive I

67 Antidepressants and PE Unlicensed application Continuous vs. loading dose / situational dosing Situational dosing taken 3-4 hours before sex Currently available antidepressants, intended for treatment of depression, have long half-lives There is a trade-off between beneficial effects on ejaculation and adverse effects : there are reports of around 60% of patients treated for depression with SSRIs experiencing delayed or absent orgasm I

68 Tricyclic Antidepressants Antidepressant effects are due to serotonin and noradrenaline reuptake inhibition Ejaculatory effects due to SRI Other side effects due to other receptor effects Antihistamine: drowsiness, weight gain Antimuscarinic: dry mouth, constipation, blurred vision, drowsiness 1 -blocker: hypotension, dizziness, drowsiness, ejaculatory pain I

69 Rapid ejaculation: Pharmaceutical methods Clomipramine : 5 HT- uptake inhibitor mg OD or 50 mg prn - side effect profile Serotonin-reuptake inhibitors (SSRI s) - Prozac (fluoxetine) mg - Paxil (paroxetine) mg - Zoloft (sertraline) mg

70 SSRI s for PE Need to be taken daily to be most effective Off label use If primed by po intake may work PRN after 4 6 hours Side effects ( about 50%) can include reduced sex drive or ED, nausea, dry mouth, headache,diarrhea, restlessness, rash, increased sweating, weight gain, drowsiness, insomnia Have to watch coming off SSRI s

71 Dapoxetine Mode of Action Dapoxetine increases serotonin levels in the synaptic cleft by inhibiting re-uptake into the axonal terminal ( supraspinal) Dapoxetine undergoes rapid absorption (peak conc 1.3 hrs) and elimination, resulting in minimal drug accumulation (24 hours < 5% of peak) Not yet approved in Canada J & J Pharmaceutical Services LLC, 2007

72 On Demand Treatment The 30- and 60-mg doses of dapoxetine demonstrate dose-proportional pharmacokinetics, which are unaffected by multiple dosing Nausea is the most common adverse event Mild in severity, decreases with continued doses, resulted in limited discontinuation despite 9 months of treatment No tolerance after 12 months J & J Pharmaceutical Services LLC, 2007

73 Peak drug concentration (% of maximum) Dapoxetine has More Rapid Absorption and Elimination than Antidepressant SSRIs Dapoxetine 60 mg Paroxetine 40 mg Sertraline 100 mg Fluoxetine 20 mg Time post dosing (hours) Hours post dosing J & J Pharmaceutical Services LLC, 2007 data compiled from several studies Andersson et al. BJU International 2006; 97: Antidepressive SSRI data based on Summary Basis of Approval and published reports

74 Time (Minutes) Dapoxetine Significantly Improves IVLT Placebo (N=385) Dapoxetine 30mg (n=388) Dapoxetine 60mg (n=389) * * * * * p<0.001 vs placebo Baseline Week 12 Week 24 Study conducted in EU, Mexico, Canada, South America, South Africa and Israel J & J Pharmaceutical Services LLC, 2007 Study 3001: Data-on-File

75 Take Home Message Mild PE : try behavioural methods first : takes a motivated patient Dampening the afferents doesn t fix the rapid reflex, but sustains it Once off the drugs that raise the orgasmic threshold, the threshold (and patient) back to pre-med state Lifelong, more severe PE: combination therapy is best ( may be a role for mindfulness in PE!)

76 (a) (b) Seen in neurological disorders such as MS and Parkinson s Maybe an issue of low drive or arousal

77 Delayed ejaculation Common with : - increasing age - low androgen level - antidepressant use - low sexual interest primary problem

78 Delayed Ejaculation Sensory Enhancement Orgasmic Threshold Tactile Emotional Augment Sensory stimulation Tactile Emotional

79 Delayed Ejaculation Mental Arousal Enhancement Tactile Orgasmic Threshold Tactile Augment Psychogenic stimulation Tactile Emotional Emotional

80 Medications to reduce delayed ejaculation or inhibited orgasm Rule out low testosterone and maximize sexual techniques for improved sensation On an antidepressant? Can switch to something else (moclobemid, trazodone, bupropion, mirtazpine?) On antipsychotic? Switch to aripripazol or try adding wellbutrin in to push up dopamine Can a prn sympathomimetic be safely used (pseudoephedrine, midodrine?) If there is a prolactin issue try cabergoline?

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82 Difficult ejaculatory problems Retrograde ejaculation solvable Anejaculation for fertility solvable Anhedonic ejaculation - difficult Spontaneous ejaculation difficult Pain with ejaculation : r/o prostatitis and bladder/urethral problems : can be very difficult Neurogenic inhibited ejaculation very difficult Psychogenic delayed orgasm - specialist

83 The role of the pelvic floor Don t forget this in men! Helps with improvement of poor orgasmic sensation ( anhedonic ejaculation) Improves force of expulsion phase May assist with erection Does help bladder and bowel incontinence especially if neurogenic issue

84 Thanks for listening!