Erectile Dysfunction [Dr. Edmond Wong]
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Erectile Dysfunction [Dr. Edmond Wong]

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Summary of Male sexual dysfunction

Summary of Male sexual dysfunction

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  • Key Presentation Points <br /> Cavernosal tissue is sponge-like, with a mesh of interconnected cavernosal spaces, which are also called cavernous sinuses or lacunar spaces. <br /> The cavernosal spaces are lined with vascular epithelial cells and are separated by trabeculae, which are composed of bundles of smooth muscle fibers, with an extracellular matrix of elastin, collagen, and fibroblasts. <br /> Blood supply to the penis is provided by the cavernosal arteries, which are branches of the penile artery that itself originates from the internal pudendal artery. <br /> The cavernosal arteries run the length of the corpora cavernosa and subsequently divide into twisting branches called helicine arteries. <br /> Three sets of veins drain blood from the penis—the deep, intermediate, and superficial veins. <br /> The deep veins drain the corpora cavernosa and the corpus spongiosum. <br /> Andersson K-E, Wagner G. Physiology of penile erection. Physiol Rev 1995;75:191-236. <br />
  • The most common factor involved in organic erectile dysfunction (ED) is impaired blood flow into the penis, which is common in patients with <br /> atherosclerosis (associated with approximately 40% of ED cases in men over 50 years of age1) <br /> diabetes (occurring in an estimated 50% [range, 28% - 59%] of patients with diabetes, regardless of type, with prevalence dependent on age and diabetes severity2-5) <br /> Other chronic illnesses and medical conditions associated with ED include: <br /> chronic renal failure (40%)6 <br /> multiple sclerosis (71%)8 <br /> chronic obstructive respiratory disease (30%)10 <br /> penile abnormalities, such as those found in Peyronie’s disease11 <br /> endocrine disorders (eg, hypogonadism, hyperprolactinemia, hypothyroidism, and hyperthyroidism) <br /> psychiatric disorders (~ 90% of men with severe depression).12 <br />
  • . <br />
  • Both men and his partners <br />
  • Lifelong condition : present since the onset of sexual maturity <br /> Acquired condition : that develops after an interval of normal sexual function <br /> Natural variable PE: occurs in specific situations. <br /> Premature-like ED: men with ejaculatory latency times in the normal range perceive their ejaculation to be premature <br />
  • Physiology of ejaculation in unimpaired in patient with ED, however the lack of voluntary control is distressing <br /> Shamloul R: Chronic prostatitis in PE : a cohort study in 153 men <br />
  • The ejaculatory center in the spinal cord (L2 –L3) is activated when arousal reaches a certain threshold (!A2). Immediately prior to ejaculation, <br /> efferent sympathetic impulses trigger the partial evacuation of the prostate gland and the emission of semen from the vas deferens to the <br /> posterior part of the urethra. This triggers the ejaculation reflex and is accompanied by orgasm, the apex of sexual excitement. The effects <br /> of orgasm can be felt throughout the entire body, which is reflected by perspiration and an increase in respiratory rate, heart rate, blood pressure, and skeletal muscle tone. During ejaculation, the internal sphincter muscle closes off the urinary bladder while the vas deferens, seminal vesicles and bulbocavernous and ischiocavernous muscles contract rhythmically to propel the semen out of the urethra. <br />
  • 5-HT1A & 5-HT2C plays a key role in regulating ejaculation at the central level <br />
  • 12-week placebo-controlled trails in USA of 2614 men <br />
  • Winter Shunt <br /> El-Ghorab <br /> Quackels /Sacher <br /> Grayhack <br />

Erectile Dysfunction [Dr. Edmond Wong] Erectile Dysfunction [Dr. Edmond Wong] Presentation Transcript

  • Male sexual dysfunction Edmond Wong
  • A B C • Name the structures A, B, C and D (0.5 mark each) D
  • • A : Skin (0.5) • B : Dartos fascia (0.5) • C : Buck’s fascia (0.5) • D : Tunica albuginea (0.5)
  • What is the definition of ED? • Persistent inability to initiate and maintain an erection sufficient for satisfactory sexual activity • Better not to use “Impotence” as it is less precisely defined
  • What is prevalence & severity? • Massachusetts Male Aging Study (MMAS) • Prevalence – – Men 40-70yo • ~50% have ED • Mild ED: 17% • Moderate ED : 25% • Complete ED : 10% • ED prevalence increases with age – 50% at age 50, 60% at age 60, 70% at age 70
  • What is innervation of erection and ejaculation? • Autonomic – Sympathetic nerves from T11-L2 – Parasympathetic from S2-4, form the pelvic plexus – The cavernosal nerves are branches of pelvic plexus (i.e. parasympathetic) that innervate the penis – Parasympathetic stimulation causes erection – Sympathetic activity causes ejaculation and detumescence (loss of erection)
  • What is innervation of erection and ejaculation? • Somatic – Somatosensory information travels via the pudendal nerves – Onuf’s nucleus (S2-4) is the somatic centre for efferent innervation of the ischiocavernosus and bulbocavernosus muscles of the penis • Central – Medial preoptic area and paraventricular nucleus (PVN) in the hypothalamus are important centres for sexual function and penile erection
  • What is the arterial blood supply of penis? • Originate from internal pudendal artery • Three branches of common penile artery which join to form vascular ring near the glans • Bulbourethral artery – Supplying the bulb and corpus spongiosum • Dorsa penile artery – Skin, fascia and the glans penis and forms anastomoses with the bulbourethral artery at he glans. These anastomoses allow division the the urethra during urethral stricture surgery without compromising the blood supply to the distal urethral • The cavernous artery – Supplies only the cavernosal bodies & gives off many helicine arteries which supply the trabecular erectile tissue & sinusoid. Does not anastomose with other 2 penile arteries • Pulsations absent in penile vessels – likely vascular cause of ED
  • What is the venous blood supply of penis? • Skin and subcutaneous tissue  saphenous vein • Emissary veins draining corpus cavernosum and corpus spongiosum  deep dorsal vein  periprostatic venous plexus • Emissary veins draining proximal corpora cavernosa  nternal pudendal veins
  • Physiology of Erectile ResponsePhysiology of Erectile Response Complex process combining • psychological stimuli • neurologic event • smooth muscle relaxation • arterial dilation • venous compression
  • What are the five phases of erection? Phase Term 0 Flaccid phase 1 Latent (filling) phase 2 Tumescent phase 3 Full erection phase 4 Rigid erection phase 5 Detumescence phase
  • What is mechanism of erection? • Neuroendocrine signals from the brain, created by audiovisual or tactile stimuli • Signals are relayed via the cavernosal nerve to the erectile tissue of the copora cavernosa, activating the veno-occlusive mechanism • This triggers increased arterial blood flow into sinusoidal spaces with relaxation of cavernosal smooth muscle, and opening of the vascular space • Compressing the subtunical venous plexuses, decreasing venous outflow • Both spongiosus and cavernosus are surrounded by tunica albuginea, which consist of outer longitudinal and inner circular layers. The sliding of 2 layers over each other during engorgement lead to occlusion of emissary veins • Rising intracavernosal pressure and contraction of the ischiocavernosus muscles produces a rigid erection
  • Mechanism of erection • Full erection phase: – Compression of the deep dorsal and cricumflex vein btw Buck’s fascia & engorged cavernosa  glanular tumescence • Rigid –erection phase: – Ischiocavernosus and bulbocavernosus muscle forcefully compress the spongiosum and penile veins  further engorgement and increase pressure in glans and spongiosum
  • Mechanism of PDE5-i • nitric oxide is synthesized from L-arginine and released by neurons, endothelial cells, and possibly corporal smooth muscle cells of the penis in response to sexual stimulation • Nitric oxide enter SM cell • Activate soluble form of enzyme guanylate cyclase (sGC) • sGC convert guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) (an active intracellular 2nd messenger) • cGMP lead to SM relaxation thru reduction of intracellular Ca  erection • cGMP is metabolize to GMP (inactive) by PDEs • Thus PDE inhibitor facilitate NO induced SM relaxation by increase accumulation of intracellular cGMP
  • What is mechanism of erection?
  • Pathophysiology of Erectile Dysfunction Inflow Outflow Failure to initiate Psychogenic / Neurogenic Failure to store Venous leak Failure to fill Arterial insufficiency
  • What is the mechanism of venogenic erectile dysfunction?
  • • What physiological process is this chart describing? (1) • What are the top and bottom row depicting? (2) • Can you name the 6 columns? (2) Q57
  • • Tumescence / erection (1) • Top row : artist depiction of the state of the cavernosal arteries during different phases of erection induced by prostaglandin injection (1) • Bottom row : Doppler waveform of the cavernous arteries during this erection (1) • Flaccid, latent, tumescent, full, rigid, detumescent • (2 marks for ALL 6 correct answers)
  • What is the mechanism of ejaculation? • Tactile stimulation of the glans penis causes sensory information to travel (via the pudendal nerve) to the lumbar spinal sympathetic nuclei • Sympathetic efferent signals (travelling in the hypogastric nerve) cause contraction of smooth muscle of the epididymis, vas deferens, and secretory glands, propelling spermatozoa and glandular secretions into the prostatic urethra • There is simultaneous closure of the internal urethral sphincter and relaxation of the extrinsic sphincter • Rhythmic contraction of the bulbocavernosus muscle leads to the pulsatile emission of the ejaculate from the urethra
  • Risk Factors for ED • Aging • Systemic diseases: D.M., hypertension, atherosclerosis, hyperlipidemia • Endocrine disorders: hypogonadism, hyperprotactinemia • Alcohol abuse or smoking • Trauma or surgery to pelvis or spine • Depression or stress • Drugs: antihypertensives, antidepressants, hormones
  • What are the causes of ED? • IMPOTENCE – Inflammatory – prostatitis – Mechanical – Peyronie’s disease – Psychological – depression – Occlusive vascular factors – arteriogenic, PVD – Trauma – pelvic fracture – Extra factors – pelvic surgery/RRP – neuro (cavernosal nerve)-vascular (to cavernosa) injury – Neurogenic – stroke/spinal cord defect – Chemical – alcohol, smoking, drugs (diuretics/anti-HT) – Endocrine – DM
  • Aetiological Causes Psychogenic • anxiety • depression Endocrine • hormonal deficiency Neurogenic • surgery or trauma to pelvis or spine • diabetes mellitus or alcohol
  • Aetiological Causes Arteriogenic • hypertension, smoking, D.M. • hyperlipidaemia • surgery or trauma to pelvis Venous • functional impairment of the veno-occlusive mechanism Drugs • antihypertensives, antidepressants
  • What medication asso with ED? • Diuretics & antihypertensive • Antidepressant • Anti-anxiety • Anti-epileptic drugs • Pakinson’s disease med • Antihistamines • NSAIDs • Antiarrhythmics • H-2 blockers • Muscle relaxants • Prostate cancer medication • Chemotherapy
  • What is the difference between psychogenic vs organic causes? • Psychogenic – Sudden onset – Situational – Morning erection +ve – Rigidity of morning erection – Other psychological complaints – Spouse relationship – Abnormal sexual development • Organic – Gradual onset – Always – Morning erection –ve – Chronic medical illness (DM, HT, IHD) – Pelvis trauma / surgery – Endocrine / Neurological disease – Recreational drugs – +/- Loss of libido – +/- Reduced size of penis
  • DiagnosisDiagnosis
  • Scenario • M/70 • HT/DM • Worsening erectile function for 1 year • Affecting relationship with 30-year-old wife
  • What is the specific history for ED? • Sexual – Onset (sudden or gradual) – Duration, severity – IIEF – Early morning erections? – Loss of libido, sexual relationship issues (different partners) – Previous treatment – Patient’s expectation • Medical and surgical – Hypertension; cardiac disease; peripheral vascular disease; diabetes mellitus; endocrine or neurological disorders; pelvic surgery, radiotherapy, or trauma • Drugs – Antipsychotic drugs, anti-anxiety drugs, diuretics, chemotherapy, etc • Psychosocial – Anxiety, depression • Social – Smoking, alcohol consumption
  • What is IIEF? • IIEF (International Index of Erectile Function) 1997 • For assessment of intensity of ED • Best description of own situation in last 6 months of sexual activity
  • What is IIEF? • Five domains 1. Erectile function 2. Orgasmic function 3. Sexual drive 4. Intercourse satisfaction 5. Overall satisfaction • Short form: IIEF-5 – Scoring 1-5 for each, Total 25 – No ED: 22-25 – Mild ED: 17-22 – Mild to moderate: 12-16 – Moderate ED: 8-11 – Severe ED 1-7
  • What is IIEF-5?
  • What is the physical examination? • Height , weight BMI , BP • Secondary sexual characteristics to rule out hypogonadism • Thyroid evaluation • Cardiovascular system – LL pulses • Abdominal – Waist cricumference • Neurological system – Penile Sensatiion, bulbocarvernosus reflex, LL neurology • Genital-urinary system – Penile deformity, phimosis, Peyronie's plaques – Testicular size, consistence and mass – DRE: anal tone, prostate
  • What is the Ix? • L/RFT • PSA • Fasting glucose • Lipid profile • TFT • Hormone profile – Testosterone – Prolactin • Urinalysis
  • Why should ED be investgiated ED is associated with other morbidities in 20% • DM • Occult cardiac disease • Dyslipidaemia • Endocrine disorders: hypogonadism • CVA – 50%
  • Cardiovascular assessmentCardiovascular assessment
  • What is cardiac evaluation in ED? • If happened to men having symptomatic coronary artery disease ( CAD ), ED precedes 55 – 65% CAD by 3 – 4 years • Sex energy expenditure is equal to 15min walk or climbing 2 flights • Absolute risk that sex can trigger MI is 1- 2 per million
  • Princeton II consensusPrinceton II consensus ED as warning sign of vascular / cardiac disease
  • What is Princeton II consensus?
  • What is Princeton II consensus?
  • What is Princeton II consensus? • Low risk – Controlled HT, NYHA 1, <3 risk factors for IHD, stable angina, uncomplicated past MI • Intermediate risk – >/= 3 risk factors, NYHA 2, <6 weeks from MI • High risk – High risk arrhythmia, unstable angina, recent MI (<2 weeks), HOCM, NYHA 3-4, uncontrolled HT
  • What are the indications for specific diagnostic tests? • Primary erectile disorder (not caused by organic disease or psychogenic disorder) • Young patients with a history of pelvic or perineal trauma • Patients with penile deformities that might require surgical correction, e.g. Peyronie’s disease, congenital curvature • Those unresponsive to medical therapy • Complex psychiatric or psychosexual disorders • Complex endocrine disorders • Medicolegal reasons, e.g. implantation of penile prosthesis, sexual abuse
  • What are the special Test? 1. Nocturnal penile tumescence (NPT) 2. Caverject Trial 3. Vascular imaging 4. Duplex USG 5. Cavernosometry 6. Penile arteriography
  • What is nocturnal penile tumescence testing? • 80% Noctural Penile Tumescence (NPT) occurs during REM sleep • Rigiscan device contains 2 rings which are placed around base and distal penile shaft to measure tumescence and number, duration, and rigidity of nocturnal erections • Should be done on at least two nights. • A functional erectile mechanism is indicated by an erectile event of – at least 60% rigidity recorded on the tip of the penis – that lasts for 10 min or more • Gold Standard – Organics vs Psychogenic
  • What is nocturnal penile tumescence testing?
  • What is intracavernous injection test? • A positive test is a rigid erectile response (unable to bend the penis) that appears within 10 min after the intracavernous injection and lasts for 30 min • This response indicates a functional and rule out veno-occlusive dysfunction, although co-exist with arterial insufficiency • If inconclusive as a diagnostic procedure and Duplex ultrasound of the penile arteries should be requested • Assisted in Ix including Duplex USG / DICC / penile arteriogram • Positive test shows that a patient will respond to the intracavernous injection program
  • What is duplex ultrasound of penile arteries? • Assess cavernosal arterial inflow to corpora cavernosa • Normal value – Peak systolic blood flow >35 cm/s – End diastolic velocity <5 cm/s and – Resistance index >0.8 • Further vascular investigation is unnecessary when a Duplex examination is normal
  • • Name this investigation (1) • In investigating what condition is this used? (1) • What is the finding shown? (1) Q27
  • • Pharmacologic cavernosography (1)/ Dynamic infusion cavernosgraphy & cavernosometry (DICC) (1) • ED (1) • Venous leakage along pelvic veins suggestive of veno-occlusive dysfunction (1)
  • Cavernosography • Indication: 1. evaluate venous problems in men with ED 2. Investigation of priapism (high flow) 3. Assessment of penile fractures/injury to assess cavernosal damage 4. Assessment of Peyronie’s disease (rarely used) • Contraindication: – Hx of contrast allergy
  • Carvernosography • Two 19–22 G butterfly needles inserted into the corpora • 60-100ml Omnipaque or urograffin infused slowly to obtain penile pressure 90mmHg • If penis not erection , contrast leakage • Fluoroscopy: AP , Rt, Lt oblique view • Normal: no contrast visualized outside the 2 corpora cavernosa • Abnormal: Contrast leakage or significant curvature • Patient asked to squeeze penis for 5min to ensure complete emptying
  • • Advantage: more sensitive and accurate compare to doppler USG for venous leakage • Disadvantage: – Invasive – Can be painful – Risk of infection – Contrast related fibrosis within corpora – Risk of priapism
  • Dynamic Infusion Cavernosometry & Cavernosography • 4 phases – Injection of vasoactive agents (alprostadil, Bimix, Trimix) into one corpus cavernosum to relax the corporeal smooth muscles – Pharmacologic cavernosometry (infusing the penis with heparinized saline whilst monitoring the intracavernosmal pressure) – Cavernosal artery systolic occlusion pressure (CASOP) reached as intracavernosal pressure drops – Pharmacologic cavernosography (infusing contrast into the corporeal tissue and obtaining radiographic images of the penis and perineum to see if there is venous leakage • Normal: – A gradient between the CASOP and the brachial artery pressures of <35mmHg – an equal pressure between the right and the left cavernous arteries Venous leakage: -Inability to occlude systolic pressure -Large gradient between CASOP & brachial systolic pressure -Rapid drop of intracavernosal pressure upon stopping of infusion
  • What is the indication of arteriography and dynamic infusion cavernosometry or cavernosography? • Arteriography and DICC: dynamic infusion cavernosometry or cavernosography should be performed only in patients to rule out venous leakage who are being considered for vascular reconstructive surgery
  • TreatmentTreatment
  • Treatment of Erectile Dysfunction • Treat underlying disease to preserve health • Elimination of modifiable risk factors • Disorders that need treatment as part of ED management - relationship conflict - depression, psychogenic ED - hypogonadism, hyperprolactinaemia
  • Treatment of Erectile Dysfunction • Cardiovascular status of the patient • Is the patient able to resume sexual activity? - if not, cardiovascular assessment and intervention may be appropriate • Patient and partner choices play important role in identifying successful treatment
  • What are the treatment options? • First-line therapies – Lifestyle modification, psychosexual therapy – PDE5i • Second-line therapies – Intraurethral injection of alprostadil – Intracavernosal injection of alprostadil – Vacuum constriction devices • Third-line therapy – Surgical implantation of prosthesis – Penile vascular reconstruction
  • What is the lifestyle modification to improve ED? • Smoking • Alcohol • HT, DM • Obesity (BMI), exercise • A multicentre, randomised study – In obese men with moderate ED compared 2 years of intensive exercise and weight loss – Significant improvements in body mass index (BMI) and physical activity scores, as well as in erectile function • Esposito K, et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 2004 Jun;291(24):2978-84
  • What is pyschosexual therapy? • Identify and treat underlying psychological diseases • Provides information and treatment in the form of sex education, instruction on improving partner communication skills, cognitive therapy, and behavioral therapy
  • What is the general efficacy of various treatment? • PDE5i - 80% success – DM 60%, NSRRP 70% • ICI - 90% • VCD - 90% • MUSE - 50%
  • Phosphodiesterase type-5Phosphodiesterase type-5 (PDE5) inhibitors(PDE5) inhibitors
  • What is Phosphodiesterase type-5 (PDE5) inhibitors? • sildenafil (Viagra) – half-life 4h • tadalafil (Cialis) – half-life 17.5h • vardenafil (Levitra) – half-life 4h • All have similar effect and outcome • Enhance cavernosal smooth muscle relaxation and erection by blocking the breakdown of cGMP to 5GMP. Sexual stimulus is still required to initiate events • Make sure no Contraindications – Concomitant use of nitrates – Hx of retinitis pigmentosa – Princeton high risk group – Severe liver function impairment • IC50 is the concentration of drug required to produce 50% inhibition of target enzyme. Vardenafil has the lowest IC50 0.7nM compared to 0.9 for tadalafil and 3.5 for sildenafil
  • Character of PDE5-i Sildenafil (Viagra) Vardenafil (Levitrat) Tadalafil (Cialis) Onset of action 15 min -1hr 15min -1hr 15min -2 hr Effect of food Reduced absorption with fatty food Reduced absorption with fatty food NONE Dosage 20,50,100mg 5,10,20mg 5,10,20mg Side effects Headache, dyspepsia, facial flushing, blurred/blue vision, backache, myalygia Headache, dyspepsia, facial flushing, blurred/blue vision, backache, myalgia Prolong QT Headache, dyspepsia, facial flushing , blurred/ blue vision , backache, myalgia Contraindications Nitrates Nitrates, anti- arrhythmics Nitrates
  • How to counsel patient for PDE5-i? • No data comparing the efficacy for sildenafil, tadalafil and vardenafil • Choice of drug will depend on the patient preference – Unplanned sex: tadalafil – Planned sex: Sildenafil & verdenafil • Taken at least 30min to 1hr before sex, with empty stomach • Medication need appropriate sexual stimulation • Explained potential side effect
  • Adverse effect • Headache (20%) • Flushing (15%) • Dyspepsia (10%) • Rhinitis (6%) • Blurred/ blue vision (6%) (Chromatopsia) – Cross activity with PDE6 (retinal phototransduction enzyme) • Myalgia and back pain (5%) • Dizziness (5%) • Priapism (rare)
  • What to do if failed PDE5-i • 20% do not respond to any PDE5 inhibitors • Can change to another if one ineffective • Exclude fake drug • Should at least try 4 times for at least 2 drug with maximal dosage before considering failure • Re-education: – Dose , timing of med – Alcohol, interaction with fatty food – Adequate sexual arousal – Try few more times • Check testosterone: make sure not hypogonadal • Addition testosterone if hypogonadal: – General improvement in sexual function – Improved erection – Enhanced responsiveness of PDE5-I • Lipitor (Atorvastatin) improve response to sildenafil (Hermann JSM 2005)
  • What is non-arteritic anterior ischaemic optic neuropathy? • FDA alert 7/2005: small number of men had lost of eyesight after taking Levitra, viagra and cialis. This non arteritic ischemic optic neuropathy cause sudden painless loss of eyesight because blood flow to the optic nerve is blocked. (disc edema) • It is not known whether these drugs cause NAION, as the condition also occur in men not taking such drugs • High risk patients for NAION include – Over 50 – DM – Hypertension – High cholesterol – Smoker – Certain eye problem
  • How about Cardiovascular safety? • No increase in myocardial infarction rates • Nitrates are totally contraindicated with PDE5 inhibitors – cGMP accumulation and unpredictable falls in blood pressure – If PDE5I is taken and the patient develops chest pain, nitroglycerine must be withheld for at least 24 hours for viagra and levitra, and for at least 48 hours for cialis
  • What is the evidence of Changing the PDE5 inhibitor in non- responder? • A randomized, open-label, crossover trial comparing sildenafil and tadalafil • Some patients might respond better to one PDE5 inhibitor than to another and vice versa • Might be explained by variation in drug pharmacokinetics – Eardley I, et al. Factors associated with preference for sildenafil citrate and tadalafil for treating erectile dysfunction in men naive to phosphodiesterase 5 inhibitor therapy: post hoc analysis of data from a multicentre, randomized, open-label, crossover study. BJU Int 2007 Jul;100(1):122-9
  • What is the evidence of regular dosing of PDE5 inhibitor in non-responder? • No randomized trials to support this intervention • Although tadalafil is licensed for daily dosing at a dose of 2.5 mg and 5 mg, neither sildenafil nor vardenafil are licensed for use in this way
  • What is the difference between on- demand and chronic use of PDE5 inhibitors? • Double-blind, placebo-controlled, multicentre, parallel-group study • Mild-to-moderate ED randomised to receive once-daily vardenafil 10 mg plus on-demand vardenafil • Once-daily dosing does not offer any sustainable effect after cessation of treatment
  • What is the evidence of PDE5 inhibitors in post-RRP? • Early use of a high dose of sildenafil after RP is associated with the preservation of smooth muscle within the human corpora cavernosa • The response rate to sildenafil treatment for ED after RP in different trials up to 70% among those who underwent bilateral NSRP and up to 15% among those who underwent non-NSRP • Daily sildenafil also resulted in a greater return of spontaneous normal erectile function post RP compared to placebo following bilateral nerve-sparing RP in patients who were fully potent before surgery
  • What is the evidence of PDE5 inhibitors in post-RRP? • A randomized, double-blind, multicentre study • Compared on- demand and nightly dosing of vardenafil in men with ED following bilateral NSRP • Vardenafil was efficacious when used on demand, supporting a paradigm shift towards on-demand dosing Montorsi F, et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol 2008;54(4):924-31
  • What is the precaution with anti-hypertensive drugs? • Small additive drops in blood pressure, which are usually minor • Even when the patient is taking several antihypertensive agents
  • How about Alpha-blocker interactions? • Viagra: 50, 100mg not to be taken within a 4 hour window of an alpha blocker • Levitra: safe to use with tamsolusin. (label changed in US from previous total contraindication with alpha blockers) • Cialis: safe to use with tamsolusin 0.4mg
  • ApomorphineApomorphine
  • What is Apomorphine? • Dopamine receptor agonist • Sublingual (Uprima SL) – Erections are achieved within 20 min • Efficacy rates (erections sufficient for intercourse) range from 30% to 55%) • Acts centrally on dopaminergic receptors in the paraventricular nucleus of the hypothalamus to enhance and co-ordinate the effect of sexual stimuli • Adverse effects: nausea; headache; dizziness • Apomorphine is not contraindicated in patients taking nitrates or antihypertensive drugs • Used in patients with certain contraindications for the use of PDE5 inhibitors, e.g. nitrates • Multiple daily dosing possible: once / 8 hours
  • Intraurethral therapyIntraurethral therapy
  • What is the mechanism of prostaglandin E? • Prostaglandin E binds to PGE receptor, activating adenylate cyclase which converts ATP to cAMP • cAMP activate PKA which brings about the relaxation of the smooth muscle directly without NO pathway
  • What is intraurethral therapy? • Alprostadil • Synthetic prostaglandin E1 (PGE1) pellet administered into the urethra via a specialized applicator • Once inserted, the penis is gently rolled to encourage the pellet to dissolve into the urethral mucosa, from where it enters the corpora • Efficacy – 50% • Side-effects: penile pain; priapism; local reactions
  • Intracavernosal therapyIntracavernosal therapy
  • What is Intracavernosal therapy? • Alprostadil • Increase cAMP within corporal smooth muscle  relaxation of SMC • Right angle at lateral mid-penile shaft • Efficacy rates for intracavernous alprostadil - 90% • Adverse effects: pain; priapism; haematoma • Contraindications: men at risk of priapism (1%) and men with bleeding disorders
  • What is Intracavernosal therapy?
  • What is Intracavernosal therapy? Locate the area of injection. Wipe off with an alcohol swab. Grasp the head of the penis, not the skin. Position the penis along your inner thigh. Maintain traction on the head after cleaning the side of the penis.
  • What is Intracavernosal therapy? • Most long-term injection users can switch to sildenafil despite underlying pathophysiology • Almost one-third of long-term intracavernous injections users who subsequently responded also to sildenafil preferred to continue with an intracavernous injection programme
  • What is combination therapy? • Papaverine – combination therapy today due to its high incidence of side-effects as monotherapy • Phentolamine - in combination therapy to increase efficacy. As monotherapy, it produces a poor erectile response
  • What is combination therapy? • Papaverine plus phentolamine plus alprostadil have never been licensed for ED • Combination had similar side-effects as alprostadil monotherapy, but a lower incidence of penile pain due to lower doses of alprostadil • Fibrosis and priaprism were more common when papaverine was used. In addition, mild hepatotoxicity has been reported with papaverine
  • What is the action to be taken with a prolonged erection? • 19-gauge needle is used to aspirate blood • If failed, an intracavernous injection of phenylephrine, starting at a dose of 200 μg every 5 min and increasing to 500 μg if necessary
  • Vacuum erection deviceVacuum erection device
  • Vacuum Constriction Device
  • • What is this device? (0.5) • Name one condition it is used for (0.5) • Name one complication from its use? (1)
  • • Vaccum constriction device (0.5) • ED, Peyronie’s disease (0.5) • Cold penis, difficulty with ejaculation, bruising, penile numbness (1 max)
  • Vaccum constriction device • Erections with these do not use physiological erection pathways • Plastic cylinder connected directly or by tubing to a vacuum- generating source (manual or battery-operated pump) • Penis is engorged by the negative pressure • Constricting ring is applied to the base to maintain the erection  should not be left in place > 30 minutes • Can be used successfully by men with a malfunctioning penile prosthesis in place • Used after explanation to prevent shortening • Disadvantage: cold numb penis, no ejaculation, discomfort in orgasm • Patients taking aspirin or warfarin should exercise caution when using these devices • Erections satisfactory for intercourse, is as high as 90%, but decreases to 50-64% after 2 years. Most men who discontinue within 3 months
  • Penile prosthesisPenile prosthesis
  • What is Penile prosthesis? • Third-line therapy • Surgical implantation into the corpora to provide penile rigidity and sufficient erectile size for sexual intercourse • Two types of prosthesis exist: malleable (semi-rigid) and inflatable (two- or three-piece) • Most patients prefer the three-piece inflatable devices due to the more ‘natural’ erections obtained. • Two-piece inflatable prosthesis can be a reliable option with fewer mechanical complications and is easier to implant • A semi-rigid prosthesis provides a constantly rigid penis and may be suitable in older patients with infrequent sexual intercourse with less mechanical failure but erosion and chronic pain
  • • AMS 700 • 5YS 90% • Side-effects: mechanical failure (5% per year); erosions (5%); infections (2%) • Reservoir in abdomen • Pump in scrotum, pair of cylinders implant into penis • Infection rate may be reduced to 1% by implanting an antibiotic- impregnated prosthesis • Infection rate is similar between primary VS revision, DM VS non-DM • Staphylococcus epidermidis- commonest • Mulcahy technique has been described in an attempt to salvage the situation and insert a new prosthesis at the time of the infected one. It involves copious wound irrigation with kanamycin, bacitracin, iodine, hydrogen peroxide, vancomycin and gentamycin. The success rate is 80% at 3 years
  • Surgical penileSurgical penile revascularizationrevascularization
  • What is surgical penile revascularization? • Post-traumatic arteriogenic ED in young patients • In young patients with pelvic or perineal trauma, surgical penile revascularization has a 70% long- term success rate • The lesion must be demonstrated by Duplex ultrasound and confirmed by selective internal pudendal arteriogram • Corporeal veno-occlusive dysfunction is a contraindication to revascularization and must be excluded by DICC • Vascular surgery for veno-occlusive dysfunction is no longer recommended because of poor long- term results
  • Androgen deficiencyAndrogen deficiency
  • hypogonadism • 95% testosterone is produce by Leydig cells • Serum level peak at 7-8am and lowest at midnight. Clinically serum testosterone is best estimated in the morning • Incidence of late-onset hypogonadism: 20% of men over 70 • <10% ED due to hypogonadism • Serum testosterone is loosely bound to albumin in 50% and 50% to sex hormone binding globulin (SHBG). Whereas 2% is free. The bioactive testosterone refers to free and albumin bound serum testosterone (~50%) • Estimation of the bioavailable testosterone is a more accurate test than total serum testosterone when investigating hypogonadism • SHBG is increase in: ageing , cirrhosis, hyperthyroidism , anticovulsants, oestrogen, HIV infection
  • Approach • History: – loss of libido, low mood, lethargy – Change in sexual function • Physical examination: – Loss of muscle mass & hair loss – regression of secondary sexual characteristics – softer and smaller testis, – gynaecomastia (aromatisation of testosterone in fatty tissue to oestrogen) • Investigation: – fasting glucose, lipid, – total testosterone, free testosterone, FSH and LH – Oestradiol, TFT & prolactin in selected case
  • Late-onset male hypogonadism • Symptom complex resulting from age- related decline in testosterone level in men • Cause: – Primary: Testicular failure – Secondary: • Pituitary or hypothalamic disorder (Kallman’s syndrome) • Conbined hypogonadism
  • Treatment • Weight loss • Clomiphene citrate • Androgen replacement therapy –CI: polycythemia, fluid retention, Ca prostate and breast , sleep apnoea, heart failure, severe renal and liver failure –Oral – first pass to liver for metabolism > too fast to have an effect –Transdermal, subcutaneous, intramuscular
  • Monitor • Serum testosterone level • Clinical signs and symptoms • Assess bone mineral density • Adverse effect: – Excessive rise in hematocrit (>54%) – Raised PSA or abnormal DRE – Ance – Increase oliness of skin – Gynaecomastia – Suppression of fertility – Some testicular atrophy
  • Testosterone & Ca Prostate? • No positive correlation btw testosterone level and Ca Prostate in prospective epidemiological studies • Small clinical trails have not shown increase in clinical prostate cancer in the testosterone group compared with the placebo groups • But no sufficient data to drawn conclusion
  • Ejaculatory disorder
  • Ejaculatory disorder • Hematospermia • Retrograde ejaculation • Premature ejaculation • Ejaculatory failure
  • Hematospermia • Commonly seen after prolonged period of sexual abstience, always resolved spontaneously • Investigation if beyond several weeks • History: – Exclude hematuria – Recent trauma – Infection (STD) – Bleeding disorder – PMH: TB, Ca prostate • Three important point need evaluation: – Patient age – Duration & recurrence – Associated hematuria
  • • Physical examination: – Blood pressure – Genital: TB, bead cord vas – Penis – DRE: prostate • Investigation: – Bld, PSA – MSU : sterile pyuria – Urethral swab for younger pt – Cytology – FR + RU if slow stream
  • Cause • Infection (40%): TB, HIV, CMV • STD: herpex, chlamydia, ureaplasma • Prostatitis (30%) • Post-TRUS + bx • Prostate cancer • Urethritis and urethral stricture • Acquire or congenital cyst of the seminal vesicle • Systemic disorder: HT, liver disease, lymphoma
  • Further investigation • TRUS: reveal abnormalities in 95% – Prostatic calcification (40%) – Ejaculatory duct calculi (40%) – Dilated ejaculatory duct (30%) – Ejaculatory duct cyst (10%) – BPH (30%) – Dilated or clacified SV (20%) – Mullerian duct remnants (7%) • Treatment: – Reassurance – Antibiotics ?
  • Retrograde ejaculation • History: – Low ejaculate volume – Post- ejaculate urine cloudy • Investigation : post-ejaculate urine examination for sperm • Cause : – Post- RPLND – DM – Bladder neck surgery, TURP – Trauma – Alpha- blockers – Urethral stricture – Spinal cord injury
  • Treatment • Medication: to close the bladder neck – Sympathomimetic : pseudoephedrine & ephedrine – TCA: imipramine – Efficacy : 50% • IVF: – Sperm retrived from alkalinised post-ejaculate urine – Fertilization rate: 50% • How to alkalinise urine? – Sodium bicarbonate: 1gm at night before & 1mg in the morning of sperm collection – Or use Liverpool solution : NaCl + NaHCO3 – Empty bladder before masturbation – Obstain post-ejaculated urine & send to lab ASAP
  • Premature ejaculationPremature ejaculation
  • Premature Ejaculation • Most important point: 1. Short ejaculatory latency time 2. Lack of ejaculatory control 3. Decreased satisfaction with sexual intercourse • Interpersonal distress • Negative man’s self-esteem • Reduced sexual function and QOL Patrick DL et al ,J Sex med 2005 Giuliano F et al, Eur Urol 2008 Rowland DL et al, J Urol 2007
  • DSM-IV-TR 2000 • Persistent or recurrent ejaculation with minimal sexual stimulation; –Before, on , or shortly after penetration –Before the person wishes it; • Must also cause marked distress or interpersonal difficulty; • Cannot be due exclusively to the direct effects of a substance.
  • The International Society for Sexual Medicine (ISSM) • The first evidence-based definition • ‘Premature ejaculation 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 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
  • Classification • Lifelong condition • Acquired condition • Natural variable PE • Premature –like ejaculatory dysfunction Cooper AJ et al, J Sex Maritla Ther 1993 Waldinger MD et al, Drugs 2007
  • What is the prevalence? • Major problem in assessing the prevalence of PE is the lack of an accurate (validated) definition • The most common male sexual dysfunction, with prevalence rates of 20- 30% • Prevalence of PE is not affected by age
  • Etiology Psychogenic: • Anxiety • Early sexual experience • Infrequent sexual intercourse • Poor ejaculatory control technique • Negative conditioning Biological cause: • Penile hypersensitivity • Hyperexcitable ejaculatory reflx • Endocrinopathy • Genetic predisposition • 5HT- receptor dysfunction
  • Neurophysiology of ejaculation
  • Neurophysiology • Ejaculatory control centers in spinal cord • Received peripheral afferents and supraspinal influences • Coordinate sympathetic , parasympathetic and somatic outputs to pelviperineal structrues
  • 5-HT neurons • Activation of 5-HT1A autoreceptors  decrease 5-HT release by presynaptic neurons (-ve feedback) • Activation of 5-HT1A decrease ejaculatory latency • Activation of postsynaptic 5-HT2C or 5-HT1B receptors prolongs ejaculatory latency • PE may be due to imbalance btw 5-HT1A (hypersensitivity) and 5-HT2C or 5-HT1B (hyposensitivity) • Increase central 5-HT  delay ejaculation
  • What is the approach to PE? • History and physical examination – Intravaginal ejaculatory latency time (IELT) • Clinical use of self-estimated IELT is adequate, stopwatch- measured IELT is necessary in clinical trials – Patient-reported outcomes (PROs) have the potential to identify men with PE • Patient-reported outcomes (PROs) have the potential to identify men with PE • Further research is needed before PROs can be recommended for clinical use – Duration time of ejaculation, degree of sexual stimulus, impact on sexual activity and QoL, and drug use or abuse – It is also important to distinguish PE from ED – ED develop secondary PE caused by the anxiety – Examination of the vascular, endocrine and neurological systems • Routine laboratory or neurophysiological tests are not recommended
  • Measurement of response • Intravaginal ejaculatory latency time (IELT) – Time between vaginal intromission & ejaculation • Perceived controlled over ejaculation • Improvement of personal distress
  • What are behavioural therapy? • ‘Stop-start’ programme developed by Semans • ‘Squeeze’ technique, proposed by Masters and Johnson • Masturbation before anticipation of sexual intercourse • Success rates of 50-60% in short term • Time intensive, require the support of a partner and can be difficult to do • Recurrence is likely after treatment cessation
  • Pharmacotherapy for PE • Anti-depressant: –TCA: Clomipramine –SSRIs: paroxetine, fluoxetine, sertraline, etc • Phosphodiesterase-5 inhibitors (PDE-5i) • Tramadol • Topical agents: lidocaine/prilocaine
  • SSRI • Increase synaptic 5-HT concentration via blockade of 5-HT transporters • Paroxetine (20-40mg), Clomipramine (10-50mg) or fluoxetine (20- 40mg) • Meta-analysis: Paroxetine produce strongest delay in ejaculation • Daily txn, effect start on 2 week • Need to withdrawn gradually over 4 week (except fluoxetine) • SE: – Psychiatric and neurological – Dermatological reaction – Anticholinergic SE – Change in body weight – Cognitive impairment – Drug-drug interactions – Sexual SE: ED and loss of libido
  • SSRI discontinuation syndrome • Especially in paroxetine • 1-3 days after drug discontinuation • Median duration: > 1 week • Reversible when SSRI reintroduced • Dizziness, nausea and emesis, headache, gait instability, lethargy, agitation , anxiety and insomnia Black K et al, J Psy Neurosci 2000 Haddad P et al, J psychopahrmacol 1998 Tamam L et al, Adv ther 2002
  • Serotonin syndrome • SSRI with long half-lives • Interactions with agents that enhance 5- HT CNS activity • Myoclonus, hyper-reflexia, sweating, shivering , lack of coordination and mental status changes Nelson EB et al, J Clin Psychiatry 1997 Lane R et al, J Clin Psychopharmacol 1997
  • Dapoxetine • New agents under development • Rapid onset (1.29hr) and short half-live (1.49hr) • On-demand dapoextine 30 or 60mg significantly improved outcome vs placebo • IELT increase 3.6x from baseline • SE: nausea, diarrhoea, headache, dizziness and insomnia Pryor JL et al, Lancet 2006
  • PDE-5i • Results has been conflicting • No pharmacological rationale • Paroxetine + sildenafil vs paroxetine: increased IELT and satisfaction but with more SE (headaches and flushing) Salonia A et al, J Urol 2002 • No effect in men without coexiting ED, cause decrease in post-ejaculatory refractory period Chen J et al, Urology 2002
  • Tramadol • Centrally acting synthetic opioid • Inhibit nor-adrenaline and serotonin reuptake • Rapidly absorbed and eliminated • Increased IELT, sexual satisfaction and ejaculatory control vs placebo (p<0.05) Safarinejad MR et al, J Clin Psychopharmacol 2006 Salem EA et al, J Sex Med 2008
  • Topical agents • Topical lidocaine/prilocaine cause desensitization • Increase mean IELT by 2.4x vs placebo (p<0.01) Dinsmore WW et al, BJU Int 2006 • SE: local numbness(12%), loss of erection • Severance Secret cream: increase IELT and sexual satisfaction vs placebo Choi HK et al, Urology 2000 Choi HK et al, Int J impot Res 1999
  • Conclusion • PE is an under-treated condition due to lack of understanding of its cause and potential therapy, and because of its sensitive nature • 5-HT has been implicated as a key mediator of ejaculatory control
  • Conclusion • Available therapy include off-label use of SSRIa and PDE-5i , as well as topical anaesthetics • New on-demand agents like tramadol and dapoxetine are currently under evaluation • Role of other central neurotransmitter as future targets to delay ejaculation needs further investigation
  • Ejaculatory failure • Cause: Post SCI, RPLND , psychogenic • History: what level , bowel and bladder fxn • Investigation: – SA: azzospermia – Post-orgasmic urine  no fructose • Treatment: Electro-ejaculator – Seager electro-ejaculator – Rectal probe to stimulate perirectal, periprostatic sympathetic nerves – May require GA – Watch out for autonomic dysreflexia in above T6 lesion – Sperm: poorere quality & mobility • Alternative: sperm retrieval technique (pregnancy rate 70%)
  • Peyronie’s diseasePeyronie’s disease
  • What is Peyronie’s disease? • Fibrous plaque within tunica albuginea of penis • associated with DM, antiepileptic drugs and beta blockers • Curvature, penile pain or shortening • Erectile dysfunction
  • What is the cause? • Trauma to tunica albuginea • Wound healing > excessive fibrotic plaque • Dorsal plaque more common • Penile curvature as corpus cavernosum can’t lengthen fully on erection limited by plaque • Associated with Dupuytren’s contracture 30% • Incidence <5%, men aged 40-70 years
  • What is natural course of the disease? • Active phase 6 months, painful erection with changing deformity • Quiescent phase 9-12 months stable deformity, painless • Natural Hx over 18 m – 13% improved – 40% stable – 47% progress
  • How to make diagnosis? • By history and P/E – History • Disease Duration • Pain • Penile deformity –angle, direction • Stability • Penile length • Erections , able to penetrate • IIEF • Risk factor for ED – P/E • Assess degree of curvature by 1 photogragh, 2 IC PGE1 • Exam for plaques, location, size • Penile length, stretched & flaccid state • Extremeties for Dupuytren’s contracture
  • What is the treatment? • Early disease <3m consider medical Tx / injection / ESWL, low successful rate – Oral vit E • 200mg tds for 3 months • In a randomized trial vitamin E has been shown to improve pain in 75% of patients and improves the deformity in 10% – Oral colchicine x3m (limited evidence for efficacy) – Intralesional verapamil, steroid x 6m
  • Photograph taken during a procedure • What is being done? (1) • What procedure is this? (0.5) • Name 3 complications from this procedure (0.5 each) Q45
  • • Artificial erection from injection of saline into corpus cavernosum (1) • Correction of penile curvature eg. in Peyronie’s disease (0.5) • Shortening of penis, erectile dysfunction, deformity recurrence, palpable suture through penile shaft skin, altered/decreased penile sensation (0.5 each, total 1.5)
  • Is ESWL useful? • Initiating an inflammatory reaction thru direct damage to plaque and result in plaque resorption • No study has demostrate any improvement in plaque size or curvature • NICE do not recommend
  • What are the indications for Surgery? • Disease present for at least 12m • stable for at least 3m • Deformity makes intercourse difficult • Quality of erection important • ED > ? Prosthesis
  • Surgery: Penile shortening • Indicated in pt: no ED , <60degree curvature, no hourglass demormities or hinge effect • Must warn pt of Penile shortening effect • Nesbit – Penis degloved via circumglandular incision – Artificial erection with NS – ellipitcal incision: 1mm for 10 degree deformity curvature on convex side – Complication: all penile shortening, 1% ED rate, recurrence of deformity – Success rate 80%
  • Surgery: Penile maintaining • Lue’s procedure – By incising the plaque and interposing a graft (fascia lata / vein graft/ Gortex graft) – Do cause penile shortening but not to the extent that corporal plication – More ED – 15% – Not recommended for complete excision of the plaque due to compromising veno-occlusive mechanism and causing ED • Surgery in general – Success rate: 80% – Risk: bleeding, infection , bruising – Loss of 1cm in 26% – ED in 15% – Recommend penile traction device or penile rehab with PDE5-i • About 10% of patients will subsequently require circumcision due to secondary phimosis
  • When is prothesis required? • Penile prosthesis is indicated in patients with both Peyronie’s disease and severe ED • After insertion and inflation of penile prosthesis, the penis is bent in opposite direction to break the plaque (modelling) – 90% successful rate
  • PriaprismPriaprism
  • Priapism • Definition: – Persistent erection > 4 hours – Not related to sexual desire • Two age group: – 5-10 yo – 20-50 yo 3. Stuttering priaprism – repeated, shorter self-
  • Presentation • FOUR Main questions: 1. Duration of erection > 4 hours? 2. Painful / non painful ? (Ischemic vs nonischemic) 3. Previous history of priapism 4. Predisposing factors • Physical examination: – Rigid corpora cavernosa – Flaccid Corpus spongiosum and glans penis
  • Investigation • Blood: CBP, Hb/electrophoresis (SSD) • Urine: C/ST , toxicology • Penile blood gas: – Aspirate blood directly from either corpora • Duplex USG of carvernosal arteries: – Ischemic ( inflow low or absent) – Non ischemic (inflow normal or high) • Penile pudenal arteriography: not readily available Appearance pH PO2 (mmHg) PCO2 (mmHg) Low flow Dark red <7.25 <30 >60 High flow Bright red = 7.4 >90 <40
  • Treatment • Conservative • Medical • Minimally invasive • Surgical treatment • Always warn patient about the possibility of impotence due to cavernosal fibrosis
  • Doppler USG can differentiate high or low flow priaprism
  • Treatment for Priapism • Cavernosal aspiration successful rate: 1/3 • Distal shunt – Winter (large biopsy needle , corporo-glanular) – Ebbehoj (Scalpel, corporo-glanular) • Lue’s modification “T-Shunt” (scalpel, corporo-glandular) – El-Ghorab: piece of tunic albuginea excised at tips of coprora via a dorsal transverse incision just distal to corona • Proximal shunt: – For failed distal shunt or severe distal penile edema – 80% successful rate, but ED > 90% – Quackels /Sacher (corporo-spongiosal) – Grayhack (corporo-saphenous) • Supra-selective embolisation of common penile artery – successful rate 80% – Absorbable materials like clots and gel cause less ED than coils or permanent chemical
  • El-Ghorab
  • Quackels /Sacher
  • Grayhack
  • A procedure for a urologic emergency is about to be performed • What is the name of this procedure? (2) • What is it used for? (1) Q20
  • • Ebbehoj shunt, a type of distal cavernoglandular shunt (2, 1 mark for mentioning just “shunt” without name) • Ischemic priapism not responsive to injectional medical treatment (1)
  • How about high-flow priaprism? • Not a urological emergency • Duplex USG can confirm diagnosis • Selective internal pudendal embolisation, better with absorbable material including clots or gels • Successful rate up to 80% • If failed > open exploration and direct ligation