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Campbell’s Chapter 22

Campbell’s Chapter 22. Evaluation and Nonsurgical Management of Erectile Dysfunction and Premature Ejaculation. Brent Zamzow DO January 14, 2008. ED - Historical. Before 1970 – Psychotherapy 1970’s - Penile prosthesis & psychotherapy, sleep lab

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Campbell’s Chapter 22

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  1. Campbell’s Chapter 22 Evaluation and Nonsurgical Management of Erectile Dysfunction and Premature Ejaculation Brent Zamzow DO January 14, 2008

  2. ED - Historical • Before 1970 – Psychotherapy • 1970’s - Penile prosthesis & psychotherapy, sleep lab • 1980’s - Yohimbine, intracavernous & transurethral therapy, vacuum device, testosterone, ultrasound • 1990’s to present - oral PDE-5 inhibitors • ED treatment • Psychologist → Urologist → Primary Care

  3. ED - Historical • 1999 - 1st International Consultation on Sexual Medicine (ICSM) • ED redefined as consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual performance • ED is a symptom of many medical problems • requires physician involvement • internet prescribing condemned • Goal-directed approach

  4. ED - Historical • 2nd ICSM - 2004 • Patient-centered & evidence-based • See illness through patient’s eyes • Holistic approach - biologic, psychologic & social aspects • Flexible & individualized approach • Let patient choose his best therapy • 3rd ICSM - July 10-13, 2009

  5. Self-Administered Questionnaires • International Index of Erectile Function (IIEF) • most common questionnaire • addresses erectile function, orgasmic function, desire, intercourse satisfaction, overall satisfaction • Male Sexual Function Scale • 2nd ICSM • Doesn’t take into account partner

  6. History Taking • Medical • atherosclerosis, DM, depression • organic vs. psychogenic • medications, pelvic surgery?, trauma? • Sexual • severity, onset, duration • Psychosocial • social, occupational, family, financial • Don’t assume everyone’s involved in monogamous, heterosexual relationship

  7. Exam & Labs • Physical Exam • General screening for risk factors • body habitus, cardiovascular, neurologic, genital • Labs • Fasting glucose, lipids, hormonal profile, thyroid function • Findings • Educate patient on modifiable risk factors • stress, marital conflict, smoking, EtOH, obesity, bicycle riding, prescription drugs

  8. ED Treatment Options

  9. Vascular Evaluation • Goal - diagnose & quantify arterial & veno-occlusive dysfunction • Options: • Combined intracavernous injection & stimulation (CIS) • Duplex ultrasound • Dynamic infusion cavernosometry & cavernosography (DICC) • Selective penile angiography

  10. Evaluation of Penile Blood Flow 1stline • Combined Intracavernous Injection & Stimulation (CIS) • Inject vasodilator, stimulate, assess • Most commonly performed diagnostic procedure for ED • Bypasses neurologic & hormonal influences to evaluate vascular status • Use: • alprostodil 10-20ug • papaverine & phentolamine (Bimix 0.3 mL) • Trimix 0.3 mL • 27 or 29g needle, compress for 5 min after injection

  11. 1st line - CIS • Normal results = normal venous occlusion • False negative up to 20% w/ borderline arterial flow

  12. Evaluation of Penile Blood Flow 2nd Line • Duplex Ultrasonography • Penile blood flow study (CIS & blood flow measurement by US) is most reliable & least invasive evidence based assessment of ED • Red = towards probe • Blue = away from probe • Can visualize dorsal & cavernous arteries in real time • Can diagnose high flow priapism

  13. 2nd line - Ultrasound • Technique • Measure flow velocities 5-10 min after injection • Rate erectile quality • Look at both cavernous arteries & diameters • Asymmetric cavernous arterial flow >10cm/s or reversal of flow across a collateral may mean atherosclerotic lesion

  14. 2nd line - Ultrasound • Doppler Waveform

  15. 2nd line - Ultrasound • Peak Systolic Velocity (PSV) • PSV < 25 correlates with abnormal pudendal arteriography • Severe unilateral arterial insufficiency >10 cm/s asymmetry • Severe vascular ED, diameter increase is <75%, diameter rarely exceeds 0.7 mm • Be aware of variant vessel anatomy

  16. 2nd line - Ultrasound • Veno-occlusive Dysfuntion • Need to trap blood & limit venous outflow • Venogenic impotence • High systolic flow (>25 cm/s) • Persistent end-diastolic flow (EDV) (>5 cm/s) • Resistive Index (RI) • RI = PSV – EDV/PSV • Measure 20 min after injection & stimulation • RI > 0.9 normal • RI < 0.75 venous leakage

  17. ISCM Recommendations on US • Intracavernosal injection with color duplex Doppler ultrasound • Most informative diagnostic test • Least invasive for vascular ED, high vs. low flow priapism, Peyronie’s plaque • Useful measurements • PSV, cavernous artery diameter, EDV, RI • PSV <25 = severe cavernous artery insufficiency • PSV >35 = normal inflow • Negative relationship between age & PSV

  18. Evaluation of Penile Blood Flow3rd line • Cavernous arterial occlusion pressure • Basically penile blood pressure measurement – 1989 • Technique • Inject vasodilator • infuse saline into corpora to get pressure > systolic BP • apply Doppler to penile base • Pressure when cavernous arterial flow becomes detectable is cavernous artery systolic occlusion pressure (CASOP) • Gradient between cavernous & brachial artery pressure <35 & equal pressure on L & R is normal

  19. 3rd line – Penile Blood Flow • Pharmacologic Arteriography • Technique • Inject vasodilator • Cannulate internal pudendal artery • Inject contrast • Look at anatomy of iliac, internal pudendal, penile arteries • Aberrant anatomy in 50% of normal volunteers • Useful for anatomy, not function • Indication: • Young pt w/ ED due to traumatic arterial disruption or perineal compression injury. Essential for planning reconstruction

  20. 3rd line – Penile Blood Flow • Pharmacologic Cavernosometry & Cavernosography • Cavernosometry • Saline infusion while monitoring intracavernous pressure • Assesses penile outflow • Cavernosography • Infusion of contrast into corpora after vasodilator induced erection • Good for young men who may be candidates for penile vascular operations

  21. Historical & Investigational • Penile Brachial Pressure Index • Inaccurate • Penile Plethysmography • Penile pulse volume recording • Infrared Spectrophotometry • Radioisotopic Penography • MRA • Cavernous Smooth Muscle Content

  22. Nocturnal Penile Tumescence (NPT) • 80% NPT during REM sleep • Total tumescence time • 20% of night at puberty • Adults – 27 minutes/night • RigiScan - 1985 • Monitors radial rigidity, tumescence, number, duration of erectile events • Portable – can use at home • Can record 3 different nights up to 10 hrs each • Results • Radial rigidity >70% = good erection • <40% = flaccid penis • Normal = 3-6 erections/night, 10-15 minutes per episode

  23. NPT • NEVA device • Uses electrobioimpedance to assess volumetric changes in penis during nocturnal erections • Undetectable alternating current from glans to hip electrodes • Penile base electrode measures impedance & changes in penile length • Mean volume change in controls = 213% increase (14.4 mL)

  24. NPT Summary • Freedom from psychological influences & its ability to detect sleep-related abnormalities • Full erection = neurovascular axis is functionally intact & cause is likely psychogenic • Disadvantages • Age dependent • Costly • Not recommended as routine test for ED • Indications: • Suspected sleep disorder • Obscure cause • Nonresponse to therapy • Planned surgical treatment • Legally sensitive case • Measurement of drug effects in placebo-controlled drug trials • Suspected psychogenic cause

  25. Psychological Evaluation • ED associated with: • Anxiety • Depressive symptoms • Low self-esteem • Negative outlook on life • Emotional stress • History of sexual coercion • General vs. Situational? • Primary vs. Acquired • Substance abuse, psychiatric illness • Noncoital erections • ?Masturbatory, nocturnal, morning

  26. Hormonal Evaluation • Hypogonadism increases with age • Decrease or absence of hormonal secretion from the gonads in men • Draw testosterone between 8-11am • For screening – total testosterone • If testosterone low or low-normal • Confirm with 2nd draw + LH + prolactin

  27. Testosterone • Men produce 4-8 mg/day in pulsatile manner • Peaks in morning, nadir in evening • Converts to DHT by 5α-reductase in skin, liver, prostate • Metabolized to estradiol by aromatase in brain, fat, liver, testes • 2% unbound – free testosterone • 30% bound to SHBG • Rest bound to albumin & other serum proteins • Bioavailable testosterone = free + albumin bound • SHBG made by liver – downregulated by androgens, upregulated by estrogens • Estrogens, thyroid hormone, aging increase serum SHBG & decrease bioavailable testosterone • Exogenous androgens, growth hormone, obesity depresses SHBG & increases free testosterone

  28. Lifestyle Change & ED • Obesity • Decreased BMI = improvement in ED • Physical Activity • Sedentary = highest risk • Cigarette Smoking • Statin to lower cholesterol may improve ED • Long distance bicycle riding • No Effect • Education level • Marital status • Urban vs. Rural • Coffee • EtOH

  29. Medications & ED • Nonspecific alpha-blockers have most severe effect on erectile function • Methyldopa & Reserpine • Thiazide diuretics • Spironolactone interferes with testosterone synthesis • SSRI’s – ED & ejaculation problems • Calcium channel blockers & ACE inhibitors don’t cause ED • Alpha-1 blocker is protective • Doxazosin reduces incidence of ED

  30. Herbal Supplements for ED • 25-50% placebo response • Acupuncture – psychogenic ED • Androstenedione – may benefit men w/ low testosterone, lowers HDL 10% • Ginko biloba – may have blood-thinning effect • Korean red ginseng – may benefit • L-Arginine – precursor to Nitric Oxide, may lower BP • Yohimbine – most supplements contain little or none, can have serious side effects • Zinc – good if low zinc, can be immunosuppressive

  31. Testosterone Therapy • Injectable (IM) • Least expensive • 200-250mg q2wks • Do not replicate normal circadian rhythm • Testosterone “rush” for 72 hrs, then low by 10-12 days • Transdermal • Can simulate normal circadian levels if applied in AM • Patch – 2.5-5 mg/day • Applied daily to arm, back, or upper butocks • Side effects – itching, chronic irritation, contact dermatitis • Gel – 50, 75, or 100 mg packs • Applied daily to arms, abdomen, or shoulders • Wash hands after application • Pellet – 75mg/pellet • 2-6 pellets implanted subQ q3-6months • Buccal – 30mg tablet BID • Oral – 200mg/d • Become metabolically inactive after 1st pass through liver • Large doses toxic to liver

  32. Hormonal Therapy • DHT • Cannot be aromatized to estradiol – pure androgen • Good for hypogonadal men w/ gynecomastia, boys w/ delayed puberty • Dehydroepiandrosterone (DHEA) • Controversial • End Points • General well-being, mood, sexual interest, sexual activity

  33. Adverse Effects of Testosterone Replacement • Infertility • Suppresses LH, FSH • Breast tenderness & gynecomastia • Erythrocytosis • Mean Hct increases from 42-47% after 3 months • Induce or worsen sleep apnea • May increase PSA • ? Exacerbates prostate cancer • Prostate or breast cancer = contraindication • Monitoring • DRE & PSA q6months • Periodic H&H, LFT’s, lipid profile • Efficacy of testosterone determined by clinical response • If hyperprolactinemia – testosterone does not improve sexual function

  34. Phosphodiesterase Type-5 Inhibitors • Sildenafil (Viagra) • FDA approved 1998 • Vardenafil (Levitra) • FDA approved 8/2003 • Tadalafil (Cialis) • FDA approved 11/2003

  35. Arousal Pathway • Sexual arousal stimulates NO release at penile nerve endings • NO diffuses into vascular & cavernous smooth muscle cells • Stimulation of guanylyl cyclase & elevation of cGMP • Hyperpolarization & lowers cytoplasmic calcium • Smooth muscle relaxation & erection • PDE-5 inhibitors potentiate NO’s effect • Do not increase NO levels • Need sexual stimulation for PDE-5 inhibitors to work

  36. PDE-5 Inhibitors • Sildenafil & Vardenafil cross-react slightly w/ PDE-6 • ? Reason for visual disturbances • Tadalafil minimally cross-reacts with PDE-11 • Consequences unknown • Other side effects: • Headache, flushing, low BP, dyspepsia due to PDE-5 inhibition in vascular or GI smooth muscle • Sildenafil 20mg TID FDA approved in 2005 for pulmonary HTN

  37. PDE-5 Inhibitors • Very effective at enhancing erectile function • Good for different patient subgroups, ED causes, outcomes measured • Difficult to Treat Patients • All effective in ED + DM • All improve ED following prostate cancer • Nerve sparing pts respond better • Daily PDE-5 inhibitor may be beneficial • Sildenafil + testosterone if ED & low testosterone • Cumulative probability of success increases w/ 1st 9-10 attempts • Tadalafil – less planning, longer half-life, more convenient for some

  38. PDE-5 Inhibitors • Side effects peak at first 2wks of use • Package Insert Warnings • MI within 90 days • Unstable angina, or angina w/ intercourse • NY Heart Association class II or greater heart failure in last 6 months • Uncontrolled arrhythmias, hypotension (<90/50), or HTN (>170/100) • Stroke in past 6 months • Known hereditary degenerative retinal disorders, including retinitis pigmentosa • Tendency to develop priapism (sickle cell, anemia, leukemia) • Impairs metabolic breakdown • Ketoconazole, itraconazole, protease inhibitors (ritonavir) – lower dose • Enhances breakdown • Rifampin – increase dose

  39. PDE-5 Inhibitors • Recommended starting dose • 50mg sildenafil • 10mg vardenafil & tadalafil • Cardiovascular safety • They do not worsen cardiac events • Vardenafil not recommended w/ type IA antiarrythmics (quinidine or procainamide) or type 3 (sotalol or amiodarone), or congenital prolonged QT syndrome • Use w/ caution in aortic stenosis, left ventricular outflow obstruction, hypotension, hypovolemia due to vasodilator effects • Nitrates – absolute contraindication • Use >2 wks ago, not contraindication • Don’t take nitrate for at least 24 hrs after (48hrs for tadalafil) • Alpha-blocker – use caution due to vasodilation & hypotension

  40. Intracavernous Injection • 1983 AUA meeting, Brindley personally demonstrated erection after injection of phenoxybenzamine • 1985 – papaverine & phentolamine injection use reported • Papaverine • Isolated from opium poppy • Inhibitory effect on PDE, increased cAMP & cGMP, blocks calcium channels • 1-2 hr half-life • Good • Low cost • Stable at room temp • Bad • Priapism (up to 35%) • Corporal fibrosis (1-33%) due to acidity • <55% effective • Not FDA approved

  41. Intracavernosal Injection • Phentolamine (alpha1 & alpha2-antagonist) (Regitine) • Side effects • Hypotension • Reflex tachycardia • Nasal congestion • GI upset • 30 min half-life • Increases corporal blood flow, but does not cause significant increase in intracavernous pressure

  42. Intracavernosal Injection • Alprostadil (Caverject & Edex 2-40mcg) - Prostaglandin E1 • Exogenous form of a naturally occurring fatty acid • Causes smooth muscle relaxation, vasodilation, inhibition of platelet aggregation by elevating cAMP • Metabolized by prostaglandin-15-hydroxydehydrogenase in corpora cavernosa • 96% locally metabolized after 60 min • Side effects • Pain at injection site or during erection • Hematoma • Priapism • Much lower incidence of fibrosis • Once reconstituted into liquid from powder, has shortened half-life if not refrigerated

  43. Intracavernosal Injection • Combinations • Papaverine + Phentolamine • Papaverine + Phentolamine + Alprostadil • Lower incidence of painful erection • As effective as alprostadil alone • Good for failed therapy or painful erection w/ PGE1 • Serious side effects • Priapism • Alprostadil 1.3% • Papaverine 10% • Papaverine/phentolamine 7% • Fibrosis • Alprostadil 1% • Papaverine 12% • Papaverine/phentolamine 9%

  44. Intracavernosal Injection • Contraindications • Sickle cell • Schizophrenia • Other severe psychiatric disorders • Severe systemic illness • If on anticoagulant, compress injection site for 7-10 min • Poor manual dexterity – have partner inject

  45. Intraurethral Therapy • Alprostadil (Muse) • Absorbed in spongiosum & transported to cavernosa through venous channels (circumflex & emissary veins) • 3mm x 1mm pellet • 500 mcg Muse = 10 mcg injected alprostadil • 2/3 respond • Side effects • Penile pain/dull ache in penis, scrotum, legs

  46. Central Acting Drugs • Yohimbine • Alpha2-antagonist from bark of yohim tree • Good for psychogenic ED • Side effects • GI upset, anxiety, HA, agitation, palpitations, HTN • AUA stance – no efficacy of yohimbine over placebo with organic ED • Trazadone • Apomorphine • Dopaminergic agonist

  47. Vacuum Constriction Device • Plastic cylinder connected to vacuum-generating source • Place constriction ring after engorgement • Remove ring within 30 min • Satisfaction rate 68-83%

  48. Premature Ejaculation (PE) • DSM-IV • Persistent or recurrent ejaculation with minimal stimulation before, on, or shortly after penetration and before the person wishes it • Short ejaculatory latency, lack of control, sexual dissatisfaction • Latency <2 min suggests possible PE • Excludes PE secondary to EtOH, substance abuse, medication

  49. Premature Ejaculation • Etiology • Penile Hypersensitivity • 5-Hydroxytryptamine-Receptor Sensitivity • Hyperarousability • Hyperexcitable ejaculatory reflex • Genetic predisposition • Psychogenic • Poor control techniques • Early sexual experience • Anxiety • Infrequent sex

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