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( Lecture ) Andrology [ Erectile dysfunction ] Goals and Objectives Define erectile dysfunction (ED) Discuss the most common causes of ED Review a practical evaluation of men with ED Review the treatment options Provide suggestions for urologic referral What is ED? ED is the inability to achieve and maintain an erection adequate for intercourse to the mutual satisfaction of the man and his partner. Remember, both partners in a relationship are affected. Incidence 20-30 million American men suffer ED Age dependent 2% men age <40 years 25% men age 65 75% men >75 years Not a necessary occurrence of the aging process How Does an Erection Occur? The brain controls all sexual functions, from perceiving arousal to initiating and controlling the psychological, hormonal, nerve, and blood flow changes that lead to an erection. Hormones, including testosterone, control the male sex drive How Does an Erection Occur? (cont.) Nerve impulses relay signals of arousal and sensation to and from the penis Arteries deliver extra blood to the penis that causes it to stiffen. Veins then drain the blood out of the penis after intercourse. Physical or Psychological Stimuli Results Sacral parasympathetics (S2,3,4) stimulation to the penile nerves Dilation of the penile arteries Relaxation of the smooth muscle in the corporal bodies of the penis Decrease venous outflow An Erection Requires a Coordinated Interaction of Multiple Organ Systems Psychological Endocrine Vascular Neurologic Mechanism of Smooth Muscle Relaxation Release of Neurotransmitters-nitric oxide Conversion of GTP to cGMP - erection Breakdown of cGMP by PDE type 5 detumesence Cause of ED Psychogenic Causes: Anxiety Depression Fatigue Guilt Stress Marital Discord Excessive alcohol consumption Causes of ED Organic Causes Cardiovascular disease Diabetes mellitus Surgery on colon, bladder, prostate Neurologic causes (lumbar disc, MS, CVA) Priapism Hormonal deficiency Causes of ED Risk Factors Massachusetts Male Aging Study¹ Treated heart disease Treated diabetes 28% Treated hypertension 15% ¹Feldman Ha, J Urol 1994; 151:54-61 39% Causes of ED Other risk Factors ² Diabetes 27% - 59% Chronic renal failure 40% Hepatic failure 25% - 70% Multiple Sclerosis 71% Severe depression 90% Other (vascular disease, low HDL, high cholesterol) ²Benet et al. Urol Clinic North Am. 1995; 151:54-61 Causes of ED Hormone Deficiency End Organ Failure Blockage of Blood Vessels Venous Leak Causes of ED Spinal cord injuries: 5% - 80% Pelvic and urogenital surgery and radiation Substance abuse Alcohol: >600ml/wk Smoking amplifies other risk factors Medications may be responsible for ~25% of cases of ED Bicycle riding Causes of ED Medication: Most common cause of ED in men >50 Many men are polymedicated Also have co-morbid conditions Causes of ED Medications (cont.) Anti-hypertensive drugs All capable Common: thiazides and beta blockers Uncommon: calcium channel blockers, alphaadrenergic blockers, and ACE inhibitors Causes of ED Medications (cont.) CNS drugs: Antidepressants, tricyclics, SSRIs Tranquilizers Sedatives Analgesics H1 and H2 receptor blockers Causes of ED Medications (cont.) Anticholinergics LHRH agonists (Lupron, Zolladex) Alcohol Tobacco Drug abuse Estrogens, Ketoconazole A Practical Evaluation of Men with ED Basic evaluation Medical History Cardiovascular history Endocrine history Sexual history/questionnaire A Practical Evaluation of Men with ED Basic evaluation (cont.) Physical exam: Focused neurovascular exam Size of testis DRE Lab tests UA Testosterone, CMP, Lipid panel PSA in men >50 years A Practical Evaluation of Men with ED Sexual History Premature ejaculation Retarded ejaculation Painful intercourse Anorgasmia Decreased Libido Dissatisfaction with sex life A Practical Evaluation of Men with ED Sexual History (cont.) Do you have any problems with intimacy with your partner? Do you have early morning erections? Do you have erections with self-stimulation? Are you able to consistently obtain and maintain an erection sufficient for sexual intimacy? Does it hurt to have an erection or intercourse? A Practical Evaluation of Men with ED Sexual History (cont.) Do you ejaculation sooner than you would like? Does it take too long to reach an orgasm? Do you fail to reach an orgasm? Did your erection problems start suddenly or over time? A Practical Evaluation of Men with ED ED Questionaire³ When you had erections with sexual stimulation, how often were your erections hard enough for penetration? How do you rate your confidence that you could get and keep an erection? ³The International Index of Erectile Function, Urol 1997;49:822-830 A Practical Evaluation of Men with ED Questionaire (cont.) During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner? During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? When you attempted sexual intercourse, how often was it satisfactory for you? A Practical Evaluation of Men with ED Differentiating Psychogenic from Organic ED Psychogenic Impotence: Younger patient (<40) Preservation of morning erections and nocturnal erections Achieve erection with masturbation May be partner-specific Often sudden onset A Practical Evaluation of Men with ED Differentiating Psychogenic from Organic ED Organic ED: Gradual deterioration Decrease in morning erections and nocturnal erections No erections with masturbation No loss of libido Presence of co-morbid conditions A Practical Evaluation of Men with ED Physical Examination Blood pressure Examine penis (R/O Peyronie’s disease) Determine size and consistency of testes Digital rectal exam Focused vascular exam/peripheral pulses Focused neurologic exam A Practical Evaluation of Men with ED Laboratory Tests UA (glycosuria) – Fasting if elevated PSA in men over 50 Testosterone (best to draw in A.M.) Prolactin, Thyroid function, Lipid profile, Liver function, Creatinine A Practical Evaluation of Men with ED Other Tests NPT – Nocturnal Penile Tumescence Test Penile doppler Injection of vasoactive drugs NEVA (Nocturnal Electobioimpedance Volumetric Assessment) Treatment Options Goal directed therapy 4 4 Find out what the patient wants Try to tailor the treatment to the patients needs and wants Etiology rarely affects treatment choice for the patient Lue TF, World J. Urol 8:67,1990 Treatment Options Nonpharmacologic Non-invasive Minimally invasive Invasive Counseling and/or sex therapy Treatment Options Oral medications - Viagra, Levitra, Cialis Urethral suppositories (MUSE) Injection therapy - Caverject, Trimix, Bimix Vacuum constriction device Surgery Sex therapy Counseling and/or Sex Therapy Rule out depression Try oral medication in patient with psychogenic impotence Refer to sex therapist or psychiatrist for sever psychopathology Nonpharmacologic Treatment Options Lifestyle changes: Reduce fat and cholesterol in diet Decrease or limit alcohol consumption Eliminate tobacco use and substance abuse Weight loss if appropriate Regular exercise Ideal Medication for Treatment of ED Effective Available on demand Free of toxicity and side effects Easy to administer Inexpensive Medication (Viagra, Levitra, Cialis) Mechanism of Action: PDE inhibitor and increases the cGMP that promotes and sustains smooth muscle relaxation Medication (PDE Inhibitors) Indications: Psychogenic ED Mild vasculogenic ED Neurogenic ED Side effects from medication(s) patient is already taking Medication (PDE Inhibitors) Side effects: Headache Flushing Dyspepsia Nasal congestion Visual disturbances Priapism Medication (PDE Inhibitors) Contraindications: Organic Nitrites: Oral Sublingual Severe cardiac disease Obtain stress testing Medication (Yohimbine, Yocon, Erex, Yohimex) Alpha 2 andrenoreceptor antagonist Dose: 5.4 mg TID Results: ~20% (same as placebo) Side effects: increase blood pressure, tachycardia, anxiety Medication Trazodone(Desyrel) Anti-depressant associated with priapism Mechanism of action nor fully understood Nor FDA approved for ED Side effects: drowsiness, dry mouth, sedation, priapism Medication Apomorphine (Spontane) Dopaminergic mechanism with hypothalamic activity Sublingual administration 64% to 67% response rate with ED Side effects: nausea, sweating, hypotension, yawning Awaiting FDA approval Medication Phentolamine (Vasomax) Alpha-blocker Relaxes smooth muscle tissue 40% efficacy in mild organic ED Side effects: nasal congestion, tachycardia, dizziness, hypotension Awaiting FDA approval Medication Side effects Discontinue tobacco, alcohol, and abusive drugs Alter dosage of drugs with ED side effects Change to another class of drugs Transurethral Therapy Alprostadil - MUSE Mechanism of Action: vasodilator Administration: 125, 250, 500. 1000ug Insert in the urethra Erection occurs 10-15 minutes later Erection lasts 30-45 minutes Results: 10-65% Side effects: Pain, bleeding, priapism (<3%) Penile Injection Therapy Caverject, Edex, Tri/Bi-Mix Mechanism of action: smooth muscle vasodilator Administration: 10, 20, 40ug Inject directly into corporeal bodies of the penis Results: 70%-90% Dropout rates: 25%-60% Side effects: pain (36%), priapism (4%), fibrosis Androgen Replacement Therapy Indications: hypogonadism (<285ng/dl) Avoid oral estrogens-increase LFTs Injectable – 200mg testosterone (cypionate, enathate, propionate), q2-3 weeks Transdermal Patch gel Androgen Replacement Therapy Avoid in patients with prostate or breast cancer Slight increase risk of BPH Monitor all patients with annual DRE and PSA Vacuum Constriction Device Mechanism of Action: Penis placed in plastic tube Air evacuated from the tube Blood trapped in penis with constricting ring Vacuum Constriction Device Erection limited to 30 minutes Results: 80%-90% Contraindications: bleeding disorders, sickle cell disease, anticoagulation Complications: coolness, petechiae, numbness, pain with ejaculation High drop out rate Vacuum Constriction Device Was previously first-line treatment for ED Seldom used now that oral therapy is available Considered an alternative if patient fails oral therapy and does not want to proceed with surgery Penile Prosthesis Indications: Patients who have failed other therapies Peyronie’s disease Severe vasculogenic disease Choosing a Penile Prosthesis Considerations: Medical condition Lifestyle Cost Insurance coverage As with all prescription products, complications are possible Malleable Prosthesis Easy for patient and partner to use Few mechanical parts Same-day surgery usually possible Least expensive type of prosthesis Two-Piece Inflatable Prosthesis Small inflation pump provides comfort and ease Fast and easy one-step deflation procedure Better conceal ability when flaccid than with malleable or self-contained devices Three-Piece Inflatable Prosthesis Most closely approximates the feel of a natural erection Cylinders expand in girth Some cylinders have the potential to expand in length When inflated, it feels more firm and more full than other prosthetic erections When deflated, it feels softer and more flaccid with better conceal ability than with other prosthetic devices Penile Prosthesis Advantages: Low-morbidity Low-mortality surgery Low complication rates High success rates – 5% malfunction rate at 5 years High satisfaction rate – 87% High partner satisfaction rate Penile Prosthesis Advantages (cont.) Good rigidity Freedom from medications Outpatient/24HR surgery Resume sexual activity 4-6 weeks No loss of ability to ejaculate or achieve orgasm Penile Prosthesis Disadvantages: Surgery Expensive Possible mechanical failure Penile Prosthesis Insurance Reimbursement Covered by most companies, including Medicare No co-payment for men with Medicare supplemental insurance