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Erectile Dysfunction And it’s Multiple Treatment Options Priapus son of Zeus and Aphrodite Cursed by Hera with eternal impotence, ugliness and foul mindedness. Due to hero, Paris judging Aphrodite to be more beautiful than Hera. Erectile Dysfunction (the inability of a man to achieve or maintain an erection sufficient for his sexual needs and the needs of his partner) Erectile Dysfunction can mean inability to achieve erection, inconsistent ability of having an erection, or ability to achieve only brief encounters. 1. Incidence of ED a. National Institutes of Health, estimates 30 million men in US have ED. b. Transient ED and inadequate erections occur in 50% of males between the ages of 40 and 70y/o. c. Psychological factors account for 10 to 20% of cases of ED. d. 35 to 50 % of men with diabetes have ED. e. 68% of men with hypertension have some degree of ED. f. Highly related to age. g. ED maybe the first sign of CVD. h. Smoking increases rate of ED at all ages. Harvard School of Public Health ◦ ◦ ◦ ◦ Study of 31,742 men between the ages of 53 and 90. Mailed questionnaire in 2000. (Published in Annals of Internal Medicine, Aug5 2003.) At age 40 to 50-----4% ED At age 50 to 59 ---26% ED At age 60 to 69----40% ED At age >70 --------61%ED Estimated Prevalence of ED in U.S. Prevalence and count (in millions) of US men aged 20 years and older by category of erectile function. Full-Size Image close The American Journal of Medicine Volume 120, Issue 2 , Pages 151-157, February 2007 Causes of Erectile Dysfunction Vascular ◦ ◦ ◦ ◦ ◦ Diabetes Hypertension Cardiac Dz Dyslipemia Smoking Neurogenic ◦ Stroke and or trauma Psychogenic ◦ Stress and/or Anxiety ◦ Depression Hormonal ◦ ◦ ◦ ◦ Hypogonadism Hyperprolactinemia Chronic Disease Thyroid Disease Physical ◦ Renal Failure ◦ Liver Failure ◦ Alcoholics and/or Drug Addicts Medications associated with ED Antihypertensive medications Antidepressants Tricyclic antidepressants Antipsychotic agents Antihistamines CNS depressant narcotics Sympatholytics Physiology of Erection Penile erection elicited by central psychogenic and reflexogenic mechanism. ◦ Psychogenic erections are elicited by auditory, visual, olfactory, or imaginary stimuli. ◦ Reflexogenic erections are elicited by stimulation of sensory receptors on the penis, which through spinal interactions cause somatic and parasympathetic efferent actions. With arousal, parasympathetic activity triggers release of nitric oxide. ◦ The increased nitric oxide causes increased levels of intracellular mediator cyclic guanosine ◦ monophosphate (cGMP) ◦ Increase in cGMP causes penile vascular and trabecular smooth muscle relaxation. Blood flow then increases into the corpora cavernosa. The rapid filling of the cavernosal spaces compresses venules and causes a decrease in venous outflow. This causes increased inflow and decrease in outflow causing the erection. (Veno-occlusive mechanism) Testosterone Hypothalamus –GnRH Fsh + LH Testicles Testosterone Production Aromatase enzyme in fat Estradiol Testosterone Effects Increased Libido Enhances Mood Increases Energy Increases Bone Density Decreases body fat and increases lean muscle mass. ◦ Men with low T are 2x as insulin resistant as men with normal T. ( Pitteloud et al 2005 ) Responsible for secondary sex characteristic. Testosterone improves neuron survival in brain regions vulnerable to neurodegenerative disease. Cognition and alertness Low Testosterone Effects Poor Libido and ED Lower blood Hb and loss of body hair Decrease muscle mass and Fatigue Osteoporosis Depression Decrease in cognitive function Decrease sperm production Ranges of normal testosterone levels PRL Lab ◦ Total Testosterone 240-950ng/dl ◦ Free Testosterone 9-30ng/dl Quest Labs ◦ Total Testosterone 241-827ng/dl ◦ Free Testosterone 46-224 pg/ml Lab Corp ◦ Total Testosterone 348-1197ng/dl ◦ Free Testosterone 6.6-25.1 pg/ml Normal Testosterone Levels in Men (Non-Diabetic) Measurements in Conventional Units (ng/dl) Age Number of Subjects Mean Total Test <25 125 158 697 408 468 956 25-29 354 692 669 206 637 388 438 1005 30-34 330 621 194 597 348 388 975 35-39 212 189 567 329 388 945 40-44 148 198 597 319 378 936 45-49 154 163 527 329 358 846 50-54 164 187 518 289 348 936 55-59 155 597 597 546 544 552 174 547 319 338 866 Stand. Dev. Median Total Test 5th % 10th % 95th % Vermeulen, A. (1996). Declining Androgens with Age: An Overview. In Vermeulen, A. & Oddens, & B. J. (Eds.), Androgens and the Aging Male (pp. 3-14). New York: Parthenon Publishing. Testosterone side effects: Sleep apnea Polycythemia Liver toxicity Prostate disease Shrinkage of testes Estradiol levels in Men Estradiol levels greater than 34.1 pg/ml are associated with: ◦ 2.2 greater risk of stroke (Abbott RD, et al, Neurology, 2007, Feb 20) These were 2,197 men aged 71 to 93 yrs. ◦ Men have excess estrogen due to decreasing testosterone and increased weight with aging. Aromatase enyme is increasing the amount of estrogen present. High Estrogen in men with Coronary Atherosclerosis Carotid artery intima-media thickens with high estrogen. Low testosterone and high E-2 is associated with lower extremity peripheral artery dz in elderly men. Aromatase Blocking Agents Non-steroidal aromatase inhibitors (AIs) anastrozole (Arimidex®) and letrozole (Femara®) ◦ Anastrozole .5 to 1mg weekly and check estradiol levels . Keep estradiol above 20 and below 35 pg/dl. ◦ Letrozole 2.5mg weekly and off when estradiol level below 35 pg/dl. PDE-5 inhibitor, this increases cGMP causing smooth muscle relaxation Sildenafil Citrate (Viagra) lasts 4 hrs. ◦ 25,50,100mg take 1hr prior to sex Tadalafil (Cialis) takes effect in 15 mins and last 36 hours. Greasy food doesn’t effect this. (2.5,5,10,20mg) Vardenafil (Levitra) given 1hr prior to sexual activity and last 5 hrs. ◦ 2.5, 5,10, and 20mg. First line drugs for ED Male Sexual Response (4 phases) Desire Arousal Orgasm Relaxation PDE-5 inhibitor Side Effects Headaches Facial flushing Indigestion Nasal Congestion Failures of oral and intraurethral medications are txed with: Vacuum pump TriMix QuadMix Vacuum Constrictive Devices Has been utilized for the last 100 years Has gained popularity in last 20 years Is FDA approved for ED Negative pressure of 200 to 250 mmHg ◦ This neg. pressure increases inflow of blood ◦ into the corporal bodies, both in arteries and veins. Vacuum Constrictive Device for ED Effective for mild to moderate ED. 70 to 80% effective for erection. Suction increases blood flow and a ring goes on the penis after the erection occurs. The ring must be removed in 20 to 30 minutes. Vacuum Devices Double pumping using vacuum increases comfort for pt. ◦ Generate neg. pressure and then let some out and wait for 2 to 3 mins, then rebuild neg pressure until a erection occurs. Penis tends to be purple in color and cold, due to neg. pressure. Decrease in force of ejaculation and amount of ejaculate, this is due to the constriction ring. Premature Ejaculation the occurrence of ejaculation prior to the wishes of both partners. 1.Global Study of Sexual Attitudes and Behaviors and other sources suggests a global prevalence of PE of approximately 30% across all age groups. Treatment of PE Sexual therapy ◦ The squeeze technique Medications Antidepressants Topical anesthetic creams Desensitization of penis Cognitive behavioral therapy IC injection with Trimix or Quadmix Indications for TriMix and QuadMix Failure Failure of oral therapy of intraurethral prostaglandin.(Muse) Failure of Vacuum Device Treatment of Premature Ejaculation TriMix First Introduced by Bennett et.al..,1991 ◦ His success rate was 92% in 116 pts. American Urologic Association feels the intracavernous injection is the most effective non-surgical treatment for erectile dysfunction Formula of Trimix and QuadMix Trimix ◦ Contains prostaglandin, papaverine, phentolamine. Good refrigerated for 1 month. Frozen, good for 6months. At room temp, Trimix is good for 1 week. QuadMix ◦ Contains small amount of prostaglandin, and normal amount of papaverine, and phentolamine. Also contains atropine. Atropine is used for the firmness. The prostaglandin can cause groin pain for some pts. Prostaglandin E-1(Alprostodil) 1.Prostaglandin E-1 is used to increase firmness of the erection and to manipulate the duration as well. a. A potent vasodilator, causing muscle cells of penile arteries to relax. Blood increases in penis and erection becomes firmer. b. May cause transient dull ache at base of penis, usually resolves in 15 mins. ◦ c. Rarely causes priapism by itself. Papaverine (phosphodiesterase inhibitor) Increases the duration of the erection. Relaxes muscle cells in arterial wall. This causes dilation and increases blood flow in the penis. May cause increase in liver enzymes (rarely). Phentolamine (alphaadrenergic antagonist) Blocks nerve transmission that causes the arterial wall to contract. This causes artery to dilate. Helps with engorgement of the penis. Quad-Mix also has atropine, as well as papaverine, phenolamine, and prostaglandin E-1. Used to increase firmness when patient has pain from PGE-1. a. Not to be used in glaucoma or if pt is on nitrates for cardiac Dz. TriMix and QuadMix Formulations Intracavernosal Injection Possible Side Effects of Trimix Bruising at injection site Penile pain or groin pain Hypotension Fibrosis Rare increase in liver enzymes Priapism Complications of Intra-Corporeal (IC) Penile Injections: a. Hematoma at injection site. Apply pressure to site and bleeding stops. b. Priapism, an erection lasting 4 hours or more. Tx –1%phenylepherine .2ml with.2ml lidocaine given IC. b. Pt. usually complains of severe pain in groin and penis, if the penis is 100% plus erect. c. Inadvertent injection into urethra. Contraindications for Tri-Mix a. Severe Peyronies Dz or Cancer of the Penis. b. Sickle Cell Dz or Fabry Dz ( glycogen storage dz ) c. Poor manual dexterity or poor vision. (Who is going to give the injection?} d. Unreliability, with potential for misuse and abuse. e .Liver Dz or elevated liver enzymes, or malaria. f. Blood coagulation disorders ( 30 gauge needle ). g.HIV positive. h. Gastrointestinal bleeding or ulcer dz, or IBD i. Severe cardiac dz or on nitrates. j. Glaucoma, if plan on using atropine. Surgical Inflatable Penile Implants