Prof Dr dr H Rusdi Lamsudin SpS (K), M.Med.

Sc

Faculty of Medicine Indonesian Islamic University Yogyakarta, Indonesia

Prof.Dr.dr. H. Rusdi Lamsudin, M.Med.Sc Spesialis Saraf (Konsultan)

Medical Doctor, Faculty of Medicine, UGM, 1971 Neurologist, Unair-UGM, 1978 Master of Medical Sciences, New Castle Univ, Australia, 1986 Head of Executive Board Muhammadiyah Hospital, Yogyakarta, 1993-1999 Vice Dean, Faculty of Medicine Muhammadiyah Yogyaakarta University, 1993-1999 PhD, UGM, 1996 Short-course, Unit Stroke & Neuro-Intensive, Insburck, Austria,15 July-15 October, 1997 Head of Stroke Unit, Sardjito Hospital, Yogyakarta, 2001-2005 Head of Neurology Department Faculty of Medicine, UGM, 2001-2005 Dean of Faculty Medicine, Indonesia Islamic University, Yogyakarta, 20012006, 2006-2010 Head of Neurology Departement Yarsis Hospital, Surakarta Head of Stroke Unit, Yarsis Hospital, Suraakarta
How to organize stroeke unit care 2

What constitutes an Erection ?

Outline
Definition Epidemiology Causes Pathophysiology Neurological aspect Conclusion

Definition of Erectile Dysfunction

Inability

to achieve and maintain an erection sufficient to allow penetrative sexual intercourse to occur (.... with satisfaction to the patient and his partner)

Epidemiology

Massachusetts Male Aging Study, Feldman et al. J Urol 1994; 150:54-61 Reproduced from Carson C,Holmes S,Kirby R. Fast Facts-Erectile Dysfunction. Oxford: Health Press Limited; 2002 : 7

Prevalence and significance of E.D.

Exact incidence unknown May affect 1 in 10 men Affects 10 million men in

US alone, 400,000 OPD visits and 30,000 hospital admissions (1992 figs) Significance to Urologists Increased public awareness of new treatments has resulted in increase in referrals

Prevalence of Erectile Dysfunction among men 40-70 yrs is approximately 52% (minimal 17.2%, moderate 25.2%, and complete 9.6%)

Probability of Erectile Dysfunction increases with age and typically associated with other medical conditions

Incidence of ED
in 40 y. - 22 % pts. in 70 y. - 49 % pts.
Massachusetts Male Aging Study (1994)

140 mili. men in all world 500 800 000 men in R

+ 40 000 every year

Massachusetts Male Aging Study:

Feldman HA, et al. J Urol. 1994;151:54-61.

Causes of erectile dysfunction

Aging

Psychological Depression, anxiety

Neurological Hormonal Vascular Medications Habits Other Cerebral, spinal, peripheral neuropathy, pudendal nerve Hypogonadism, prolactin, thyroid, Cushings, Atherosclerosis, venous incompetence Antihypertensives, antidepressants, estrogen, antiandrogens Cannabis, alcohol, narcotics, tobacco Diabetes, renal, hypertension, COPD

Male Genital Anatomy

Two paired corpora cavernosa (erectile bodies) and a single corpus spongiosum surrounding the urethra, all encased within Bucks fascia The erectile tissue is comprised of a network of vascular sinusoids surrounded by trabecular smooth muscle.

Anatomy and Physiology of erection

Reproduced from Carson C, Holmes S, Kirby R. Fast Facts- Erectile Dysfunction. Oxford: Health Press Limited; 2002: 8

Vascular Supply
The blood supply to the penis is derived from the pudendal artery which branches from the internal iliac (hypogastric) artery. Cavernosal arteries course through the center of each corporal body and give rise to multiple helicine arteries which open into the lacunar spaces.

Mechanism of Erection
Two types of erections a) Reflexogenic b) Psychogenic
Blood flow increases secondary to vasodilatation of the cavernosal arteries Relaxation of smooth muscle dilates the lacunar spaces causing engorgement Increased intracorporal pressure expands the trabecular wall against the tunica albuginea

Compression of the subtunical veins along with a reduction of venous blood flow results in elevated pressures in the lacunar spaces, veno-occlusive mechanism

Flaccid penis - arterial pressure 20mm/Hg

Fully erect - arterial pressure 80-100mm/Hg

Physiologic Indicators of ED
Atherosclerosis in narrow penile arteries may manifest as ED before becoming apparent in other arteries.

Detecting atherosclerosis in 1 set of blood vessels increases the chance of finding it in other vessels.

Physiological Causes of Erectile Dysfunction

Hypertension
Anemia Vascular surgery Smoking Alcohol abuse PVD Depression Drug abuse CAD

Endothelial dysfunction ED

Hypogonadism Peyronies disease

Trauma/surgery to pelvis or spine

Endocrine Disorders

Hyperlipidemia
Benet AE, Melman A. Urol Clin North Am. 1995;22:699-709

Veno-occlusive Mechanism

Reproduced from Carson C,Holmes S,Kirby R. Fast Facts-Erectile Dysfunction. Oxford: Health Press Limited; 2002 :12

Risk Factors: Similar between Heart Disease and Erectile Dysfunction

Risk factors very similar smoking dyslipidemia hypertension diabetes obesity lack of exercise/sex Both are vascular conditions

Medications Associated With ED

Estrogens Antiandrogens H2-receptor blockers Anticholinergics Ketoconazole Marijuana Alcohol

Antihypertensives
Narcotics

-blockers Psychotropics Cigarettes Cocaine Spironolactone Lipid-lowering agents NSAIDs Cytotoxic drugs Diuretics

Benet AE, Melman A. Urol Clin North Am. 1995;22:699-709

Endothelial dysfunction is a risk factor for CVD and ED

Heart failure Atherosclerosis Smoking

Hypertension

Oxidative stress

Diabetes

Endothelial dysfunction

ED
Adapted from Rubanyi GM. J Cardiovasc Pharmacol 1993; 22 (Suppl 4): S1S4

Signs and Symptoms Suggestive of Psychogenic vs Organic ED

Psychogenic
Sudden onset Complete immediate loss

Organic
Gradual onset Incremental progression

AM erections present Varies with partner and circumstance

Lack of AM erections
Lack of erections under most sexually stimulating circumstances

Adapted from Ralph D, et al. BMJ. 2000;321:499-503.

Psychogenic vs Organic

Tiefer L, Schuetz-Mueller D. Urol Clin North Am. 1995;22:767-773.

Risk factors for ED

Vasculogenic factors
Age Certain medications

Psychosocial/psychological factors
Neurogenic factors Hormonal factors

Causes of ED 1. Organic (80 %) diabetes mellitus, hypertension,

hyperlipidemie, benign prostate disease, peripheral vascular disease, cardiac problems, hormonal problems (pituitary, testis, thyroid, adrenal), neurogenic (cerebral, spinal, dorsal nerve, cavernous nerve) postsurgical: radical prostatectomy, abdominoperineal resection

2. Psychogenic, drugs (20 %)

Arteriogenic Cause of ED
Hypertension
Smoking Diabetes

Hyperlipidaemia
Peripheral vascular disease Blunt perineal or pelvic trauma Pelvic irradiation

Psychogenic and Psychiatric causes

Anxiety
Loss of attraction to partner Relationship difficulties

Stress
Depression

Psychogenic ED

Reproduced from Carson C,Holmes S,Kirby R. Fast Facts-Erectile Dysfunction. Oxford: Health Press Limited; 2002 : 33

Endocrine causes of ED
Hypogonadism Low testosterone Raised SHBG Raised Prolactin Thyroid disease

Drugs associated with ED

Antihypertensives
Thiazides B blockers Centrally acting drugs

Antipsychotics
Phenothiazines

Anxiolytics
Benzodiazepines

Antidepressants
Tricyclics MAO inhibitors SSRI

Psychotropic drugs
Alcohol Opiates Amphetamines Cocaine

Anticholinergics
Atropine

Mechanism of erection
Depends on integrated processes of :

increased arterial inflow to penis filling of sinusoids of the corpora cavernosa, aided by relaxation of cavernosal smooth muscle passive occlusion of the venous plexus provides increased resistance to outflow and aids rigidity

Mechanism of erection

The role of chemical mediators

Previously suggested that erection under

parasympathetic, and detumescence under sympathetic, control - over simplified view Non-adrenergic non-cholinergic (NANC) mechanisms now believed to be important

The role of chemical mediators

Nitric oxide (NO) now appears to be the final element

in the NANC pathway and may be derived from nerve endings NO raises cyclic GMP levels leading to penile smooth muscle relaxation

Pathophysiology of E.D.
Robert Krane, BAUS 1996 Arterial insufficiency in E.D. may lead to

hypoxia of the corpora Imbalance between PGE1 and TGF-B1 Excess Collagen Deposition Fibrosis of the corpora cavernosa Dysfunction of the veno-occlusive mechanism

Pathophysiology of E.D.
Flaccid state Hypoxia, increased TGF-B1, and fibrosis Asleep Nocturnal penile tumescence 3-5x per night, 40 mins per time. Normoxic episodes increase PGE1, decrease collagen, and decrease TGF Established E.D. Hypoxia all the time; dont get the benefit of NPT episodes

Pathophysiology of E.D.
Use it or lose it!
More erections = increased normoxia Increased PGE and cAMP

Decreased TGF-B
?? decrease fibrosis already present

Neurological Aspect of ED

Anatomy and Physiology of erection

Parasympathetic nerves S2-4 mediate erection
Sympathetic nerves T11-L2 control ejaculation and

detumescence Smooth muscle relaxation

Nitric oxide diffuses into cavernosal smooth muscle cells, activates

Guanylate cyclase converts guanosine triphosphate to cGMP resulting in smooth muscle relaxation. Effect of cGMP stopped by Phosphodiesterase type 5 which exists primarily in corpora cavernosa.

BRAIN CENTERS INVOLVED IN SEXUAL FUNCTION

Level

Region Stria terminalis Pyriform cortex Hippocampus Right insula and inferior frontal cortex Left anterior cingulate cortex
Controls

Function sexual motivation

Forebrain

Inhibits sexual

drive (hypersexuality when destroyed) Involved in penile erection Increased activity during visually evoked sexual stimulation (sexual arousal)
Ability to recognize a sexual

Medial

Hypothala ms

preoptic area Paraventricular nucleus

partner, integration of

hormonal and sensory cues Facilitates penile erection (via oxytocin neurons to lumbosacral spinal autonomic and somatic efferents)
Inhibits penile

Nucleus

Brain Stem

paragigantocellularis A5 catecholamine cell group, locus coeruleus

Periaqueductal Medial

erection (via serotonin neurons to lumbosacral spinal neurons and interneurons) Noradrenergic innervation of anterior horn motor neurons to perineal striated muscles
Relay center for sexually relevant stimuli

Midbrain

gray

amygdala

Neuroanatomy
The parasympatheticc nervous system provides excitatory input causing vasodilation and erection. (autonomic) The sympathetic nervous system provides input which results in detumescence, maintains flaccidity,and emission. (autonomic) Somatic sensory nerves provide sensation of the penile skin, glans, and urethra. (dorsal nerve). The motor pathway lies within the sacral nerves to the pudendal nerve and innervate the bulbocavernous and ischiocavernous muscles and allow for ejaculation.

Neurogenic causes of ED
Lesions of medial preoptic nucleus, paraventicular nucleus,

hippocampus Spinal trauma Myelodisplasia (spina bifida) Pelvic surgery/radiotherapy Multiple sclerosis Intervertebral disc lesion Peripheral neuropathies Alcohol Diabetes HIV

Causes of ED Neurogenic Parkinsons disease 60% Multiple sclerosis 70% Spinal cord trauma, tumor etc. Peipheral neuropathy: diabetes, alcoholism,
chronic renal failure

Neurovascular Bundle

Putting it all together

Tests to evluate the sensory afferent and motor efferent (autonomic neurophaty)
Bulbocavernosus reflex

Penile thermal sensory threshold measurement

Corpus cavernosum electromyogram (CC-EMG) signal

assessment Somatosensory evoked potentials Anal or urethral sphincter EMG Vibration perseption sensitivity

Conclusion
The male erectile response is a neurovascular even reliant on

complex interaction between neurological and vascular responses

Erectile dysfunction is multifactoral and has been typically

classified by primary presumed cause:

Vasculogenic Psychogenic Neurogenic endocrinologic disease

Any condition or injury that impairs the transmission of impuls

along the psycogenic or reflexogenic neurological pathway, maybe associated with neurogenic ED