MANAGEMENT OF ERECTILE DYSFUNCTION

• ERECTILE DYSFUNCTION: Erectile dysfunction (ED), defined as the persistent inability to achieve and maintain penile erection sufficient to permit satisfactory sexual performance

• EPIDEMIOLOGY

– Prevalent; 1 in every 10 men

– Frequency & severity varies with age

– Uncommon in young men except those with psychological problem

– More common in middle age & highly prevalent >60years

– Peculiarities in our environment:

• Reluctance in discussing sexual issues

– Consequence:

• Loss of confidence & self esteem, negative feelings & depression.

• TERMINOLOGY

– Erection- Tumescence

– Flaccid- Detumescence

• ANATOMY

• Key organ: paired corpora carvenosa- composed of vascular spaces(multiple lacuna spaces lined by vascular endothelium), smooth muscles & fibro-elastic tissues.

• Arterial supply:

– Carvenosal artery(run centrally in corpus carvenosa giving off multiple helicine arteries)

• NB. Carvenosal art. -a branch of common penile artery derived from perineal art(a branch of internal pudendal art which is a branch of internal iliac art.)

• Venous drainage:

– Deep dorsal vein: drains the distal 2/3rd of corpora carvenosa, corpus spongiosum & glans. It drains into vesico-prostatic plexus

– Carvenosal veins: emissary veins in proximal 1/3rd

join to form 1 or 2 carvenosal veins- drains into internal pudendal vein.

• Innervation:

– 3 sets of nerves involve in penile tumescence & detumescence

– Parasympathetic:

• S2-S4( as nervi erigentes to reach pelvic plexus

• Produces nitric oxide(NO) as neurotransmitter) which causes dilation of the carvenosal tissue

– Sympathetic:

• T10-L2( via hypogastric nerve): causes tonic contraction of the carvenosal smooth muscle.

– Somatic:

• via pudendal nerve: supply propioception & sensory sensation to penile skin & glans penis

• MECHANISM OF ERECTION

• Detumescence phase is maintained by tonic sympathetic discharge with contraction of the smooth muscle of carvenosal tissue- leads to decrease blood flow into the carvenosal tissue

• Tumescence phase: occur by relaxation of carvenosal tissue which allow inflow of blood. Mediated by Nitric oxide (NO)

– Effect of Nitric oxide is terminated by 5-phosphodiesterase enzymes

– Other neurotransmitters involve in tumescence

• Prostaglandin E1: relaxes carvenosal smooth muscle

– Other neurotransmitters involve in detumescence:

• Endothelin 1: vasoconstrictory effect

• maintenance of erection:

– maintained by veno-occlusive mechanism which prevents venous drainage from carvenosal tissue. This is achieved by the high intra-corporeal pressure causing compression of the emissary veins which drain the carvenosal tissue.

• Prevention of coagulation of blood in carvenosal tissue is by prostacylin: prevent coagulation & has anti-platelet aggregation activity.

• PATHOPHYSIOLOGY OF ED

• ORGANIC CAUSES

1. Vascular causes(60%):

A. Arterial insufficiency

– Atherosclerosis of internal iliac artery & carvenosal art.

– Vascular damage from previous pelvic surgery/trauma

B. Veno-occlusive abnormality:

– venous leakage due to decrease distensibility of the carvenosal tissue

C. Intra-carvenosal smooth muscle fibrosis:

• loss of elasticity & distensibility of carvenosal tissue

– Causes

• Neglected priapism

• Peyronie's disease

• Aging process

2. Neurogenic causes:

– CNS: CVA, Parkinson’s disease, multiple sclerosis

– Peripheral Nv: diabetic neuropathy, cauda equinalesion, perineal Nv injury during surgery,

3. Endocrine causes:

– Low testosterone

– hypogonadism

4. Aging :

– Affect distensibility of carvenosal tissue

– Impairs neurogenic erectile function with increase latency to achieve erection

– Decrease in NO synthesis

• 5. Drug Induced:

– Antihypertensive- moduretics, Aldomet, Beta blockers, diuretics

– Anti-psychotics- TCAs

– Some aphrodisiacs

• PSYCHOGENIC CAUSES:

• Anxiety increases sympathetic vasomotor tone of carvenosal tissue(detumescence)

• Depression

• RISK FACTORS

1. Diabetes mellitus: can lead to diabetic neuropathy, damage of blood vessels & autonomic neuropathy

2. Hypertension: damage blood vessels, some anti-hypertensives. e.g. Beta blockers, diuretics

3. Hyperlipideamia: damage peripheral blood vessels

4. Hypercholesterolemia & increased triglyceride associated with ED

5. Smoking: has damaging effect on blood vessels

6. Peyronie's disease: fibrous tissue in tunica albuginea which affect the veno-occlusive mechanism & distensibility of carvenosal tissue

7. Previous surgery: Radical prostatectomy, Abdomino-perineal resection

8. Penile trauma: penile fracture

9. Depression: 90% of depressed men have ED

EVALUATION• HISTORY

– Ascertain the patient’s problem: distinguish ED from loss of libido or premature ejaculation

– Determine the duration, nature of onset, consistency or severity.

– Ascertain sexual gratification of his partner:

• Emphasis on:

–Previous & present relationship

–Attitude of partner towards the problem

–Effect of ED on the relationship

– Ascertain early morning tumescence( help distinguish psychogenic from organic ED. Unlikely to be organic if present).

– Drug history:

• LHRH, flutamide, bicalutamide: loss of libido, ED.

• Anti-hypertensives:

• diuretics: thiazide, spironolactone

• Methyl dopa, clonidine, reserpine

• Beta blockers: atenolol, propanolol

• Hydralazine

• ACEI

• Antidepressant:• TCA: amitriptylline, nortriptyline• Transquilizers: haloperidol, chlorpromazine• Anxiolytics: diazepam• Others: cimetidine, ketoconazole,

metoclopropamide, baclofen

– Systemic disease Hx:• DM• HTN• Vascular disease: intermittent claudication in the

gluteal and calf– Social history: smoking, alcohol, marijuana, nicotine,

opiates, some herbal concoction

– History of previous pelvic surgery/radiation

– History of trauma/pelvic fracture

• PHYSICAL EXAMINATION

• General appearance: may reveal androgen state, obesity

• Chest: gynaecomastia

• Abdomen : DRE: anal tone/ bulbocarvenous reflex- if depressed may be suggestive of neurological disorder

• External genitalia: may detect

– Peyronie’s disease

– Testicular abnormalities

– Loss/ abnormalities of penile sensation

• Extremities: palpate to detect peripheral vascular disease

• INVESTIGATION

• Urinalysis: may be glycosuria in DM

• Fasting blood sugar: elevated in DM

• Liver function test: abnormal values in patient with liver failure /high alcohol intake

• Serum testosterone: low in hypogonadism, post Orchidectomy

• Fasting lipid profile: hypercholesterolemia, increased triglycerides

• SPECIAL INVESTIGATIONS

• Nocturnal penile tumescence testing:

– help differentiate psychogenic from organic causes

– Use snap gauge device or ring of postage stamps

• Diagnostic intra-corporeal injection: induction of artificial erection to:

– Determine the distensibility of carvenosal tissue

– Determine feasibility of use of injection pharmacotherapy in ED treatment

– Drugs used: papaverine, phentolamine, PGE1

• Color duplex Doppler ultrasound assessment of intra-corporeal blood flow:

– done by inducing erection with PGE1 injection & assessing blood flow into the carvenosal tissue

• Dynamic infusion carvenosometry & carvenosography:

– Help to identify venous leakage and intra-corporeal pressure.

• Angiography:

– To determine arterial insufficiency

TREATMENT

• Done step wise: from least invasive to most invasive

• Behavioural modification

– Stop smoking, alcohol, weight loss, physical exercises

• Treat co-morbidities: HTN, DM, statins to lower lipoprotein cholesterol

• Stop use of drugs predisposing to ED

• Psychosexual counseling:

– NB: all patients have psychological component to their problem

• Psychological problem is mostly due to unrealistic expectation by one or both sides of the relationship

• Emphasis is on:

–Understanding of the problem

–Overcoming anxiety

–Teaching communication skills

–Re-learning sexual behaviour

• MEDICAL THERAPIES

• A. ORAL AGENTS:

• α- adrenoceptor antagonist

– Yohimbine HCl: causes corporal vasodilation & erection. Dose 10mg t.d.s

• Side effects: tremulousness, headache, palpitation, increase in BP

– Phentolamine: vasodilators but has narrow safety margin

• Dopamine agonist:

– apomorphine; side effects: persistent yawning, nausea & vomiting

• Serotonin agonist:

– trazodone- has sympatholytic effect . S/E: drowsiness, hypotension

• 5-Phosphodiesterase inhibitors(PDE-5I):

– increases level & effect of NO

– Sidenafil citrate: dose: 25 to 50mg/day; used 1hour before intercourse

• Half life: 3.8hours

• Efficacy: 96%

• S/E: facial flushing. Headache, effect on color vision, GI disturbances,

• Contra-indication: avoid in patients on nitrates: glycerl trinitrate, Nitroprusside- can lead to profound hypotension & cardiac arrest.

– Tadanafil: dose: 10 to 20mg/day

• Half life: 17.5 hours

• contra-indicated in : concomitant use of organic nitrates & α blocker

• S/E: headache, nasal stuffiness, dyspepsia

– Verdenafil HCl: dose 5 to 20mg

• Seems to be more effective in DM & post prostatectomy patient with ED

• Half life: 4.7hours

• S/E: as in sidenafil, prolong QT interval on ECG

• C/I: nitrate therapy & α blocker

• B. TRANSDERMAL DRUG DELIVERY:

– application of paste which contain PGE1 or Papaverine

• C. TRANSURETHRAL CORPOREAL DRUG DELIVERY:

– insertion of drug pellets intra-urethral. e.g PGE1

– S/E”: urethral pain, occasional bleeding & priapism

• D. INTRA-CORPORAL INJECTION:

– Injection of vasodilators into the carvenosal tissue e.g. Papaverine, phentolamine, PGE1

– S/E: priapism, ischemic injury to smooth muscles of carvenosal tissue

• VACUUM DEVICES & CONSTRICTION RING

– Vacuum device suction effects increase arterial inflow while the constriction reduces venous leakages

– S/E: penile bruising, may be uncomfortable, pain at ejaculation

• SURGICAL THERAPY

1. Correction of venous leakage by ligation

2. Arterial re-vacularization of damage arterial supply

3. Implantation of penile prosthesis: insertion of silicon prosthesis into corpora carvenosa

4. Penile enlargement: some attribute ED to small penile size:

• Division of suspensory ligament

• Advanced V-Y plasty of intra-pubic skin.