Erectile Dysfunction · •Lack of exercise •Obesity •Smoking •Hypercholesterolaemia...

Erectile Dysfunction

George Yardy

The Ipswich Hospital

COI

Pfizer

GSK

Ipsen

Speciality European Pharma

Ferring

Astellas

Ethicon

AstraZeneca

Aspire Pharma

Teva

Outline • GWY

• ED epidemiology and causes

• Assessment

• 1st / 2nd / 3rd line treatments

• A few irrelevant things

• Summary

Erectile Dysfunction

• The inability to attain / maintain an erection sufficient for satisfactory sexual performance

Epidemiology

• Incidence and prevalence high worldwide

• Massachusetts Male Aging Study (1994)– 52% of men (aged 40-70) affected– mild 17%, moderate 25%, severe 10%

• Average GP 1-4 consultations / month

• Incidence related to age:– Cologne study: 2.3% at age 30, 53.4% at age 80

• 10-20% solely psychogenic cause, but even patients with physical cause have psychogenic component

Risk factors for ED

• Lack of exercise• Obesity• Smoking• Hypercholesterolaemia• Hypertension• Metabolic syndrome• Diabetes mellitus

• Same as risk factors for cardiovascular disease

Metabolic syndrome

• ≥3 of 5:– Abdominal obesity

– High blood pressure

– High fasting blood glucose / insulin resistance

– High serum triglycerides

– Low high-density lipoprotein (HDL) levels

ED causes – organic:

• Vascular– Cardiovascular disease– Atherosclerosis– Hypertension– Diabetes– Hyperlipidaemia– Smoking– Surgery or radiotherapy to pelvis / retroperitoneum– trauma

• Neurological – central– Parkinson’s disease– Multiple Sclerosis– Tumours– Traumatic brain injury (esp hypothalamic-pituitary deficiency)– Cerebrovascular disease– Spinal cord disease / injury

ED causes – organic:

• Neurological – peripheral– Polyneuropathy– Peripheral neuropathy– Diabetes mellitus– Alcoholism– Uraemia– Surgery (pelvic, retroperitoneal)

• Hormonal– Hypogonadism– Hyperprolactinaemia– Thyroid disease– Cushing’s disease

• Anatomical– Peyronie’s disease– Other penile anomalies

ED causes – organic:

• Drugs– Antihypertensives, beta blockers, diuretics

– Antidepressants: both tricyclics and SSRIs

– Antipsychotics: phenothiazines, risperidone

– Hormonal agents: cyproterone, LHRH agonists, finasteride

– Antihistamines

– Recreational drugs

– H2 antagonists – cimetidine, ranitidine

ED – psychogenic causes:

• Psychosexual factors– General (disorders of intimacy, lack of arousability)

– Situational (partner, performance or stress)

• Psychiatric illness– Generalised anxiety

– Depression

– Psychosis

– alcoholism

ED assessment

• Sexual history

– Current and past relationships

– Current emotional status

– Erectile symptoms – onset and duration

– Arousal, ejaculation and orgasmic difficulties

• Past medical history and medication

• Validated symptom questionnaire

History suggesting psychogenic causes

• Sudden onset

• Early collapse of erection

• Self-stimulated or waking erections

• Premature ejaculation or inability to ejaculate

• Problems or changes in a relationship

• Major life events

• Psychological problems

History suggesting organic causes

• Gradual onset

• Normal ejaculation

• Normal libido (except hypogonadal men)

• Risk factor in medical history (CVS, endocrine, neurol)

• Surgery / radiotherapy / trauma to pelvis or scrotum

• A current drug recognised assoc with ED

• Smoking, high alcohol consumption, recreational or body-building drugs

Physical examination

• Genitals – Peyronie’s, foreskin, testis size

• Prostate examination not mandatory but consider if urinary symptoms

• BP, heart rate, waist circumference, weight

Laboratory testing

• Serum lipids, fasting plasma glucose, HbA1c

• Testosterone – early morning sample

• Consider PSA – selected pt.s but definitely before starting testosterone therapy

ED and cardiovascular system

• Coronary heart disease (CHD) same risk factors as ED

• Coronary artery disease (CAD) and ED are both features of a generalised arteriopathy.

• ED in an otherwise asymptomatic man may be a marker for underlying CAD.

Management

• Diagnose and treat cause of ED when possible

• Address modifiable factors – lifestyle, drug-related

• Other treatments selected according to efficacy, safety, invasiveness, cost, patient preference

Lifestyle

• Address

– Smoking

– Obesity

– Alcohol consumption

– Lack of physical activity

Medication review

• Stop any medication assoc with ED?

• Change anti-hypertensive

– ACE inhibitors (eg. Lisinopril) can cause ED; Angiotensin II receptor antagonists (eg. Losartan) can improve ED

ED: treat the cause

• Hormonal causes:

– Testicular failure – treat with testosterone

– Pituitary / hypothalamic causes – see an endocrinologist

• Post-traumatic arteriogenic ED in young patients

– Few pt.s for whom vascular recon surgery appropriate

• Psychosexual therapy

First-line therapy for ED

• Oral agents: Phosphodiesterase inhibitors (PDE5 inhibitors) sildenafil, tadalafil, vardenafil, avanafil)

– Proven efficacy and safety both in non-selected pt.s and specific sub-groups (DM, prostatectomy)

– Vary in duration of action, side effects, interactions

– Not initiators of erection – still require sexual stimulation

– Contraindicated if receiving nitrates (ISMN etc) for angina (-> severe unpredictable hypotension)

Sildenafil

• Viagra and generic

• Generally well tolerated

• Effective from 30-60 min

• Efficacy reduced after fatty meals and alcohol

• 25 / 50 /100mg – start at 50mg?

• Adverse events rare and drop-out rate similar to placebo

Tadalafil

• Cialis

• Longer half-life -> greater spontaneity? Effective 30 min, peak efficacy 2hrs, lasts up to 36 hrs

• 5 / 10 / 20mg – start at 10mg?

• Also few adverse events

• Better in difficult-to-treat subgroups?

Vardenafil

• Levitra

• Effective after 30 min

• Difficult-to-treat sub-groups?

• Less interaction with food

• Oro-dispersible (rapid onset preparation)

Avanafil

• Spedra

• Effective 30 min – fastest action?

• Highly selective PDE5 inhibition – minimises side-effects

• Less interaction with food

Side effects

NHS prescriptions for drugs for ED

• Since 1999 drugs for ED at NHS expense only if:

– Have any of the following conditions:• Diabetes, MS, Parkinson’s, polio, prostate cancer• severe pelvic injury, single gene neurological disease• Spina bifida, spinal cord injury

– Receiving renal dialysis– Had radical pelvic surgery, prostatectomy (inc. TURP), kidney trasplant– Receiving ED drugs on NHS prior to Sept 1998– Suffering “severe distress” as a result of impotence

• Since 2014– Generic sildenafil can be prescribed to all where clinically appropriate

Non-invasiveNo limit to frequency of use

CumbersomePainAppearanceSensationPainful ejaculationMax 30 minutesCost

Vacuum Devices

Second-line therapy for ED

• Alprostadil (prostaglandin E1) injection, tablet, cream

Intracavernosal Injections - Alprostadil

• Causes smooth muscle relaxation, vasodilatation, inhibition of platelet aggregation.

• Erection appears 5 – 15mins after taking, lasts according to dose

• Patient must be trained at OP clinic how to use

• Efficacy thought to be around 70% with reported sexual activity after 94% of injections

Vardi Y, Sprecher E, Gruenwald I. Logistic regression and survival analysis of 450 impotent patients treated with injection therapy: long-term dropout parameters. J Urol 2000;163:467–70.

Caverject (alprostadil)

Adults• 1.25 to 60 micrograms as a single dose once a

day. • Injection - very slowly ten to thirty minutes

before intercourse. • Allow five to ten seconds to completely inject

the dose. • Do not inject more than one dose within

twenty-four hours. • Also, do not use this medicine for more than

two days in a row or more than three times a week.

• 41 – 68% drop-out rate

• Complications:– Haematomata

– Penile pain

– Priapism

– Fibrosis (rare)

• Efficacy can be improved by using combination injection with papaverine and phentolamine; risk of fibrosis and priapism much higher.

Intra-Urethral Alprostadil Pellet (MUSE)

• Lower efficacy than injection

• Band at base of penis may increase rigidity

• 70% of patients are satisfied

• Side effects:

– Pain

– Dizziness

– Urethral bleeding

The Medicated Urethral System for Erections

Doses (examples)• spinal cord injury at 125 mcg

• psychogenic impotence or men <50 of age with no identifiable cause at 250 mcg

• clearly evident organic dysfunction, post-radical prostatectomy, and men >50 years of age at 500 mcg

MUSE

Topical Alprostadil

• Vitaros

• Applied 5-30 min before intercourse

• Plunger delivers the cream to tip of penis and surrounding skin

Penile implants

third-line therapy for ED

Indications

Failure of other “less invasive” treatments

ED associated with penile deformity/fibrosis

Refractory priapism

Selected patients (referral to specialist centre)

Patient choice

What type of implant?

Malleable & Semirigid

Inflatable

2 Components 3 Components1 Component

Malleable/semi rigid

Advantages• Oldest of PP• Easy to insert• Does not require much dexterity to use• 1st choice in ischaemic priapism

Disadvantages• Always rigid• No increase in girth compared to other

options• May increase risk of erosion in “at risk

patients”

AMS malleable

Coloplast GenesisⓇ

Inflatables

More complicated to insert

Provide better appearance and function than malleable

Choice depends on patient factors and surgeon preference

Most implants are still noticeable in the flaccid state

Considerations before inflatable Penile implants

Co-morbidity

Dexterity

Previous surgery

RP/Cystectomy/Transplant?

Penile length

Patient expectations

Single component

Self contained inflatable Two cylinders

Pain at penile tip (due to activation method)

Not commonly used now

Single component

Two-component

Reservoir in the base of the cylinders

Scrotal pumpFlaccidity and erection worse compared to 3- piece systems

Three component

Two cylinders, balloon reservoir and pump

Different cylinder and reservoir configurations

RTE for proximal end

Some models antibiotic coated (Inhibizone™)

AMS 3-piece implants

• AMS 700-LGX offers girth and length expansion up to 20%

• AMS 700 -CX features controlled expansion

• AMS 700 -CXR for difficult cases where length is reduced

AMS 700™

Coloplast TitanⓇ

Coloplast Titan• Three component as seen

with the AMS 700

• Bioflex material (?more durable than silicon)

• One-touch release (OTR) pump

• Lock-out™ system

Complications

ED - summary

• Address cardiovascular risk factors

• Lifestyle changes

• Medication changes

• PDE5 inhibitors, vacuum device

• Prostaglandin injection / cream

• Implants