Erectile Dysfunction George Yardy The Ipswich Hospital
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