1. Erectile Dysfunction - A rising problem
Mr C Dawson MS FRCS
Consultant Urologist
Edith Cavell Hospital
Peterborough

2. 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
Incidence unknown because of acceptance or embarrassment (#671)
Prevalence figs from # 95
This lecture will therefore identify those areas in which progress has been made and outline ways in which patient investigation and management has been amplified.

3. 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)”

4. Myths surrounding E.D. “Nothing can be done”
“It’s to be expected at my age, isn’t it?”
“Do you think it’s all in my mind doctor?”

5. Erectile Dysfunction and ageing
Testosterone levels decline with age
Effects of testosterone on erectile capacity is not clear
Wide variation in “normal” levels of testosterone
Therefore, ageing and reduced testosterone may be independently associated with E.D.
See Campbell’s page 3041 & Goldstein’s slide notes:
2) Castrated patients may achieve erection in response to visual stimuli
hypogonadal patients with E.D. may have effects reversed by androgens
3) Testosterone levels may be no lower in ageing men with E.D. than controls
Major effect of testosterone appears to be on libido (Gillenwater p1959)

6. Psychological cause?
Careful history will usually determine those patients with a psychological element to their E.D.
Persistent E.D., especially of insidious onset is more likely to have an organic cause
More than 90% of cases of E.D. have an organic basis

7. 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
See # 117
During flaccidity the cavernosal smooth muscles are contracted and a small quantity of blood flows through the sinusoids
During erection, relaxation of the SM of the sinusoidal space allows it to fill with blood and brings about mechanical veno-occlusion
Veno occlusion is passive: during flaccidity the contracted trabecular SM allows unhindered venous drainage via subtunical venous plexus. Increased art inflow and lacunar filling compresses this plexus and increases resistance to outflow

8. Mechanism of erection

9. 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
Experiments with drugs blocking the sympathetic and parasympathetic ns do not prevent erection

10. 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

11. 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
Flaccid state: NO synthesis and PG synthesis are inhibited. Endothelial cells of the lacunae exposed to pO2 of 35mmHg. NO production decreased by hypoxia
Art inflow leads to normoxia, and endothelial cells relax, leading to lacunar filling. NO synthesised leading to SM relaxation
Arterial insufficiency (any cause) leads to corporal fibrosis and corpora don’t relax sufficiently to compress venules - “venous leak”. ?? explains impotence of ageing. TGF-B1 (found in diffuse intimal thickening of coronary arteries) lnhibits SM growth.

12. Pathophysiology of E.D. Flaccid state Asleep Established E.D.
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; don’t get the benefit of NPT episodes

13. Use it or lose it! Pathophysiology of E.D.
More erections = increased normoxia
Increased PGE and cAMP
Decreased TGF-B
?? decrease fibrosis already present

14. Assessment of the patient with E.D.
Careful History
Examination
Further investigations

15. Points to note in the initial history
Duration, ?insidious or acute onset
Absence of erections or diminished quality
Penetrative SI possible? Able to masturbate? Early morning erections?
Libido normal, or decreased
Pain or curvature of erection (?Peyronie’s disease)
Related psychosocial factors
Acute onset related to a specific event classically indicates psychological cause. Patient may have nocturnal or masturbation related erections. Slow, insidious and consistent loss of erections involving morning, coital and masturbation related erections suggests organic cause
Diminished libido may result from hypogonadism or psychosocial factors. Reactive loss suggested if patient expresses desire for SI once problem corrected.

16. Medical History Chronic systemic medical disease Neurological Problems
Previous surgery
Vascular risk factors
Drug History
Chronic medical diseases such as MS, Cirrhosis, Chronic alcoholism, CRF, Diabetes - Prevalence of E.D. in impotence approx 35-50%
History of spinal cord injury or of associated symptoms such as bladder/bowel altered function, paraesthesiae, change in balance etc. may suggest neurological cause
Vascular risk factors - hypertension, hyperlipidaemia, cigarettes, DM, pelvic DXT
Drugs - esp: Cimetidine (anti androgenic effect?), phenothiazines and tricyclic antidepressants, antihypertensives - methyldopa, spironolactone prazosin, propranolol, hydralazine, bendrofluazide. Antihypertensives may have their effect by lowering blood pressure where there is pre-existing occlusive disease (Campbells p 3036)

17. Physical examination Endocrine Neurological Vascular
Assessment of secondary sexual characteristics
Examine neck for Thyroid
Gynaecomastia
Size and consistency of testes
Neurological
Sensory deficit in sacral dermatomes
Vascular
BP, Carotid Bruits, AAA, Foot pulses
Local - examine penis for plaques or fibrosis

18. Laboratory Investigations
No single diagnostic test
FBC, U+E, LFT - to screen systemic medical disorders

19. Role of Hormone evaluation
Testosterone affects secondary sex characteristics; effects on erections unclear - If libido is reduced, testosterone should be measured
If Testosterone repeatedly low check LH
Low Testosterone and Low LH may indicate hypothalamic or pituitary defect (CT advised)
Low Testosterone and High LH suggests testicular failure
Hyperprolactinaemia inhibits LHRH pulse
Abnormal thyroid function may cause E.D.
Hyperprolactinaemia may be due to
pituitary microadenoma
drug induced
CRF
Idiopathic
Hyperthyroidism is commonly assoc with decreased libido but less commonly with E.D.
Hypothyroidism may be a cause of E.D. secondary to assoc low testosterone and elevated PRL
(Campbells p3041)

20. Further Management of E.D.
Pragmatic approach best, based upon available treatments
Diagnostic intracavernosal injection
Normal erection suggests normal vascular dynamics, and precludes further investigation
Poor, or absent, erectile response may be followed by investigations in certain circumstances
Rajfer - #621
Most people with a poor response to diagnostic injection have vasculogenic problem. The long term results of specific therapies in these situations are marginal at best and thus further studies such as duplex scanning or dynamic infusion cavernosometry or cavernosography are not warranted unless patient is young with no other risk factors
Patients with a normal response, thought to have psychological cause for E.D., are also not investigated as penile haemodynamics must be well compensated

21. Further Management of E.D.
Medical therapy
“Magic Pill” still sought
Yohimbine - may improve erectile capacity in some men
Yohimbine - see #670 - seems to work in men with performance anxiety. Results not confirmed in randomised trials

22. Intracavernosal Pharmacotherapy
Papaverine +/- Phentolamine
Prostaglandin E1 (Caverject)
Combination therapies
Requires trained supervision until patient competent to give injection
Trained supervision need not be by the Urologist in charge of patient
Could be done by nurse practitioner
Possibly the GP practice could do this
?how many already do
Papaverine - non specific PDE inhibitor, metabolised in liver. Priapism is a concern, as is fibrosis
PGE1 - acts via raising cAMP. Degraded in lung and possibly cavernous tissue. Less priapism and fibrosis. Pain on erection in up to 25%

23. Results of intracavernosal therapy
Papaverine alone -30% success rate
PGE1 alone - 70% success rate
Combination therapies may have success rates of 85-90%
Priapism less with PGE1 (0.4% vs 6% for Papaverine
Early drop-out rate as high as 50%

24. Vacuum device Vacuum results from Gillenwater p1974
Less invasive than intracavernous injection
Results good - up to 92% success in some series
Bruising reported so contraindicated in bleeding diathesis or anticoagulant treatment
Expensive for patient to purchase
Vacuum results from Gillenwater p1974

25. Penile Prosthesis
Usually tried only after injections and vacuum device have failed, or for E.D. associated with Peyronie’s disease
Rigid, or inflatable types
Insertion requires strict asepsis under GA
Infection is the most important complication, necessitating removal
Erosion of one or both cylinders may occur

26. The Future
Better understanding of chemical mediators may lead to pharmacological treatments? - e.g. Sildenafil
Sildenafil - type V PDE inhibitor to be marketed by Pfizer. In trials has shown >80% success rates (#605)

27. Conclusions
Media attention and public awareness has led to increased referrals
Better understanding of mechanism of erection, and pathophysiology of E.D. has rationalised investigation and treatment

28. Conclusions
Current management relies on pragmatic approach, and response to intracavernosal injection of PGE
Good success rates with either injections or vacuum device. Prosthesis rarely required
Future developments likely to radically alter management of this condition