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

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.

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)”

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?”

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)

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

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

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

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 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.

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

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

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

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.

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)

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

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

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)

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

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

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%

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%

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

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

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)

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

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