CLINICAL Erectile dysfunction Ian A R Smith When tablets don’t work Nicholas McLeod Prem Rashid with cardiovascular disease including Background lack of exercise, obesity, smoking, Erectile dysfunction (ED) is a common clinical problem managed in the general practice hypercholesterolaemia and the metabolic setting. While the majority of men will find phosphodiesterase-5 (PDE-5) inhibitors syndrome.6,7 This is an important consideration effective, there is a subgroup of men who require second and third line therapies. as ED may be an early marker of subclinical Objective metabolic and vascular disease.8 Many This article provides an overview of ED and its management with particular focus on the medications can potentiate ED including group of patients in whom oral agents fail. commonly used antihypertensives such as Discussion calcium channel blockers, angiotensin II Erectile dysfunction is a multifactorial condition that affects approximately 40% of receptor antagonists, angiotensin converting Australian men. The incidence of ED is age related however, it shares common risk factors enzyme receptor antagonists, beta blockers with cardiovascular disease and metabolic disorders. The management of ED should and thiazides. begin with an assessment of cardiovascular risk factors, advice on lifestyle modification, The physical symptoms of ED are often and a trial of PDE-5 inhibitors. Second line therapies include intracavernosal injections associated with depression, a loss of self and vacuum erection devices, while third line therapy entails penile implants. Factors confidence, loss of intimacy in a relationship, that influence treatment success include partner inclusion, good patient selection, as and a reduced quality of life.9 Although public well as ongoing support and education. awareness of ED has improved in the past Keywords: erectile dysfunction; men’s health decade, less than half the men with the disorder seek treatment.10 A delay often occurs between the onset of symptoms and attendance in the primary care setting, with a mean time of 1.0–3.5 years.10 The goals of ED treatment are to Erectile dysfunction (ED) is the persistent restore quality of life and allow the patient and inability to attain and maintain an his partner to enjoy a satisfying sex life. erection sufficient to permit satisfactory sexual performance.1 The overall Assessment prevalence of ED in Australia is estimated Consultations around the issue of erectile at 40%.2,3 The risk of developing ED is age dysfunction should be conducted in a relaxed, related, occurring in approximately 26% of reassuring, and nonjudgmental manner. The first men aged 50–59 years, and approximately step is to take a full medical, sexual, surgical 40% of men aged 60–69 years.2,4 With and psychosocial history (Table 2). A focused the advent of phosphodiesterase-5 physical examination includes: PDE-5 inhibitors, the management of ED • a genital examination occurs predominantly in the primary care • assessment of secondary sexual setting. Risk factors for ED are shown in characteristics Table 1. Guidelines for assessment and • a digital rectal examination to assess the management of ED are available from prostate gland. Andrology Australia5 (see Resources). A cardiovascular risk assessment should be performed before commencing a patient on a Erectile dysfunction is primarily an organic PDE-5 inhibitor and advising the resumption of condition, sharing common risk factors sexual activity.11,12 Kostis et al, have developed Reprinted from AUSTraLIAN FAMILY PHYSICIAN VOL. 39, NO. 5, MaY 2010 301 CLINICAL Erectile dysfunction – when tablets don’t work Table 1. Risk factors associated with Management Table 3. Stepwise approach to erectile dysfunction6,7 The management of ED should follow a stepwise management of erectile dysfunction approach as outlined in Table 3. Importantly, First line • Hypertension partners play a key role in supporting the • Lifestyle modifications (eg. quitting • Cardiovascular disease patient, allaying anxiety and achieving treatment smoking, exercise, weight loss) • Diabetes mellitus compliance; a couples based approach should be • Management of cardiovascular risk • Smoking encouraged. factors • Alcohol First line: PDE-5 inhibitors • Trial of PDE-5 inhibitors (at least • Prostate surgery four attempts with two different • Pelvic trauma There are currently three PDE-5 inhibitors on PDE-5 inhibitors) in the absence of • Pelvic radiotherapy the market: sildenafil (Viagra™), vardenafil contraindications • Medications (Levitra™) and tadalafil (Cialis™), which is Second line • Depression available as a daily dose. Features of these • Self intracavernosal injections • Penile abnormalities (eg. Peyronie medications are described in Table 4. The • Vacuum erection devices disease) efficacy of this class of medication is well • Hormonal therapies (eg. testosterone • Obesity established for the general population, as well replacement) • Sleep apnoea as in men following radical prostatectomy and • Combination therapy • Hyperlipidaemia radiotherapy for prostate cancer and those with Third line • Spinal cord trauma diabetes mellitus, spinal cord injury, multiple • Penile prostheses • Medical conditions such as multiple sclerosis, and depression.11,17,18 PDE-5s are sclerosis contraindicated following a recent myocardial successful intercourse increases with each infarction, concurrent nitrate therapy, and high treatment attempt, therefore patients should be a cardiovascular risk stratification algorithm, risk cardiovascular disease. encouraged to persevere with a trial of at least to evaluate the degree of cardiovascular risk The success rate of PDE-5 inhibitors is two PDE-5 inhibitors for up to four attempts of associated with sexual activity.13 Men who have dependent upon the aetiology of the ED and each, and at the maximum dosage.19 Information intermediate or high risk cardiovascular disease can range from approximately 43–89%.19 A regarding the need for sexual stimulation and the should obtain a cardiologist opinion before poorer response to PDE-5 inhibitors is seen onset and duration of action of PDE-5 inhibitors commencement. in the context of adverse factors such as can also increase success rates. It is important to establish the severity of ED. following prostate surgery (43%), diabetes Second line: vacuum devices, A validated questionnaire such as the Sexual with neuropathy (50%) and peripheral vascular 19 intercavernosal injections and Health Inventory for Men can accurately detect disease (63%). A better response is seen in an testosterone therapy and quantify ED.14,15 This brief questionnaire can otherwise healthy male whose ED is secondary be completed by the patient in the waiting room to depression (89%), neurological disease (85%) Following a complete trial with PDE-5 before the consultation or between the initial and smoking (80%).19 inhibitors, second line therapies can be used in consultation and follow up (see Resources). Other factors contributing to the failure combination with PDE-5 inhibitors to improve Given that ED and lower urinary tract symptoms of PDE-5s include incorrect usage, worsening response, or as a single therapy when PDE-5s commonly coexist, it is advisable to screen corporal endothelial dysfunction, poor tolerance are contraindicated. The advantages and patients for voiding symptoms using a screening to side effects, and hypoandrogenism.19 For initial disadvantages of vacuum erection devices tool such as the International Prostate Symptom nonresponders, education alone can improve (VEDs) and intercavernosal injections are shown Score Sheet7,16 (see Resources). the response by 40–55%.19 The probability of in Table 5. Vacuum erection devices Table 2. History taking in patients with erectile dysfunction Vacuum erection devices provide a safe, cost Sexual Medical Urological effective, and noninvasive alternative for men Nature of problem Medical history History of lower urinary tract who have failed oral pharmacotherapy. Negative Mode of onset Psychological history symptoms pressure is applied to the penis, producing Degree of disability Surgical history Penile complaints (eg. pain, passive engorgement of the corpora cavernosa, Precipitating factors Medications curvature) resulting in an erection that can be maintained Recreational drug use by an elastic band at the base of the penis for 30 Alcohol use minutes (Figure 1). Successful vaginal penetration Smoking history is as high as 90%, however device satisfaction 302 Reprinted from AUSTraLIAN FAMILY PHYSICIAN VOL. 39, NO. 5, MaY 2010 Erectile dysfunction – when tablets don’t work CLINICAL Table 4. PDE-5 inhibitors Drug Onset of action Half life Adverse effects Sildenafil Tmax* 30–120 2–5 hours • Headache minutes • Flushing Median 60 minutes • Dyspepsia Vardenafil Tmax 30–120 minutes 4.5 hours • Headache Median 60 minutes • Flushing • Dyspepsia Tadalafil Tmax 30–120 minutes 15.5 hours • Headache Median 120 minutes • Flushing Figure 1. Second line treatment: vacuum • Dyspepsia erection device * Tmax = median time to peak plasma concentration of drug Table 5. Advantages and disadvantages of VEDs and intracavernosal injections Therapy Advantage Disadvantage Contraindications Vacuum • Effective in all • Bruising • Bleeding disorders erection aetiological groups • Interference of • Anticoagulation devices • Do not require ejaculation due to therapy erectile reserve constriction ring • Noninvasive • Loss of acute • Low complication angle of erection rates • Pain • No restriction on • ‘Nonphysiological’