In young patients with posttraumatic arteriogenic ED, penile revascularization interventions have shown a 60–70% long-term success rate (Grade B – level IIb).20 Imaging modalities such as duplex ultrasound and penile pharmacoarteriography have to be used to demonstrate and confirm the lesion. In case of corporal veno-occlusive dysfunction revascularization is contraindicated.15,16 In patients with veno-occlusive dysfunction, surgical treatment has not shown satisfactory results and is no longer recommended.18

Medical Treatment

The majority of patients will seek medical treatment for ED. Treatment strategies depend on the patient´s risks and benefits, the cardiovascular safety (see above), costs, patient´s preferences, and partner issues. Accordingly, treatment will be selected based not only on the efficacy and safety profile of the drugs available, but also on the patient’s cultural, religious, and economic background. A treatment algorithm for ED is presented in Fig. 28.3.6

Oral Agents

Several agents are approved and available for this indication (selective PDE5 inhibitors, apomorphine and yohimbine). In most patients with ED, PDE5-inhibitors are the gold standard due to their potential benefits and lack of invasiveness.5-7

Phosphodiesterase Type 5 (PDE 5) Inhibitors PDE5-inhi- bitors are associated with the broadest efficacy and highest tolerability in the treatment of ED. Sildenafil, tadalafil, and vardenafil are commercially available potent, reversible, competitive inhibitors of PDE5 (Grade A – level Ia).

All PDE5 inhibitors are nonhydrolyzable analogues to cGMP that prevent the degradation of this cyclic nucleotide by competitive binding to the catalytic site of PDE5. Thus, enhancement of NO-initiated relaxations of cavernous erectile tissue can be obtained.21 To date, the abundant expression of PDE5 protein in the human corpus cavernosum versus other tissues is considered the main reason for the clinical efficacy of PDE5 inhibitors in the treatment of ED. In turn, this elevated expression of PDE5 in the penis

might be responsible for the low efficacy of NO donor drugs,which have not yet been introduced successfully to the pharmaceutical market.

Superiority has not been proven for any of these substances in spite of existing differences in pharmacokinetic and adverse event profiles (Table 28.2). Sildenafil was approved worldwide in 1998 and vardenafil and tadalafil in 2003. PDE5 inhibitors are effective and well tolerated as demonstrated in controlled clinical trials and clinical practice experience. In general ED, a high level of evidence exists for the efficacy of all three drugs.As side effect, mild transient systemic vasodilation may occur; this effect may be aggravated by alpha-blocking therapies for lower urinary tract symptoms due to bladder outlet obstruction (BOO). PDE5 inhibitors are strictly contraindicated in patients receiving organic nitrates and nitrate donors. The onset of nonarteritic anterior ischemic optic neuropathy (NAION) has not been proven to be associated with the use of PDE5-inhibitors.

Nonresponders to PDE5 Inhibitors In spite of the excellent clinical effects of PDE5-inhibitors, about 20–30% of patients do not respond to PDE5 inhibitors. Particularly, patients suffering from ED associated with diabetes and after radical prostatectomy for prostate cancer are difficult to treat. These patients should receive a minimum of four of the highest tolerated dose of at least two drugs.5 In case of failure, it is recommended to reinstruct the patient on how to use the drug correctly (Grade B – level Ib), re-evaluate (new) risk factors, treat concurrent hypogonadism (Grade A – level Ib), change to another drug (Grade C – level IIa), and prescribe more frequent dosing regimes (Grade B – level Ib) (Fig. 28.4).

Apomorphine SL Apomorphine SL (sublingual), administered in 2- or 3-mg doses, is a centrally acting nonselective dopamine agonist (mainly D2), improving erectile function by enhancing the natural central erectile signals that usually occur during sexual stimulation.22 It acts with modest efficacy and good tolerability in mild ED.It is associated with mild to moderate nausea and rare bradycardia/syncopy (vasovagal) syndrome. Apomorphine SL is registered in various countries (not in the US) since 2002. Efficacy rates (erections hard enough for