«GUIDELINES ON MALE SEXUAL DYSFUNCTION: Erectile Dysfunction and Premature Ejaculation (Text update March 2013) E. Wespes (chair), I. Eardley, F. ...»
GUIDELINES ON MALE SEXUAL
DYSFUNCTION: Erectile Dysfunction
and Premature Ejaculation
(Text update March 2013)
E. Wespes (chair), I. Eardley, F. Giuliano, D. Hatzichristou,
K. Hatzimouratidis (vice-chair), I. Moncada, A. Salonia, Y. Vardi
Eur Urol 2006 May;49(5):806-15
Eur Urol 2010 May;57(5):804-14
Eur Urol 2012 Sep;62(3):543-52
Definition, epidemiology and risk factors
Erectile dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Although ED is a benign disorder, it affects physical and psychosocial health and has a significant impact on the quality of life (QoL) of sufferers and their partners.
There is increasing evidence that ED can be an early manifestation of coronary artery and peripheral vascular disease;
thus, ED should not be regarded only as a QoL issue but also as a potential warning sign of cardiovascular disease including lack of exercise, obesity, smoking, hypercholesterolaemia, and the metabolic syndrome. The risk of ED may be reduced by modifying these risk factors, particularly taking exercise or losing weight. Another risk factor for ED is radical prostatectomy (RP) in any form (open, laparoscopic, or robotic) because of the risk of cavernosal nerve injury, poor oxygenation of the corpora cavernosa, and vascular insufficiency.
Male Sexual Dysfunction 125 Diagnosis and work-up Basic work-up The basic work-up (minimal diagnostic evaluation) outlined in Fig. 1 must be performed in every patient with ED.
Due to the potential cardiac risks associated with sexual activity, the three Princeton Consensus Conference stratified patients with ED wanting to initiate, or resume, sexual activity into three risk categories. The low-risk group includes asymptomatic patients with less than three risk factors for coronary artery disease (excluding male gender), mild or stable angina (evaluated and/or being treated), uncomplicated past myocardial infarction, left ventricular dysfunction or congestive heart failure (NYHA class I), post-successful coronary revascularisation, controlled hypertension, and mild valvular disease. All other patients are included in an intermediate- or high-risk category and require a cardiology consultation.
Specific examinations and tests Although most patients with ED can be managed within the
sexual care setting, some circumstances require specific diagnostic testing:
• Patients with primary erectile disorder (not caused by organic disease or psychogenic disorder).
• Young patients with a history of pelvic or perineal trauma who could benefit from potentially curative vascular surgery.
• Patients with penile deformities (e.g. Peyronie’s disease, congenital curvature) that might require surgical correction.
• Patients with complex psychiatric or psychosexual disorders.
• Patients with complex endocrine disorders.
• Specific tests may also be indicated at the request of the patient or his partner.
126 Male Sexual Dysfunction
• For medico-legal reasons (e.g. penile prosthesis implant, sexual abuse).
Specific diagnostic tests include:
• nocturnal penile tumescence and rigidity (NTPR) using Rigiscan®;
• vascular studies:
- intracavernous vasoactive drug injection;
- duplex ultrasound of the cavernous arteries;
- dynamic infusion cavernosometry/cavernosography (DICC);
- internal pudendal arteriography;
• neurological studies (e.g. bulbocavernosus reflex latency, nerve conduction studies);
• endocrinological studies;
• specialised psychodiagnostic evaluation.
The NPTR should take place for at least two nights. A functional erectile mechanism is indicated by an erectile event of at least 60% rigidity recorded on the tip of the penis, lasting for 10 min or longer.
The intracavernous injection test provides limited information about vascular status. However, Duplex ultrasound provides a simple way of assessing vascular status. Further vascular investigation is unnecessary if Duplex ultrasound is normal, as indicated by a peak systolic blood flow 30 cm/s an enddiastolic velocity of 3 cm/s and a resistance index 0.8. If ultrasound is abnormal, however, arteriography and DICC should be performed only in patients who are potential candidates for vascular reconstructive surgery.
Treatment of ED
As a rule, EC can be treated successfully with current treatment options, but cannot be cured, with the exception of:
• Psychogenic ED: psychosexual therapy may be given, either alone or with another therapeutic approach, but takes time and has had variable results.
• Post-traumatic arteriogenic ED in young patients: surgical penile revascularisation has a 60-70% long-term success rate.
• Hormonal causes of ED: testosterone replacement therapy is effective, but should only be used after other endocrinological causes for testicular failure have been excluded.
Currently, it is contraindicated in men with untreated prostate cancer, unstable cardiac disease and severe LUT obstruction. Close follow-up is necessary, including digital rectal examination (DRE), serum prostate-specific antigen (PSA) and haematocrit assessment, as well as monitoring the development of hepatic or prostatic disease.
128 Male Sexual Dysfunction Fig. 1: Minimal diagnostic evaluation (basic work-up) in patients with ED
IIEF = International Index for Erectile Function; ED = erectile dysfunction.
Male Sexual Dysfunction 129 The use of pro-erectile drugs following RP is very important in achieving erectile function after surgery. Rehabilitation should start as soon as possible following RP.
Most men with ED will be treated with treatment options that are not cause-specific. This approach requires a structured treatment strategy that depends on efficacy, safety, invasiveness, and cost, as well as patient and partner satisfaction. A treatment algorithm for ED is given in Fig. 2.
First-line therapy Oral pharmacotherapy Three potent, selective PDE5 inhibitors (PDE5Is) have been approved by the European Medicines Agency (EMA) for the treatment of ED. They are not initiators of erection and require sexual stimulation for an erection to occur. Efficacy is defined as rigidity sufficient for vaginal penetration.
Sildenafil (Viagra™) Sildenafil is effective after 30-60 min from administration.
A heavy, fatty meal may reduce or prolong absorption. It is administered in 25, 50 and 100 mg doses. The recommended starting dose is 50 mg and adapted according to patient response and side-effects. Efficacy may be maintained for up to 12 h. Efficacy rates (erections sufficient for successful intercourse) are 56%, 77% and 84% of men taking 25, 50 and 100 mg of sildenafil, respectively. The efficacy of sildenafil in almost every subgroup of patients with ED has been well established.
Tadalafil (Cialis™) Tadalafil is effective from 30 min after administration but its peak efficacy occurs after about 2 h. Efficacy is maintained for up to 36 h and is not affected by food. It is administered in 10 and 20 mg doses. The recommended starting dose is 10 130 Male Sexual Dysfunction mg and is adapted according to patient response and sideeffects. Efficacy rates are 67% and 81% of men taking 10 mg and 20 mg of tadalafil, respectively. Tadalafil also improves erections in difficult-to-treat subgroups.
Vardenafil (Levitra™) Vardenafil is effective after 30 min from administration. A fatty meal, 57% in fat, reduces its effect. It is administered in 5, 10 and 20 mg doses. The recommended starting dose is 10 mg and adapted according to the response and side-effects.
In vitro, it is 10-fold more potent than sildenafil. However, this does not necessarily mean greater clinical efficacy. Efficacy rates are 66%, 76% and 80% of men taking 5 mg, 10 mg and 20 mg of vardenafil, respectively. Vardenafil also improves erections in difficult-to-treat subgroups.
Choice of, or preference for, different PDE5Is The choice of a PDE5I depends on the frequency of intercourse (occasional use or regular therapy, 3-4 times weekly) and the patient’s personal experience of the agent. Patients need to know whether a drug is short- or long-acting, possible disadvantages, and how to use it.
On-demand or chronic use of PDE5Is Although PDE5Is were introduced as on-demand treatment, in 2008, tadalafil was also approved for continuous, everyday use in 2.5 and 5 mg doses. Daily dosing was well tolerated and significantly improved erectile function. Similar results have been found in diabetic patients. Daily tadalafil provides an alternative to on-demand dosing for couples that prefer spontaneous rather than scheduled sexual activity or who have frequent sexual activity.
Adverse eventsCommon adverse events include headache, flushing, dizzi-
Male Sexual Dysfunction 131 ness, dyspepsia, and nasal congestion. Sildenafil and vardenafil have been associated with visual abnormalities in less than 2% of patients, while tadalafil has been associated with back pain/myalgia in 6% of patients. However, adverse events are generally mild in nature, self-limited by continuous use, and the dropout rate due to adverse events is similar to placebo.
Cardiovascular safety Clinical trials and post-marketing data of all PDE5Is have demonstrated no increase in myocardial infarction rates. No PDE5I has adversely affected total exercise time or time to ischaemia during exercise testing in men with stable angina.
In fact, they may improve exercise tests.
Nitrates are totally contraindicated with all PDE5Is due to unpredictable hypotension. The duration of interaction between organic nitrates and PDE5Is varies according to the PDE5I and nitrate. If a patient develops angina while using a PDE5I, other antiangina agents may be used instead of nitroglycerine or until after the appropriate time has passed (24 h for sildenafil or vardenafil and 48 h for tadalafil).
In general, the adverse event profile of the PDE5I is not worsened, even when the patient is on multiple antihypertensive agents.
Alpha-blocker interactions All PDE5Is appear to interact with alpha-blockers, which under some conditions may result in orthostatic hypotension.
Patients should be stable on alpha-blocker therapy prior to initiating combined treatment, and that the lowest dose should be started initially of PDE5Is.
Dosage adjustments Lower doses of PDE5Is may be required in patients taking
132 Male Sexual Dysfunction ketoconazole, itraconazole, erythromycin, clarithromycin, and HIV protease inhibitors (ritonavir, saquinavir). Higher doses of PDE5Is may be necessary in patients taking rifampicin, phenobarbital, phenytoin, or carbamazepine. Kidney or hepatic dysfunction may require dose adjustments. In patients with hypogonadism, androgen supplementation improves erectile response.
Management of non-responders to PDE5Is Physicians should check that the patient is using a licensed medication and that the medication has been properly prescribed and correctly used (adequate sexual stimulation, dosage, and enough time between taking the medication and attempt at intercourse).
Provided a patient is using a PDE5I appropriately, there are several ways of improving efficacy. They include modification of associated risk factors, treatment of associated hypogonadism, changing to another PDE5I, or continuous use of a PDE5I.
Vacuum erection devices A vacuum erection device (VED) applies a negative pressure to the penis to draw venous blood into the penis, which is then retained by application of a visible constricting band at the base of the penis. Efficacy, defined by an erection satisfactory for intercourse, is as high as 90%. Satisfaction rates range between 27% and 94%. Adverse events include penile pain, numbness, and delayed ejaculation and occur in less than 30% of patients. VED is acceptable for couples in a stable relationship.
Male Sexual Dysfunction 133 Second-line therapy Patients not responding to oral drugs may be offered intracavernous injections. Alprostadil (Caverject®, Edex/Viridal®) is the only drug approved for intracavernous treatment of ED.
It is the most efficacious monotherapy for intracavernous treatment using 5-40 μg doses. The patient should been rolled in an office-based training programme (one or two visits) to learn the correct injection process.
Complications of intracavernosal prostadil include penile pain (50% of patients), prolonged erections (5%), priapism (1%), and fibrosis (2%). Drug combinations (mainly the three-drug combination of alprostadil + papaverine + phentolamine) may increase efficacy by up to 90%. Fibrosis was found to be more common (5-10%) if papaverine was used (depending on total dose).
After 4 h of erection, patients are advised to consult their doctor to avoid any damage to the intracavernous muscle, as this will result in permanent impotence. Blood aspiration and injection of phenylephrine are used to treat prolonged erections. If this problem occurs, the dosage of the next intracavernosal injection is usually reduced.
Prostaglandin E1 may be administered intra-urethrally as a semi-solid pellet (125-1000 µg). A band placed at the base of the penis improves the resulting rigidity. The clinical success rate is lower than with intracavernosal injections, but about 70% of patients are satisfied with treatment. Side-effects include local pain (29-41%), dizziness (1.9-14%), and urethral bleeding (5%).
Third-line therapy (penile prostheses) Surgical implantation of a penile prosthesis may be considered in patients who fail pharmacotherapy or who want a 134 Male Sexual Dysfunction permanent solution. Prostheses are either malleable (semi rigid) or inflatable (two- or three-piece). Most patients prefer the three-piece inflatable devices because erections are more ‘natural’, but these implants are much more expensive.
Satisfaction rates of 70-87% are reported from patients after appropriate consultation.
Complications include mechanical failures and infections.