Overview
It is estimated that erectile dysfunction (ED) affects as many as 30 million men in the United States. Patient interest in and treatment for ED surged with the introduction of oral phosphodiesterase-5 inhibitors (PDE-I) in 1998, and expenditures for office visits and other outpatient treatments increased during that time. The available data likely underestimate current treatment utilization given that in the 22 months after the first PDE-I, sildenafil (Viagra™), was launched, nearly 18 million prescriptions were filled at an approximate cost of $90 per 10-tablet prescription. The emergence of effective, convenient, and generally well-tolerated new treatment options (along with educational campaigns initiated by the pharmaceutical industry) has contributed to increased public awareness and a greater acceptability of and attention to the health and socioeconomic impacts of male sexual health.
While ED is not life threatening, the condition may result in withdrawal from sexual intimacy, reduced quality of life, decreased working productivity, and increased healthcare utilization. Patterns of care may shift away from surgical and device therapies provided by urologists and toward pharmacologic treatments and/or multidisciplinary approaches. With men increasingly seeking to preserve sexual function and quality of life as they age, the treatment of ED will take on even greater importance in the years to come.
Symptoms
ED is defined as the persistent “inability to achieve or maintain an erection sufficient for satisfactory sexual performance.” The experience of ED may vary based on patients’ and partners’ perceptions and expectations about erectile function and sexual performance. As the public has become more aware of ED, the reported prevalence and severity of this condition have increased. Comprehensive questionnaires have been developed (e.g., the International Index of Erectile Function (IIEF)) to define ED presence, severity, and response to treatment. Symptom-based definitions are rapidly replacing the routine use of physiologic measures of erectile function such as penile tumescence. The definition of ED provided by the National Institutes of Health does not include the duration of dysfunction; subsequent recommendations by the World Health Organization specify a three-month minimum duration of symptoms to establish that diagnosis except in cases of trauma or surgically induced ED. Objective physiologic testing may be used to support the diagnosis of ED, but it cannot substitute for the patient’s self-report in establishing the diagnosis.
Diagnosis
The diagnosis of ED requires a detailed sexual and medical history, physical examination, and laboratory tests. Self-administered questionnaires are useful adjuncts to the case history, but they are not sufficient to diagnose ED correctly or treat it safely. Pharmacological, radiological, and psycho-physiological tests are used in efforts to determine the cause of ED. Intracavernosal injection, penile duplex Doppler ultrasonography, dynamic infusion cavernosometry and cavernosography, and internal pudendal arteriography all may be used to identify vasculogenic ED. Nocturnal penile tumescence testing can be useful to document an intact neurovascular axis, and the absence of nocturnal erectile activity may imply a neurogenic etiology. However, since the introduction of oral PDE-I therapy and the acceptance of goal-oriented therapy for most cases of ED, the rationale for extensive testing has weakened. For example, elderly patients may be less willing to undergo invasive testing for the evaluation and treatment of ED.
Only a small subset of men with ED benefit from vascular testing, which can identify specific arterial or venous dysfunction amenable to surgical reconstruction. For the vast majority, such testing is unlikely to change management strategy. Thus, specialized testing is now limited to PDE-I non-responders, young men with post-traumatic or primary ED, men with Peyronie’s Disease, and legal investigations.
Treatment
Treatment options for ED have evolved considerably over the past decade to encompass psychological counseling; oral, topical, intraurethral, and intracavernosal vasoactive therapy; oral therapies with other or unknown mechanisms; hormone replacement; vacuum constriction devices; and surgery, including vascular bypass procedures and penile implants. The goal of treatment is to restore satisfactory erections with minimal adverse effects. Men have demonstrated a strong preference for oral treatments even if they have low efficacy.
General Considerations
Appropriate treatment options should be applied in a step-wise fashion, balancing invasiveness and risk versus efficacy. If possible, the partner should be involved in the decision-making. The decision depends on the patient preferences and expectations as well as the experience and judgment of the physician. Oral phosphodiesterase type-5 inhibitors are first line therapy.
The efficacy of sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) are very similar. All drugs induce significant increases in erectile function at their highest dose. In general, an intermediate dose should be administered first to assess side effects. As long as side effects are minimal, patient should increase to the maximum recommended dosage (100 milligrams for Viagra, 20 milligrams for Levitra, and 20 milligrams for Cialis. Because efficacy is very similar amongst the three agents, side effects and time-to-onset will be the main distinguishing factors. Viagra and Levitra feature rapid-onset of action, whereas Cialis has the long window of opportunity for use. Maximum levels in the bloodstream are reached within 45 minutes with Levitra, an hour and 10 minutes with Sildenafil, and 2 hours with Tadalafil. Conversely, the half-life of Viagra is 4 hours, for vardenafil 4 to 5 hours, and for Cialis 17 to 21 hours. In young men, one study has shown a preference for Cialis over sildenafil. However, this was open-label. The mean age of the patients was only 54 years, and outcomes were not well defined. In another study, looking at prescription refill rates, sildenafil was associated with a higher likelihood of refilling the initial prescription compared to vardenafil or tadalafil, which had a significantly lower odds of prescription refill.
It is recommended that prior to proceeding with other therapies, patients reporting failure of their PDE5 inhibitors should be evaluated to determine whether the trial was adequate. This would include discussion of fatty food ingestion, which is important with sildenafil, and specific patient population such as prostatectomy and diabetes. Furthermore, patients should be encouraged to continue attempts at intercourse up to the eighth to tenth dose of PDE5 inhibitor as improvements in success rate are seen up to the eighth to tenth dose.
Risk exposure is important to consider in the PDE5 inhibitors. Cardiovascular diseases may be a contraindication to treatment, as severely impaired patients may run the risk of a cardiac complication related to vigorous sexual activity. Likewise, patients actively taking nitrates, including nitroglycerine and other agents, are contraindicated from receiving prescriptions for PDE5 inhibitor. Relative contraindications to the use of PDE5 inhibitor include alpha-adrenergic antagonists.
Visual disturbances can be seen with sildenafil (blue haze to the visual field) as a result of inhibition of the PDE6 enzyme.
A very rare but more serious visual complication is shared by all PDE5 inhibitors. This would be non-arteritic anterior ischemic optic neuropathy (NAION). A number of cases have been reported and generally risk factors for this very rare form of blindness are severe cardiovascular conditions.
In summary, men at high-risk for cardiovascular disease with congestive heart failure or unstable angina should not receive treatment for sexual dysfunction until their cardiac condition has stabilized. The FDA advises patients to stop taking these medicines and call a doctor immediately, if they experience sudden or decrease vision loss in one or both eyes. Furthermore, patients taking or considering taking these products should inform their healthcare professionals if they have ever had severe loss of vision, which may reflect a prior episode of NAION. Such patients are at an increased risk of developing NAION again.
Men with diabetes, radical prostatectomy, and other complicating factors may still benefit from treatment with a phosphodiesterase type-5 inhibitor such as Viagra. Patients who fail a trial of PDE5 inhibitor should be informed of the benefits and risks of other therapies. This of a different PDE5 inhibitor is unlikely to have a profound effect on sexual function and someone who fails a first drug trial, but should be considered in selected cases. Second-line therapies include intra-urethral suppositories, intra-cavernous drug injection, vacuum-constriction devices, and penile prosthesis.
Medicated Urethral System for Erection (MUSE). MUSE is an intra-urethral suppository of alprostadil, of vaso-active drug that relaxes smooth muscle in the penis and induces penile erection. Although not as effective as intra-cavernosal penile injection, MUSE is a less invasive treatment option. An initial trial dose of intra-urethral alprostadil should be administered under healthcare provider supervision due to the risk of fainting. The cost of intra-urethral suppositories is high with respect to the overall success and therefore should be used judiciously.
Intra-cavernosal Injection
Nearly 85% of men with erectile dysfunction in a clinical trial responded adequately enough to intra-cavernosal injection to have successful intercourse. Intra-cavernosal injection is the most effective non-surgical treatment for erectile dysfunction. However, it is invasive and has the highest potential for priapism (prolonged painful erection). Thus, the initial trial dose of intra-cavernosal injection therapy should be administered under healthcare provider supervision. An erection lasting more than four to five hours associated with pain is an indication for an immediate evaluation and treatment. Patients who are considering ICI should be informed of the potential occurrence of prolonged erections, have a plan for urgent treatment of prolonged erections, and be within access to healthcare. Alprostadil (prostaglandin E-1) is an FDA approved agent for the treatment of erectile dysfunction by intra-cavernosal injection. Other agents used in combination with alprostadil include phentolamine and papavarin.
Vacuum Constriction Devices
Nearly 95% of men with erectile dysfunction can obtain an erection sufficient for sexual satisfaction with a vacuum constriction device. Only vacuum constriction devices containing a vacuum limiter should be used. All FDA approved devices have such a limiter. Vacuum constriction devices can be a useful second-line treatment option especially in the patient with a supportive partner in a stable relationship. Virtually all men of all ages and with all types of erectile dysfunction can have successful intercourse with a vacuum constriction device.
Several medications are not recommended for the treatment of erectile dysfunction. These include trazadone, yohimbine, and herbal therapies, as there is no evidence to support their safe use for the treatment of erectile dysfunction. It is important to note that testosterone therapy is not indicated for the treatment of erectile dysfunction in the patient with a normal serum testosterone level.
Penile Implant
When other treatment options are not successful, penile implant surgery can provide excellent patient and partner satisfaction. Both malleable (bendable) and inflatable devices can be implanted to allow penile rigidity and satisfactory sexual intercourse.
The patient considering prosthesis implantation, should be aware of the different types of prosthesis, risks of infection and erosion, mechanical failure and resulting re-operations, differences from the normal flaccid and erect penis including the possibility of penile shortening, and the potential reduction in the effectiveness of other therapies if the device is subsequently removed.
Penile implant surgery can be very effective, provided that precautions are taken to avoid infection. Prosthesis surgery is contraindicated if systemic cutaneous or urinary infection is present. Antibiotics should be provided pre-operatively, and the surgical site should be shaved immediately prior to surgery. We use both Mentor and AMS penile implants with specialized antibiotic coats. Patients are hospitalized overnight for closed suction drainage and sent home on seven days of post-operative antibiotics. Using these and other precautions, our implant infection rate is comparable to national averages (2-4%, 1-2% for antibiotic coated implants).
Vascular surgery is recommended only in healthy individuals with recently acquired erectile dysfunction due to a focal arterial narrowing (usually related to trauma) and in the absence of generalized vascular disease.
Physicians
