Approach
Shared decision-making with discussion about invasiveness, efficacy, safety, and cost, as well as patient preference of all treatment modalities, directs the management strategy.[48][66]
ED-specific therapy involves pharmacotherapy, external devices, and surgical therapy. Psychosocial interventions such as individual and/or couples psychotherapy may improve erectile function.
Medication is given orally (phosphodiesterase-5 [PDE5] inhibitors) or locally delivered (vasoactive compounds) by penile injection or intraurethral suppository. Vacuum constriction devices can be employed, and penile prosthesis implantation is undertaken in some cases.
Initial management of underlying conditions
Primary management of underlying conditions is indicated.
Nonpharmacologic intervention strategies for reducing weight, improving quality of diet, and increasing physical activity can improve erectile function in men at risk and should be recommended prior to beginning medical therapy.[49][67][68]
Patients with stable Peyronie disease should be referred to a urologist for consideration of intralesional injection into the plaque to reduce penile curvature, as well as assessment for surgical correction.[42] Collagenase Clostridium histolyticum injection is approved for the treatment of Peyronie disease in several countries.
Patients with previous pelvic injury with arterial compromise should be referred to a urologist for vascular evaluation and consideration of penile revascularization or prosthesis.
Men with post-prostatectomy ED can be considered for early dosing of PDE5 inhibitors (daily if required), or intracavernous injection under the direction of a urologist or sexual medicine specialist.[69]
PDE5 inhibitors
PDE5 inhibitors are the primary pharmacotherapy used in ED patients.[70] Discussion on the goals of the man and his partner, the need to prescribe an effective dose, and the need to minimize adverse effects is key.[48][66]
These agents potentiate the activity of cyclic guanosine monophosphate, facilitating improved cavernosal smooth muscle relaxation, which results in penile erection. In most studies, PDE5 inhibitors have been shown to effectively and safely improve erectile function regardless of cause, severity, or presence of comorbid conditions, including hypertension, diabetes mellitus, and hypogonadism.[71]
Adverse effects are generally mild and relate to cross-reactivity of the drugs with other phosphodiesterase isoforms. Commonly reported adverse effects include headache, flushing, dyspepsia, nasal congestion, and dizziness.[72] Minor adverse visual effects occur in 3% to 11% of users, but they are mild and reversible.[73]
Four oral agents are in current use: sildenafil, vardenafil, tadalafil, and avanafil.[71] Safety and efficacy seem similar for all four agents.[70] Tadalafil has a substantially longer half-life compared with the other PDE5-inhibitors. This longer half-life allows for continuous daily dosing, as well as the ability to have improved erections for 36 hours (in contrast to 4-6 hours with the shorter acting agents).[74][75] Continuous daily therapy with tadalafil has been shown to be efficacious and well tolerated, and may be an alternative to "as required" treatment with tadalafil or the other PDE5 inhibitors for some men.[71] Daily dosing with tadalafil has a lower incidence of acute side effects compared with "as required" dosing with tadalafil or other PDE5 inhibitors, and allows for not having to plan sexual activity around taking a pill (i.e., increased spontaneity).[74]
Treatment failure with >4 attempts with a PDE5 inhibitor is recommended before moving on to a new agent. Continuous daily dosing regimens with tadalafil may be considered as salvage of on-demand PDE5 inhibitors for nonresponders.[75]
PDE5 inhibitors are contraindicated in patients with:
Concurrent use of organic nitrates; it should be emphasized to patients that coadministration of nitrates is contraindicated outside of a monitored medical setting
Severe cardiovascular disease and left ventricular outflow obstruction
Myocardial infarction within the previous 90 days
Unstable angina or coital angina
New York Heart Association class II or greater in last 6 months
Uncontrolled arrhythmias
Hypotension (BP <90/50 mmHg)
Uncontrolled hypertension (BP >170/100 mmHg)
Stroke within previous 6 months
Known hereditary degenerative retinal disorders, including retinitis pigmentosa
Tendency to develop priapism.
Caution is recommended with concurrent use of alpha-blockers, as orthostatic hypotension can be compounded by concurrent use with PDE5 inhibitors; the Food and Drug Administration (FDA) recommends dose-spacing of >4 hours.
Priapism is rare for oral agents, but a strategy to manage iatrogenic priapism should be offered to the patient at initiation of therapy. Persistence of an erection >3 hours is considered significant, can be associated with tissue ischemia, and requires emergent evaluation and management.
In a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest, but statistically significant, increased risk of malignant melanoma. However, the pattern of association (e.g., the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.[76]
Intracavernosal injections
Men who do not respond to PDE5 inhibitors can be considered for locally delivered drug therapy by intracavernosal injection.[77] The primary option in this situation is alprostadil (prostaglandin E1).[78] Alprostadil is the only agent that is FDA-approved; however, it is associated with penile burning as it can activate sensory nerve fibers.
Secondary options include papaverine alone or in combination regimens such as BiMix (papaverine and phentolamine) or TriMix (papaverine and phentolamine and alprostadil).[78] The concept behind TriMix is to decrease the dose of alprostadil while maintaining efficacy. Papaverine generally is less effective than BiMix or TriMix. The initial test-dose of these regimens can be given in the clinic to ascertain the efficacy and to assess the risk of priapism.
Either the patient or his partner can perform the injection. Using a 30-gauge needle, the drug is injected on the lateral aspect of the penis near the base, after cleansing the skin with an alcohol swab. The patient is instructed to self-stimulate until the onset of erection, with the goal of an erection lasting <1 hour. Titration to lowest effective dose with small increases is pursued under physician supervision.
Due to the risk of the patient developing priapism, intracavernosal injection is contraindicated in patients with sickle cell anemia, patients taking medication for schizophrenia or other severe psychiatric disorders, patients with severe systemic disease, and patients with a history of priapism. Injection site compression for 7 to 10 minutes is recommended to prevent hematoma formation. Mild bruising and pain at the injection site are common. Potential serious adverse effects include priapism and penile fibrosis, which can cause pain or penile curvature. A strategy to manage iatrogenic priapism should be offered at initiation of therapy. Persistence of an erection >3 hours is considered significant, as it can be associated with tissue ischemia and requires emergent evaluation and management.
Intraurethral suppository
Intraurethral suppositories deliver the medication into the corpus spongiosum (not the corpus cavernosum) and include alprostadil. These can be used in men where treatment with PDE5 inhibitors or intracavernous injection has failed or is contraindicated.[79] Men unwilling to self-inject using a needle may also prefer this treatment; however, this treatment is rarely used clinically because of cost and inability to provide for consistently rigid erections.
Vacuum devices
Vacuum erection devices can be used if other treatments fail or are unsuitable.[78] Use of a pump with a pressure limiter is important to avoid unnecessary injury.
Topical therapies
A topical formulation of alprostadil has been approved in Europe for the treatment of ED; however, it is not currently available in the US. It is delivered with a permeation enhancer to facilitate absorption into the systemic circulation. The onset of action is purportedly faster than that of orally absorbed agents, although its efficacy has not been compared with oral therapies to date.[80] Other benefits include avoidance of a contraindication with organic nitrates and minimal drug to drug interactions.
Surgery
May be considered if other treatments have failed.[78] Referral to a urologist is necessary. The choice to proceed with surgical therapy requires a candid discussion detailing the available devices, risks of complication (i.e., infection, malfunction, reoperation), and the expectations for psychosomatic changes such as penile shortening and loss of flaccidity. Men should be aware that surgical therapy is permanent, in that placement of a prosthesis (inflatable and malleable prostheses are available) removes the ability to achieve erections naturally at any time. In general, the devices are well tolerated. Common complications include mild penile length loss, pain, swelling, and infection.
Penile curvature corrective surgery is indicated for patients with stable Peyronie disease, whose penile deformity is sufficient to impair coitus.
A unique group of patients are those with previous pelvic injury and with penile arterial compromise. In these patients, early referral to a urologist is indicated for specialized vascular evaluation and consideration of penile revascularization or prosthesis.[81] Specifically in young, healthy patients with focal endothelial thickening or narrowing after a traumatic insult, penile arterial reconstruction should be strongly considered.[48] However, thorough workup of these patients to rule out other causes is required prior to intervention.
There is research into the role of endovascular arterial stents for a minimally invasive approach to penile revascularization, however there is limited data on outcomes available.[82]
Psychogenic ED
Patients with psychogenic ED should be referred to a specialist for psychosexual therapy, which can be given alone or with another therapeutic approach.[66] It should be noted that the efficacy of psychosexual therapy is varied and, when effective, the therapy may take time.
Psychosocial interventions
Psychosocial interventions such as individual and/or couples psychotherapy may improve erectile function.[83] The etiology of ED is multifactorial and can include psychological stressors.[13] Similarly, having ED can be a source of stress, anxiety, and concern, which, in turn, can further exacerbate a man's sexual dysfunction. Additionally, if men are not responding to the different treatment options, they may become discouraged and even depressed about their condition.
Sexual therapy and psychological counseling for these patients and their partners should be considered as part of ongoing treatment of ED based on the patient's history and symptoms, as well as their response to other therapies.[13][84]
Use of this content is subject to our disclaimer