Erectile Dysfunction Treatment & Management

After all the information regarding the patient's status has been gathered, the various options for management of erectile dysfunction (ED) can be discussed. It is best to include the patient's partner in this discussion.^[35]

Enough options are available that every man who wants to be sexually active can be. These include sexual counseling if no organic causes can be found for the dysfunction, oral medications, external vacuum devices, or some type of invasive therapy. One of the most difficult aspects is teaching men that sex entails more than simply achieving an erection.

Many patients with ED also have cardiovascular disease, as the two disorders share a common etiology. Treatment of ED in these patients must take cardiovascular risks into account.

Sexual activity in itself increases the chances of ischemic events and MI, because of the exertion and the sympathetic activation that may accompany sexual activity. The absolute risk of MI during sexual activity and for 2 hours afterward is only 20 chances per million per hour in post-MI patients and is even lower in men without a history of MI.^[36]

The Princeton Consensus Panel has produced updated guidelines for managing ED in patients with cardiovascular disease.^[37] The panel advises that a man with ED and no cardiac symptoms should be considered to have cardiac or vascular disease until proven otherwise. ED patients should be assessed and categorized as high, intermediate, or low risk. This stratification can guide management.

Risk-factor modification, including lifestyle interventions (eg, exercise, weight loss) is strongly encouraged for ED patients with cardiovascular disease. A study by Gupta et al supports that for men with cardiovascular risk factors, modifications in lifestyle along with pharmacotherapy are helpful in improving sexual function.^[38]

Patients who have serious cardiac disease, have exertional angina, or are taking multiple antihypertensive medications are advised to seek the advice of a cardiologist before beginning therapy with a PDE-5 inhibitor. Nevertheless, a number of studies examining the cardiac effects of sildenafil and tadalafil have demonstrated that there is no increased risk of cardiovascular events compared with placebo.^{[39, 40]} No significant difference in the incidence of myocardial infarction (MI), myocardial ischemia, or postural hypotension has been reported.

The oral phosphodiesterase type 5 (PDE-5) inhibitors are the most commonly used treatment for ED in current practice. Guidelines from the American Urological Association (AUA) recommend offering these agents as a first-line of therapy for ED unless the patient has contraindications to their use.^[36]

Updated guidelines from the American College of Physicians on hormonal testing and pharmacologic treatment of erectile dysfunction, issued in 2009, strongly urge physicians to initiate therapy with a PDE-5 inhibitor in men seeking treatment for ED who have no contraindications (eg, receiving nitrate therapy) to the use of PDE-5 inhibitors.^[41]

The ACP recommends choosing a specific PDE-5 for patients with ED, taking into account the patient’s preferences, ease of use, cost of medication, and adverse effects. They stress that PDE-5 inhibitors are relatively well tolerated by patients, and adverse effects are usually mild or moderate.^[41]

In patients with ED refractory to oral PDE-5 inhibitors, one of these agents can be combined with an injection of prostaglandin E1 (PGE1).^[42] Gutierrez et al demonstrated that this combination was more effective than either one alone.^[43] The combination of a PDE-5 inhibitor with intraurethral PGE1 has also proved successful.

Men who have a vascular-leak (venous leak) phenomenon may need a constriction device placed at the base of the penis to maintain their erection (see the image below). Such a device may be effective by itself or in combination with a PDE-5 inhibitor. In selected cases, combination therapy with one of the PDE-5 inhibitors plus intraurethral or intracavernosal agents can be tried.

Men who present with diminished libido and ED may be found to have low serum testosterone levels. Hormone replacement may benefit men with severe hypogonadism and may possibly be useful as adjunctive therapy when other treatments are unsuccessful by themselves. Libido and an overall sense of well-being are likely to improve when serum testosterone levels are restored to the reference range.^{[44, 45, 46, 47, 48, 49]}

According to the 2009 ACP guidelines, evidence is inconclusive with regard to the efficacy of hormonal treatment of ED in men with low testosterone levels. The ACP is neither in favor of or opposed to routine hormonal blood tests or hormonal treatment in patients with ED, although they state that measurement of hormone levels may be appropriate in certain patients.^[41]

The ACP guidelines state that clinicians should assess the presence or absence of symptoms of hormonal dysfunction when deciding whether to measure hormone levels in men with ED. Symptoms of hormone dysfunction include decreased libido, premature ejaculation, fatigue, and physical findings such as testicular or muscle atrophy.^[41]

Replacement androgens are available in oral, injectable, gel, and transdermal preparations. Oral therapy is rarely used; it is the least effective and the most likely to be associated with hepatotoxicity, even though this is a relatively small risk.

Parenteral therapy is most likely to restore androgen levels to the reference range, but this therapy requires periodic injections, usually every 2 weeks, to sustain an effective level. Measurement of peak and trough levels can help avoid symptomatic troughs and supernormal peak levels, although this is rarely done in clinical practice. Typically, a level is obtained one week after an injection. Weekly injections using lower doses can be used to minimize the wide swings in blood levels with less frequent dosing.

Skin patches deliver a sustained dose and are generally accepted by patients. Testosterone gels (AndroGel, Testim, Fortesta, Axiron) are available for daily topical use for male hypogonadism and have the advantage of minimizing the peaks and troughs of injectable agents. However, they require daily application and are relatively expensive.

Longer-acting testosterone pellet implantation (Testopel) has become increasingly popular. The pellet is placed during an office visit. These pellets have the benefit of requiring administration only every 3-6 months.

The use of exogenous androgens suppresses natural androgen production. Elevation of serum androgen levels has the potential to stimulate prostate growth and may increase the risk of activating a latent cancer. Periodic prostate examinations, including digital rectal examinations, prostate-specific antigen determinations, and blood counts (ie, complete blood count), are recommended in all patients receiving supplemental androgens. Obtaining a testosterone level while on therapy is necessary to optimize the dosage.

While many substances are touted as aphrodisiacs, the modern age of pharmacotherapy began in 1993, when the injection of papaverine, an alpha-receptor blocker that produces vasodilatation, was shown to produce erections when injected directly into the corpora cavernosa. Soon afterwards, other vasodilators, such as alprostadil (a synthetic PGE1) and phentolamine (Regitine),^[20] were demonstrated to be effective either as single agents or in combination.^{[50, 51]}

Alprostadil is the most common single agent used for intracavernosal injections. In one study of 683 men, 94% reported having erections suitable for penetration after alprostadil injections.^[52] Self-injection of these agents has been of enormous benefit because they represent an effective way to achieve erections in a wide variety of men who otherwise would be unable to achieve adequately rigid erections.

If the vasculature within the corpora cavernosa is healthy, the use of injectable agents is almost always effective. Patients need to be carefully instructed on how to perform the injections. The dosage is adjusted to achieve an erection with adequate rigidity for no more than 90 minutes. Up to 40 mcg of alprostadil can be used. An abnormal finding after biothesiometry testing has been suggested as an indicator of possible heightened sensitivity to intracavernosal injections, but this is unproven.

The main adverse effects of intracavernosal injection are a painful erection, priapism, or the development of scarring at the site of the injection.^{[52, 53, 54]}

Another option for ED is the Medicated Urethral System for Erections (MUSE). MUSE involves the formulation of alprostadil (PGE1) into a small intraurethral suppository that can be inserted into the urethra (see the image below). In a selected group of men, the agent was effective in 65%.^[55] Widespread use has been limited by its inability to consistently provide rigid erections and its cost.

This agent may be effective in men with vascular disease, diabetes, and status post prostate surgery. This is a useful agent for men who do not want to use self-injections or for men in whom oral medications have failed. It has been successfully used together with sildenafil in cases in which each agent alone failed.

The 2009 ACP guidelines state that improvement in erectile function was related to higher doses of sildenafil and vardenafil; this was not the case for tadalafil. Higher doses of these medications were also linked to a higher risk of adverse effects.^[41]

Few adverse effects occur. The most common is a painful erection and urethral burning, which occurs in less than 10% of patients.

A topical gel formulation of alprostadil for treatment of ED has been developed.^[56] However, it has not been approved for use by the US Food and Drug Administration (FDA).

As a relatively inexpensive method for producing an erection, vacuum devices for drawing blood into the penis have been used for many years. These are plastic cylinders that are placed over the penis. Air is pumped out, causing a partial vacuum. Releasing the vacuum after a few minutes and then reapplying the vacuum sometimes gives a better result. After an erection is obtained, a constricting band is placed at the base of the penis (see the images below).^[57]

This technique is effective in 60-90% of patients and maintains the erection for up to 30 minutes. (The erection would last until the constricting band is released, but longer than 30 minutes is not recommended.) The devices are very reliable and seem to work better with increased use and practice. They can be operated and used quickly with experience but still tend to be less romantic than other therapeutic options.

Vacuum devices are generally safe, but hematomas, petechia, and ecchymosis have been reported. Other adverse effects include pain, lower penile temperature, numbness, absent or painful ejaculation, and pulling of scrotal tissue into the cylinder, where it becomes trapped under the ring. Many of these problems can be alleviated by proper selection of the tension rings and cylinders.

One drawback to the use of these external vacuum devices is the need to assemble the equipment and the difficulty in transporting it. Many patients lose interest in using the device because of the preparations that are necessary, the lack of easy transportability, the inability to hide the tension ring, and the relative lack of spontaneity. Approximately half the men who use a vacuum device obtain very good erections, but only half of these men consistently use the device for a prolonged period.

Selected patients with ED are candidates for surgical treatment.

Revascularization surgery

A small number of healthy young men have developed ED as a result of trauma to the pelvic arteries. Revascularization procedures such as rotating the epigastric artery, or even smaller vessels, into the corpora have been attempted. The long-term results have been marginal. AUA guidelines recommend arterial reconstructive surgery as a treatment option only in healthy patients who have recently acquired ED dysfunction due to a focal arterial occlusion and who have no evidence of generalized vascular disease.^[36]

Surgical elimination of venous outflow

Men who have difficulty maintaining erections as a result of venous leaks occasionally may benefit from a surgical procedure to eliminate much of the venous outflow. While initial enthusiasm for this and other surgical approaches was significant, this type of surgery has become rare because of a lack of long-term efficacy. AUA guidelines recommend against the use of such procedures.^[36]

Placement of penile implant

In the past, the placement of prosthetic devices within the corpora was the only effective therapy for men with organic ED. At present, this is the last option considered, even though more than 90% of men with an implant would recommend the procedure to their friends and relatives. Before selecting this form of management, the patient and his sexual partner should be counseled regarding the benefits and risks of this procedure.^{[58, 59]} See table below.

Table 2. Penile Implants for Erectile Dysfunction (Open Table in a new window)

Implants are usually used for men in whom other therapies have failed or in those who require penile reconstructions. Men who have had a radical prostatectomy for prostate cancer and in whom a nerve-sparing procedure was not performed or was not successful often do not respond to oral PDE-5 inhibitors, and these men are good candidates for an implant. The same is true for men treated with radiation therapy, although more of these men tend to respond to oral agents.

Some data indicate an additional benefit in some men who have an implant but also take an oral PDE-5 inhibitor. Sexual stimulation and sensation is enhanced.

Two types of devices are available, a semirigid and a multicomponent inflatable system. With the semirigid prosthesis, 2 matching cylinders are implanted into the corpora cavernosa (see the image below). These devices provide enough rigidity for penetration and rarely break. The major drawbacks are the cosmetic appearance of the penis, which remains semi-erect at all times, the need for surgery, and the destruction of the natural erectile mechanism when the prosthesis is implanted.

The inflatable devices consist of 2 Silastic or Bioflex cylinders inserted into the corpora cavernosa, a pump placed in the scrotum to inflate the cylinders, and a reservoir that is contained either within the cylinders or in a separate reservoir placed beneath the fascia of the lower abdomen (see the images below). The inflatable prosthesis generally remains functional for 7-10 years before a replacement may be necessary. Improvements in these devices have resulted in a failure rate of less than 10%.

Patient acceptance of these devices is very high, with nearly 100% of the patients expressing satisfaction. Part of this enthusiasm is related to the failure of other therapies and the highly motivated patient population.

Rajpurkar and Dhabuwala reported significantly better erectile function and satisfaction with a penile implant than with sildenafil or intracavernous prostaglandin E1 (PGE1).^[60] This was a nonrandomized study in which all 138 subjects were initially offered sildenafil. The mean follow-up was 19.54 months, and questionnaires were used to obtain the data.

Complications include infections in 2% of patients, erosion of the device through the urethra or skin in 2% of patients, and painful erections in 1% of patients. A newer antibiotic-coated device has further reduced the infection rate. Patients should also be counseled that the penis does not lengthen as much as with normal erections.

Before the advent of oral PDE-5 inhibitors, a variety of other medications were investigated for treatment of ED. These medications included neuropharmacologic agents that are adrenergic receptor antagonists (eg, phentolamine, yohimbine, delequamine), dopamine receptor antagonists (eg, apomorphine, bromocriptine), serotoninergic receptor activators (eg, trazodone), xanthine derivatives (eg, pentoxifylline) and oxytocinergic receptor stimulators (eg, oxytocin).^[61] The AUA does not recommend the use of any of these agents.^[36]

Yohimbine

Yohimbine (Yocon) has been available for many years. It has both a central and a peripheral effect. Even in properly conducted, well-controlled studies, yohimbine is only slightly more effective than placebo. AUA guidelines do not recommend its use, based on a lack of peer-reviewed evidence.^[36] Nevertheless, there has been a renewed interest in this agent, particularly when combined with an oral PDE-5 inhibitor.^[62] Yohimbine is a safe agent with few known adverse effects. It is administered in a dosage of 5.4 mg (1 tab) 3 times daily.

Apomorphine

A sublingual formulation of apomorphine has demonstrated some benefit in ED. Apomorphine is not approved by the FDA for this indication.

Phentolamine

Phentolamine (Vasomax) is an alpha-receptor blocker that has not been approved by the FDA for the treatment of ED. However, it has undergone limited clinical testing. Two placebo-controlled trials reported effectiveness in 42% and 32% of patients taking 50 mg compared with 9% and 13% in the control group, respectively. The erections occurred in 20-30 minutes. The drug was well tolerated, with mild-to-moderate adverse effects, usually headaches or light-headedness, occurring in less than 10% of patients.

One current research area has involved the use of vascular endothelial growth factor (VEGF), which is an angiogenic growth factor and endothelial cell mitogen. VEGF is produced by vascular smooth muscle, endothelial, and inflammatory cells. It increases the production of nitric oxide (NO), which improves endothelial function and blood flow in chronic ischemic disorders.^{[63, 64]}

Direct intracavernosal injection of recombinant VEGF protein or adenoviral VEGF that contains plasmids has shown dramatic results based on cavernosography findings in animal models with arteriogenic, venogenic, and neural forms of ED. Burchardt et al identified VEGF 165 as the predominant isoform in the corpora cavernosa, as well as a novel splice variant.^[40]

Although VEGF is a potent and important vascular regulator, it probably acts together with other vascular factors. Although a single-agent VEGF is unlikely to ever be used as monotherapy for ED, this represents an important step in understanding the normal and abnormal vascular physiology associated with ED.

The American Urological Association (AUA) observes that since diabetes, heart disease, and hypertension increase the risk of developing ED, optimal management of these diseases may prevent the development of ED. Similarly, since attaining and maintaining a firm erection requires good vascular function, it is reasonable to assume that lifestyle modifications to improve vascular function (eg, not smoking, maintaining ideal body weight, and engaging in regular exercise) might either prevent or reverse ED. The AUA notes, however, that currently there are only minimal data exists today to support these suppositions.^[36]

Currently, any man who wishes to have erectile function can do so regardless of the etiology of the problem. Many therapeutic options are available, and the task of the physician is to help the patient seek the best solution. Finding a trained and understanding physician who is willing to take the time to understand the patient's problem is the first step in identifying which therapeutic option will ultimately be most appropriate and successful.

Sexual counseling

Sexual counseling is the most important part of the treatment for patients with sexual problems. Many professional sexual counselors are skilled in working with patients, but the primary care physician, the urologist, and the gynecologist also serve in this capacity to some degree. These are usually the first professionals to learn about the problem, and they often have to extract the information about the sexual problem from the patient.

Men are frequently reluctant to discuss their sexual problems and need to be specifically asked. Opening a dialogue allows the clinician to begin the investigation or refer the patient to a consultant. Regardless of any subsequent therapy the patient may receive, the emotional aspects of the disorder must be addressed. Ideally, the patient's partner should be involved in the counseling, but, even when this is not possible, the time spent may help resolve or at least clarify the problem and certainly helps in deciding which of the other options would be most beneficial and appropriate.

Psychological care

Regardless of the etiology of ED, a psychological component is frequently associated with this disorder. The ability to achieve erection is intimately connected to a man's self-esteem and sense of worth. Pure psychogenic ED is generally evident when a man reports that he has normal erections some of the time but is unable to achieve or to maintain a full erection at other times. Once the man has doubt regarding sexual performance, he loses confidence; thus, future attempts to have sexual relations provoke anxiety.

In many instances, the couple needs to work together to resolve the problem, although the relationship may be responsible for the problem. Referral to a sex therapist may be helpful.

Men with organic ED can be treated with one or more of the various available therapies. However, if they have lost confidence in their ability to obtain and maintain an erection suitable for penetration, a few words of encouragement from their physician can be of great help.