Overview of Erectile Dysfunction Treatments
This section of the website provides basic information on how erectile dysfunction is treated. This overview of treatments is intended for general information on the various products used to treat ED. For a complete overview of treatments, please consult your physician and for more information about the particular products, please consult the manufacturers or their respective websites.
A number of therapy options are currently available for the management of ED. These include:

• intracavernosal injections of vasoactive substances
• intraurethral delivery of vasoactive substances
• oral drugs
• hormonal supplementation
• topical drug treatment
• external vacuum constriction devices (VCD)
• venous Flow Controllers
• penile prosthetic implants
• psychotherapy
• vascular surgery

Each therapy option is associated with advantages and disadvantages, and different therapeutic options may be more appropriate for specific patients. All treatments should be discussed with physicians

Intracavernosal Injection
Intracavernosal injection to produce erection was introduced in the 1980s. It is a therapy prescribed throughout the world for ED. It is also commonly used as a diagnostic tool in the evaluation of ED. The most commonly used products approved for ED are Caverject (Pharmacia & Upjohn), which is approved for both diagnostic and therapeutic intracavernosal injection and Edex, Viridal, and Virilan (Schwarz Pharma). These products are used to cause an erection and must be administered with the help of a physician until the appropriate dose is determined for the patient. Please check the website of these products for more information.
Although intracavernosal therapy has a high reported efficacy, voluntary cessation is also high, most often due to its mode of adminstration. In this treatment method, agents that relax smooth muscle are injected into the corpora cavernosa. The events that follow are as follows:

• the smooth muscle relaxes, allowing increased blood flow into the penis
• the corpora cavernosa enlarge, compressing venules against the tunica albuginea and preventing blood outflow
• the penis becomes erect and rigid (the penis will become erect regardless of whether or not sexual stimulation occurs)

The only other products approved for intracavernosal injection in one or more countries are prostaglandin E 1 and moxisylyte. Several other agents have historically also been used for intracavernosal injection, even though none of these agents are approved for this use. These drugs are available commercially because they are indicated for other uses. These agents, and combinations of these agents, are most often papaverine, phentolamine or a mixture of the two in either a bi-mix and tri- mix.
Other agents are also in the investigational stage for intracavernosal injection. One of these is vasoactive intestinal polypeptide (VIP) in combination with phentolamine, a product that is being developed as Invicorp by Senetek. A quad mix (PGE 1/papaverine/phentolamine/VIP) is also under investigation.
The most commonly reported side effect with intracavernosal injection is penile pain. Pain more commonly occurs with PGE 1 compared with other intracavernosal agents. The goal of intracavernosal injection is to produce an erection that lasts long enough for satisfactory sexual intercourse, but that does not last longer than 1 hour. The most serious short-term side effect seen with intracavernosal injection is prolonged erection (> 4 hours and < 6 hours) and priapism. Because prolonged erection and priapism can result in irreversible smooth muscle tissue damage in the penis due to lack of oxygen, these represent medical emergencies. Prolonged erection is most commonly seen during office diagnostic testing, dose titration, and early home use. Patients with ED due to psychogenic or neurologic causes are more likely to be more sensitive to the effects of vasoactive agents, and these patients thus face a greater risk of prolonged erection and priapism.Treatment of prolonged erection can include, depending on its severity:

• single or multiple penile injections of phenylephrine or epinephrine
• aspiration of blood from the penis
• irrigation of the corpora with saline
• surgical placement of a shunt between the corpora cavernosa and the corpus spongiosum

It should be noted that phenylephrine and epinephrine themselves can produce severe side effects, such as cardiac arrhythmia, hypertensive crisis, and angina.
The most important long-term complication of intracavernosal injection is corporal fibrosis. Fibrosis hinders future erections, since this tissue is not elastic like smooth muscle tissue. Fibrosis can occur as disfiguring nodules in the corpora cavernosa, a plaque similar to that occurring in Peyronie's disease, or penis curvature without any detectable plaque or nodule.

Intraurethral Drug Therapy
With intraurethral drug therapy, a vasoactive agent is administered within the urethra. The drug is absorbed from the urethra into the surrounding corpus spongiosum and then transported into the corpora cavernosa via the blood vessels that link the corpora cavernosa and the corpus spongiosum.
The only approved product is MUSE, marketed by Vivus Inc., in the U.S. and by Astra in Europe, Australia, New Zealand, and Latin America. It consists of a plastic applicator and a semi-solid pellet of alprostadil (PGE1). The patient inserts the applicator stem into the urethra, depresses a button at the end of the applicator and holds this position for 5 seconds. After the applicator is withdrawn, the patient rolls the penis between his hands for 10 seconds to distribute the medication along the urethral walls. The patient then walks around for about 10 minutes, an activity that improves blood flow to the penis.
Intraurethral drug delivery offers the advantages of a less invasive method of administration compared to intracavernosal injection, and no requirement for continuous administration. Because there is no need for injections, patients may prefer this method to intracavernosal injection. However, this method is also associated with pain as reported by patients. In clinical trials, penile pain occurred in 36%, urethral pain in 13%, and testicular pain in 5% of patients and 7% of patients withdrew due to side effects. The product labeling also carries a warning that the initial use of MUSE should be in a physician's office due to the risk for hypotension and syncope.
Harvard Scientific is also developing a product that administers PGE1 intraurethrally.

Oral Drug Therapy
Among all the treatment approaches for ED, it is widely believed that oral therapy would be the most desirable and acceptable to patients. Numerous agents have been used off-label, and others are being investigated for oral use, but only a few can meet the criteria of demonstrated efficacy with a well-tolerated safety profile and prn administration. The following provides an overview of the products used around the world.

Yohimbine
Yohimbine is an alpha 2-adrenergic antagonist that has long been considered an aphrodisiac. It is available both as branded prescription products and over the counter, and it is the most widely prescribed oral treatment for ED. Branded forms include Yohimex (Kramer), Yocon (Glenwood-Pallisades), Aphrodyne (Star Pharmaceuticals), and Erex (Ion Laboratories).
The effects of yohimbine occur primarily through the central nervous system. Several recent clinical studies show only modest success versus placebo, with response greater in men with psychogenic ED compared to organic ED. It is generally administered as 10 mg three times daily on a chronic basis. However, some recent studies have evaluated higher doses (20 mg to 30 mg) as prn therapy. Because it produces relatively mild side effects, including tremulousness, insomnia, headache, palpitations, minor elevations in blood pressure, and gastric intolerance, it is quite commonly prescribed. However, the overall consensus of many leading urologists is that the efficacy of yohimbine remains unproven.

Trazodon
Trazodone (Desyrel/Bristol-Myers Squibb) is an antidepressant that has been on the market for some time. It has been investigated for ED therapy because it was noted that priapism occurs as a side effect in some men taking trazodone for treatment of depression. The mechanism of action of trazodone includes a combination of inhibition of serotonin (5-HT) reuptake, alpha 1-adrenergic antagonism, and 5-HT 2C receptor agonism. Its activity in ED is thought to be a combination of both central nervous system effects and local effects in the penis. While erections have been reported in some studies, they have occurred in the presence of significant sedation (a common side effect of trazodone).

Pentoxifylline
Pentoxifylline (Trental/Hoechst Marion Roussel) is an agent indicated for claudication that decreases the viscosity of blood. Improvement of erectile dysfunction in men taking pentoxifylline for claudication has been noted, and it has also improved erectile function in 9/18 men in a small trial specific to ED. Overall, the action of pentoxifylline in ED seems to be in improving fluidity of red blood cell membranes, rather than on vascular smooth muscle in the penis.

Dietary, Homeopathic, and Herbal Remedies, and Traditional Medicines
Throughout the world a variety of dietary, homeopathic, and herbal remedies are used to improve erectile function. For example, evening primrose oil has been suggested to help improve ED due to diabetic nerve dysfunction. Other examples are an extract made from green oats, rhino horn, tiger penis and many various Chinese herbal remedies.

Phosphodiesterase Inhibitors
Nitric oxide is the chemical messenger thought to be primarily responsible for penile smooth muscle relaxation and erection. Nitric oxide causes an increase in cyclic guanosine monophosphate (cGMP), which, in turn, decreases the amount of calcium in the smooth muscle cells, causing their relaxation and penile erection. Phosphodiesterases are enzymes that break down cGMP and cAMP (cyclic adenosine monophosphate). Inhibiting phosphodiesterases would thus be another way to increase the amount of cGMP in a smooth muscle cell and enhance erectile function. Several companies have phosphodiesterase inhibitors under development.
There are several different types of phosphodiesterases and each type exists in different concentrations in various tissues. Type V phosphodiesterase (PDE5) is specific for cGMP and exists in high concentrations in the penis. VIAGRA(sildenafil/Pfizer) is a specific PDE5 inhibitor that has been recently approved in the USA and other countries around the world. Its mode of action is that it targets the penile tissues specifically and allows blood to flow to the penis, thereby enabling men with ED to achieve an erection in the presence of sexual stimulation. VIAGRA is an oral formulation and can be taken prn, once daily. Its efficacy rate is about 70 to 80 % in ED etiology of both psychogenic and organic origin. The side effects are those commonly associated with vasodilators including headache, flushing, nasal congestion, though they are mild to moderate and often transient in nature. Approximately 2 –3 % of the patients involved in clinical trials withdrew due to side effects. It is important to note that nitrates in any form are contraindicated with the use of VIAGRA.

Hormonal Supplementation
Testosterone replacement therapy is an option for men with documented low levels of testosterone, approximately 2% to 12% of men with ED. However, testosterone supplementation is not appropriate, and in fact is medically dangerous, in men with normal testosterone levels. Testosterone supplementation can be administered in the form of depot intramuscular injections. Injections are usually given every 2 to 3 weeks. With this method of administration, however, the patient is exposed to higher than normal levels of testosterone right after the injection, and lower than normal levels near the time for a subsequent injection. Transdermal preparations of testosterone are also available. These patches are applied daily. Transdermal patches produce systemic testosterone levels that more closely mimic physiologic levels throughout the dosing period.

Topical Drug Therapy
Another method of delivering vasoactive drugs that has been investigated is topical administration. This route has the advantages such as a noninvasive method of administration and not requiring continuous administration. Agents that have been investigated for topical administration include:

• minoxidil
• nitroglycerin paste and transdermal patches
• papaverine
• PGE1

These agents have all produced some increase in arterial blood flow into the penis and penile tumescence. However, rigid erections have only rarely been produced. While topical administration produces few side effects, patients who used nitroglycerin noted headaches, even after pretreatment with analgesics. Headache may also be a risk for the patient's partner if a condom is not used.

Vacuum Constriction Devices
Vacuum constriction devices (VCDs) produce erections by pulling blood into the penis with a vacuum, and then trapping the blood in the penis with a constricting band around its base. Although VCDs have only been commercially available since the late 1980s, they are now widely prescribed for erectile dysfunction. The most reliable models are available by prescription; in fact, the Clinical Practice Guidelines developed by the American Urological Association (AUA) recommend that only prescription models be used. Their advantages include their safety and low long-term cost (although their initial cost is high). Furthermore, they are a therapy option for almost all patients with ED.
The erection produced by a VCD differs from a physiologic erection because the elastic ring causes far more reduction in blood flow in and out of the penis. Thus, the skin temperature of the penis is reduced, the veins are distended and cyanotic, and the circumference of the penis is increased. Also, the penis will pivot at the constriction band, which may require the patient to stabilize the penis during intercourse.
There are very few safety issues related to VCDs. The most important is that the constriction band be removed by 30 minutes so as to prevent ischemic damage to the tissues of the penis. Some patients develop minimal superficial bruising or petechiae, and pain due to trapping of ejaculatory fluid has been rarely reported.
As is the case with many treatments for ED, there is a significant rate of voluntary cessation (dropout) of use of VCDs. Reasons for discontinuation include the lack of spontaneity in sexual relations that can occur with this procedure, and the degree of manual dexterity needed, which may be difficult for some elderly patients.

Venous Flow Controllers
Constriction devices that are used without a vacuum that decrease venous outflow are also available; these are termed venous flow controllers (VFCs). One such product, Actis, is marketed by Vivus. This device consists of U-shaped latex that is adjustable. It is designed to prevent venous outflow in patients whose ED is due to dysfunction of the veno-occlusive mechanism. Similar to the constriction rings used with VCDs, the VFC should not be tightened around the penis for longer than 30 minutes or damage due to lack of oxygen can occur in the tissues. Overtightening can also result in stopping arterial inflow, which can result in a poor erection. Other constriction devices are available without a prescription.

Psychotherapy
Psychotherapy is another treatment option for some men with ED. Its aim is to restore erectile functioning to the level that is possible based on the limits of physiological functioning. A variety of studies have shown that psychotherapy can be an effective treatment for ED when the etiology of the ED is at least partially based on psychological issues resulting from life events—that is, due to precipitants such as performance anxiety, deterioration of a relationship, divorce, spousal death, vocational failure, or loss of personal or spousal health. However, patients with lifelong ED that is due to psychological factors derived from remote developmental processes have responded less well to psychotherapy.

Penile Implants
Penile implants have been available since the early 1970s. While the early models had high failure rates, most of these models are now off the market, and the implants now available are quite dependable. Despite the many other available therapies for ED, penile implants are still chosen by some men. There are two basic types of implants: semirigid or malleable prostheses and inflatable (hydraulic) devices with one, two, or three components. Penile implants have generally had relatively high satisfaction rates in retrospective studies.

Vascular Surgery
Vascular problems are a key risk factor for ED in many patients. Atherosclerotic disease in the arteries can reduce the blood flow into the penis, and dysfunction in veins can reduce the effectiveness of the veno-occlusive mechanism. Vascular surgery has thus seemed a logical way to restore natural erectile function. Bypass surgery or percutaneous transluminal angioplasty can be performed in an effort to improve blood supply to the penis. However, these procedures have not met with great success. Furthermore, the interpretation of the diagnostic procedures required to appropriately select patients has not been standardized. Surgery of the venous system usually involves ligation of the veins transporting blood out of the penis. However, spontaneous erections are produced in only about 50% of patients, and long-term success rates are even less. As with arterial surgery, the nonstandardized interpretation of diagnostic procedures does not yet allow appropriate selection of patients for venous surgery. Furthermore, it is now thought that veno-occlusive dysfunction can be caused by a number of factors, and that patients with primary venous pathology represent only a small subset of these. Overall, the general consensus is that both arterial and venous surgery have a limited role in the treatment of ED and are considered investigational.