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Impotence/Erectile Dysfunction (cont.)

What Are Impotence/Erectile Dysfunction Treatment Options and Medications?

Prior to starting with treatment of erectile dysfunction, it is important to make sure that it is safe from a medical standpoint to participate in sexual activity. Sexual activity is physical exertion, and in some men with significant heart disease, this increase in physical exertion can increase the risk of a heart attack. Thus, it is very important to discuss your cardiovascular risks with your doctor prior to trying any medication or treatment for erectile dysfunction.

A number of treatments are available to treat erectile dysfunction. The typical treatment strategy starts with simple to use, noninvasive therapies and progresses to more invasive surgical therapies as needed. In all men, the first step is determining if there are any modifiable risks factors that can either improve or prevent progression of erectile dysfunction. Since the risk of developing ED is increased in the presence of diabetes, heart disease, and hypertension, it is thought that better control/prevention of these conditions may have a benefit in ED. Similarly, it is thought that lifestyle modifications to improve vascular function such as avoiding smoking, maintaining ideal body weight, and engaging in regular exercise might either prevent or reverse ED. Sexual counseling may also be useful in addressing relationship stressors as you work on improving your erectile function.

First Line Treatment for Erectile Dysfunction

Oral phosphodiesterase type 5 inhibitors (PDE5 inhibitors) unless contraindicated are the recommended first line medical therapy for erectile dysfunction. Currently, there are four different PDE5 inhibitors available. They all work the same way and have essentially the same results. They differ in how long they last in your body and in side effects.

PDE5i medications include the following:

How Do PDE5 Inhibitors Work?

When sexually stimulated/aroused, the nerves supplying the penis release a chemical, nitric oxide (NO). Nitric oxide is important because it stimulates the production of a chemical called cyclic guanosine monophosphate (cGMP). cGMP causes the muscle in arteries of the penis to relax and increase blood flow into the penis. NO is broken down in the body by phosphodiesterase enzymes. PDE5 inhibitors thus prevent the breakdown of NO and thus promote increased blood flow into the penis.

Since the release of NO is dependent on sexual stimulation/arousal, PDE5 inhibitors only work if there is sexual stimulation. Simply taking the pill will not produce an erection. This is important because this is different than other treatments for erectile dysfunction.

In general, PDE5i works successfully in about 65%-70% of all men with erectile dysfunction (impotence). The greater the degree of damage to the normal erection mechanism and severity of the ED, the lower the overall success rate. Men with diabetes and those with spinal cord injury reported between 50%-60% responding successfully to treatment with oral PDE5i medications. The lowest success rate has been in men who developed ED (impotence) after prostate cancer surgery (radical prostatectomy) for more advanced prostate cancer that required removal of both sets of nerves around the prostate. In men who did not have the nerves removed/damage, there is a better chance of response to PDE5 inhibitors.

Use of PDE5 Inhibitors

All four of the PDE5 inhibitors (Viagra, Cialis, Levitra, and Stendra) are approved by the Food and Drug Administration for on-demand use for erectile dysfunction.

Typically, they are taken 30-60 minutes prior to engaging in sexual activity and should not be used more frequently than once a day. Tadalafil (Cialis) is the only PDE5 inhibitor that is approved for daily use to avoid the timing factor and planning sexual activity.

All PDE5i medication does not improve erections in normal men, only in those with difficulty in achieving or maintaining erections sufficient for sexual intercourse due to a true medical problem.

PDE5i medications do not work like an aphrodisiac and will not increase desire or libido.

Unlike other treatments for erectile dysfunction, PDE5i medications requires sexual stimulation to function. Without stimulation, these medications will not provide any effect.

The dose of PDE5 inhibitor that you start with may vary with underlying medical conditions and medications that you are taking. Thus, it is important to review all medications (even over the counter medications) with your physician. Typically, one starts with a lower dose and increases as needed. Some medical conditions prevent going up to higher doses. You can review the drug prescribing information or consult with your doctor regarding the dose(s) that are appropriate for you.

Side Effects of PDE5 Inhibitors

The various PDE5 inhibitors share several common side effects, including flushing, nasal congestion, nausea, dyspepsia (stomach discomfort/indigestion), and diarrhea. Differences exist in side effects of the different PDE5 inhibitors, and thus it is important to be familiar with the prescribing information of the PDE5 inhibitor you are prescribed.

There have been rare reports of priapism (prolonged and painful erections lasting six or more hours) with the use of PDE5 inhibitors. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, if your erection lasts four hours, you should seek emergency care.

Rare side effects of all PDE5 inhibitors include a sudden loss of vision in one or both eyes, NAION (nonarteritic anterior ischemic optic neuropathy), and sudden loss of hearing. These rare side effects have been reported with all of the PDE5 inhibitors, and should you develop loss of vision or hearing, you should seek immediate medical care.

Unlike the other PDE5 inhibitors, sildenafil (Viagra) may affect another phosphodiesterase enzyme in the eye, causing transient abnormal vision (a bluish hue or brightness).

Men with a rare heart condition known as long QT syndrome should not take vardenafil since this may lead to abnormal heart rhythms. The QT interval is the time it takes for the heart's muscle to recover after it has contracted and is measured on an electrocardiogram (EKG). In addition, vardenafil is not recommended for men taking medications that can affect the QT interval such as quinidine, procainamide, amiodarone, and sotalol.

Tadalafil (Cialis) has an effect on another phosphodiesterase enzyme, PDE11, which is located in muscle. Tadalafil is associated with muscle aches in some men.

Avanafil has similar adverse effects as the other PDE5 inhibitors but is not associated with the visual changes of sildenafil or muscle aches of tadalafil.

Contraindications to PDE5i Medications

PDE5i medications are absolutely not to be taken by men with heart conditions who are taking nitrates such as nitroglycerine or isosorbide (Isordil, Ismo, Imdur). Those with serious heart disease, exertional angina (chest pain), and those taking multiple drugs for high blood pressure are advised to seek the advice of a heart specialist before beginning therapy with sildenafil.

No nitrate-based drugs should be given to men with suspected heart attacks if they have taken PDE5i medications within 24 hours. Combining PDE5i with nitrate-based medications can cause a severe and dramatic drop in blood pressure with potentially very dangerous consequences. This is also why someone should absolutely never share PDE5i medications with anyone else. If they happen to be taking one of the drugs that interacts dangerously with PDE5i medications, the results could be very serious. If there is any question about possible drug interactions, always check with a doctor or pharmacist.

Certain street drugs such as "poppers" also can cause serious problems if taken with PDE5i medications. These poppers are often types of nitrates and can cause severe drops in blood pressure. Ecstasy is another street drug that may increase sexual desire but interferes with performance. This has prompted some men to combine ecstasy with PDE5i medications. This mixture (a combination sometimes called "sextasy") can improve erection ability but also causes severe headache and priapism. (Priapism is an abnormally prolonged erection that becomes extremely painful and may result in permanent damage to the erection mechanism.) There are also potentially dangerous effects to your heart from mixing PDE5i medications with various other street drugs.

Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.

Congestive heart failure with borderline low blood pressure and borderline low blood volume is a contraindication to PDE5 inhibitors, as is high blood pressure requiring multiple medications to treat the blood pressure as PDE5 inhibitors could lead to lowering of the blood pressure and medical problems.

PDE5 inhibitors have not been studied in individuals with a condition, retinitis pigmentosa, and thus their use is not recommended for these individuals.

PDE5 inhibitors should not be used in men with unstable angina.

One must be very careful using both PDE5 inhibitors and medications commonly used to treat an enlarged prostate, alpha-blockers (for example, tamsulosin [Flomax], terazosin [Hytrin]). It is recommended that one be on a stable dose of the alpha-blocker prior to starting a PDE5 inhibitor and that one start on a low dose of the PDE5 inhibitor and increase as tolerated and needed to treat the erectile dysfunction. Similarly, if you are on a PDE5 inhibitor and your doctor recommends that you start an alpha-blocker for your prostate, you should start at a low dose and increase as tolerated and needed to treat your prostate symptoms.

Men with mild to moderate kidney or liver disease will need to use lower doses of the PDE5 inhibitors. None of the PDE5 inhibitors are recommended for men with severe kidney disease, those on dialysis, and those with severe liver disease.

Second Line Therapies for ED

Second line therapies for ED include the use of intraurethral prostaglandin E1 (Muse), the vacuum device, and intracavernous injection therapies.

Intraurethral Suppository PGE1 Medication

Intraurethral therapy (Medicated Urethral System for Erections, or MUSE): Alprostadil (PGE1) has been formulated into a small suppository that can be inserted into the urethra (the canal through which urine and semen are excreted). The suppository is preloaded into a small applicator and by placing the applicator into the tip of the penis and compressing the button at the other end of the applicator and wiggling the applicator, the suppository is released into the urethra. Gentle rubbing/massaging of the penis will cause the suppository to dissolve and the medication is absorbed through the urethra and passes into the penis where it stimulates the relaxation of the muscle in the arteries and increases blood flow to the penis. It takes 15 to 30 minutes for this to occur. Success rates in the clinical studies were noted to be about 65%, however lower rates were noted when it started being used in the real world setting. This drug may be effective in men with vascular disease, diabetes, and following prostate surgery. This is a useful alternative for men who do not want to use self-injections or for men in whom oral medications have failed. Few side effects occur. The most common side effect is penile pain, which can vary from minor to uncomfortable. MUSE use has been associated with lowering of the blood pressure and thus it is recommended that the first time using the MUSE be in the physician's office so that you can be monitored. One cannot use lubricants of any type to help with the insertion of the applicator thus to make it easier to insert you should urinate immediately before using the MUSE system as this will lubricate the urethra. A temporary tourniquet is often helpful in allowing the medication to stay in the erectile tissue a little longer and seems to give a somewhat better response.

MUSE should not be used in men with a history of urethral stricture (narrowing of the tube in the penis that urine and semen pass through), inflammation or infection of the glans (tip) of the penis (balanitis), severe hypospadias (a condition where the opening of the urethra is not at the tip of the penis, rather on the underside of the penis), penile curvature (abnormal bend to the penis), and urethritis (inflammation/infection of the urethra).

Individuals at higher risk for priapism (painful erection lasting longer than six hours), including men with sickle cell anemia, thrombocytopenia (low platelet count), polycythemia (increased red blood cell count), multiple myeloma (a cancer of the white blood cells), and history of blood clots (for example, deep venous thrombosis [DVT]) or hyperviscosity (thick blood) syndrome are at increased risk for priapism with MUSE.

Penile Injection of Vasoactive Medications (Intracavernous Injection Therapy)

There are several different types of injection therapy ranging from injection of a single chemical (monotherapy) to a combination of chemicals, Bimix and Trimix. The selection of which therapy to use will vary with the severity of your erectile dysfunction and whether or not you tried and had pain with MUSE.

Injection therapy: The modern age of such drug therapies began in 1993 when the injection of papaverine (Pavabid), an alpha-blocker that produces vasodilatation (widening of the blood vessels), was shown to produce erections when injected directly into the penis. Soon afterward, other vasodilators, such as prostaglandin E1 (PGE 1) monotherapy (Caverject, Edex), PGE1 and phentolamine (Regitine), and Trimix (papaverine, phentolamine and prostaglandin E1), were demonstrated to be effective. The benefit of combination therapy is the decreased dosing of each with less side effects. Most important is the reduction of the prostaglandin PGE1 dosing, which is associated to the localized pain.

  • Self-injection of these agents has been of enormous benefit because they represent the most effective way to achieve erections in a wide variety of men who otherwise would be unable to achieve adequate rigid erections. The need for intact nerve pathways to the penile tissue is not needed. The locally injected medication directly relaxes the arteriole vessels and penile cavernosal tissue. Thus, this therapy is not dependent on sexual stimulation.
  • If the structure of the penis is healthy (not fibrosed or scarred), the use of injectable drugs is almost always effective. If one chooses this therapy, a doctor or nurse will teach the individual how to perform the injections, and the urologist (specialist) must determine the appropriate dose. The dosage is adjusted to achieve an erection with adequate rigidity for no more than 90 minutes.
  • Alprostadil, a synthetic PGE1, is the most commonly used single drug for injections into the penis as a treatment for ED. It works well in the majority of men who try it. In one study of 683 men with ED, 94% reported having erections suitable for penetration after PGE1 injections. When PGE1 is used in combination with papaverine and Regitine, the mixture is called Trimix, which has roughly twice the effectiveness of alprostadil alone. However, Trimix is quite expensive and is usually not covered by insurance, while PGE1 is often a covered benefit in most insurance medication plans. The main side effects are pain from the medication (not from the injection), priapism (persistent or abnormally prolonged erection), and scarring at the site of the injection. It is recommended that one alternate the side of the penis being injected to help decrease the risk of penile scarring. Many men are uncomfortable with penile injection therapy even though the injection itself is painless. The injection cannot be done more often than every other day. Men on anticoagulant medications (blood thinners) must be careful with injection therapy.

External Vacuum Devices

  • Vacuum devices: Specially designed vacuum devices to produce erections have been used successfully for many years. They are safe and relatively inexpensive. They work by creating a vacuum around the penis that draws blood into the penis, engorging it, and expanding it. There are three components to the device, a plastic cylinder in which the penis is placed, a battery or hand operated pump that draws air out of the cylinder creating the vacuum, and an elastic band (constriction device) that is placed around the base of the penis, to maintain the erection after the cylinder is removed and during intercourse by preventing blood from flowing out of the penis back into the body.
  • This technique is effective in 60%-90% of men. It is not recommended to leave the tension ring in place longer than 30 minutes. The vacuum device may be the only therapy that is effective after removal of a penile prosthesis. The vacuum device has become a commonly used therapy as part of penile rehabilitation after radical prostatectomy to preserve the tissue of the penis and prevent scarring within the penis and loss of penile length.
    • These devices are generally safe, but bruising can occur. Other unwanted effects include pain, lower penile temperature, numbness, no or painful ejaculation, blood in the ejaculate or urine, and pulling of scrotal tissue into the cylinder. Partners may complain about the bluish discoloration and coolness of the penis. Many of these problems can be helped by proper selection of the tension rings and cylinder, use of adequate lubrication, and proper technique.
    • 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 are perceived to be less romantic than other options.
    • It is important when purchasing a vacuum device that you make sure that it has a mechanism to prevent the development of an excessive vacuum, as this could cause harm.
    • One drawback to the use of these external vacuum devices is the need to assemble the equipment and the difficulty in transporting it. Many men lose interest in using the device because of the preparations that are necessary, lack of easy transportability, inability to hide the tension ring, and the relative lack of spontaneity.
    • About half the men who use a vacuum device obtain good or excellent erections with them, but only half of these men consistently use the device over long periods of time.

Summary of Various Medical Therapies

Types of Medical Therapy Available to Manage Erectile Dysfunction
MedicationAdvantagesDisadvantages
PDE5 Inhibitor Medical Therapy
Sildenafil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)
Avanafil (Stendra)

Safe
No surgery required
Painless
May use treatment only when desired
Easily hidden and transportable
If unsuccessful, does not interfere with other treatments
Can be used in combination with other therapies under proper supervision
Maximum use is once per day
Benefit lasts between four to six hours (Viagra) or up to 36 hours (Cialis)
Side effects, if present, usually quite mild
Very effective with overall success rate of 65%-70%
Inexpensive
Frequent side effects (40%) include headache, indigestion, facial flushing, nasal stuffiness, and rarely visual changes (temporary blue tint)
Potentially lethal interaction when used together with nitrate medications such as nitroglycerin, isosorbide mononitrate (Imdur), isosorbide dinitrate (Isordil)
Risk of an interaction is present for 24 hours after taking sildenafil
Must be taken on an empty stomach
Maximum effect takes 45-60 minutes
Does not "cure" underlying problem
No effect on libido (desire) or sensation
Penile Injection TherapyRefrigeration not required for some of the therapies
If unsuccessful, does not interfere with other treatments
70%-75% success rate
Highly effective
Inexpensive
Requires injections directly into the penis
Risk of infection, bruises, pain, and permanent scarring inside the penis
Possible painful permanent erection (priapism)
Optimal combination of drugs not known
Lacks formal FDA approval (except for prostaglandin [Caverject, Edex])
May not be covered by some insurance companies
Most effective form (Trimix) not covered by most insurance plans and may be quite expensive
Cannot be used by patients on MAOIs
Intraurethral Pellet Therapy (MUSE)No surgery required
Painless
May use treatment only when desired
Easily hidden and transportable
If unsuccessful, does not interfere with other treatments
Maximum usage up to two times per day
No needles, injections, or scarring
Approved by FDA
45% success rate
Reasonably effective
Inexpensive
45%-65% success rate
Can be part of a combination therapy plan if properly supervised
Pellet must be inserted directly into penis through urethral opening
Requires refrigeration
Mild occasional burning or discomfort (experienced by about one-third of uses)
Possible priapism (rare <1%)
Can cause mild dizziness, faintness, or low blood pressure
Only four dosages are available
May require a tension ring or penile tourniquet for best results
Contraindicated in individuals prone to priapism
External Vacuum TherapySafe
No surgery required
Painless
May use treatment only when desired
May improve natural erections in some users
Used for penile rehabilitation after prostate cancer surgery
If unsuccessful, does not interfere with other treatments
75%-85% success rate
Highly effective
Inexpensive
Requires some manual dexterity and strength
Not easily hidden
Somewhat bulky to transport
Removing tension ring within 30 minutes recommended
Tension ring necessary to maintain erection
Possibly uncomfortable ejaculation
May need to interrupt foreplay
Proper tension ring size crucial for best results
Requires practice

*Monoamine oxidase inhibitors

Medically Reviewed by a Doctor on 9/11/2017
Medical Author:

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