Impotence/Erectile Dysfunction

Erectile dysfunction (ED) or male impotence is defined as the inability of a male to achieve and/or maintain a hard enough erection sufficient for satisfactory completion of sexual activity.

Sexual health and function are important determinants of quality of life. As males age, erectile dysfunction (ED) or impotence is more common. Erectile dysfunction often has a negative impact on sex life and overall quality of life for both the male experiencing the erectile troubles and his partner.

Erectile dysfunction is often associated with a number of common medical conditions, such as diabetes, high blood pressure, heart disease, nervous system disorders, depression, and the medications used to treat these conditions. Psychologic problems such as anxiety and stress can also affect erectile function.

The successful treatment of erectile dysfunction (impotence) has been demonstrated to improve couple intimacy, improve sexual satisfaction, improve male self-esteem, and overall quality of life. In some men, it may also relieve symptoms of depression.

Erectile dysfunction is only one cause of sexual dysfunction. Other causes of sexual dysfunction include troubles with ejaculation, decreased libido, and troubles achieving an orgasm (climax). Some men may have premature ejaculation, which is a condition in which the entire process of arousal, erection, ejaculation, and climax occur very rapidly, often in just a few minutes or even seconds, leaving the partner unsatisfied. Premature ejaculation may accompany an erection problem such as ED but is generally treated differently. Troubles with erectile function may lead to decreased libido or interest in sex, however, many men with decreased libido have normal erectile dysfunction. Libido may be affected by psychologic factors, such as stress, anxiety, or depression but often is the result of a low testosterone (the male hormone) level.

As sexual activity often involves a partner, it is important to try to involve the partner in the evaluation and management of erectile dysfunction and determine if assistance with relationship problems will be needed. Sex therapists are helpful in assisting couples deal with sexual relationship difficulties.

Physiology of a Natural Erection

Penile Anatomy and Function

The penis is composed of three cylinders, two on the top and one on the underside of the penis. The top two cylinders are involved in the erectile process. The urethra, the tube that urine and semen pass through, is on the underside of the penis. The top two penile cylinders, the corpora cavernosa, are composed of tissue that is analogous to a sponge, containing spaces that can fill with blood and expand. These two cylinders are surrounding by a strong layer of tissue, like Saran wrap, the tunica albuginea. For an erection to occur, there must be properly functioning nerves, arteries, veins, and normal penile tissues.

• When aroused, stimulated nerves supplying the penis release chemicals that cause the muscle that surrounds blood vessels in the penis to relax. As the blood vessels relax, there is an increase in blood coming into the penis. This blood fills the spaces in the corpora cavernosa, allowing each of the corpora to expand. As the corpora expand, the veins that drain blood out of the penis are compressed against the tunica albuginea. Compression of the veins prevents blood from leaving the penis and results in a fully rigid penis. When the stimulation/arousal subsides, there is a decrease in the chemicals from the nerves, the muscle around the arteries tightens, decreasing inflow of blood, resulting in a lack of compression of the veins and the drainage of blood out of the penis.
  • Thus, any medical condition that affects nerves, arteries, or veins may have an impact on erectile function.

Incidence of Erectile Dysfunction

• Erectile dysfunction is extremely common in men and the risk of developing erectile dysfunction increases with age.
  • In the Massachusetts Male Aging Study (MMAS) among a community-based survey of men aged 40-70 years, 52% of the men reported some degree of erectile difficulty. Complete ED, defined as the total inability to obtain or maintain suitable erections during sexual stimulation, as well as the absence of nocturnal erections (normal erections [four to six/night], which occur during sleep), occurred in 10% of the men in the study. Lesser degrees of mild and moderate ED occurred in 17% and 25% of participants.
  • In the National Health and Social Life Survey (NHSLS), a nationally representative sample of men and women 18-59 years of age, 10.4% of men reported being unable to achieve or maintain an erection during the past year.
  • Judging from research results, an estimated 18-30 million men are affected by ED.

Incidence of Premature Ejaculation

• Other form of sexual dysfunction, such as premature ejaculation and loss of libido (decreased sexual desire), are also very common. The NHSLS found that 28.5% of men 18-59 years of age reported premature ejaculation, and 15.8% lacked interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% indicated a lack of pleasure from sexual activity.

Erectile dysfunction can be caused by any number of medical and psychological conditions. In general, ED is divided into organic (having to do with a bodily organ or organ system) and psychogenic (mental) impotence. Interestingly, and not surprisingly, most men with organic causes have a mental or psychological component, as well.

Male erectile problems often produce a significant emotional reaction based on the impact of erectile dysfunction on confidence, self-esteem, and morale in most men. This is described as a pattern of anxiety and stress that can further interfere with normal sexual function. Such "performance anxiety" needs to be recognized and addressed by a doctor.

• The ability to achieve and sustain erections requires the following:
  1. A healthy nervous system that conducts nerve impulses from the brain, spinal column, and the penis
  2. Healthy arteries in and near the corpora cavernosa of the penis so that when stimulated there is an increase in blood flow to the penis
  3. Healthy smooth muscle and fibrous tissue within the corpora cavernosa so that it can fill with blood
  4. An adequate amount of nitric oxide (NO) in the penis to help with the stimulation of blood flow into the penis
  5. Normal functioning of the tunica albuginea, the layer of tissue surrounding the corpora cavernosa and responsible for the compression of the veins to keep blood in the penis
  6. Appropriate psychosocial interactions to enhance sexual stimulation/arousal and decrease anxiety/stress

Erectile dysfunction can occur if any of these requirements are damaged. The following are causes of erectile dysfunction in men, and many men may have more than one cause.

• Arterial vascular diseases account for nearly half of all cases of ED in men older than 50 years of age. Arterial vascular disease includes atherosclerosis (fatty deposits on the walls of arteries, also called hardening of the arteries), which may affect the heart (history of heart attacks, angina, coronary artery disease, myocardial infarct) or blood vessels in the legs, peripheral vascular disease (problems with blood circulation to the legs), as well as other areas of the body including blood vessels supplying blood to the penis and high blood pressure. Prolonged tobacco use (smoking) is considered an important risk factor for ED because it is associated with poor circulation and reduced blood flow in the penis. This is related to microvascular damage (stiffening of the artery as well as smaller caliber vessel size secondary to endovascular atherosclerotic plaques).
• The presence of ED is correlated to the presence of cardiac disease. In some studies, the onset of ED can precede a heart attack by five to seven years. As such, particularly for younger men with acute onset of ED, cardiovascular investigation may also be suggested.
• Chronic medical conditions have been associated with ED. Systemic diseases associated with ED include the following:
  • Hypertension can worsen atherosclerosis.
    • The treatment of hypertension can cause dysfunction (most commonly, treatment with beta-blocker medications and thiazide diuretics, which have the biggest implication on ED).
  • Diabetes can cause erectile dysfunction by affecting the arteries, nerves, and tissue in the corpora cavernosa.
  • Enlarged prostate (benign prostatic hyperplasia, or BPH): There is a class of medications called 5ARI (5-alpha-reductase) that have a notable impact on both libido and erectile dysfunction in men. Finasteride (Proscar) and dutasteride (Avodart) are in this drug class.
  • Psychiatric disorders (anxiety, depression, psychosis)
  • Scleroderma
  • Renal (kidney) failure
  • Liver cirrhosis
  • Hemochromatosis (too much iron in the blood)
  • Cancer and cancer treatment (related to its surgery, radiotherapy, or chemotherapy, which all affect peripheral nerves and small blood vessels)
• Respiratory disease associated with ED: chronic obstructive pulmonary disease
• Endocrine conditions associated with ED
  • Hyperthyroidism
  • Hypothyroidism
  • Hypogonadism (low testosterone levels, also known as andropause): It appears that adequate levels of testosterone are needed to maintain nitric oxide levels in the penis.
  • Abnormalities of the pituitary gland, prolactinoma, can cause hormonal issues that may affect erectile function.
• Psychological conditions associated with ED
  • Depression
  • Widower syndrome
  • Performance anxiety
• Nutritional states associated with ED
  • Malnutrition
  • Zinc deficiency
• Blood diseases associated with ED
  • Sickle cell anemia
  • Leukemias
• Trauma to the pelvic blood vessels and nerves is another potential factor in the development of ED. Bicycle riding for long periods has been implicated, so some of the newer bicycle seats have been designed to soften pressure on the perineum (the soft area between the anus and the scrotum). Certainly, history of pelvic bone fracture, as well as previous pelvic surgery (orthopedic, vascular, colon-rectum, and prostate) may result in injury to the arteries or nerves that go to the penis.
• Surgical procedures associated with ED include the following:
  • Procedures on the brain and spinal cord
  • Retroperitoneal or pelvic lymph node dissection
  • Aortoiliac or aortofemoral bypass
  • Abdominal perineal resection
  • Proctocolectomy
  • Radical prostatectomy for prostate cancer
  • Transurethral resection of the prostate for BPH (enlarged prostate)
  • Cryosurgery of the prostate
  • Radical cystectomy for bladder cancer
• Peyronie's disease is a condition that is thought to occur due to minor trauma to the penis that results in injury to the tunica albuginea and scarring; Peyronie's may cause erectile dysfunction due to lack of compression of the veins by the scarred tunica. The penile curvature that develops due to this scarring may make penetration difficult or impossible.
• Priapism, an erection lasting longer than four to six hours, can be associated with subsequent troubles achieving an adequate erection, and the treatment of long-standing priapism may also cause erectile dysfunction.
• Medications used to treat other medical disorders may cause ED. Common medications associated with ED include the following:
  • Antidepressants
  • Antipsychotics
  • Antihypertensives (for high blood pressure)
  • Antiulcer drugs such as cimetidine (Tagamet)
  • Hormonal medication, such as goserelin (Zoladex), leuprorelin (Lupron), finasteride (Proscar), or dutasteride (Avodart)
  • Drugs that lower cholesterol
  • Substance abuse: Marijuana, cocaine, heroin, methamphetamines, crystal meth, and narcotic and alcohol abuse can contribute to erectile dysfunction. Alcohol abuse can also affect the testicles and lower testosterone levels.
• Nervous system disorders associated with ED include the following:
  • Epilepsy
  • Stroke
  • Multiple sclerosis
  • Guillain-Barré syndrome
  • Alzheimer's disease
  • Trauma (spinal cord and peripheral nerve injury)
  • Parkinson's disease

The diagnosis of erectile dysfunction relies on the history. It is important to ensure that the problem is truly erectile dysfunction and not a different type of sexual dysfunction. The evaluation of erectile dysfunction focuses on identifying possible medical causes of the erectile dysfunction. Thus, the physician should conduct a full medical history (reviewing past medical and surgical history, medications, and social history) as well as physical examination. Thereafter, a more focused and thorough sexual, medical, and psychosocial history should be performed. Erectile dysfunction is a delicate topic, and a doctor should be sensitive and caring to make you comfortable about sharing these intimate details of your private life. Prior to your visit, you may also complete a validated ED questionnaire such as the IIEF-SHIM questionnaire.

What to Expect During Your Physician Visit

• Your doctor will ask if you have difficulty obtaining an erection, if the erection is suitable for penetration, if the erection can be maintained for completion of sexual activity. You will be asked about the onset of the erectile dysfunction, whether the problem is persistent or intermittent.
• You will be asked about current medications you are taking, including over the counter medications and illicit drug use, about any surgery you may have had, and about other disorders (history of trauma, prior prostate surgery, or radiation therapy, for example).
• The doctor will want to know all medications you have taken during the past year, including all vitamins and other dietary supplements.
• Tell the doctor about your tobacco use, alcohol intake, and caffeine intake, as well as any illicit drug use.
• Your doctor will be looking for indications of depression. You will be asked about libido (sexual desire), problems and tension in your sexual relationship, insomnia, lethargy, moodiness, nervousness, anxiety, and unusual stress from work or at home.
• You will be asked about your relationship with your partner. Does your partner know you are seeking help for this problem? If so, does your partner approve? Is this a major issue between you? Is your partner willing to participate with you in the treatment process?
• Your doctor will want your candid answers to questions like these:
  • How long has a problem existed? Did a specific event such as a major surgery or a divorce occur at the same time?
  • Do you have diminished sexual desire? If so, do you think it is just a reaction to poor performance?
  • How hard or rigid are your erections now? Are you ever able to obtain an erection suitable for penetration even momentarily? Is maintaining the erection a problem?
  • Can you achieve orgasm, climax, and ejaculation? If so, does it feel normal to you? Does the penis become somewhat rigid at climax?
  • Do you still have morning erections?
  • Is penile curvature (Peyronie's disease) a problem? Is there any pain with erections?
  • What would be your preferred frequency of intercourse, assuming the erections were working normally? How would your partner answer this same question? What was your frequency before the erections became a problem?
  • Have you already tried any treatments for ED yet? If so, what were they and how did they work for you? Were there any problems or side effects to their use?
  • Are you interested in trying a particular treatment first? Are you against trying a particular type of therapy? If so, what caused you to make this judgment?
  • To what degree do you wish to proceed in determining the cause of your ED? How important is this information to you?
• A physical examination is necessary. The doctor will pay particular attention to the genitals and nervous, vascular, and urinary systems. Your blood pressure will be checked because several studies have demonstrated a connection between high blood pressure and erectile dysfunction. The physical examination will confirm information you gave the doctor in your medical history and may help reveal unsuspected disorders such as diabetes, vascular disease, penile plaques (scar tissue or firm lumps under the skin of the penis), testicular problems, low male hormone production, injury, or disease to the nerves of the penis and various prostate disorders.

• Laboratory testing: Laboratory testing is not necessary for all men, rather it will depend on your symptoms, physical examination and medical history.
  • If laboratory tests are performed, they would normally start with an evaluation of your hormone status (testosterone or male hormone), particularly if one of your symptoms is low sexual desire (low libido). Blood tests for testosterone should ideally be taken early in the morning because that's when levels are usually at their highest. It is recommended that if the first testosterone level is low to repeat it as testosterone levels can vary. If the testosterone level is low, other blood tests, such a luteinizing hormone and prolactin, can help determine if there is a problem with the pituitary gland.
  • Your blood may be checked for glucose, cholesterol, thyroid function, triglycerides, lipid/cholesterol profile if these blood tests have not already been obtained and your evaluation suggests risk factors. A prostate-specific antigen (PSA) level may be obtained if your physician is considering the use of testosterone therapy.
  • A urinalysis looking for blood cells, protein, and glucose (sugar) may also be done.
• Imaging: An ultrasound may be performed but is not commonly obtained in the initial evaluation and management of erectile dysfunction.
  • A duplex ultrasound is a diagnostic technique that uses painless, high frequency sound waves to visualize structures beneath the skin's surface. The principle is similar to the sonar used on submarines. Sound waves are reflected back when they contact relatively dense structures such as fibrous tissue or blood vessel walls. These reflected sound waves can be converted into pictures of the internal structures being studied.
  • This procedure is usually performed before and after injection of a smooth-muscle-relaxing medication into the penis, which normally should significantly increase the diameter of the penile arteries. The procedure itself is painless. Duplex ultrasonography is most useful in evaluating possible penile arterial disorders, but in those individuals considering surgery for problems with the arteries to the penis, a more invasive study, angiogram, is needed to identify the location of the damaged artery.
  • Nocturnal penile tumescence testing (NPT) may be useful in distinguishing mental from physical impotence. This test involves the placement of a band around the penis that you would wear during two or three successive nights. If an erection occurs, which is expected during rapid eye movement (REM) sleep, the force and duration are measured on a graph. Inadequate or no erections during sleep suggests an organic or physical problem, while a normal result may indicate a high likelihood of emotional, psychological, or mental causes.
  • Formal neurological testing is not needed for most men. But anyone with a history of nervous system problems, such as loss of sensation in the arms or legs, and those with a history of diabetes may be asked to undergo testing. This could include an MRI imaging of the spine or electro-conductive studies to assess nerve distribution and function.
  • The sensitivity of the skin of the penis to detect vibrations (biothesiometry) can be used as a simple office nerve function screening test. This involves the use of a small vibrating test probe placed on the right and left side of the penile shaft as well as on the head of the penis. The strength of the vibrations is increased until you can feel the probe vibrating clearly. Although this test does not directly measure the erectile nerves, it serves as a reasonable screening for possible sensory loss and is simple to perform. More formal nerve conduction studies are only performed in selected cases.

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:

• Sildenafil (Viagra) 50 mg and 100 mg on demand
• Tadalafil (Cialis) 10 mg and 20 mg on demand; 2.5 mg and 5 mg once daily
• Vardenafil (Levitra) 10 mg and 20 mg on demand
• Avanafil (Stendra) 50 mg, 100 mg, and 200 mg

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

*Monoamine oxidase inhibitors

Penile prosthesis is the primary form of surgical therapy and is reserved for those men who fail, are intolerant of, or have contraindications to other forms of therapy. Currently, there are several different types of penile prostheses. The simplest is the malleable penile prosthesis, and the most complex is the three-piece inflatable penile prosthesis.

A malleable penile prosthesis usually consists of paired rods that are inserted surgically into each of the corpora cavernosa. The rods are stiff, and basically to have an erection, one bends them up and when finished with intercourse they are bent down. They do not change in length or width. The malleable penile prosthesis has the lowest risk of malfunction, however they have the least normal appearance.

The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of a pair of cylinders that are surgically placed into the corpora cavernosa, a reservoir containing sterile fluid that is placed in the abdomen and a pump that is placed in the scrotum. Tubing connects the cylinders, reservoir, and the cylinders. By pressing the pump several times, fluid is transferred from the reservoir into the cylinders. As the cylinders fill with fluid, they increase in width and this causes the erection. When one is finished with sexual activity, pressing the release valve on the pump allows the fluid to drain out of the cylinders back into the reservoir. Given the mechanical nature of the three-piece prosthesis, it has a greater risk of mechanical malfunction; however, modifications have been made such as lock out valves to prevent the prosthesis from automatically inflating as well as improving the tubing to prevent tubing leaks.

The placement of a penile prosthesis is typically an outpatient procedure and is typically performed through a single incision. All of the parts of the prosthesis are hidden under the skin. Antibiotics are given to decrease the risk of an infection. A catheter may be left in the penis in some men for a short period. After placement, there will be a time period of healing prior to the ability to use the prosthesis.

Penile prostheses are very effective, and most patients who have a penile prosthesis placed are satisfied with the prosthesis. Different than a normal erection, the prosthesis does not elongate, in fact, some men notice that after the prosthesis is placed their penis appears a little shorter.

Infection is a concern after placement of a penile prosthesis and is reported as a complication in up to 20% of men undergoing placement of a penile prosthesis. If the device becomes infected more commonly, it needs to be removed. Another prosthesis can be placed after the infection is treated and the penile tissues have healed, but it is a difficult surgery. Erosion of the prosthesis, whereby it compresses through the corporal tissue, into the urethra may occur. Symptoms include pain, blood in the urine, discharge, abnormal stream, and malfunction of the prosthesis. If the prosthesis erodes, it will need to be removed. A catheter is placed to allow the urethra to heal.

Alternative Surgical Procedures

Similar to heart-disease-related to atherosclerosis (plaque formation within the blood vessels), the concept of bypassing or angiographically dilating and stenting penile arteries has been entertained recently with improvements in microvascular surgery and interventional radiology. However, the main drawback with most erectile dysfunction is the failure of vascular relaxation within the corpora cavernosa rather than the one feeding penile artery. Stenting or surgical grafting to bypass a blockage would be ideal for a single obstruction site along a penile artery. Because most erectile dysfunction pathology resides within the sponge-like vascular plexus of the penis, the ability of diffusely dilating and expanding the many vascular chambers of the penis is difficult to impossible. As such, unless the situation is that the penile artery was injured during a pelvic trauma, and the potential to bypass another vessel into the single penile artery, the concept of vascular reconstruction or angio-radiology stenting has very low yield.

Hormonal Therapy and ED

Hormonal therapy is not used as a primary therapy for the treatment of ED. Testosterone therapy is used if there is ED and symptoms of low testosterone, as well a low blood level of testosterone.

Testosterone replacement: Men with low sex drive (libido) and ED may be found to have low testosterone levels. Hormone replacement may be of benefit by itself or as a complementary therapy used with other treatments. Libido and an overall sense of well-being are likely to improve when serum testosterone levels are restored. The constitution of symptoms of low libido, fatigue, decreased muscle mass and force, and increased body fat may be related to andropause. As mentioned previously, in the patient workup section, serum total testosterone and bioavailable testosterone blood tests can be performed to evaluate for low serum levels. If determined to be below normal, replacement of testosterone may be suggested as a treatment option. The primary objective of testosterone replacement is to improve libido, energy levels, and symptoms of andropause. Only secondarily would correction of low testosterone levels potentially have impact on erectile function. Some studies suggest that in men with low or low normal testosterone levels and ED who fail PDE5 inhibitors that the use of hormone therapy may improve the success of PDE5 inhibitors.

• Replacement testosterone is available as oral pills, intramuscular injections, skin patches, and a gel that is rubbed into the skin. Men with low sexual desire and ED may have low testosterone (male hormone) levels. Hormone replacement may occasionally be of some benefit, especially when used in combination with other therapies. Testosterone supplementation alone is not particularly effective in treating erectile dysfunction. Sexual desire and an overall sense of well-being are likely to improve when serum testosterone levels (the levels in the blood) are restored. This can take several months after starting testosterone replacement.
• The normal range of testosterone levels in healthy adult males is between 280-1,100 nanograms per deciliter (ng/dL). Less is considered low, but this varies depending on the laboratory that does the testing.
• Oral therapy (pills) is the least effective and the most likely to be associated with liver problems, even though this is a small risk. This is related to the first-pass effect of all medications ingested via the digestive system. Once absorbed from the intesting, all food materials must pass through the hepatic (liver) system and be metabolized. As such, the actual delivery to the systemic blood system is low due to the liver metabolism of the testosterone. For this reason, the oral doses are quite high in order to get serum levels higher.
• Injections are most likely to restore testosterone levels, but this therapy requires periodic injections, usually every two to four weeks, to sustain an effective level. As such, it is less ideal for patients to depend on frequent medical visits for long-duration therapy. Coupled with injection-related pain, hematoma formation, and inconvenience, the serum blood levels of testosterone are also variable. Injection therapy should not be used in men who wish to father children due to the abnormally high levels of testosterone that occur initially after the injection.
• More recently developed skin patches and daily applied skin gels deliver a more stable, sustained dose and generally are well accepted by patients. The latter involves AndroGel, Testim, and Axiron.
• Proper informed consent with your physician should be performed to understand all risks and benefits of hormonal replacement therapy. Follow-up testosterone (hormone) levels and periodic blood counts as testosterone therapy is associated with a risk of an abnormally high red blood cell count, and prostate checks are necessary for all men on long-term testosterone replacement therapy as there are concerns regarding the risk of testosterone therapy in men with an underlying prostate cancer. The use of testosterone therapy does not cause the development of prostate cancer. Testosterone therapy may increase the size of the prostate and cause urinary troubles.
• Additional lifestyle modifications of cardiovascular conditioning, improved sleep, stress reduction, and increased smooth muscle mass can be beneficial to improving testosterone levels without an exogenous chance.

Erectile dysfunction is common, increases with age, and is associated with multiple common medical problems. A variety of successful therapies exist for men with erectile dysfunction. The success of the therapies can vary with the cause of the erectile dysfunction. A stepwise approach to the treatment of ED allows one to identify the therapy that is effective and the least invasive for the individual. Oral therapy remains the first line medical therapy for ED, however, is effective overall in 40%-80% of individuals. For those individuals who cannot take PDE5 inhibitors or fail from an efficacy or side effect standpoint, a number of alternatives exist. Intracavernous injection therapy is the most effective therapy for ED, however, the invasive nature can affect compliance. Penile prosthesis is a highly effective surgical procedure, but men undergoing placement of a penile prosthesis should be aware of the benefits and risks associated with placement of a penile prosthesis. Other surgical therapies, such as arterial surgery, are rarely needed.