Erectile Dysfunction

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Pathophysiology of Penile Erection

The development of an erection is a complex event involving integration of psychological, neurologic, endocrine, vascular, and local anatomic systems. Sexual arousal is activated in higher cortical centers, which stimulates the medial preoptic and paraventricular nuclei of the hypothalamus. These signals ultimately descend through a complex neural network involving the parasympathetic nervous system and eventually activate parasympathetic nerves in the sacral area (S2 to S4). Ultimately neurovascular events occur, that results in the inhibition of adrenergic tone and release of the nonadrenergic and noncholinergic neurotransmitter nitric oxide.

Nitric oxide is believed to be released from nonadrenergic noncholinergic (NANC) nerves and endothelial cells which stimulates the guanylate cyclase enzyme system in penile smooth muscle. This results in increased levels of cyclic guanosine monophosphate (GMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity.


Erectile Dysfunction is divided into organic (having to do with a bodily organ or organ system) and psychogenic (mental) impotence, but most men with organic causes has a mental or psychological component as well. The various causes that contribute to erectile dysfunction are:

  • Psychological and emotional reaction in men, often described as a pattern of anxiety and stress can interfere with normal sexual function. This "performance anxiety" needs to be recognized and addressed by a doctor.
  • Disease can affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the penis or influence mood and behavior.
  • Vascular diseases account for nearly half of all cases of ED in men older than 50 years. Vascular disease includes atherosclerosis (fatty deposits on the walls of arteries, also called hardening of the arteries), a history of heart attacks, peripheral vascular disease (problems with blood circulation), and high blood pressure.
  • Prolonged tobacco usage (smoking) is considered an important risk factor for ED because it is associated with poor circulation and reduced blood flow in the penis.
  • Trauma to the pelvic blood vessels and nerves is another potential factor in the development of ED.
  • Medications used in treating other medical disorders may cause ED.

Below is the list of various conditions that might result in Erectile Dysfunction:

Systemic Diseases

  • Diabetes
  • Scleroderma
  • Renal (kidney) failure
  • Liver cirrhosis
  • Hemochromatosis (too much iron in the blood)
  • Cancer and cancer treatment

Diseases of the Nervous System

  • Epilepsy
  • Stroke
  • Multiple sclerosis
  • Guillain-Barré syndrome
  • Alzheimer disease
  • Trauma
  • Parkinson disease

Endocrine Conditions

  • Hyperthyroidism
  • Hypothyroidism
  • Hypogonadism

Penile conditions

  • Peyronie’s disease
  • Priapism (painful, abnormally prolonged erections)

Mental conditions

  • Depression
  • Widower syndrome
  • Performance anxiety

Nutritional States

  • Malnutrition
  • Zinc deficiency

Blood Diseases

  • Sickle cell anemia
  • Leukemias

Surgical Procedures

  • Procedures on the brain and spinal cord
  • Retroperitoneal or pelvic lymph node dissection
  • Aortoiliac or aortofemoral bypass
  • Abdominal perineal resection
  • Proctocolectomy
  • Radical prostatectomy
  • Transurethral resection of the prostate
  • Cryosurgery of the prostate
  • Cystectomy

Common Medications

  • Antidepressants
  • Antipsychotics
  • Antihypertensives (for high blood pressure)
  • Antiulcer drugs such as cimetidine
  • Hormonal medication such as finasteride
  • Drugs that lower cholesterol
  • Alcohol abuse
  • Mind-altering agents such as marijuana and cocaine
For diagnosing the exact cause of Erectile Dysfunction (ED), thorough examination of your sexual, medical and psychological history is essential. You doctor will require the following information:

  • If you have difficulty obtaining an erection, if the erection is suitable for penetration, if the erection can be maintained until the partner has achieved orgasm, if ejaculation occurs, and if both partners have satisfaction
  • The current medications you are taking (if any) including all medications you have taken during the past year, vitamins and dietary supplements, about any surgery you may have had, and about other disorders (history of trauma, prior prostate surgery, or radiation therapy).
  • If you are using tobacco, alcohol, and caffeine, as well as any illicit drug use.
  • Your libido (sexual desire), problems and tension in your sexual relationship, insomnia, lethargy, moodiness, nervousness, anxiety, and unusual stress from work or at home.
  • Your relationship with your partner. If your partner knows you are seeking help for this problem and whether your partner approves it. Is this a major issue between you? Is your partner willing to participate with you in the treatment process?
  • Since when has this problem occurred and if any specific event such as a major surgery or a divorce has occurred.
  • If you have a 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?
  • If you can you achieve orgasm, climax, and ejaculation? If so, does it feel normal to you? Does the penis become somewhat rigid at climax?
  • If you still have morning erections?
  • Is penile curvature (Peyronie's disease) a problem?
  • 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?
  • If you are 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?

After the questionnaire session, the doctor will do a thorough physical examination of your body while paying 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.

The diagnosis will involve the following procedures:

Laboratory Testing

Evaluation of your hormone status (testosterone or male hormone) will be done, 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. 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, and prostate-specific antigen (PSA)
  • A urinalysis looking for blood cells, protein, and glucose (sugar) may also be done.

Duplex Ultrasound
It is a diagnostic technique which uses painless, high frequency sound waves to visualize structures beneath the skin's surface. These reflected sound waves are converted into pictures of the internal structures to be 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. Duplex ultrasonography is most useful in evaluating possible penile arterial disorders, but further studies of the venous drainage system as well as arterial x-rays are usually recommended if vascular reconstructive surgery is anticipated.

Intracavernous Injection 

One of the most common tests used to evaluate penile function is the direct injection of PGE1 into the penis. (PGE1 is a medication that increases blood flow into the penis and normally produces erections.) If the penile structure is normal or at least adequate, an erection should develop within several minutes. You and your doctor can judge the quality of the erection. If successful, this test also establishes penile injections as one possible therapy.

Nocturnal penile tumescence testing (RIGISCAN)

It 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 2 or 3 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.

Cavernosometry and Cavernosography

It is the measurement of the vascular pressure in the corpus cavernosum. Saline is infused under pressure into the corpus cavernosum with a butterfly needle, and the flow rate needed to maintain an erection indicates the degree of venous leakage. The leaking veins responsible may be visualised by infusing a mixture of saline and x ray contrast medium and performing a cavernosogram.

Angiography is useful if the patient has undergone a vascular surgery. Vascular reconstruction is done in young men with traumatic vascular injuries resulting in ED

The first step in treating Erectile Dysfunction (ED) involves finding a well-trained, experienced, and compassionate doctor who is willing to take the time to understand you and fully discuss the treatments available to you.

Primary care doctor and urologist are usually the first professionals to learn about your ED. You might be reluctant to discuss your sexual problems with your doctor. Opening a dialogue allows your doctor to begin the investigation or refer you to a consultant. Your doctor can discuss your particular situation, the most likely cause, and reasonable treatment options. In many cases erectile dysfunction can be managed through sex counseling.

Treatment options include sex counseling, medications, external vacuum devices, hormonal therapy, penile injections or intraurethral suppositories. In highly selected cases, combination therapy can be used under the supervision of a urology specialist in ED. If none of these therapies is satisfactory, penile prosthesis implants can be considered.

An increasing array of medications is available to assist in the management of erectile dysfunction (ED). New agents are still undergoing clinical testing, and more are in the early phases of development.
For any medication to be effective, the physiologic components involved in the erectile process must be functional. Serious impairments render the medication either completely or partially ineffective.
An ideal agent should be rapidly effective, easy to administer, affordable, applicable to a wide range of patients, and minimally toxic. The types of medications can be divided into oral, topical, injectable, and intraurethral insertion. Phosphodiesterase (PDE) type 5 inhibitors are the principal oral agents used in ED.

Phosphodiesterase Inhibitors
At least 7 phosphodiesterase (PDE) classes are known, many with subtypes identified by structure and function. The most commonly used agents are sildenafil , vardenafil and tadalafil. Sildenafil was the first in this series of PDE inhibitors. The newer agents, vardenafil and tadalafil, are more specific and potent cGMP inhibitors than sildenafil. Both of the newest agents are PDE-5 inhibitors, which are significantly more selective in their inhibition. PDE-5 is cGMP specific and is a major cGMP-hydrolyzing enzyme in the vascular smooth muscle of the penis. The agents rely on the role of nitric oxide (NO) in inducing vasodilatation. NO relaxes the smooth muscle of the corpora cavernosa peripherally by stimulating guanylyl cyclase activity, which raises the intracellular concentrations of the cyclic nucleotide cGMP, which, in turn, induces vasodilation.
Intracellular cGMP is hydrolyzed by PDEs, terminating their action. PDEs are a diverse family of enzymes with different tissue distributions and functions, but all exert their effect by lowering intracellular cyclic nucleotide levels.

Sildenafil is a PDE-5 selective inhibitor. Inhibition of PDE-5 increases cGMP activity, which increases vasodilatory effects of NO. Sildenafil is most effective in men with mild-to-moderate ED. It is to be taken on an empty stomach approximately 1 hour before sexual activity. Sexual stimulation is necessary to activate response. Sildenafil is available as 25-, 50-, and 100-mg tablets. The onset of action varies from 15-60 minutes, with duration of action of 4-6 hours. Its half-life is 4-5 hours.

Vardenafil is a PDE-5 selective inhibitor. Inhibition of PDE-5 increases cGMP activity, which increases vasodilatory effects of NO. Vardenafil is effective in men with mild-to-moderate ED. It is to be taken on an empty stomach approximately 1 hour before sexual activity. Sexual stimulation is necessary to activate response. Increased sensitivity for erections may last 24 hours. It is available as 2.5-, 5-, 10-, and 20-mg tablets. Vardenafil acts within 15-30 minutes and can be taken with food, although a high-fat meal can inhibit absorption. Its half-life is 4.8-6 hours.

Tadalafil is a novel PDE-5 selective inhibitor chemically unrelated to sildenafil and vardenafil. It is most effective for mild-to-moderate ED of varying etiologies, including both organic and psychogenic causes. PDE-5 inhibition increases cGMP activity, which increases vasodilatory effects of NO. Sexual stimulation is necessary to activate response. Because sexual stimulation is required to initiate local release of NO, tadalafil has no effect in the absence of sexual stimulation. Increased sensitivity for erections may last 36 hours with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (eg, twice weekly); men can attempt sexual activity at any time between daily doses.

Tadalafil is available as 2.5-, 5-, 10-, and 20-mg tablets. The major difference between tadalafil and the other PDE-5 inhibitors is its longer half-life of 17.5-21 hours compared with sildenafil (4-5 h) and vardenafil (4.8-6 h). In patients who respond, coitus has been recorded from 30 minutes to 36 hours after administration.

Androgens are primarily of benefit in men with low levels of serum testosterone. Men with hypogonadism who desire a restoration of libido and who wish to become sexually active usually benefit from the exogenous supplementation of androgens. This can be accomplished with injections, cutaneous application via gel or skin patches, or oral administration.

Testosterone promotes and maintains secondary sex characteristics in androgen-deficient males. Depot injections can produce high levels of serum testosterone when administered in adequate doses.

Injection Therapy
Although many aphrodisiacs substances are available (meant to arouse sexual desire), the modern age of such drug therapies began in 1993 when the injection of papaverine, 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 PGE1 and Regitine, were demonstrated to be effective either as single drugs or in combination.

  • 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.
  • If the structure of the penis is healthy, the use of injectable drugs is almost always effective. If you choose this therapy, your doctor will teach you 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 alprostadil (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.

Many men are uncomfortable with penile injection therapy even though the injection itself is painless. The injection cannot be done more often than 3 times a week. Men on anticoagulant medications (blood thinners) should probably choose an alternate therapy.

Vacuum Erection Devices
Specially designed vacuum devices to produce erections have been used successfully for many years. They are safe and relatively inexpensive. They work by using a manually generated vacuum to draw blood into the penis to create the erection. When used successfully, their other significant benefit is a high degree of reliability compared to drug treatments, which tend to be less predictable. The typical vacuum device consists of a plastic cylinder that is placed over the penis, tension rings of various sizes, and a small hand pump. Air is pumped out, causing a partial vacuum, which creates the erection. Once an erection is obtained, a tension ring, which acts like a tourniquet to keep the blood in the penis and maintain an erection, is placed at the base of the penis. This technique is effective in 60-90% of men. It is not recommended to leave the tension ring in place longer than 30 minutes.

Though vacuum erection devices are very reliable and can be operated safely with experience, they are still perceived to be less romantic than other options. The other drawbacks include:

  • Bruising, pain, lower penile temperature, numbness, no or painful ejaculation and pulling of scrotal tissue into the cylinder are some of the unwanted effects. Proper selection of the tension rings and cylinder, use of adequate lubrication, and proper technique might ease of the pain.
  • Another drawback 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.

Surgical Treatment
Various surgical treatments are available to correct ED. Penile Prosthesis is a treatment option available for men with Erectile Dysfunction. There are two categories of penile implant available:

Semirigid (Malleable) Penile Prostheses
This device consists of specially constructed silicone rubber rods, which are placed inside the penis (Corpora Cavernosa). A small skin incision is made underneath the penis and one rod is inserted in each cylinder of the penis. It is particularly useful for the elderly and those with reduced strength of hands because no special manipulation is needed.

The first inflatable penile prostheses was designed and marketed by Scott, Bradley and Timm in 1973. It has undergone many modifications. The most commonly used implants have three pieces. It consists of a set of two cylinders which are inserted into the penile cylinders and one control pump to inflate and deflate the cylinders. A reservoir shaped like a small balloon, holds the fluid which is used to inflate and deflate the cylinders. This device is inserted into the body through a small incision either below the penis or above the penis. After insertion there is a healing period of 8 weeks during which the device cannot be used. This device is significantly superior to the Semirigid one, in terms of penile girth and natural looking erection. Those patients who lack manual dexterity are not good candidates for this type of device.

The advantages include:

  • High mechanical reliability, only 5% have mechanical failure after 10 years of use.
  • Greater partner satisfaction reported to increase from 60% to 80%.

The complications involve:

  • Infection might occur during the first three months following surgery.
  • Antibiotics to be administered whenever they are going to have dental work or any other surgery.
  • Diabetic patients with poor control are more at risk, because tissue quality is poor due to decreased blood circulation.

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