Male Sexual Dysfunction

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[edit] Male Sexual Dysfunction

Michael D. LaSalle

Irwin Goldstein

Robert J. Krane

[edit] MALE DYSFUNCTION

Erectile dysfunction is the consistent inability to obtain or maintain a penile erection of sufficient rigidity for satisfactory sexual performance.^[1] Erectile dysfunction is a significant health problem for many reasons. According to the Massachusetts Male Aging Study, a community-based survey of men aged 40 to 70 years, the prevalence of erectile dysfunction is 52%.^[2] Extrapolating this data to the general population, it has estimated that more than 20 million American men suffer from some form of this disorder. Erectile dysfunction also appears to be an age-related phenomenon. At 40 years of age, approximately 40% of men have some degree of dysfunction, whereas at 70 years, the prevalence approaches 70%. With the increasing aging population demographics, the numbers of men complaining of erectile dysfunction and seeking treatment will continue to grow.

Psychologic problems such as depression and poor self-esteem were once believed to be primary causes of most cases of erectile dysfunction. However, erectile dysfunction is now viewed as a very common and reversible health-related problem, often with an organic etiology. Medical risk factors associated with erectile dysfunction include hypertension, hypercholesterolemia, diabetes, cigarette smoking, alcoholism, atherosclerosis, neurologic disorders, and peripheral vascular disease.

Historically, the urologist was the sole physician diagnosing and treating erectile dysfunction. Now, the primary care physician is the first to diagnose and treat such disorders. This shift is a direct result of many factors. First, the managed care environment exposes large numbers of patients to the primary care physician for treatment, thereby diminishing referrals to specialists. Second, an expanding aging population presents more patients to their primary care physicians for other health-related problems. Finally, erectile dysfunction issues are no longer viewed as “taboo” by the public, allowing patients to willingly and openly discuss them with their doctors. Given these reasons, primary care physicians must now be more comfortable with (1) discussing sexuality issues with their patients, (2) identifying when a problem exists, and (3) offering appropriate therapy when indicated. More important, the physician must understand that the presenting complaint of erectile dysfunction may signal an underlying and potentially threatening concurrent illness.

This section emphasizes the basic elements for understanding normal penile anatomy and erectile physiology as well as the pathophysiology associated with erectile dysfunction. Coordinated functioning of these anatomic and physiologic systems is needed for the initiation and maintenance of an erection. A detailed medical history, psychosexual history, and focused physical examination must be performed by the physician. In addition, diagnostic testing can be used to establish an etiology, and then appropriate therapeutic options can be offered to the patient for successful treatment.

[edit] Penile Anatomy

Anatomically, the penis contains three chambers. These chambers include two paired dorsal erectile bodies (i.e., corpora cavernosa) and a ventrally located spongy tissue cylinder (i.e., corpus spongiosum). Each chamber has an arterial blood supply, a venous drainage system, and neural innervation that contribute to normal physiologic function.

[edit] Corpora Cavernosa.

Each corpus cavernosum is surrounded by a thick fascial investment called the tunica albuginea. The tunica albuginea has two concentric layers (an inner circular and an outer longitudinal layer) that, along with its elastic fibers, allows it to stretch when filled with arterial blood. Each cylinder contains venous sinusoids that trap blood when filled. These venous sinusoids are surrounded by trabeculae consisting of connective tissue and smooth muscle. After blood enters the penis, each cylinder increases in volume. When each cylinder has reached maximal volume, pressure rises, and the penis gains rigidity. Penile rigidity (both axial and radial components) is what ultimately facilitates vaginal penetration.

[edit] Corpus Spongiosum.

The corpus spongiosum is the chamber located ventrally within the penis and contains the urethra. This chamber mushrooms out distally on the penis, forming the glans. Although the corpus spongiosum lacks a tunica albuginea covering, its tissues still become engorged with blood during sexual arousal. Venous communications often exist between the corpus spongiosum and the corpora cavernosal bodies.

[edit] Penile Arterial Blood Supply.

Branches of the iliohypogastric-pudendal arterial system supply blood to the sexual organs. The internal pudendal artery is the main blood supply to each cavernosal body of the penis. One branch, the common penile artery, further bifurcates into the dorsal penile artery and the cavernosal artery (Fig. 154A-1). Each cavernosal artery enters the corpus cavernosum at the penile hilum. Helicine arteries branch along its course and provide the blood supply to the sinusoidal tissue. The cavernosal artery and the deep dorsal penile artery often communicate. This is important for understanding penile revascularization surgery because a new blood supply is brought into the cavernosal bodies via the deep dorsal artery. Blood flow can travel either retrograde into the corpora cavernosa from the cavernosal artery or antegrade via branches off the dorsal penile artery that penetrate directly through the tunica albuginea to supply the cavernosal bodies.

Figure 154A-1 A, Normal pudendal arteriogram showing a patent pudendal-penile artery bifurcating (arrow) into normal dorsal and corporal arteries. B, Arteriogram showing a diseased pudendal artery and obstruction at the takeoff of the corporal artery (arrow). In this case the dorsal artery is well visualized.

[edit] Penile Venous Blood Supply.

The cavernosal bodies contain numerous venous sinusoids that coalesce and drain into one another. Blood progressively moves outward toward the most peripheral sinusoids. Small venules drain these sinusoids and then travel below the tunica albuginea, forming the subtunical venular plexus. These subtunical venules drain into the emissary veins, which pierce through the tunica albuginea. During an erection, the tunica albuginea stretches, and the subtunical and emissary veins become elongated, causing a functional closure of their lumina. This venoocclusive mechanism acts like a valve during an erection, preventing the release of blood from the penis back into the general circulation. This mechanism is very important in establishing and maintaining penile rigidity.

[edit] Penile Neuroanatomy.

The penis is innervated by both the autonomic and somatic nervous systems. The erectile autonomic nerve fibers are known as the cavernous nerves. The parasympathetic nerve components originate in the second, third, and fourth sacral vertebrae (S2, S3, and S4 [the spinal erection center]). The preganglionic parasympathetic fibers enter the pelvic plexus and are subsequently joined by sympathetic nerves to form the cavernous nerves. The cavernosal nerves enter the penile hilum anterior to the bulbous urethra. Stimulation of the cavernous nerves induces an erection.

The parasympathetic nerves are responsible for initiating tumescence. The most potent neurotransmitter for the erectile process is nitric oxide. Postganglionic nerves secrete nitric oxide (NO), which subsequently causes cavernosal smooth muscle relaxation. Smooth muscle relaxation allows for increased blood flow into the penis. In contrast, stimulation of the sympathetic plexus causes an increase in vascular smooth muscle tone that results in a decrease in arterial blood flow into the penis. Detumescence occurs primarily through the action of the neurotransmitter norepinephrine.

Somatic sensory innervation of the penile shaft and glans is derived from the dorsal penile nerve. These afferent nerves coalesce into the internal pudendal nerve (S2 to S4), which travels along the ischiopubic ramus of the pelvis through Alcock's canal. Crushing of this nerve can cause penile and glandular numbness. Such injuries can result from blunt pelvic trauma or chronic compression to the perineum (i.e., a motor vehicle accident with fracture of the ischiopubic ramus or perineal compression from a bicycle seat).

Afferent stimulation of the penis causes erection via spinal pathways. The pudendal nerve is responsible for initiating most erections, but psychologically and centrally mediated erections do occur. Psychogenic erections are caused by signals from the brain that are transmitted to the spinal erection center. The pudendal nerve also carries the somatic motor innervation to the bulbocavernosus and ischiocavernosus muscles. Contraction of these muscles occurs during sexual excitation and compresses the corpora cavernosal muscles further, increasing overall intracavernosal pressure. The somatic component of the pudendal nerve also is important in the ejaculatory process, causing the bulbocavernosus muscles to contract rhythmically, resulting in propulsion of semen through the urethra.

[edit] Erectile Physiology and Pathophysiology

An erection is primarily a hemodynamic phenomenon. Two processes must be intact and functionally coordinated for a successful erection to occur. First, blood flow must increase to the corpora cavernosa via the internal pudendal artery. When blood volume increases, tissues expand, and intracavernosal pressure rises. Second, venous outflow resistance must increase as a direct result of the trapping of blood via an intact venoocclusive mechanism. Further increases in blood inflow without venous outflow allow higher intracavernosal volume and pressure, increased penile length, and ultimately, penile rigidity.

Anatomically, smooth muscle cells line both the cavernosal sinuses and the afferent arterioles. When the smooth muscle relaxes, the lumina increase in size, and blood flow increases. When the smooth muscle lining the cavernosal sinuses relaxes, the sinuses can accommodate more blood. Thus they increase in size with subsequent compression of the subtunical venules, causing venous trapping. If inadequate blood flow reaches the penis, inadequate rigidity is achieved. If inadequate venous trapping occurs, even with good inflow, the penis does not become rigid. Therefore smooth muscle relaxation and a normal venoocclusive mechanism are the key factors in achieving an erection. Often, explaining this concept to a patient can be difficult. A simple analogy of attempting to fill a tire connected to an air hose helps the physician describe this process more easily to patients. If the tire does not become full after inflating, there can either be a kink in the air hose (i.e., an arterial problem) or a leak in the tire (i.e., a venous trapping problem).

In addition to having a functional hemodynamic system, the patient must also be neurologically intact to receive afferent stimuli and transmit autonomic signals for initiation of an erection. Neurologic disorders resulting in decreased cavernosal nerve function diminish the patient's spontaneous erections even though the hemodynamic vascular system is intact. The psychologic and hormonal milieus are also significant factors affecting erection. Disorders such as depression, anger, and hypogonadism can disrupt erectile function. Patients may not be satisfied with the quality of their erectile potency either in terms of performance or in comparison with previous performance. Therefore in addition to all other factors that affect potency, the quality of the erection must be evaluated in terms of rigidity or sustaining ability.

Rigidity is highly dependent on penile geometry (its dimensions), its biomechanical properties, and intracavernosal pressure for proper function. The achievement of intracavernosal pressure depends on hemodynamic factors and proper smooth muscle relaxation. Rigidity has two major components: radial and axial. Axial rigidity (i.e., the columnar component) is needed for vaginal penetration.

[edit] Erectile Dysfunction Evaluation

The primary purposes for erectile dysfunction evaluation are to determine an etiology and to direct a method of therapy. Although some patients may require a comprehensive evaluation, other patients may need only basic screening before treatment. For example, an explanation of etiology may be unnecessary for older patients with known risk factors for erectile dysfunction, since they may simply want to regain potency without specifically identifying an etiology. For many other patients, the evaluation may simply provide a better means of understanding why they developed erectile dysfunction. Many patients and their partners are relieved to know that the problem is not necessarily psychologic.

The physician must realize that at least a minimal evaluation is needed before treatment. Erectile dysfunction may be the presenting complaint of a previously undiagnosed illness (e.g., hypertension, hypercholesterolemia, diabetes mellitus, vascular disease). The patient's medical and psychosexual history and physical examination provide the basis for diagnosis and management; they may also result in the identification of other conditions.

[edit] Patient History.

As in many medical disciplines, the diagnosis of erectile dysfunction is frequently apparent from the patient history. The first goal of the history is to determine exactly what type of problem exists. The physician must distinguish among problems with libido, ejaculation, orgasm, and erection. These other disorders should be treated independently of erectile dysfunction issues.

One simple way to assess whether a patient has erectile dysfunction is the administration of a validated erectile dysfunction questionnaire such as the International Index of Erectile Function (IIEF).^[3] This questionnaire not only acts as a screening device but can also be used for a baseline index comparison of function before treatment starts. Such questionnaires may identify patients who cannot specifically identify which aspects of erection are problematic. Next, the effects of the erectile dysfunction on the patient and his partner must be assessed. Such issues may have a significant impact on the form of treatment recommended. Finally, the physician must understand the patient's goals for receiving treatment.

The medical history can often direct the physician to the etiology of erectile dysfunction. The onset of the problem may help differentiate between psychologic and organic etiologies. If the erectile problems are of acute onset after some traumatic event and occur during sexual encounters but not during sleeping or masturbation, a psychologic etiology may be suspected (but is not necessarily ensured). Psychosexual assessment is important in determining what psychologic factors could be affecting the patient's erections and what psychologic effects the patient's erections have had on him. A psychologic cause can be associated with an organic etiology in up to 90% of cases.

When the onset of erectile dysfunction is slow and is not associated with a specific event or life situation, an organic etiology is more likely. The medical history often plays a more crucial role in the evaluation of such cases of organic erectile dysfunction. Medical disorders such as diabetes, atherosclerosis, neurologic disease, hypercholesterolemia, hypertension, and sickle cell disease are frequently associated with erectile dysfunction. Many medications have adverse effects on erections. Antihypertensive medications often cause erectile dysfunction not directly at the penile level, but by lowering systemic blood pressure and thus decreasing intracavernosal pressure. Surgical history can also indicate a potential iatrogenic etiology. Previous pelvic surgery or abdominal surgery may have injured the neurologic innervation of the penis or its vascular supply. Arterial or venoocclusive dysfunction may be associated with a prior history of penile or perineal trauma.

[edit] Physical Examination.

A comprehensive physical examination should be completed on each patient with erectile dysfunction. This examination should not differ significantly from a routine physical performed by a primary care physician. However, it should emphasize evaluation of the genitourinary, vascular, and neurologic systems. Vital signs, including blood pressure and peripheral pulse measurements, may reveal problems with hypertension, heart disease, or peripheral vascular disease. Aneurysmal disease can be detected by listening and palpating for abdominal bruits. Secondary sexual characteristics such as sparse hair growth and gynecomastia may indicate an endocrinologic disorder. The genitalia should be assessed for testicular size, penile length, penile geometry, curvature, or other penile deformities such as Peyronie's plaques. Sensory neurologic assessment can be easily performed by evaluating sensory changes in the genitalia. The digital rectal examination not only screens for prostate cancer but also detects the integrity of the neurologic innervation of the external anal sphincter (S2 to S4). Although the physical examination provides a source of valuable information for the physician, it also provides a great opportunity for patient education and reassurance.

[edit] Laboratory Tests.

Screening for systemic medical disorders, endocrine disease, and vascular risk factors is appropriate in the workup for erectile dysfunction. Complete blood counts, standard serum chemistry analysis (including a fasting glucose test), and a cardiac profile (fasting cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride tests) should be obtained. If libido is diminished, serum testosterone and prolactin levels should be measured. This assessment determines the integrity of the pituitary-gonadal axis. Serum determinations for prostate-specific antigen (PSA) should be performed after the screening tests done according to the American Urological Association or AFP guidelines. Tests for thyroid disease, such as thyroid-stimulating hormone levels, should be used in highly selected cases.

[edit] Diagnostic Testing

[edit] Nocturnal Penile Tumescence.

Nocturnal penile tumescence testing uses a strain gauge placed around the penile shaft. It measures changes in penile circumference and erectile activity during a night of sleep. Normally, a male subject will have three to five physiologic erections lasting approximately 25 to 35 minutes every night. Men with psychogenic erectile dysfunction usually have normal sleeping erections. On the other hand, men with an organic etiology to their erectile dysfunction usually have abnormal nocturnal erections. The most notable exception to this is patients who have neurologic impotence that affects their afferent sensory nerves. Thus this test is a useful screening tool for aiding in the differentiation between psychogenic and organic erectile dysfunction. It is a simple test that may be performed at home or in a sleep laboratory. A portable machine measuring both circumferential penile size changes and rigidity (Rigiscan) is available for home use. One major limitation to this test is that it only measures radial rigidity and not axial rigidity.

[edit] Neurologic Testing.

Neurologic disorders producing erectile dysfunction may be present in either the peripheral or central conduction pathways. Ultimately, some interference within the motor efferent autonomic nerves to the penis must allow smooth muscle relaxation to occur. Many devices for neurologic assessment are available for the evaluation of the patient with neurogenic erectile dysfunction. Biothesiometry is a simple screening tool that assesses the ability to sense vibration and peripheral afferent nerve transmission. A vibratory device is placed on the penis and on the extremities to detect whether sensory deficits exist between the different areas tested. Dorsal nerve conduction velocity testing or bulbocavernosus reflex latency testing can be used to detect sacral or peripheral nerve pathology. Other tests using needle electrodes (intracavernosal electromyography) or patch electrodes on the penile shaft can determine the electrical activity of the cavernosal nerve as transmitted to corporal smooth muscle. For evaluation of the central nervous system, a genitocerebral evoked potential study can determine conduction times after electrically stimulating the penis and recording the sensory input to the cerebral cortex.

[edit] Psychologic Testing.

Psychologic aspects in the diagnosis of erectile dysfunction are often difficult to identify, since multifactorial etiologies are often present. Each patient evaluated for erectile dysfunction should have a psychosexual evaluation. This evaluation not only helps differentiate between psychogenic and organic causes of erectile dysfunction but also helps determine the effects of the problem on the patient and his partner as well as their goals in seeking treatment.

Erections can be initiated with or without direct penile stimulation. Therefore positive psychologic stimuli can create or enhance an erection, and negative psychologic stimuli can inhibit them. Negative psychologic input can inhibit the sacral cord–mediated reflexogenic erections. In addition, excessive adrenergic states associated with disorders such as anxiety can increase penile smooth muscle tone. Such psychologic disturbances can oppose the normal smooth muscle relaxation needed for an erection.

[edit] Hormonal Testing.

The role of testosterone in the evaluation of erectile dysfunction remains unclear. Patients with decreased libido or poor virilization often undergo serum testosterone screening. Since serum testosterone levels vary throughout the day, early morning specimens are optimally measured. If morning testosterone levels are consistently low, luteinizing hormone and prolactin levels are then obtained. Low serum testosterone levels have been associated with disorders such as hyperprolactinemia. However, if serum prolactin levels remain elevated, potency is restored in only half the patients whose testosterone concentrations are normalized by exogenous replacement. When hyperprolactinemia is identified on screening, it requires its own investigation. Pituitary adenomas can be manifested first by symptoms such as erectile dysfunction. Often magnetic resonance imaging of the pituitary is required.

Hyperthyroidism can also be associated with diminished libido and occasionally with erectile dysfunction. Hypothyroidism may cause erectile dysfunction secondary to associated low testosterone and elevated prolactin levels.

[edit] Vascular Testing.

As stated previously, an erection is a complex hemodynamic event requiring both adequate arterial inflow and venous trapping. Vascular testing allows the physician to identify which system is functionally disrupted. It is important to distinguish between these two components for two reasons: first, quantifying which component is faulty helps direct appropriate therapy, and second, identification of the indicated therapy improves clinical outcomes. For instance, isolated blockages in the penile arterial tree (as opposed to diffuse disease) are often surgically corrected by microvascular arterial bypass procedures. On the other hand, disorders such as diffuse arterial disease and venous leakage are not amenable to corrective therapy. Therapy under these circumstances may attempt to override (penile injection therapy) or completely circumvent (prosthesis or vacuum erection devices) the problem.

[edit] Arterial testing.

Penile arterial testing can be performed in either the erect or flaccid state. As in any hemodynamic system, more accurate information is obtained in the active state. However, the flaccid state may give some clues as to the etiology of the problem. Intracavernosal injection of vasoactive agents such as papaverine, phentolamine, prostaglandins, and combinations thereof have been used for vascular testing during the erect state.

[edit] Penile brachial index.

The systolic pressure of all arteries should be theoretically the same. Thus if there is no arterial blockage, the systolic pressure in the arm (brachial pressure) should be similar to the systolic pressure in the penis. The penile pressure may be measured by placing a small cuff around the base of the penis and inflating it until the arterial pulse, as determined by Doppler ultrasound, disappears. The penile brachial index (PBI) is the ratio of penile systolic pressure to brachial systolic pressure. Normal PBI values should be greater than 0.85.

[edit] Duplex ultrasonography.

Duplex ultrasonography is a noninvasive method for evaluating the arterial system's ability to deliver blood to the erectile chambers during an erection. Medications injected intracavernosally during arterial testing can cause smooth muscle relaxation with subsequent increases in arterial blood flow. Ultrasound can detect changes in both the cavernosal arterial diameter and blood velocity. When these findings are normal, arterial insufficiency can be ruled out to the level of the vessels tested. One limitation to vascular testing is the adrenergic inhibition of smooth muscle relaxation, which can override intracavernosal vasoactive medications. Excessive adrenergic tone can be induced by the anxiety of an office visit, a needle injected into the penis, or embarrassment over speaking about issues associated with erectile dysfunction. If the patient can achieve an erection that closely approximates his best erections at home, however, he can be presumed to have achieved complete smooth muscle relaxation. Many times, excessive adrenergic tone can be reversed with re-dosing of intracavernosal medications. Most investigators believe that cavernosal arterial velocities greater than 30 cm/sec are within the normal range.

[edit] Corporal venoocclusive function testing.

The ultimate test for evaluating erectile hemodynamics is the dynamic infusion cavernosometry and cavernosography test (DICC).^[4] Both cavernosal arterial insufficiency (CAI) and venoocclusive dysfunction (CVOD) are tested by this procedure using the intracavernosal injection of smooth muscle relaxants. DICC consists of two needles being placed into the cavernosal bodies of the penis. One needle is attached to a pressure transducer, which measures intracavernosal pressure, and the second is attached to an infusion pump for heparinized saline infusion.

During this procedure, it is possible to test the integrity of the cavernosal arteries by determining a PBI. Discrepancies in the PBI with a normal trapping mechanism suggest sluggish blood flow to the penis, which may be secondary to a blockage in the cavernosal/common penile arterial bed. In younger individuals with erectile dysfunction, the DICC procedure is needed as a screening device before evaluating an anatomic blockage by an arteriogram.

In addition, the DICC evaluates the venoocclusive function by determining the amount of flow required to maintain a given intracavernosal pressure. Normally in this study, only 2 to 3 ml/min of flow is required to maintain a rigid erection at 120 to 150 mm Hg. Leakage can be visualized by injecting contrast via one of the needles during this active test. In a normal penis with normal trapping, minimal to no contrast should be seen escaping from the corpora. In CVOD, there often can be an adequate arterial blood flow into the penis, but the trapping mechanism does not allow the blood to remain in the erectile cylinders long enough to maintain an erection.

[edit] Selective pudendal arteriogram.

In younger patients who demonstrate focal proximal arterial obstruction but no evidence of venous leak, penile revascularization may be considered. The patient's arterial system must be evaluated before a penile revascularization procedure can be performed. Since this is an invasive and expensive test, it is almost exclusively used for patients considering microsurgical penile revascularization procedures.

[edit] Classification of Erectile Dysfunction

[edit] Failure to Initiate.

Decreased libido may result from endocrine or psychologic disorders. Hypogonadism with low testosterone levels may cause a decrease in libido. However, men with low to normal testosterone levels are not generally treated with testosterone replacement. Patients may have a psychologic loss of libido, which is a response to their erectile problems; that is, they would be interested in increasing their sexual activity if their erections were not unreliable. Some psychologic element with or without an organic etiology can play a role in erectile dysfunction in up to 90% of cases. Orgasmic and ejaculatory disorders also can have a psychologic etiology, but any neurologic process that interferes with the somatic or sympathetic neural innervation to the pelvic structures can also contribute to these problems.

[edit] Failure to Fill.

The integrity of both the arterial and the venoocclusive systems must be intact for successful potency. Most often, arteriogenic insufficiency can be a direct result of a traumatic event or atherosclerotic disease. A proper history may provide a clue for diagnosing a failure to fill. A young man who achieves an erection, but very slowly, and who has a history of trauma would most typically have an arterial blockage causing arterial insufficiency. On the other hand, an older patient with several risk factors for vascular disease who indicates a prolonged time to obtain an erection may have diffuse arterial blockage associated with diffuse atherosclerotic disease. Some patients may have an element of both arteriogenic and venoocclusive dysfunction, which cannot be determined by history alone. Often, diagnostic testing can help differentiate etiologies.

[edit] Failure to Store.

Venous leakage can result from many etiologies (i.e., trauma, diabetes, Peyronie's disease, corporeal fibrosis, penile ischemia). The patient history may also provide a clue about the diagnosis of failure to store (venoocclusive dysfunction). For example, a man who achieves a rigid erection rapidly but loses it quickly would most typically have a venoocclusive problem. Again, diagnostic testing helps differentiate etiologies.

[edit] Failure to Achieve Rigidity or Penetration.

Failure to achieve rigidity or penetration is commonly associated with disorders affecting penile geometry and the ability to attain rigidity. Congenital penile curvature and Peyronie's disease are two such disorders. These disorders can be identified by asking the patient if there is pain with erection, penile curvature, penile lumps or plaques, or a history of penile trauma. Peyronie's disease is thought to be secondary to penile trauma (either chronic or acute) with resultant scarring of the tunica albuginea. This condition causes not only penile curvature but also in many cases an inability to achieve complete venoocclusion. In these cases, loss of rigidity and sustaining capability are noted. Documentation by a photograph of the penis in the erectile state is often clinical proof of the extent to which a deformity can be associated with erectile dysfunction.

[edit] Treatment

Many forms of treatment now exist for the patient with erectile dysfunction (Box 154A-1). Some treatments are directed solely at the underlying etiology of erectile dysfunction, whereas others are more directly focused on the patient's goals.^[5]

[edit] Psychologic Therapy.

Traditionally, most cases of erectile dysfunction were considered to be caused primarily by psychologic causes. Previously the main form of therapy, psychotherapy is now focused on correcting the immediate causes of the problem: (1) decreasing performance anxiety, (2) providing alternative methods of giving pleasure, and (3) dealing with the secondary problems that the erectile dysfunction has created. Although the etiology is psychologic in origin for some patients, oral erectogenic agents or penile injections can be used as an adjunct to help them overcome otherwise untreatable performance anxiety.

[edit] Hormonal Therapy

[edit] Testosterone.

Serum testosterone levels usually decrease as a man ages. Only men with hypogonadal disorders are candidates for testosterone replacement. A hypogonadal disorder is either hypogonadotropic hypogonadism (pituitary or hypothalamic in origin) or hypergonadotropic hypogonadism (testicular failure). Testosterone replacement can restore libido and improve potency. Treatment should be given only to patients with multiple low serum levels of testosterone levels in the morning. Unfortunately, oral testosterone replacement has side effects of hepatotoxicity. The recommended therapy is via an intramuscular injection of 200 to 300 mg of testosterone enanthate every 2 to 3 weeks. One serious problem with testosterone replacement is its potential to induce growth of a prostate carcinoma. Given the increasing incidence of prostate cancer, all men should be screened with a rectal examination and PSA testing before beginning treatment. If either value is abnormal, a transrectal ultrasound-guided biopsy should be performed.

[edit] Prolactin.

Hyperprolactinemia is usually treated by the administration of bromocriptine or by surgical ablation of a pituitary prolactin-secreting tumor. Medications causing hyperprolactinemia, including estrogens and methyldopa, should be stopped. High levels of prolactin seem to inhibit erections, since simply replacing testosterone in patients with continued hyperprolactinemia does not always restore potency.

[edit] Nonhormonal Medical Therapies.

Nonhormonal medical therapies are now the most frequently used form of first-line therapy for patients suffering from erectile dysfunction. In the past, oral agents such as yohimbine hydrochloride were prescribed with limited efficacy. Yohimbine, a centrally acting α₂-adrenergic blocking agent, showed improvement over placebo in controlled studies with patients with psychogenic erectile dysfunction. For the majority of patients, however, it did not represent an effective solution to the problem.

Newer forms of nonhormonal medical therapy with different methods of delivery and pharmacologic action have been approved by the FDA. An intraurethral suppository of alprostadil (Medicated Urethral System for Erection [MUSE]) and direct intracavernosal injection agents (prostaglandin E₁ [PGE₁] [Caverject, Edex]) have clinical efficacy of between 70% and 90%. Penile pain associated with the use of a needle for injection and exposure to prostaglandins are among some of the side effects experienced with these medications (see Intracavernosal Injection).

Recently, clinical trials with multiple oral agents with specific action on erectile activity (i.e., phentolamine, apomorphine, and phosphodiesterase type 5 inhibitors) have shown promise. Phentolamine, a competitive α-adrenergic antagonist, causes smooth muscle relaxation and increases arterial blood flow into the penis. Apomorphine, a central dopamine receptor agonist, has also shown improvement in erectile function in patients. Both agents are undergoing clinical trials but have not been approved for clinical application by the FDA in the United States.

To date, the only U.S. FDA-approved oral medication for the treatment of erectile dysfunction is sildenafil citrate, a selective phosphodiesterase type 5 inhibitor. Sildenafil citrate (Viagra), has been extensively studied in clinical trials with overall clinical efficacy in the range of 60% to 80%.^[6] Sildenafil's mechanism of action is by blocking the breakdown of cyclic guanosine triphosphate to guanosine monophosphate, thereby allowing calcium to be removed from the smooth muscle cells, resulting in smooth muscle relaxation. As previously discussed, smooth muscle relaxation is very important for increasing blood flow into the penis.

Sildenafil comes in blue tablets: 25, 50, and 100 mg. Usually, 50 mg is first prescribed, and if the results are not positive, 100 mg will be tried. The drug is taken 30 to 60 minutes before expected coitus. One must be sexually stimulated for the drug to work. Patients with significant renal or hepatic disease should begin with 25 mg. Some side effects are headaches, nausea, altered vision, and nasal congestion. Oral sildenafil is contraindicated with use of nitrates because of profound lowering of blood pressure when the two drugs are combined.

The side effects just mentioned increase with increasing dosages. In the studies performed for Food and Drug Administration (FDA) approval, only 2% to 3% of patients stopped taking sildenafil because of side effects. In addition, dosages over 100 mg do not improve erectile responses.

There were 130 sudden deaths in Viagra users by November 1998. A small percentage were in patients taking nitrates. At the moment, there is no known direct effect on the heart by Viagra that can explain the rest of the sudden deaths reported. It is recommended that an exercise tolerance test be performed in patients with heart disease or on multidrug antihypertensive therapy.

[edit] Vacuum Constriction Devices.

For many years, a variety of external penile appliances have been used for the management of erectile dysfunction. Although many different devices are now manufactured, the majority have three components, including a vacuum chamber, a vacuum pump that creates negative pressure within the chamber, and a constriction ring or tension band that is applied to the base of the penis after erection is achieved. The constriction ring provides an artificial means of venous outflow obstruction.

A vacuum-induced erection is significantly different than a physiologically induced erection. A physiologically induced erection causes rigidity along the entire length of the corpora, in contradistinction to a vacuum-induced erection, which only causes rigidity distal to the constricting band, allowing for the penis to pivot at its base. Because the constriction ring limits arterial inflow as well as venous outflow, the erect state is also an ischemic one. In most cases, manufacturers recommend that the vacuum-induced erection be maintained for less than 30 minutes.

Vacuum constriction devices (VCDs) can be considered for any patient with erectile dysfunction except those whose penis has significant intracorporal scarring and thus cannot fill with blood to achieve rigidity. VCDs are specifically used in patients with severe venous leak who are unresponsive or poorly responsive to intracavernosal injections and do not wish to consider penile prosthesis surgery. The advantages of the VCDs include a relatively low cost, noninvasiveness, and few long-term complications. Patients may experience the inability to achieve adequate rigidity, difficulty with ejaculation (secondary to the constricting ring around the urethra), or penile pain, petechiae, and ecchymoses. To date, these complications have been minor and self-limited. Patients taking aspirin or warfarin (Coumadin) are more likely to develop vascular complications. Many of the devices manufactured have a valve that limits the vacuum pressure (<250 mm Hg), which might aid in decreasing the complication rate.

Patient acceptance and satisfaction with VCDs have been reported to range from 68% to 83%, but this form of treatment has lost considerable favor in the past several years secondary to other available forms of therapy. Other reasons for discontinuing VCD use have included premature loss of penile tumescence and rigidity, penile pain, pain during ejaculation, and inconvenience.

[edit] Intracavernosal Injection of Vasoactive Agents and Penile-erection Program.

Intracavernosal injection of vasoactive agents causing pharmacologic erections has been one of the largest advances in the field of the diagnosis and treatment of erectile dysfunction. By causing localized smooth muscle relaxation, blood flow increases into the penis. Approximately 80% of patients respond to intracavernosal pharmacotherapy. Patients responding are usually those with an arteriogenic, psychologic, endocrinologic, or neurologic etiology, but not those with a pathologic condition causing a venous leak. Although patients with venous leakage may be able to overcome their leakage with increased arterial blood flow, the majority of patients with significant leakage will not respond to such therapy.

[edit] Medications.

Numerous medications have been tried as intracavernosal injection agents for the treatment of erectile dysfunction.^[7] The main medications used for intracavernosal injection include papaverine, phentolamine, and prostaglandin E₁ (PGE₁), and phentolamine. Each of these agents can be used individually or in combination.

Papaverine acts by relaxing the smooth muscle cells of the lacunar trabeculae and the penile arteries (primarily the helicine arteries). Thus more blood is brought into the penis via the arteries. As long as the venoocclusive mechanism is intact, an increase in blood flow will potentiate an erection. Although rare, side effects include hypotension, nausea, vomiting, flushing, dizziness, weakness, and sinus tachycardia. Rare elevations in liver transaminase levels have also been reported.

PGE₁ is an endogenously produced eicosanoid. It also causes smooth muscle relaxation. Side effects are all local (probably because the drug is metabolized in the penis) and include penile discomfort and pain, redness, and a burning sensation of the penile skin.

Phentolamine is an α-adrenergic antagonist and blocks sympathetic vasoconstrictive activity by blocking both α₁- and α₂-adrenergic receptors. Because it does not directly create smooth muscle relaxation, phentolamine does not work by itself to produce an erection. Rather, it is used as an adjunct to papaverine and PGE₁. Phentolamine's side effects include hypotension, tachycardia, cardiac arrhythmias, weakness, dizziness, nasal stuffiness, nausea, and vomiting.

[edit] Penile-erection Program.

Before being enrolled in a penile erection (injection) program, all patients must sign an informed consent. An explanation of the procedure, including all potential side effects, should be thoroughly understood by the patient. Although many of the medications are approved by the U.S. FDA for other medical uses, patients must understand that most medications have not been approved by the FDA for penile injection therapy. The only FDA-approved intracavernosal injection agents include Caverject and Edex (both PGE₁ medications). These medications should usually be offered as first-line intracavernosal injection agents.

The program consists of two phases. The titration phase includes injections given in the office. This phase determines how much medication the patient needs and teaches him to perform the injection. The home-trial phase includes prefilled syringes given to the patient for injections administered to himself in the privacy of his home. Once a proper dosage has been achieved, the patient is given a supply of the medication for each time he desires an erection.

Side effects of intracavernosal injections include hematomas, penile pain with injection, infection, penile fibrosis, and penile curvature. One major side effect is the potential to develop priapism. Priapism is a prolonged erection lasting longer than 4 hours. If not treated promptly, priapism may lead to severe scarring of the corpora cavernosa. This scarring is a direct result of penile ischemia and may result in a worsened erectile dysfunction that is unresponsive to future intracavernosal injections. The development of priapism almost always occurs during the dosage-determination phase, and patients should be instructed to call their physician if an erection after injection lasts for more than 4 hours. Patients with priapism are usually treated with an intracavernosal injection of an α-agonist to produce detumescence. Phenylephrine or ephedrine is the agent of choice for reversing the process. One side effect, painless fibrotic nodules within the corpora cavernosa, can develop secondary to the trauma of injection or inadequate manual compression of the injection site. Nodules usually develop after prolonged use and rarely require cessation of therapy. On rare occasions, these nodules may lead to penile curvature (Peyronie's disease).

Patient satisfaction rates with injection therapy are relatively high, and side effects are relatively few. For these reasons, intracavernosal injection of vasoactive drugs is one of the most frequently used and successful modalities available for the treatment of erectile dysfunction.

[edit] Penile Prosthesis.

The penile prosthesis is an artificial device that is implanted within the corpora cavernosa and that can provide sufficient rigidity for penetration during intercourse. Ideally, a prosthesis should mimic a normal penis, being erect only when desired; be comfortable; be infection and pain free; and have no mechanical failures.

The original prostheses were semirigid. This meant that although the length of the penis was always the same, the angle of penile protrusion could be altered by bending it. Subsequently, many variations in design have been developed, with current models being of the inflatable type (Fig. 154A-2). The inflatable penile prosthesis consists of two cylinders that are placed in the patient's corpora cavernosa. Each cylinder is connected to a pump, which is placed in the scrotum. The pump is connected to a reservoir, usually placed in the prevesical space. When the pump is compressed, it takes the fluid from the reservoir and pushes it into the cylinders. The cylinders fill and become rigid, making the penis around it larger and rigid. When the erection is no longer desired, the pump can be deactivated and cylinders deflated. For patients with severe erectile tissue leakage, this option may be the only viable one.

Figure 154A-2 After placement of an inflatable penile prosthesis, the two cylinders are within the corpora, the pump is in the scrotum, and the reservoir is in Retzius space just posterior to the pubic bone. This can all be accomplished through a scrotal incision. (From Krane RJ, Siroky MB, Fitzpatrick JM, editors: Clinical urology, Philadelphia, 1994, JB Lippincott.)

Certain disadvantages of the prosthesis insertion are clear. Insertion requires a surgical procedure. A definite mechanical failure rate exists depending on the device implanted, which over time probably approaches 30%. With the invention and introduction of devices with less compliant materials and fewer connections, this rate has fallen. Prosthesis infection rates range from 1% to 8%. In these patients the prosthesis is almost always removed. The infection usually causes severe corporitis, leading to fibrotic changes in the corpora and making subsequent prosthesis placement, although definitely possible, more difficult. Once a prosthesis is placed, the patient's corporal tissue is no longer intact, and thus the patient may not reverse the procedure and subsequently obtain normal erections. For patients with no other viable options, the prosthesis remains an excellent way to regain potency. Given all the newer treatment alternatives available, the percentage of patients requesting penile prosthesis insertion is diminishing.

[edit] Vascular Surgery.

Vascular surgery may be divided into arterial and venous techniques. Unfortunately, venous surgery does not appear to be effective in stopping venous leakage in most patients. The leak is usually secondary to a diffuse process with multiple collaterals, and simply ligating the leak does not usually correct the problem.

[edit] Arterial Surgery.

Candidates for penile revascularization include those with localized blockages in the pudendal-penile arterial tree. The ideal candidate is a younger man with a history of pelvic or perineal trauma and isolated lesions of the pudendal artery, the common penile artery, or both arteries. These patients have the greatest chance of success after reestablishing blood flow by revascularization. Erectile dysfunction may occur immediately after trauma, or it may be delayed. Complaints that are delayed are most likely secondary to damage to the vascular endothelium and subsequent atherosclerotic changes over time in the regions of injury. The inferior epigastric artery is the usual neoarterial source for penile revascularization procedures (Figs. 154A-3 and 154A-4). The arterial blockage is bypassed by anastomosing this artery to the dorsal artery of the penis. Patient selection and significant surgical experience are prerequisites for performing this technique.

Figure 154A-3 Schematic representation of a penile revascularization procedure. In the inset, note that two incisions are required. Initially, the inferior epigastric artery is harvested through a vertical abdominal incision. This neoarterial source is then brought through an incision at the base of the penis. The inferior epigastric artery can then be anastomosed in a retrograde end-to-end fashion to the dorsal arteries of the penis. (From Krane RJ, Siroky MB, Fitzpatrick JM, editors: Clinical urology, Philadelphia, 1994, JB Lippincott.)

Figure 154A-4 A, The harvested donor vessel, the inferior epigastric artery, is used for a neoarterial blood supply for penile revascularization procedures. B, Penile revascularization procedure using the inferior epigastric artery (IEA) supplying blood to the dorsal penile artery (DPA). Note the branch off the dorsal penile artery, which travels through the tunica albuginea, supplying new blood to erectile bodies.

The preoperative patient evaluation is complex and includes DICC to ensure that venous leakage is not a component and to confirm that a gradient does exist between the brachial systolic pressure and the cavernosal artery pressure. Patients also must have a selective internal pudendal arteriogram to outline their arterial anatomy. The recipient dorsal penile artery must demonstrate evidence of branching collaterals to the cavernosal tissue on preoperative arteriogram to maximize postoperative outcomes. Appropriately selected patients have a 50% to 70% success rate with these techniques and thus may have their potency fully restored.

[edit] Venous Surgery.

Venous surgery involves the surgical removal or ligation of the veins leaving the corpora cavernosa. This is usually accomplished by removing the deep dorsal vein and ligating the cavernosal veins with or without plication of the penile crura. Intuitively, venous leak should be correctable. Although in vogue for a long time, venous leak surgery has had a poor success rate, and the authors no longer routinely perform this procedure.

[edit] SUMMARY

Over the past few decades, the knowledge and understanding of the anatomy and physiology of the penis, as well as the pathophysiology of erectile dysfunction, have evolved. Technologic advances in the areas of biochemical research have led medical personnel into a new era in the development of less invasive and more efficacious treatment modalities. Many diagnostic tests have been developed to identify the etiology of erectile dysfunction and thus target appropriate treatment. These advances, as well as the heightened awareness of erectile dysfunction issues by both physicians and patients, help prevent the adverse social and behavioral changes afflicting men and their partners.

[edit] REFERENCES