AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Background

Sexual health and function are important determinants of quality of life. Disorders such as erectile dysfunction (ED) and female sexual dysfunction are becoming increasingly more important as a result of the aging US population and newer therapies. Because this subject is discussed widely in the media, men and women of all ages are seeking guidance in an effort to improve their relationships and experience satisfying sexual lives.

This review article discusses the physiology of the normal erection and the pathophysiology, etiology, and treatment of ED. For additional resources, visit Erectile Dysfunction.

Successful treatment of sexual dysfunction has been demonstrated to improve sexual intimacy and satisfaction, improve sexual aspects of quality of life, improve overall quality of life, and relieve symptoms of depression.

Although this article focuses primarily on ED in males, one must remember that the sexual partner plays an integral role. If successful and effective management is to be achieved, the evaluation and discussion of any intervention should include both partners.

The Process of Care Model for the Evaluation and Treatment of Erectile Dysfunction has been developed to advance new guidelines for the diagnosis and management of ED in the primary care and multidisciplinary setting. The model was developed under the auspices of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. The chairman of the group of experts who prepared the guidelines was Raymond Rosen, MD.

The key components of this model are (1) a rational approach to diagnosis and treatment, (2) emphasis on clinical history taking and a focused examination, (3) specialized testing and referral in predefined situations, (4) a step-wise management approach with ranking of treatment options, and (5) incorporation of patient and partner needs and preferences in the decision-making process.

An alternative model is the patient goal-oriented approach as suggested by Tom Lue, MD, in which a minimum of testing is performed. The patient and his partner express a preference for reasonable and appropriate treatment options and work with the physician to implement this plan.

The availability of three phosphodiesterase-5 (PDE-5) inhibitors, ie, sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), has permanently altered the medical management of ED. Many patients no longer expect or are willing to undergo a long evaluation and testing process to obtain a better understanding of their sexual problem, and they are less likely to involve their partner in a discussion of their sexual relationship with the physician.

Because of intense mass-media marketing efforts, the sexual expectations of men have risen to new highs and the attitude that something is wrong with a man if he does not achieve a perfect erection is prevalent. Men who have no difficulty obtaining erections are taking these PDE-5 inhibitor medications in the belief that their sexual performance will be enhanced and the opportunity for multiple orgasms will increase. Their medications are often obtained by a phone call to their doctor or even over the Internet with minimal or no physician contact at all. The misuse and overuse of these remarkable medications are likely to have a major impact on how sexual performance and sexual relationships are viewed.

Physiology of normal erections

Penile erections involve an integration of complex physiologic processes involving the CNS, peripheral nervous system, and hormonal and vascular systems. Any abnormality involving these systems, whether from medication or disease, has a significant impact on the ability to develop and sustain an erection, ejaculate, and experience orgasm. Tumescence, the vascular filling of the cavernous bodies, relies on neural and hormonal mechanisms operating at various levels of the neural axis. This is unique among visceral functions because it requires central neurological input.

Andersson summarized some of the information related to the pathways involved in erectile function.¹ The degree of contraction of corpus cavernosal smooth muscle determines the functional state of the penis. The balance between contraction and relaxation is controlled by central and peripheral factors that involve many transmitters and transmitter systems. At the cellular level, smooth muscle relaxation occurs following the release of acetylcholine from the parasympathetic nerves.

The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction.

The nitric oxide (NO) pathway is of critical importance in the physiologic induction of erections. The drugs currently used to treat erectile dysfunction were developed as a result of experimental and clinical work that demonstrated that NO released from nerve endings relaxes the vascular and corporal smooth muscle cells of the penile arteries and trabeculae, resulting in an erection.

NO is produced by the enzyme nitric oxide synthase (NOS). Three forms have been identified: nNOS, eNOS, and iNOS, which are produced by the genes NOS1 (nNOS), NOS2 (iNOS), and NOS3 (eNOS). This nomenclature is derived from the source of the original isolates. nNOS was found in neuronal tissue, iNOS was found in immunoactivated macrophage cell lines, and eNOS was found in vascular endothelium. All forms of NOS produce NO, but various factors trigger and regulate this process. NOS plays many roles, ranging from homeostasis to immune system regulation. These subtypes are not limited to the tissues from which they were first isolated. Each NOS subtype may play a different biological role in various tissues.

nNOS and eNOS are considered constitutive forms because they share biochemical features. They are calcium-dependent, they require calmodulin and reduced nicotinamide adenine dinucleotide phosphate for catalytic activity, and they are competitively inhibited by arginine derivatives. These 2 subtypes use the biochemical pathway that targets cyclic guanosine monophosphate (cGMP). They are involved in the regulation of neurotransmission and blood flow, respectively.

iNOS is considered inducible because it is calcium-independent. iNOS is induced by the inflammatory process, in which it is involved in the production nitrogenous amines. This subtype has been shown to be involved in the carcinogenic process, leading to transitional cell carcinoma.

All 3 NOS subtypes produce NO by oxidation of L-arginine, which is one of the basic amino acids. It circulates in the blood and is found in cells synthesized from the urea cycle or from oral ingestion. The concentration of L-arginine within the cell far exceeds that in the circulation. Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified.

The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells.

Potential ways to alter NO levels include the following:

• Directly administering NO as a gas
• Administering NO donors such as nitrates, nitrites, and inorganic nitroso compounds
• Administering of NO agonists such as ACE, which enhances the production of NO within endothelial cells
• Preserving cGMP: Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of sildenafil, vardenafil, and tadalafil.
• Lowering endogenous inhibitors: Some analogs of L-arginine act as competitive and sometimes irreversible inhibitors of NOS. Some of these are present in the plasma and urine.
• Administering exogenous NOS activators: One example is methylene blue.
• Increasing the substrate for NO synthesis: Oral supplementation of NO has generated interest. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED.² These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.

Increasing evidence indicates that NO acts centrally to modulate sexual behavior and to exert its effects on the penis. NO is thought to act in the medial preoptic area and the paraventricular nucleus. Injection of nitric acid synthase inhibitors prevents the erectile response in rats that have been given erectogenic agents.

Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and other factors not yet identified. Factors that mediate relaxation include acetylcholine, NO, vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.

Sexual behavior involves the participation of autonomic and somatic nerves and the integration of numerous spinal and supraspinal sites in the CNS. The penile portion of the process that leads to erections represents only a single component. The ability to achieve and maintain a full erection also depends on the status of the peripheral nerves, integrity of the vascular supply, and biochemical events within the corpora.

Erections occur in response to tactile, olfactory, and visual stimuli. The hypothalamic and limbic pathways play an important role in the integration and control of reproductive and sexual functions. The medial preoptic center, paraventricular nucleus, and anterior hypothalamic regions modulate erections and coordinate autonomic events associated with sexual responses. Afferent information is assessed in the forebrain and relayed to the hypothalamus. The efferent pathways from the hypothalamus enter the medial forebrain bundle and project caudally near the lateral part of the substantia nigra into the midbrain tegmental region.

Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.

The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation.

Sexual stimulation causes the release of neurotransmitters from the cavernosal nerve endings and relaxation factors from the endothelial cells that line the sinusoids. NOS produces NO from arginine. This, in turn, produces other muscle-relaxing chemicals such as cGMP and cyclic adenosine monophosphate, which work via calcium channel and protein kinase mechanisms. This results in the relaxation of smooth muscle in the arteries and arterioles that supply the erectile tissue, producing a dramatic increase in penile blood flow. Relaxation of the sinusoidal smooth muscle increases its compliance, facilitating rapid filling and expansion (40-52% of the corpora cavernosa tissue is composed of smooth muscle cells). The venules beneath the rigid tunica albuginea are compressed, resulting in near-total occlusion of venous outflow. These events produce an erection with an intracavernosal pressure of 100 mm Hg.

Additional sexual stimulation initiates the bulbocavernous reflex. The ischiocavernous muscles forcefully compress the base of the blood-filled corpora cavernosa, and the penis reaches full erection and hardness when intracavernous pressure reaches 200 mm Hg or more. At this pressure, both the inflow and outflow of blood temporarily cease.

Detumescence results from the cessation of neurotransmitter release, the breakdown of second messengers by phosphodiesterases, and sympathetic nerve excitation during ejaculation. Contraction of the trabecular smooth muscle reopens the venous channels, allowing the blood to be expelled, which results in flaccidity.

Pathophysiology of erectile dysfunction

ED is essentially a vascular disease. It is often associated with other vascular diseases and conditions such as diabetes, hypertension, and coronary artery disease. Other conditions associated with ED include neurologic disorders, endocrinopathies, benign prostatic hyperplasia, and depression. Conditions associated with reduced nerve and endothelium function, such as aging, hypertension, smoking, hypercholesterolemia, and diabetes, alter the balance between contraction and relaxation factors. These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation. In some patients, sexual dysfunction may be the presenting symptom of these disorders.

Additionally, ED is often an adverse effect of many commonly prescribed medications. Some psychotropic drugs and antihypertensive agents are associated with ED.

Trauma that affects the neurologic or vascular components can also lead to ED. Men with severe Peyronie disease, an inflammatory vasculitis, may have enough scar tissue in the corpora to impede blood flow. Men with sleep disorders commonly experience ED.

Another important consideration is the hormonal status of the patient. Hypogonadism that results in low testosterone levels adversely affects libido and erectile function. Hypothyroidism is a very rare cause of ED.

Most patients with ED have multiple etiological factors; thus, assessing how much each is contributing to the problem is difficult. Because most men with ED have an organic cause, a thorough evaluation is necessary to correctly identify the specific etiology in any given individual.

Frequency

United States

Sexual dysfunction is highly prevalent in men and women. In the Massachusetts Male Aging Study (MMAS), a community-based survey of men aged 40-70 years, 52% of the respondents reported some degree of erectile difficulty. Complete ED, defined as (1) the total inability to obtain or maintain an erection during sexual stimulation and (2) the absence of nocturnal erections, occurred in 10% of the respondents. Lesser degrees of mild and moderate ED occurred in 17% and 25% of responders, respectively.

In the National Health and Social Life Survey, a nationally representative probability sample of men and women aged 18-59 years, 10.4% of men reported being unable to achieve or maintain an erection during the past year. This has a striking correlation to the proportion of men in the MMAS who reported complete ED.

Both studies noted a strong correlation with age. Although the rate of mild ED in the MMAS remained constant (17%) in men aged 40-70 years, the number of men reporting moderate ED doubled (17-34%) and the number of men reporting complete ED tripled (5-15%). Extrapolating the MMAS data to the American population, an estimated 18-30 million men are affected by ED.

Other male sexual dysfunctions, such as premature ejaculation and hypoactive sexual desire, are also highly prevalent. The National Health and Social Life Survey found that 28.5% of men aged 18-59 years reported premature ejaculation and 15.8% lacked sexual interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% had a lack of pleasure in sex.

Long-term predictions based on an aging population and an increase in risk factors (eg, hypertension, diabetes, vascular disease, pelvic and prostate surgery, benign prostatic hyperplasia, lower urinary tract symptoms) suggest a large increase in the number of men with ED. Also, the prevalence of ED is underestimated because physicians frequently do not question their patients about this disorder.

International

Studies conducted around the world report similar risk factors and similar prevalence rates for ED.

Age

All studies demonstrate a strong association with age, even when data are adjusted for the confounding effects of other risk factors. The independent association with aging suggests that vascular changes in the arteries and sinusoids of the corpora cavernosae, similar to those found elsewhere in the body, are contributing factors. Other risk factors associated with aging include depression, sleep apnea, and low levels of high-density lipoproteins.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

History

Taking the patient's history is informative to the physician and is an opportunity to educate the patient. Adequate time must be set aside for a full interview and to conduct a physical examination. Even clinicians who are not comfortable dealing with ED should inquire into this important aspect of the patient's health. A simple way to do this is simply ask, "How's your sex life? Everything working all right?" This type of inquiry should elicit a clear, quick, direct "Everything's fine" from the patient. Any other response or even just a delay in answering should suggest potential ED in that patient.

• The first step in the management of erectile dysfunction (ED) is taking a thorough sexual, medical, and psychosocial history. This is a sensitive topic, and the clinician must be sensitive to the patient's comfort level. Taking the history provides an opportunity for the physician to initiate patient and partner education about ED and its treatments and to facilitate communication. It also allows the physician to establish a rapport with the couple, which assists in treatment.
• A clear description of the problem entails determining if the patient has 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 sexual satisfaction.
• Rapid (premature) ejaculation generally occurs in men younger than 40 years. This situation can cause a great deal of stress on the couple's relationship. A history of premature ejaculation can be obtained from many men who present in later years with erectile difficulty. Effective treatments, including SSRI medications and sex therapy, are available to remedy this condition. (See Premature Ejaculation.)
• Obtain information about current medications, prior surgeries, and other disorders, and begin forming an objective opinion regarding the interpersonal relationship between the partners. In addition to general medical information, any history of pelvic surgery, trauma, prior prostate surgery, or radiation to the prostate should be elicited.
• A detailed list of all medications taken during the past year, including all vitamins and other dietary supplements, should be obtained. Patients often neglect to list dietary supplements they may have tried to improve their sexual function.
• • One of the commonly used medications in the treatment of men with benign prostatic hyperplasia is one of the 5-alpha reductase inhibitors, finasteride (Proscar) or dutasteride (Avodart).
  • The Proscar Long-Term Efficacy and Safety Study was a 4-year randomized, placebo-controlled trial in 3040 male subjects aged 45-78 years. At screening, 46% of the subjects reported some history of sexual dysfunction. During the first year of the study, 15% of subjects treated with finasteride and 7% of control subjects had evidence of sexual dysfunction that was thought to be related to the drug.
  • During the second-through-fourth years of the trial, no difference was reported between these 2 groups. No difference was noted between subjects who reported prior sexual problems and those who had not.
  • Sexual dysfunction occurred in 12% of subjects taking finasteride and in 19% of control subjects. In the 4% of the subjects who discontinued the study because of this adverse effect, 50% experienced resolution of the problem. Only 2% of control subjects discontinued the study because of the adverse effect, and 41% of these men had resolution of the problem.
• Tobacco use, alcohol intake, caffeine intake, and illicit drug use should be documented.
• Explore stress factors and tension at work and at home. Assess the patient's psychological state; in particular, look for indications of depression, loss of libido, problems and tension in the sexual relationship, insomnia, lethargy, moodiness, and stress from work or other sources.
• The patient needs to explain his interpretation of the problem. Elicit information by asking the following types of questions:
• • How long has a problem existed? Did a specific event such as a major surgery or a divorce occur at the same time? Have you experienced the death of a spouse or family member?
  • Do you have diminished sexual desire? How long have you noticed this? Is your diminished sexual desire a primary symptom or a reaction to poor performance? Do you have any feelings of performance anxiety?
  • Is adequate foreplay occurring? Are you ever able to obtain an erection suitable for penetration, even momentarily? Is maintaining the erection a problem? Is your sexual partner satisfied with the sexual experience?
  • Are you able to achieve orgasm and ejaculation?
  • Do you experience nocturnal or morning erections? Does pain or discomfort occur with ejaculation? Do you have rapid (premature) ejaculation?
  • Is penile curvature (Peyronie disease) a problem?
  • What is your preferred frequency of intercourse, assuming your erections were functional? Do you and your sexual partner agree on this issue?
  • Have you already tried any treatments? If so, what were they? Are you interested in trying a particular treatment first? Are you opposed to trying a particular type of therapy?
  • To what degree do you wish to proceed in determining the cause of his ED? How important is this to you?
• Questionnaires have been developed to gather objective data regarding impotence and to assist clinicians in the evaluation of their patients.
  • The International Index of Erectile Function (IIEF) is a sensitive, specific, and standardized tool that has been validated in several languages. This 15-question method evaluates 5 domains. These include erectile and orgasmic function, sexual desire, intercourse satisfaction, and global satisfaction. The IIEF is used to evaluate pharmacologic and other therapies for the treatment of ED.
  • A 5-question tool has been developed as a sexual health inventory for men, termed the IIEF-5. This is helpful for the clinician to screen patients for ED because many men are hesitant to discuss the problem. The IIEF-5 scores the answers on a scale of 0-5. A score of 25 is typical for a healthy man, while scores of 11 or less indicate moderate-to-severe ED. The patient is asked the following 5 questions relating to the past 6 months:
    • How do you rate your confidence that you could achieve and maintain an erection?
    • When you had erections with sexual stimulation, how often were your erections hard enough for penetration?
    • During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner?
    • During sexual intercourse, how difficult was it to maintain your erection to the completion of intercourse?
    • When you attempted sexual intercourse, how often was it satisfactory for you?
  • Following completion of the IIEF or the IIEF-5 and a discussion with the patient, the physician should have a good understanding of the nature and scope of the patient's problem.

Physical

• A physical examination is necessary for every patient, with particular emphasis on the genitourinary, vascular, and neurologic systems.
• • The physical examination may corroborate history findings and reveal unsuspected physical findings, such as penile plaques, small testes, evidence of possible prostate cancer, prostate infections, or hypertension.
  • Several studies have demonstrated a strong correlation between hypertension and ED. This is not surprising since both are manifestations of a vascular disorder. In a large hypertension clinic, men who also demonstrated ED had a much higher prevalence of complications related to high blood pressure. Another investigator has suggested that hypertensive patients with ED and poor cavernosal artery blood flow as measured during duplex ultrasonography studies should proceed to a full cardiac evaluation because of the high prevalence of associated problems.
  • A number of recent studies have shown a correlation between benign prostatic hyperplasia and ED. The causality for this relationship is not yet clear.
  • A focused physical examination entails an evaluation of the patient's blood pressure, peripheral pulses, sensation, status of the genitalia and prostate, size and texture of the testes, the presence of the epididymis and vas deferens, and abnormalities of the penis such as hypospadias and Peyronie plaques.

Causes

The etiology of ED is usually multifactorial. Organic, physiologic, endocrine, and psychogenic factors are involved in the ability to obtain and maintain erections. In general, ED is divided into organic and psychogenic impotence, but most men with organic etiologies usually have an associated psychogenic component. Almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient's psychologic mood and behavior. Pure psychogenic ED is an uncommon disorder, although most ED was once attributed to psychological factors.

Diabetes is a well-recognized risk factor, with approximately 50% of diabetic men experiencing ED. The etiology of ED in diabetic men probably involves both vascular and neurogenic mechanisms. Evidence indicates that establishing good glycemic control can minimize this risk.

Cigarette smoking has been shown to be an independent risk factor. In studies evaluating more than 6000 men, the risk of developing ED increased by a factor of 1.5

Mental health disorders, particularly depression, are likely to affect sexual performance. The MMAS data indicate an odds ratio of 1.82. Other associated factors, both cognitive and behavioral, may contribute. Also, ED alone can induce depression. The new oral agents have been shown to be effective for men who develop depression following prostatectomy.

Cosgrove et al have reported a higher rate of sexual dysfunction in veterans with posttraumatic stress syndrome than in those veterans who did not develop this problem.³ The domains on the IIEF questionnaire that demonstrated the most change included overall sexual satisfaction and erectile function. This study suggests that regardless of etiology, men with posttraumatic stress syndrome should be evaluated and treated if they have sexual dysfunction.

A sedentary lifestyle is a contributing factor to ED. Exercise has a beneficial effect on the cardiovascular system, and some data from the MMAS indicate that men who exercise regularly have a lower risk of ED. However, Goldstein et al reported an increased risk of ED in men who rode a bicycle for long periods.⁴ Therefore, the type of exercise may be important.

The MMAS study also showed an inverse correlation between ED risk and high-density lipoprotein cholesterol levels but no effect from elevated total cholesterol levels. Another study involving male subjects aged 45-54 years found a correlation with abnormal high-density lipoprotein cholesterol levels but also found a correlation with elevated total cholesterol levels. The MMAS study had a preponderance of older men.

Vascular diseases account for nearly half of all cases of ED in men older than 50 years. Vascular diseases include atherosclerosis, peripheral vascular disease, myocardial infarction, and arterial hypertension.

Vascular damage may accompany radiation therapy to the pelvis and prostate in the treatment of prostatic cancer. In this situation, both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are quite susceptible to radiation damage, can induce ED. The radiation oncologist must take precautions to avoid treating this area. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy. Fortunately, some of these men tend to respond to one of the PDE-5 inhibitors.

Prostatic surgery for benign prostatic hyperplasia has been documented to be associated with ED in 10-20% of men. This is thought to be related to nerve damage from cautery. Newer procedures such as microwave, laser, or radiofrequency ablation have rarely been associated with ED.

Radical prostatectomy for the treatment of prostate cancer poses a significant risk of ED. A number of factors are associated with the chance of preserving erectile function. If both nerves that course on the lateral edges of the prostate can be saved, the chance of maintaining erectile function is reasonable. This depends on the age of the patient. Men younger than 60 years have a 75-80% chance of preserving potency, but men older than 70 years have only a 10-15% chance. Sural nerve grafts are used by some surgeons. Following surgery, one of the PDE-5 inhibitors, such as sildenafil, vardenafil, or tadalafil, is frequently used to assist in the recovery of erectile function.

Trauma to the pelvic blood vessels and nerves is another potential etiologic factor in the development of ED. Bicycle riding for long periods has been implicated as an etiologic factor by causing vascular and nerve injury. Some of the newer bicycle seats have been designed to diminish pressure on the perineum.

Diseases associated with ED are summarized as follows:

• Vascular diseases associated with erectile dysfunction
• • Atherosclerosis
  • Peripheral vascular disease
  • Myocardial infarction
  • Arterial hypertension
  • That resulting from radiation therapy
  • That related to prostate cancer treatment
  • Blood vessel and nerve trauma (eg, due to long-distance bicycle riding)
  • Medications related to treatment of vascular disease
• Systemic diseases associated with erectile dysfunction
• • Diabetes mellitus
  • Scleroderma
  • Renal failure
  • Liver cirrhosis
  • Idiopathic hemochromatosis
  • Cancer and cancer treatment
  • Dyslipidemia
  • Hypertension
• Neurogenic diseases associated with erectile dysfunction
• • Epilepsy
  • Stroke
  • Multiple sclerosis
  • Guillain-Barré syndrome
  • Alzheimer disease
  • Trauma
• Respiratory disease associated with erectile dysfunction
• • Chronic obstructive pulmonary disease
  • Sleep apnea
• Endocrine conditions associated with erectile dysfunction
• • Hyperthyroidism
  • Hypothyroidism
  • Hypogonadism
  • Diabetes
• Penile conditions associated with erectile dysfunction
• • Peyronie disease
  • Epispadias
  • Priapism
• Psychiatric conditions associated with erectile dysfunction
• • Depression
  • Widower syndrome
  • Performance anxiety
  • Posttraumatic stress disorder
• Nutritional states associated with erectile dysfunction
  • Malnutrition
  • Zinc deficiency
• Hematologic diseases associated with erectile dysfunction
  • Sickle cell anemia
  • Leukemias
• Surgical procedures associated with erectile dysfunction
• • Procedures on the brain and spinal cord
  • Retroperitoneal or pelvic lymph node dissection
  • Aortoiliac or aortofemoral bypass
  • Abdominal perineal resection
  • Surgical removal of the prostate for cancer
  • Surgical treatment of the prostate for benign disease
  • Proctocolectomy
  • Radical prostatectomy
  • Transurethral resection of the prostate
  • Cryosurgery of the prostate
  • Cystectomy
• Medications associated with erectile dysfunction
• • Antidepressants
  • Antipsychotics
  • Antihypertensives
  • Antiulcer agents, such as cimetidine and finasteride
  • 5-Alpha reductase inhibitors
  • Cholesterol-lowering agents

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Other Problems to be Considered

Cancer and cancer treatment
Epilepsy
Stroke
Multiple sclerosis
Guillain-Barré syndrome
Alzheimer disease
Hypogonadism
Epispadias
Widower syndrome
Performance anxiety
Malnutrition
Zinc deficiency
Leukemias
Antidepressant medication
Antipsychotics
Antihypertensives
Antiulcer medications
Hyperlipidemia medications

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Lab Studies

• The laboratory investigation depends on information gathered during the interview. Laboratory testing is necessary for most patients, although some may not require any laboratory work.
• Laboratory tests include an evaluation of the patient's hormone status, particularly if the symptom is diminished or absent libido.
• Patients who express a loss of libido, depression, or any signs of diminished secondary sexual characteristics should have an endocrine evaluation that consists of at least measuring morning serum testosterone levels. The relative merits of measuring total, free, and bioavailable testosterone levels and serum hormone–binding globulin are controversial. At this time, measuring total and free testosterone levels is recommended and should be performed when screening for hypogonadism. These hormone levels are generally higher in the morning than later in the day; therefore, a morning level should be checked whenever possible. Free or bioavailable testosterone is an important component because this is the testosterone that is usable. That portion attached to other proteins, the serum hormone–binding globulins, store testosterone.
• A measurement of luteinizing hormone (LH) and, in some instances, prolactin, may be helpful. A serum prolactin level is obtained if the patient has evidence of pituitary hyperfunction, a common endocrine cause of erectile dysfunction (ED), and in documented cases of low serum testosterone levels. LH levels vary according to the body's need for testosterone. The hypothalamus regulates testosterone levels by releasing or inhibiting LH-releasing hormone, which acts in the pituitary to produce LH. A high LH level associated with a low testosterone level implies primary testicular (Leydig cell) failure. Conversely, a low LH level associated with a low testosterone level suggests a central defect.
• Evaluating the patient for diabetes with a hemoglobin A1c measurement is a useful screening test.
• Hemoglobin A1c, serum chemistry studies, lipid profiles, and prostate-specific antigen levels should be obtained unless the patient has recently had these studies performed and the results are available.
• Investigate the hypothalamic-pituitary-gonadal axis by evaluating testosterone levels (a morning serum free and total testosterone level is suggested) in most patients, especially if the patient has a history of reduced libido.
• A serum thyroid-stimulating hormone evaluation is appropriate in select patients.
• A urinalysis looking for RBCs, WBCs, protein, and glucose is also important.
• Following completion of this phase, the physician should be able to determine the medical status of the patient, to identify and characterize the type of dysfunction, and to determine the need for additional testing such as penile or pelvic blood flow studies, nocturnal penile tumescence testing, or other blood tests. The patient's needs, expectations, and priorities should be discussed in order to decide about further management or referral.
• A discussion of the results should be conducted, if possible, with the patient and his partner. This educational process allows a review of the basic aspects of the anatomy and physiology of the sexual response. The possible etiology and associated risk factors, such as smoking and the use of various medications, can be reviewed. Treatment options and their benefits and risks should be discussed. This type of dialogue allows the patient and physician to develop a strategy that is most beneficial.

Imaging Studies

• Imaging studies are rarely performed, except in situations in which pelvic trauma or surgery has occurred.
• Angiography is useful if the patient is a potential candidate for some type of vascular surgery. Young men with traumatic vascular injuries resulting in ED are candidates for this study because they may qualify for a vascular reconstruction
• Vascular function within the penis can be evaluated with duplex ultrasonography. Patients are administered an intracavernosal test dose of a standard vasodilator, such as 20 mcg of prostaglandin E1 (PGE1), and the cavernosal arteries within the corpora are measured before and after the injection. A normal response indicates a peak systolic velocity of 0.35 m/s or more and an end diastolic velocity of -0.04 m/s or less. This is interpreted as adequate arterial blood flow (good peak systolic velocity) without evidence of a venous leak (end diastolic velocity below zero).
• Ultrasonography of testes may help in disclosing abnormalities in testes and epididymides. Transrectal ultrasonography can disclose abnormalities in the prostate and pelvis that may interfere with erectile function.

Other Tests

• One of the most common tests used to evaluate penile function is the direct injection of PGE1 into the corpora. If the penile vasculature is normal or at least adequate, an erection should develop within several minutes. The patient and the clinician can judge the quality of the erection. If successful, this test also establishes penile injections as one possible therapy.
• A test that was frequently performed in the past was nocturnal penile tumescence testing. This was thought to be useful in distinguishing psychogenic from organic impotence. This test involves placing a band around the penis and instructing the patient to wear it for 2-3 successive nights. If an erection occurs, which is expected during rapid eye movement sleep, the force and duration are measured on a graph. Inadequate or absent nocturnal erections suggest an organic dysfunction, while a normal result indicates a high likelihood of a psychogenic etiology. Other devices are available to provide similar information. Some are also able to measure rigidity (resistance to mild compression) and tumescence (size). This test is rarely used in current practice, but it can be helpful in situations in which the diagnosis is in doubt.
• Formal neurological testing is not needed in the vast majority of patients with ED. Those with a history of CNS problems, peripheral neuropathy, diabetes, or penile sensory deficit would probably benefit from some level of neurological testing.
• The sensitivity of the skin of the penis to detect vibrational stimuli, ie, biothesiometry, can be used as a simple nerve function office screening test. This involves the use of a small electromagnetic test probe placed on the right and left sides of the shaft and on the glans. The vibrational amplitude is adjusted until the subjective sensory threshold is reached, which is determined by questioning the patient. A series of these tests determines the average vibrational sensory threshold in each location, which are then compared to reference range standards for the patient's age group. Although this test does not directly measure the erectile nerves, it serves as a reasonable screening for possible sensory deficit and is simple to perform. Formal nerve conduction studies, such as bulbocavernosus reflex latency time, are reserved for very select situations.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Multimedia
• References

Medical Care

After all the information regarding the patient's status has been gathered, the various options in management can be discussed. This is best completed in the presence of the patient and his partner. Enough options are available that every man who wants to be sexually active can do so. These include sexual counseling if no organic causes can be found for the dysfunction, oral medications, external vacuum devices, or some type of invasive therapy, including the use of intracavernosal injection therapy or the Medicated Urethral System for Erections (MUSE), which is an intraurethral suppository. One of the most difficult aspects is teaching men that sex entails more than simply achieving an erection.

The most common form of management in current practice is the use of one of the oral PDE-5 inhibitors. If one agent does not work adequately at its maximum dosage, another agent should be tried. Trying these medications 3-4 times is sometimes necessary before concluding that the therapy is ineffective. Men who have a vascular-leak (venous leak) phenomenon may need a constriction device placed at the base of the penis to maintain the erection, which may be effective by itself or in combination with a PDE-5 inhibitor. In selected cases, combination therapy with one of the PDE-5 inhibitors plus Yohimbine, MUSE, or intracavernosal injections can be tried. Although some men have taken two different PDE-5 inhibitors simultaneously, no evidence suggests any benefit and the risk of significant adverse effects is greatly enhanced. However, the use of both a shorter-acting agent and a longer-acting agent is not unreasonable at appropriate times and intervals as long as they are not taken together.

Possible blindness due to nonarteritic anterior ischemic optic neuropathy and cilioretinal artery occlusion caused by PDE-5 inhibitors has been a concern. This is an extremely rare event, with only a handful of reported cases from the tens of millions of patients using PDE-5 inhibitor medications. This risk may be increased if the PDE-5 medication is misused or overdosed.

If none of these nonsurgical therapies is satisfactory to the patient and his partner, a discussion regarding the relative merits and adverse effects associated with penile implants can be introduced. Some data indicate an additional benefit in some men who have an implant but also take a PDE-5 inhibitor. Sexual stimulation and sensation is enhanced.

Psychogenic impotence is relatively uncommon. It is characterized objectively by the presence of good nocturnal and morning erections and negative findings from all other tests. During the interview, a history of highly variable erections that can be totally absent one day but virtually normal the next suggests a psychogenic cause. Virtually 100% of men with severe depression have erectile dysfunction (ED). Sildenafil (Viagra) works well for psychogenic ED; other treatment modalities are also effective because the tissues, nerves, hormone levels, and vasculature are normal. The authors usually recommend a full psychological evaluation in these patients so that the underlying etiology can be identified and treated appropriately rather than just treating the symptom of ED. Therefore, the authors defer treatment of the patient's ED until he has begun psychological testing and therapy for the underlying problem.

Vacuum devices

As a relatively inexpensive method for producing an erection, vacuum devices to draw blood into the penis have been used for many years. These are plastic cylinders that are placed over the penis. Air is pumped out, causing a partial vacuum. Releasing the vacuum after a few minutes and then reapplying the vacuum sometimes gives a better result. After an erection is obtained, a constricting band is placed at the base of the penis. This technique is effective in 60-90% of patients and maintains the erection for up to 30 minutes. (The erection would last until the constricting band is released, but longer than 30 min is not recommended.)

These devices are generally safe, but hematomas, petechia, and ecchymosis have been reported. Other adverse effects include pain, lower penile temperature, numbness, absent or painful ejaculation, and pulling of scrotal tissue into the cylinder, where it becomes trapped under the ring. Many of these problems can be alleviated by proper selection of the tension rings and cylinders. 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 tend to be less romantic than other therapeutic options.

One drawback to the use of these external vacuum devices is the need to assemble the equipment and the difficulty in transporting it. Many patients lose interest in using the device because of the preparations that are necessary, the lack of easy transportability, the inability to hide the tension ring, and the relative lack of spontaneity. Approximately half the men who use a vacuum device obtain very good erections, but only half of these men consistently use the device for a prolonged period.

Sildenafil (Viagra)

Sildenafil is the first oral agent to be well documented as an effective form of treatment for men experiencing ED. Since its introduction in March, 1998, no other therapy for ED has achieved such prominent public recognition. Of the 250,000 American physicians who have written prescriptions for sildenafil, 14% have been written by urologists and 82% by nonurologists.

Controlled clinical trials in selected populations of men with ED have demonstrated the efficacy of sildenafil in helping men achieve and maintain erections. The efficacy of sildenafil was demonstrated in 21 randomized, double-blind, placebo-controlled studies of up to 6 months' duration involving more than 3000 male subjects aged 20-87 years.

Sildenafil is a potent inhibitor of PDE-5, the enzyme that acts in the corpora to break down cGMP. This action is mediated by the secondary neurotransmitter NO, which is primarily responsible for smooth muscle relaxation within the corpora cavernosa. The inhibition of PDE-5 slows the degradation of NO, which enhances its effect. This permits the development of an improved and sustainable erection.

Sildenafil has been demonstrated to improve erectile function in diabetic patients, hypertensive patients, post–transurethral resection of the prostrate patients, radical prostatectomy patients following radiation therapy for prostate cancer, geriatric patients, spinal cord injury patients, and depression patients. As many as 66-90% of patients with ED secondary to brachytherapy or external beam radiation therapy for prostate cancer have significant improvements in erectile function.

The long-term efficacy of sildenafil has been shown in a 48-month, open-label, noncontrolled, flexible-dose study. One year following the initiation of therapy, efficacy and satisfaction continued to be significantly improved.

Safety concerns and adverse effects have been studied carefully. The most common adverse effects are headaches and upper GI distress. These are not usually severe and are self-limited when the drug is stopped. Sildenafil is a mild inhibitor of phosphodiesterase type 6, which is found in the retina. This inhibition is manifested by a blue haze at the periphery of the field of vision but is not dangerous. Very few patients have stopped taking sildenafil because of this effect.

The cardiac effects associated with sildenafil have been studied extensively. Sildenafil is absolutely contraindicated in patients taking nitrates such as nitroglycerin or isosorbide. This is because sildenafil, like the other PDE-5 inhibitor medications, can potentiate the vasodilatory effects of the nitrate-based medication, resulting in an exaggerated vasodilatory effect that is potentially dangerous. Patients with serious cardiac disease, with exertional angina, or taking multiple antihypertensive medications are advised to seek the advice of a cardiologist before beginning therapy with sildenafil. A number of studies examining the cardiac effects of sildenafil have conclusively shown that no adverse consequences exist under normal circumstances.

In the original clinical trials involving more than 3000 male subjects, the incidence of myocardial infarction and myocardial ischemia was not significantly different between those who took a placebo and those who took sildenafil. The same was true when postural hypotension was evaluated. Exertion associated with sexual activity has been documented to increase the chances of ischemic events and myocardial infarction. Men with ischemic heart disease who do not take sildenafil have as much as a 2-fold increase in cardiac events compared with healthy men.

Sildenafil is available in 3 doses: 25 mg, 50 mg, and 100 mg. The starting dose depends on the clinical situation. A man in his fifth decade of life with mild sexual dysfunction that is probably related to psychological factors can start on the 25-mg dose. Men with moderate-to-severe ED can begin at the 50-mg dose, and, after testing the effect of the drug on at least 3 occasions (although 5-6 tries is recommended), the dose can be modified. Men with severe ED can start on the 100-mg dose; these men are not likely to achieve a satisfactory response, but they should make 3-4 attempts before starting another form of therapy.

Sildenafil should be taken on an empty stomach approximately 30-60 minutes prior to sexual intercourse. This agent is not intended to be taken daily. Sexual stimulation is necessary to produce an erection. An increased ability to obtain erections can last up to 24 hours but is usually limited to 6-8 hours.

Patients who are refractory to sildenafil may benefit from vardenafil or tadalafil therapy. If none of these is successful, combine the agent with an injection of prostaglandin E-1. Gutierrez et al demonstrated that this combination was more effective than either one alone. Other successful combinations include using a PDE-5 inhibitor with MUSE.⁵

Vardenafil (Levitra)

This agent, which is available in 5-mg, 10-mg, and 20-mg doses, became available in 2003. These lower doses are effective because this agent has a 9-fold increase in selectivity for the specific receptor responsible for NO release in the penis. This agent can act within 20 minutes. Vardenafil has similar efficacy, side effects, and limitations as sildenafil but may be less bothered by food.

Tadalafil (Cialis)

This is available in 5-mg, 10-mg, and 20-mg doses. This agent has an extended period of responsiveness that can last 36 hours or longer in some men. This agent can be ingested without food restrictions. The other two oral agents can act within an hour; in contrast, tadalafil usually requires a 1 to 2-hour waiting period. The flexibility afforded by this agent takes away the concern about the timing of intercourse. Unlike the other agents, tadalafil has a potential back-pain side effect thought to be due to a PDE-11 effect. A single, small daily dose of tadalafil is being studied as a possible therapeutic alternative to intermittent dosing. This would eliminate the need for carefully timing the taking of the medication and would allow increased freedom of action by patients.

Tadalafil has been shown to improve endothelial function in men with ED. Rosano et al studied brachial artery blood flow in 32 men with increased cardiovascular risk factors.⁶ They found that blood flow was significantly improved and this benefit remained for 2 weeks after cessation of the medication.

Yohimbine

This oral agent has been available for many years. It has both a central and a peripheral effect. Its efficacy has been questioned because even in properly conducted, well-controlled studies, yohimbine is only slightly better than placebo. A renewed interest in this agent has occurred, particularly when combined with sildenafil or some of the other oral agents.

Yohimbine is a safe agent with few known adverse effects. It is administered daily in a dose of 5.4 mg (1 tab) 3 times/d.

Apomorphine (Uprima)

Apomorphine is a sublingual agent that is not approved by the US Food and Drug Administration (FDA). Apomorphine has a central effect on the hypothalamus. It is a D1/D2 dopamine receptor agonist from the apomorphine (nonopiate) drug class. This agent has been shown to specifically activate c-fos gene expression in the paraventricular and supraoptic nuclei of the hypothalamus in animal models. These areas are known to be involved with penile erections.

The administration of apomorphine by subcutaneous, oral, and intranasal routes results in variable effects on erectile function and moderate-to-severe adverse effects, primarily nausea and vomiting. A slow-release sublingual formulation has demonstrated erectile enhancement benefits with a significant reduction in adverse effects.

Of 977 subjects who received double-blind medication, 774 (79.2%) completed the course of treatment. Several doses were used, but patients in all of the apomorphine dose groups reported erections firm enough for penetration more often than those taking placebo (P <.01). When separated according to dose, firm erections were reported by 45% versus 35% of the control group with the 2-mg dose. The 4-mg dose elicited positive responses in 55%, compared with 36% in the placebo group. With the 6-mg dose, 60% reported positive responses, compared with 32% in control subjects. Adverse events occurring in 10% or more of the patients in any group were nausea, sweating, dizziness, somnolence, vomiting, yawning, and asthenia. Most of these were considered mild to moderate in severity. Nausea was the most common adverse effect, which was found to be dose-related and reducible with repeated exposure to the drug.

Phentolamine (Vasomax)

This agent is an alpha-receptor blocker that has not been approved by the FDA for the treatment of ED but has undergone limited clinical testing.

Detumescence is influenced by alpha-adrenergic tone. Alpha-1 receptors predominate in the trabecular smooth muscle cells of the corpora cavernosa, alpha-2 receptors are the predominant receptors in the cavernosal arteries, and both alpha-1 and alpha-2 receptors are present in the circumflex and deep cavernosal veins.

Two placebo-controlled trials reported effectiveness in 42% and 32% of patients taking 50 mg compared with 9% and 13% in the control group, respectively. The erections occurred in 20-30 minutes. The drug was well tolerated, with mild-to-moderate adverse effects, usually headaches or lightheadedness, occurring in less than 10% of patients.

Androgens

Men who present with diminished libido and ED may be found to have low serum testosterone levels. Hormone replacement may be of benefit to those with severe hypogonadism and possibly as adjunctive therapy when other treatments are unsuccessful by themselves. Libido and an overall sense of well-being are likely to improve when serum testosterone levels are restored to the reference range.

Replacement androgens are available in oral, injectable, gels and transdermal preparations. Oral therapy is the least effective and the most likely to be associated with hepatotoxicity, even though this is a relatively small risk. Parenteral therapy is most likely to restore androgen levels to the reference range, but this therapy requires periodic injections, usually every 2 weeks, to sustain an effective level. Peak and trough levels are suggested when using injectable agents to avoid symptomatic troughs and supernormal peak levels. Weekly injections using lower doses can be used to minimize the wide swings in blood levels with less frequent dosing. Skin patches deliver a sustained dose and are generally accepted by patients. Androgen creams (AndroGel and Testim) are now available for daily topical use for male hypogonadism and have the advantage of minimizing the peaks and troughs of injectable agents. However, they require daily dosing and are relatively expensive.

The use of exogenous androgens suppresses natural androgen production. Elevating serum androgen levels has the potential to stimulate prostate growth and may increase the risk of activating a latent cancer. Periodic prostate examinations, including digital rectal examinations, prostate-specific antigen determinations, and blood counts (ie, CBC counts), are recommended in all patients receiving supplemental androgens. Obtaining a testosterone level while on therapy is also suggested to optimize the dosage.

Injection therapy

While many substances are touted as aphrodisiacs, the modern age of pharmacotherapy began in 1993 when the injection of papaverine, an alpha-receptor blocker that produces vasodilatation, was shown to produce erections when injected directly into the corpora cavernosa. Soon afterwards, other vasodilators, such as PGE1 and phentolamine (Regitine), were demonstrated to be effective either as single agents 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 adequately rigid erections.

If the vasculature within the corpora cavernosa is healthy, the use of injectable agents is almost always effective. Patients need to be carefully instructed on how to perform the injections. The dosage is adjusted to achieve an erection with adequate rigidity for no more than 90 minutes. Up to 40 mcg of alprostadil can be used. An abnormal finding after biothesiometry testing has been suggested as an indicator of possible heightened sensitivity to intracavernosal injections, but this is unproven.

Alprostadil, a synthetic PGE1, is the most common single agent used for intracavernosal injections. When combined with papaverine and Regitine, the mixture is called Trimix and it has roughly twice the efficacy of alprostadil alone. In one study of 683 men, 94% reported having erections suitable for penetration after alprostadil injections. The main adverse effects are a painful erection, priapism, or the development of scarring at the site of the injection. Alprostadil is now available in a gel and a patch. No long-term studies compare the efficacy and acceptance of these new forms of therapy with that of the oral agents.

Intraurethral therapy (MUSE)

Alprostadil, PGE1, has been formulated into a small suppository that can be inserted into the urethra. In a selected group of men, the agent was effective in 65%. This agent may be effective in men with vascular disease, diabetes, and status post prostate surgery. This is a useful agent for men who do not want to use self-injections or for men in whom oral medications have failed. It has been successfully used together with sildenafil in cases in which each agent alone failed. Few adverse effects occur, and the most common is a painful erection and urethral burning, which occurs in less than 10% of the patients.

Table 1. Types of Medical Therapy Available to Manage ED

*Monoamine oxidase inhibitors

†US Food and Drug Administration

A comparison of satisfaction rates and ED in subjects treated with sildenafil, intracavernous PGE1 (alprostadil), and penile implant surgery was performed by Rajpurkar and Dhabuwala in 138 men with ED. This was a nonrandomized study in which all subjects were initially offered sildenafil. The mean follow-up was 19.54 months, and questionnaires were used to obtain the data. Their conclusions were that men with a penile implant had significantly better erectile function and satisfaction.

The development of future medical options will emphasize the restoration of physiologic function. A better understanding of the molecular biology of ED will allow the development of new classes of agents. Research involving gene therapy is beginning to show promise.

One such research area has involved the use of the angiogenic growth factor and endothelial cell mitogen, vascular endothelial growth factor (VEGF). This is produced by vascular smooth muscle, endothelial, and inflammatory cells. VEGF increases the production of nitric oxide, which improves endothelial function and blood flow in chronic ischemic disorders.

The direct intracavernosal injection of recombinant VEGF protein or adenoviral VEGF that contains plasmids have shown dramatic results based on cavernosography findings in animal models with arteriogenic, venogenic, and neural forms of ED. Burchardt et al identified VEGF 165 as the predominant isoform of the corpora cavernosa, as well as a novel splice variant.⁷ Although VEGF is a potent and important vascular regulator, it probably acts together with other vascular factors. Although a single-agent VEGF is unlikely to ever be used as monotherapy for ED, this represents an important step in understanding the normal and abnormal vascular physiology associated with ED.

Surgical Care

A small number of healthy young men have developed ED as a result of trauma to the pelvic arteries. Revascularization procedures such as rotating the epigastric artery, or even smaller vessels, into the corpora have been attempted. The long-term results have been marginal.

Men who have difficulty maintaining erections as a result of venous leaks occasionally may benefit from a surgical procedure to eliminate much of the venous outflow. While initial enthusiasm for this and other surgical approaches was significant, this type of surgery has become rare because of a lack of long-term efficacy.

Penile implants

In the past, the placement of prosthetic devices within the corpora was the only effective therapy for men with organic ED. Now, this is the last option considered, even though more than 90% of men with an implant would recommend the procedure to their friends and relatives.

Implants are usually used for men in whom other therapies have failed or in those who require penile reconstructions. Men who have had a radical prostatectomy for prostate cancer and in whom a nerve-sparing procedure was not performed or was not successful often do not respond to oral PDE-5 inhibitors, and these men are good candidates for an implant. The same is true for men treated with radiation therapy, although more of these men tend to respond to oral agents. Additionally, some patients experience increased sexual satisfaction with the combined use of an implant and an oral PD5 inhibitor.

Before selecting this form of management, the patient and his sexual partner should be counseled regarding the benefits and risks of this procedure.

Two types of devices are available, a semirigid and a multicomponent inflatable system. With the semirigid prosthesis, two matching cylinders are implanted into the corpora cavernosa. These devices provide enough rigidity for penetration and rarely break. The major drawbacks are the cosmetic appearance of the penis, which remains semi-erect at all times, the need for surgery, and the destruction of the natural erectile mechanism when the prosthesis is implanted.

The inflatable devices consist of two Silastic or Bioflex cylinders inserted into the corpora cavernosa, a pump placed in the scrotum to inflate the cylinders, and a reservoir that is contained either within the cylinders or in a separate reservoir placed beneath the fascia of the lower abdomen. The inflatable prosthesis generally remains functional for 7-10 years before a replacement may be necessary. Improvements in these devices have resulted in a failure rate of less than 10%. Complications include infections in 2% of patients, erosion of the device through the urethra or skin in 2% of patients, and painful erections in 1% of patients. A newer antibiotic-coated device has further reduced the infection rate.

Patient acceptance of these devices is very high, with nearly 100% of the patients expressing satisfaction. Part of this enthusiasm is related to the failure of other therapies and the highly motivated patient population.

Table 2. Types of Surgical Therapies for ED

Consultations

Therapeutic options in managing erectile dysfunction

Currently, any man who wishes to have erectile function can do so regardless of the etiology of the problem. Many therapeutic options are available, and the task of the physician is to help the patient seek the best solution. Finding a trained and understanding physician who is willing to take the time to understand the patient's problem is the first step in identifying which therapeutic option will ultimately be most appropriate and successful.

Sexual counseling is the most important part of the treatment for patients with sexual problems. Many professional sexual counselors are skilled in working with patients, but the primary care physician, the urologist, and the gynecologist also serve in this capacity to some degree. These are usually the first professionals to learn about the problem, and they often have to extract the information about the sexual problem from the patient.

Men are frequently reluctant to discuss their sexual problems and need to be specifically asked. Opening a dialogue allows the clinician to begin the investigation or refer the patient to a consultant. Regardless of any subsequent therapy the patient may receive, the emotional aspects of the disorder must be addressed. Ideally, the couple should be involved in the counseling, but, even when this is not possible, the time spent may help resolve or at least clarify the problem certainly helps in deciding which of the other options would be most beneficial and appropriate.

Psychological care

Regardless of the etiology of ED, a psychological component is almost always associated with this disorder. The ability to achieve erection is intimately connected to a man's self-esteem and sense of worth. Pure psychogenic ED is generally evident when a man reports that he has normal erections some of the time but is unable to achieve or to main