Prevalence and Association with Age

Estimates of the prevalence of impotence depend on the definition employed for this condition. For the purposes of this consensus development conference statement, impotence is defined as male erectile dysfunction, that is, the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. Erectile performance has been characterized by the degree of dysfunction, and estimates of prevalence (the number of men with the condition) vary depending on the definition of erectile dysfunction used.

Appallingly little is known about the prevalence of erectile dysfunction in the United States and how this prevalence varies according to individual characteristics (age, race, ethnicity, socioeconomic status, and concomitant diseases and conditions). Data on erectile dysfunction available from the 1940's applied to the present U.S. male population produce an estimate of erectile dysfunction prevalence of 7 million.

More recent estimates suggest that the number of U.S. men with erectile dysfunction may more likely be near 10-20 million. Inclusion of individuals with partial erectile dysfunction increases the estimate to about 30 million. The majority of these individuals will be older than 65 years of age. The prevalence of erectile dysfunction has been found to be associated with age. A prevalence of about 5 percent is observed at age 40, increasing to 15-25 percent at age 65 and older. One-third of older men receiving medical care at a Department of Veterans' Affairs ambulatory clinic admitted to problems with erectile function.

Causes contributing to erectile dysfunction can be broadly classified into two categories: organic and psychological. In reality, while the majority of patients with erectile dysfunction are thought to demonstrate an organic component, psychological aspects of self-confidence, anxiety, and partner communication and conflict are often important contributing factors.

The 1985 National Ambulatory Medical Care Survey indicated that there were about 525,000 visits for erectile dysfunction, accounting for 0.2 percent of all male ambulatory care visits. Estimates of visits per 1,000 population increased from about 1.5 for the age group 25-34 to 15.0 for those age 65 and above. The 1985 National Hospital Discharge Survey estimated that more than 30,000 hospital admissions were for erectile dysfunction.

Clinical, Psychological, and Social Impact

Geographic, Racial, Ethnic, Socioeconomic, and Cultural Variation in Erectile Dysfunction. Very little is known about variations in prevalence of erectile dysfunction across geographic, racial, ethnic, socioeconomic, and cultural groups. Anecdotal evidence points to the existence of racial, ethnic, and other cultural diversity in the perceptions and expectation levels for satisfactory sexual functioning. These differences would be expected to be reflected in these groups' reaction to erectile dysfunction, although few data on this issue appear to exist.

One report from a recent community survey concluded that erectile failure was the leading complaint of males attending sex therapy clinics. Other studies have shown that erectile disorders are the primary concern of sex therapy patients in treatment. This is consistent with the view that erectile dysfunction may be associated with depression, loss of self-esteem, poor self-image, increased anxiety or tension with one's sexual partner, and/or fear and anxiety associated with contracting sexually transmitted diseases, including AIDS.

Male/Female Perceptions and Influences. The diagnosis of erectile dysfunction may be understood as the presence of a condition limiting choices for sexual interaction and possibly limiting opportunity for sexual satisfaction. The impact of this condition depends very much on the dynamics of the relationship of the individual and his sexual partner and their expectation of performance. When changes in sexual function are perceived by the individual and his partner as a natural consequence of the aging process, they may modify their sexual behavior to accommodate the condition and maintain sexual satisfaction. Increasingly, men do not perceive erectile dysfunction as a normal part of aging and seek to identify means by which they may return to their previous level and range of sexual activities. Such levels and expectations and desires for future sexual interactions are important aspects of the evaluation of patients presenting with a chief complaint of erectile dysfunction.

In men of all ages, erectile failure may diminish willingness to initiate sexual relationships because of fear of inadequate sexual performance or rejection. Because males, especially older males, are particularly sensitive to the social support of intimate relationships, withdrawal from these relationships because of such fears may have a negative effect on their overall health.

Physiology of Erection

The male erectile response is a vascular event initiated by neuronal action and maintained by a complex interplay between vascular and neurological events. In its most common form, it is initiated by a central nervous system event that integrates psychogenic stimuli (perception, desire, etc.) and controls the sympathetic and parasympathetic innervations of the penis. Sensory stimuli from the penis are important in continuing this process and in initiating a reflex arc that may cause erection under proper circumstances and may help to maintain erection during sexual activity.

Parasympathetic input allows erection by relaxation of trabecular smooth muscle and dilation of the helicine arteries of the penis. This leads to expansion of the lacunar spaces and entrapment of blood by compressing venules against the tunica albuginea, a process referred to as the corporal veno- occlusive mechanism. The tunica albuginea must have sufficient stiffness to compress the venules penetrating it so that venous outflow is blocked and sufficient tumescence and rigidity can occur.

Acetylcholine released by the parasympathetic nerves is thought to act primarily on endothelial cells to release a second nonadrenergic-noncholinergic carrier of the signal that relaxes the trabecular smooth muscle. Nitric oxide released by the endothelial cells, and possibly also of neural origin, is currently thought to be the leading of several candidates as this nonadrenergic-noncholinergic transmitter; but this has not yet been conclusively demonstrated to the exclusion of other potentially important substances (e.g., vasoactive intestinal polypeptide). The relaxing effect of nitric oxide on the trabecular smooth muscle may be mediated through its stimulation of guanylate cyclase and the production of cyclic guanosine monophosphate (cGMP), which would then function as a second messenger in this system.

Constriction of the trabecular smooth muscle and helicine arteries induced by sympathetic innervation makes the penis flaccid, with blood pressure in the cavernosal sinuses of the penis near venous pressure. Acetylcholine is thought to decrease sympathetic tone. This may be important in a permissive sense for adequate trabecular smooth muscle relaxation and consequent effective action of other mediators in achieving sufficient inflow of blood into the lacunar spaces. When the trabecular smooth muscle relaxes and helicine arteries dilate in response to parasympathetic stimulation and decreased sympathetic tone, increased blood flow fills the cavernous spaces, increasing the pressure within these spaces so that the penis becomes erect. As the venules are compressed against the tunica albuginea, penile pressure approaches arterial pressure, causing rigidity. Once this state is achieved, arterial inflow is reduced to a level that matches venous outflow.

Erectile Dysfunction

Because adequate arterial supply is critical for erection, any disorder that impairs blood flow may be implicated in the etiology of erectile failure. Most of the medical disorders associated with erectile dysfunction appear to affect the arterial system. Some disorders may interfere with the corporal veno-occlusive mechanism and result in failure to trap blood within the penis, or produce leakage such that an erection cannot be maintained or is easily lost.

Damage to the autonomic pathways innervating the penis may eliminate "psychogenic" erection initiated by the central nervous system. Lesions of the somatic nervous pathways may impair reflexogenic erections and may interrupt tactile sensation needed to maintain psychogenic erections. Spinal cord lesions may produce varying degrees of erectile failure depending on the location and completeness of the lesions. Not only do traumatic lesions affect erectile ability, but disorders leading to peripheral neuropathy may impair neuronal innervation of the penis or of the sensory afferents. The endocrine system itself, particularly the production of androgens, appears to play a role in regulating sexual interest, and may also play a role in erectile function.

Psychological processes such as depression, anxiety, and relationship problems can impair erectile functioning by reducing erotic focus or otherwise reducing awareness of sensory experience. This may lead to inability to initiate or maintain an erection. Etiologic factors for erectile disorders may be categorized as neurogenic, vasculogenic, or psychogenic, but they most commonly appear to derive from problems in all three areas acting in concert.

Risk Factors

Little is known about the natural history of erectile dysfunction. This includes information on the age of onset, incidence rates stratified by age, progression of the condition, and frequency of spontaneous recovery. There also are very limited data on associated morbidity and functional impairment. To date, the data are predominantly available for whites, with other racial and ethnic populations represented only in smaller numbers that do not permit analysis of these issues as a function of race or ethnicity.

Erectile dysfunction is clearly a symptom of many conditions, and certain risk factors have been identified, some of which may be amenable to prevention strategies. Diabetes mellitus, hypogonadism in association with a number of endocrinologic conditions, hypertension, vascular disease, high levels of blood cholesterol, low levels of high density lipoprotein, drugs, neurogenic disorders, Peyronie's disease, priapism, depression, alcohol ingestion, lack of sexual knowledge, poor sexual techniques, inadequate interpersonal relationships or their deterioration, and many chronic diseases, especially renal failure and dialysis, have been demonstrated as risk factors. Vascular surgery is also often a risk factor. Age appears to be a strong indirect risk factor in that it is associated with an increased likelihood of direct risk factors. Other factors require more extensive study. Smoking has an adverse effect on erectile function by accentuating the effects of other risk factors such as vascular disease or hypertension. To date, vasectomy has not been associated with an increased risk of erectile dysfunction other than causing an occasional psychological reaction that could then have a psychogenic influence. Accurate risk factor identification and characterization are essential for concerted efforts at prevention of erectile dysfunction.

Prevention

Although erectile dysfunction increases progressively with age, it is not an inevitable consequence of aging. Knowledge of the risk factors can guide prevention strategies. Specific antihypertensive, antidepressant, and antipsychotic drugs can be chosen to lessen the risk of erectile failure. Published lists of prescription drugs that may impair erectile functioning often are based on reports implicating a drug without systematic study. Such studies are needed to confirm the validity of these suggested associations. In the individual patient, the physician can modify the regimen in an effort to resolve the erectile problem.

It is important that physicians and other health care providers treating patients for chronic conditions periodically inquire into the sexual functioning of their patients and be prepared to offer counsel for those who experience erectile difficulties. Lack of sexual knowledge and anxiety about sexual performance are common contributing factors to erectile dysfunction. Education and reassurance may be helpful in preventing the cascade into serious erectile failure in individuals who experience minor erectile difficulty due to medications or common changes in erectile functioning associated with chronic illnesses or with aging.

General Considerations

Because of the difficulty in defining the clinical entity of erectile dysfunction, there have been a variety of entry criteria for patients in therapeutic trials. Similarly, the ability to assess efficacy of therapeutic interventions is impaired by the lack of clear and quantifiable criteria of erectile dysfunction. General considerations for treatment follow:

• Psychotherapy and/or behavioral therapy may be useful for some patients with erectile dysfunction without obvious organic cause, and for their partners. These may also be used as an adjunct to other therapies directed at the treatment of organic erectile dysfunction. Outcome data from such therapy, however, have not been well-documented or quantified, and additional studies along these lines are indicated.
• Efficacy of therapy may be best achieved by inclusion of both partners in treatment plans.
• Treatment should be individualized to the patient's desires and expectations.
• Even though there are several effective treatments currently available, long-term efficacy is in general relatively low. Moreover, there is a high rate of voluntary cessation of treatment for all currently popular forms of therapy for erectile dysfunction. Better understanding of the reasons for each of these phenomena is needed.

Psychotherapy and Behavioral Therapy

Psychosocial factors are important in all forms of erectile dysfunction. Careful attention to these issues and attempts to relieve sexual anxieties should be a part of the therapeutic intervention for all patients with erectile dysfunction. Psychotherapy and/or behavioral therapy alone may be helpful for some patients in whom no organic cause of erectile dysfunction is detected. Patients who refuse medical and surgical interventions also may be helped by such counseling. After appropriate evaluation to detect and treat coexistent problems such as issues related to the loss of a partner, dysfunctional relationships, psychotic disorders, or alcohol and drug abuse, psychological treatment focuses on decreasing performance anxiety and distractions and on increasing a couple's intimacy and ability to communicate about sex. Education concerning the factors that create normal sexual response and erectile dysfunction can help a couple cope with sexual difficulties. Working with the sexual partner is useful in improving the outcome of therapy. Psychotherapy and behavioral therapy have been reported to relieve depression and anxiety as well as to improve sexual function. However, outcome data of psychological and behavioral therapy have not been quantified, and evaluation of the success of specific techniques used in these treatments is poorly documented. Studies to validate their efficacy are therefore strongly indicated.

Medical Therapy

An initial approach to medical therapy should consider reversible medical problems that may contribute to erectile dysfunction. Included in this should be assessment of the possibility of medication-induced erectile dysfunction with consideration for reduction of polypharmacy and/or substitution of medications with lower probability of inducing erectile dysfunction.

For some patients with an established diagnosis of testicular failure (hypogonadism), androgen replacement therapy may sometimes be effective in improving erectile function. A trial of androgen replacement may be worthwhile in men with low serum testosterone levels if there are no other contraindications. In contrast, for men who have normal testosterone levels, androgen therapy is inappropriate and may carry significant health risks, especially in the situation of unrecognized prostate cancer. If androgen therapy is indicated, it should be given in the form of intramuscular injections of testosterone enanthate or cypionate. Oral androgens, as currently available, are not indicated. For men with hyperprolactinemia, bromocriptine therapy often is effective in normalizing the prolactin level and improving sexual function. A wide variety of other substances taken either orally or topically have been suggested to be effective in treating erectile dysfunction. Most of these have not been subjected to rigorous clinical studies and are not approved for this use by the Food and Drug Administration (FDA). Their use should therefore be discouraged until further evidence in support of their efficacy and indicative of their safety is available.

Intracavernosal Injection Therapy

Injection of vasodilator substances into the corpora of the penis has provided a new therapeutic technique for a variety of causes of erectile dysfunction. The most effective and well-studied agents are papaverine, phentolamine, and prostaglandin E[sub 1]. These have been used either singly or in combination. Use of these agents occasionally causes priapism (inappropriately persistent erections). This appears to have been seen most commonly with papaverine. Priapism is treated with adrenergic agents, which can cause life-threatening hypertension in patients receiving monoamine oxidase inhibitors. Use of the penile vasodilators also can be problematic in patients who cannot tolerate transient hypotension, those with severe psychiatric disease, those with poor manual dexterity, those with poor vision, and those receiving anticoagulant therapy. Liver function tests should be obtained in those being treated with papaverine alone. Prostaglandin E[sub 1] can be used together with papaverine and phentolamine to decrease the incidence of side effects such as pain, penile corporal fibrosis, fibrotic nodules, hypotension, and priapism. Further study of the efficacy of multitherapy versus monotherapy and of the relative complications and safety of each approach is indicated. Although these agents have not received FDA approval for this indication, they are in widespread clinical use. Patients treated with these agents should give full informed consent. There is a high rate of patient dropout, often early in the treatment. Whether this is related to side effects, lack of spontaneity in sexual relations, or general loss of interest is unclear. Patient education and followup support might improve compliance and lessen the dropout rate. However, the reasons for the high dropout rate need to be determined and quantified.

Vacuum/Constrictive Devices

Vacuum constriction devices may be effective at generating and maintaining erections in many patients with erectile dysfunction and these appear to have a low incidence of side effects. As with intracavernosal injection therapy, there is a significant rate of patient dropout with these devices, and the reasons for this phenomenon are unclear. The devices are difficult for some patients to use, and this is especially so in those with impaired manual dexterity. Also, these devices may impair ejaculation, which can then cause some discomfort. Patients and their partners sometimes are bothered by the lack of spontaneity in sexual relations that may occur with this procedure. The patient is sometimes also bothered by the general discomfort that can occur while using these devices. Partner involvement in training with these devices may be important for successful outcome, especially in regard to establishing a mutually satisfying level of sexual activity.

Vascular Surgery

Surgery of the penile venous system, generally involving venous ligation, has been reported to be effective in patients who have been demonstrated to have venous leakage. However, the tests necessary to establish this diagnosis have been incompletely validated; therefore, it is difficult to select patients who will have a predictably good outcome. Moreover, decreased effectiveness of this approach has been reported as longer term followups have been obtained. This has tempered enthusiasm for these procedures, which are probably therefore best done in an investigational setting in medical centers by surgeons experienced in these procedures and their evaluation.

Arterial revascularization procedures have a very limited role (e.g., in congenital or traumatic vascular abnormality) and probably should be restricted to the clinical investigation setting in medical centers with experienced personnel. All patients who are considered for vascular surgical therapy need to have appropriate preoperative evaluation, which may include dynamic infusion pharmaco-cavernosometry and cavernosography (DICC), duplex ultrasonography, and possibly arteriography. The indications for and interpretations of these diagnostic procedures are incompletely standardized; therefore, difficulties persist with using these techniques to predict and assess the success of surgical therapy, and further investigation to clarify their value and role in this regard is indicated.

Penile Prostheses

Three forms of penile prostheses are available for patients who fail with or refuse other forms of therapy: semirigid, malleable, and inflatable. The effectiveness, complications, and acceptability vary among the three types of prostheses, with the main problems being mechanical failure, infection, and erosions. Silicone particle shedding has been reported, including migration to regional lymph nodes; however, no clinically identifiable problems have been reported as a result of the silicone particles. There is a risk of the need for reoperation with all devices. Although the inflatable prostheses may yield a more physiologically natural appearance, they have had a higher rate of failure requiring reoperation. Men with diabetes mellitus, spinal cord injuries, or urinary tract infections have an increased risk of prosthesis-associated infection. This form of treatment may not be appropriate in patients with severe penile corporal fibrosis, or severe medical illness. Circumcision may be required for patients with phimosis and balanitis.

Staging of Treatment

The patient and partner must be well informed about all therapeutic options including their effectiveness, possible complications, and costs. As a general rule, the least invasive or dangerous procedures should be tried first. Psychotherapy and behavioral treatments and sexual counseling alone or in conjunction with other treatments may be used in all patients with erectile dysfunction who are willing to use this form of treatment. In patients in whom psychogenic erectile dysfunction is suspected, sexual counseling should be offered first. Invasive therapy should not be the primary treatment of choice. If history, physical, and screening endocrine evaluations are normal and nonpsychogenic erectile dysfunction is suspected, either vacuum devices or intracavernosal injection therapy can be offered after discussion with the patient and his partner. These latter two therapies may also be useful when combined with psychotherapy in those with psychogenic erectile dysfunction in whom psychotherapy alone has failed. Since further diagnostic testing does not reliably establish specific diagnoses or predict outcomes of therapy, vacuum devices or intracavernosal injections often are applied to a broad spectrum of etiologies of male erectile dysfunction.

The motivation and expectations of the patient and his partner and education of both are critical in determining which therapy is chosen and in optimizing its outcome. If single therapy is ineffective, combining two or more forms of therapy may be useful. Penile prostheses should be placed only after patients have been carefully screened and informed. Vascular surgery should be undertaken only in the setting of clinical investigation and extensive clinical experience. With any form of therapy for erectile dysfunction, long-term followup by health professionals is required to assist the patient and his partner with adjustment to the therapeutic intervention. This is particularly true for intracavernosal injection and vacuum constriction therapies. Followup should include continued patient education and support in therapy, careful determination of reasons for cessation of therapy if this occurs, and provision of other options if earlier therapies are unsuccessful.