Core document on erectile dysfunction: key aspects in the care of a patient with erectile dysfunction

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1 (2004) 16, S26 S39 & 2004 Nature Publishing Group All rights reserved /04 $ : key aspects in the care of a patient with erectile dysfunction FB Brotons 1 *, JC Campos 2, R Gonzalez-Correales 3, A Martín-Morales 4, I Moncada 5 and JM Pomerol 6 1 Vila-real II Health Center, Castellon, Spain; 2 Villamarxant Health Center, Valencia, Spain; 3 Piedrabuena Health Center, Ciudad Real, Spain; 4 Department of Urology, Carlos Haya University Hospital, Malaga, Spain; 5 Department of Urology, Gregorio Maranon University General Hospital, Madrid, Spain; and 6 Department of Andrology, Fundación Puigvert, Barcelona, Spain The aim of this Core Document of the Spanish Consensus on Erectile dysfunction (ED) is to offer guidance to the nonspecialist physician in the management of patients with ED. ED is one of the most frequent chronic health problems in men older than 40 y of age and may also act as a sentinel symptom for other important underlying diseases. Its etiology can be classified into organic, psychogenic, or mixed. In most cases, the underlying cause of ED is usually a chronic health problem (such as diabetes, hypertension, atherosclerosis, and so on) or an adverse drug effect. The initial step in the management is to assess erectile function in patients with risk factors for ED. Once ED has been established, a detailed sexual, medical, and social history, including a review of medications used, is the most important aspect of a patient s assessment. Generally, examination should be limited to the cardiovascular, neurological, and urogenital systems. Fasting glucose and blood lipid profile should be performed in every man with ED, and free testosterone levels in men older than 50 y or if hypogonadism is suspected; other diagnostic tests are optional and should be requested on an individualized basis. In many cases, the most likely cause of ED can be identified based on the above information. Therapeutic intervention should be patient-oriented and based on the expectations and wishes of the patient and his partner, who should be included in discussions whenever possible. Basic interventions common to any type of ED include sexual counseling, lifestyle modifications, treatment of associated medical conditions, and switching to alternative drugs with lower risk of ED. In certain cases, an etiologic treatment may be performed (sex therapy, revascularization surgery, and hormonal therapy). Most patients with ED will benefit from symptomatic treatments; first-line therapy may be prescribed by physicians who are not specialists in ED, and includes oral agents such as inhibitors of phosphodiesterase type 5, currently considered the drugs of choice for initial treatment of ED. Intracavernous drugs are the second-line therapy, and surgical treatments, such as implantation of penile prostheses, are reserved for urologists/ andrologists who specialize in ED. Referral may be appropriate where indicated by age, clinical findings, or the patient s request. (2004) 16, S26 S39. doi: /sj.ijir Keywords: erectile dysfunction Key aspects in the care of a patient with erectile dysfunction: practical guide Erectile dysfunction (ED) is one of the most frequent chronic health problems in men older than 40 y of age 1 and therefore is one of the most frequent reasons for consultation of family physicians and *Correspondence: FB Brotons, Vila-real II Health Center, Castellon, Spain. fbrotonsm@papps.org specialists. ED may also be an indicator for other underlying disease such as diabetes, hypertension, or atherosclerosis. In addition, ED has a negative impact on the quality of life of both the patient and his partner. 2 Taking these factors into consideration with the current availability of safe and effective treatments should prompt physicians to proactively discuss ED with their patients, particularly those at risk of developing ED. ED is defined as the persistent or recurrent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse and does not include disorders of sexual desire, ejaculation, or orgasm. 3 To rule out temporary disorders, the patient must

2 experience ED for at least 3 months, 4 except in cases of ED secondary to trauma or surgery. Prevalence The Massachusetts Male Aging Study (MMAS) 1 investigated 1290 men between the ages of 40 and 70 y in the United States. The prevalence of ED in any degree reported from this study was 52% (mild: 17%; moderate: 25%; severe: 10%). The Epidemiology of Male Erectile Dysfunction (EDEM) study 5 conducted on 2476 Spanish men between the ages of 25 and 70 y found some degree of ED in 12.1% of men (mild: 5.2%; moderate: 5%; severe: 1.9%). Based on the census of the male population, the estimated prevalence of ED in Spain is million men. Of men aged y, 17.7% are affected by ED, a lower prevalence than that reported in the MMAS. Etiology A variety of physical and psychological factors are involved in erectile function, and alteration of one or more factors may lead to ED. We can thus classify ED into the following categories: 3,6 Organic ED: organic causes may be secondary to vascular injury (the most common cause), neurogenic, hormonal, or local. Psychogenic ED: caused by central blockade of the erectile mechanism without physical injury. ED of mixed etiology: caused by a combination of physical and psychological factors. In the vast majority of ED cases due to physical causes, a psychological component is also present. Risk factors and causative diseases The major causes of ED are listed in Tables 1 3. In most cases, the underlying cause of ED is a chronic health problem or an adverse drug effect. The major risk factors for ED are discussed in the following sections. Age. Both the prevalence for and severity of ED increase with age, and this is an independent risk factor for the disorder. 1,5 However, ED should not be considered an inevitable consequence of age because 68% of men between 60 and 70 y of age did not have erection problems in the EDEM study. 5 Diabetes. Diabetes is the endocrine disease most commonly associated with ED, and the probability of developing ED is three times higher in treated diabetic men compared with nondiabetic men. 1 Anywhere from 25 to 75% of diabetic men will develop ED. 1,7 9 It has been observed that 15% of S27 Table 1 Major causes of ED Vascular 60 80% Neurological 10 20% Hormonal 5 10% Arteriosclerosis CNS Estrogen excess Smoking Stroke Iatrogenic exogenous Hyperlipidemia Sleep apnea syndrome Liver diseases High blood pressure Alzheimer s disease Estradiol- or hcg-producing tumors Diabetes Parkinson s disease Hyperprolactinemia Peyronie s disease Brain tumor Iatrogenic drug-induced Pelvic fractures Spinal cord Pituitary tumor Perineal trauma Trauma Hypogonadism Fracture of the corpora cavernosa Compressive cause (herniated disk) Hypogonadotropic Heterotopic renal transplantation Demyelinating disease (multiple sclerosis) Hypergonadotropic Leriche s syndrome Tumor cause (spinal cord tumor) Thyroid dysfunction Aortoiliac or aortofemoral bypass Vascular disease (spinal infarction) Hyperthyroidism Radiotherapy sequelae Infectious diseases (tabes dorsalis) Hypothyroidism Priapism sequelae Myelomeningocele Adrenal dysfunction Degenerative diseases Cushing s syndrome or disease Iatrogenic damage Adrenal insufficiency Peripheral nerves Severe undernutrition Diabetic neuropathy Alcoholic neuropathy Postsurgical sequelae Prostatectomy Cystoprostatectomy Transurethral resection of the prostate Spinal cord surgery Rectal amputation CNS: central nervous system; hcg: human chorionic gonadotropin.

3 S28 Table 2 Major drug-related causes of ED Drugs with hormonal action Psychotropic drugs Antihypertensive drugs Decrease or block the action of testosterone: antiandrogens, estrogens, anabolic drugs, steroids, spironolactone, ketoconazole, digoxin, clofibrate, cimetidine Increase prolactin levels: cimetidine, metoclopramide, phenothiazines, opiates, endorphins, tricyclic antidepressants, methyldopa Antipsychotics and neuroleptics: phenothiazines, thioxanthenes, thioridazines, butyrophenones Antidepressants: tricyclic antidepressants, tetracyclic antidepressants, MAOIs, SSRIs Anxiolytics: benzodiazepines Sympathomimetics: clonidine, methyldopa, reserpine, guanethidine b-adrenergic blockers: propranolol, pindolol, atenolol, metoprolol Diuretics: spironolactone, thiazides MAOIs: monoamine oxidase inhibitors; SSRIs: selective serotonin reuptake inhibitors. Table 3 Some psychological and sexual causes of ED Partner conflicts Self-image problems Low self-esteem Stress Social or work environment problems Factors related to sexual upbringing or education Highly restricted sexual upbringing Erroneous sexual beliefs Sexual traumas in childhood or first experiences Sexual abuse in childhood Excessive fear of pregnancy or sexually transmitted diseases Other sexual and sexual identity disorders Paraphilias Sexual identity problems Sexual orientation problems Premature ejaculation Sexual desire disorders Performance anxiety and spectator role Psychiatric disorders Depression Anxiety Psychosis healthy men have an altered glucose tolerance curve. 10 The pathophysiologic mechanisms involved in the development of ED in diabetics are vascular, neuropathic, or due to gonadal dysfunction. Cardiovascular disease. Epidemiological studies have demonstrated that the presence of heart disease, high blood pressure, peripheral vascular disease, and decreased high-density lipoprotein (HDL)-cholesterol is associated with ED. 1 The prevalence of ED in hypertensive patients ranges from 15 47%, 1,11,12 depending on associated diseases and the presence or absence of pharmacological treatment. A study on the prevalence of ED in hypertensive patients in the autonomous community of Valencia was conducted on a sample of 507 hypertensive men and results found an ED prevalence of 46% (95% CI 42 51), of which 6% was severe and 5% was moderate. 12 Furthermore, high blood pressure, smoking, diabetes mellitus, and hyperlipidemia were more frequent in subjects with ED than in the general population. Smoking. Smoking has been shown to be associated with ED independent of smoking-related chronic diseases. 1,13 Secondary to prescribed medications. Approximately 25% of ED cases have been associated with drug use (Table 2). 14 Secondary to recreational drug use. Both the abuse of alcohol and of other drugs (cocaine, heroin) has been associated with ED. 1 Mood disorders. In the MMAS, 1 approximately 90% of men with severe depression, 60% of men with moderate depression, and 25% of men with mild depression reported having moderate or severe ED. Diagnosis These data suggest that ED should be considered a highly prevalent health problem, which makes it advisable that both primary and secondary physicians participate in patient care to optimize diagnosis and treatment. Investigation of erectile function, particularly in men with risk factors for ED (hypertension, diabetes, heart disease, and so on), should be a systematic practice of both family physicians and other specialists. All men with the aforementioned risk factors should be questioned in a natural and opportune manner about erectile function. A simple way to ask the patient is to use the following question: Some patients, such as diabetics, experience sexual problems. Has this happened to you? Specific questionnaires such as the International Index of

4 Erectile Function (IIEF) and the Sexual Health Inventory for Men (SHIM) may present additional tools. The IIEF 15 is a simple and easy-to-administer test with good sensitivity and specificity. The IIEF has been translated and validated in several languages, including European Spanish. It consists of 15 questions that assess male sexual function in five domains: erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. It has been shown that the erectile function domain, which includes six questions (maximum score of 30), provides a reliable measurement for classifying the severity of ED as mild, moderate, or severe. This questionnaire is usually reserved to standardize the diagnoses in epidemiological studies, grade the severity of ED, and quantify the impact of different treatments for ED (Appendix A). A shortened version of the IIEF, the SHIM, 16 has been developed to provide a more rapid diagnostic tool for ED. It consists of five questions (#5, 15, 4, 12, and 7 from the IIEF) and also has high sensitivity and specificity. It has also been translated and validated in European Spanish. The principal use for the SHIM is as a screening test for subjects with risk factors for ED. Subjects with a score of 21 or lower are diagnosed with ED (Appendix B). After a patient has been diagnosed with ED, a thorough medical history should be taken to determine the most likely cause, differentiating between a predominantly organic or psychogenic cause (Table 4). The following sections should be included. Sexual history 1. Duration: How long has the patient had this problem: months or years? 2. Form of onset: How did it start? Was it insidious, progressive, or abrupt? 3. Type of course: Did the problem worsen progressively or intermittently, with good and bad periods? Table 4 Differential diagnosis of organic and psychogenic ED Characteristics Organic ED Pyschogenic ED Age 450 y o40 y Onset Gradual Sudden Duration 41y o1y Occurrence Persistent Situational Course Constant Variable Extracoital erection Poor Rigid Psychosexual problems Secondary Long history Partner problems Secondary At start Anxiety and fear Secondary Primary 4. Is the quality of erection currently sufficient for the patient to have sexual intercourse with his partner? 5. Quality of erection in other situations: Does the patient have nocturnal or morning erections, erections with masturbation, erotic images, or another partner? 6. Is sexual desire normal, diminished, or absent? 7. Does the patient have normal, premature, or delayed ejaculation or anejaculation? 8. What are the patient s and partner s expectations? Is the partner willing to cooperate? Does the couple have a reasonable good relationship? How knowledgeable are they about sexual function? 9. Does the patient s partner have a sexual function disorder (hypoactive sexual desire, orgasmic disorder, or dyspareunia)? Medical history (Refer to Tables 1 3) 1. Presence of chronic diseases, hypertension, peripheral vascular disease, endocrine disorders, and so on. 2. Pharmacological treatments that the patient is currently receiving that may be associated with ED. 3. Substance abuse (tobacco, alcohol, drugs). 4. Presence of mood disorders (depression, anxiety). 5. Abdominal or pelvic trauma or surgery. Social history. Stressful situations such as a change in social status, divorce, death of spouse, loss of job, family problems, and so on may influence ED. 17 Physical examination. When the etiology of ED has not been established in a patient, the physical examination should focus on ruling out the following causes: Vascular diseases: measurement of blood pressure and heart rate, palpation of peripheral pulses, presence of peripheral vascular bruits (abdominal, femoral). Neurological diseases: the superficial anal reflex (assessed by touching the perianal skin and noting contraction of the external anal sphincter muscles) and bulbocavernous reflex (performed by placing a finger in the rectum and noting its contraction when the glans penis is squeezed); normal reflexes indicate the integrity of sacral nerve roots. Genital disorders: examination of the penis (presence of fibrous plaques suggesting Peyronie s disease, presence of phimosis, and so on) and scrotal content (examination of size and consistency of testes). Endocrine diseases: palpation of neck (goiter), breasts (gynecomastia), testicles, and secondary sexual characteristics. S29

5 S30 When prostate gland disease should be excluded owing to the age of the patient or before the start of treatment with testosterone, digital rectal examination should be performed to assess the size, symmetry, and consistency of the prostate gland. 18 Laboratory tests. The most likely cause of ED may be identified based on the following information in most cases. However, if the cause remains unclear or the patient requests a definitive pathophysiologic diagnosis, the patient should be referred to a specialist to complete the diagnosis: fasting blood glucose; lipid profile; determination of free (preferred) or total testosterone in men over 50 or in younger men in the presence of symptoms of hypogonadism (diminished sexual desire, bilateral testicular volume, or secondary sexual characteristics); other determinations are optional and should be requested on an individualized basis: * complete blood count, * renal function: if impaired renal function is suspected, * hepatic function: if impaired hepatic function is suspected, * luteinizing hormone: only if testosterone is decreased, * prolactin: if testosterone is decreased and/or diminished sexual desire is present, * thyroid-stimulating hormone and free T4 : if thyroid disease is suspected, * plasma and/or 24-h urinary free cortisol if accompanied by manifestations of adrenal dysfunction. 18 Treatment Because ED is often triggered by multiple factors, therapeutic intervention should cover the various aspects involved and be patient-oriented, based on his expectations and wishes. The patient s partner should participate in both the discussion and choice of treatment. Basic interventions common to any type of erectile dysfunction. Sexual counseling: ED is a multifactorial process with broad variations in both its severity and the way it is experienced by each patient or partner, depending on their expectations about the final outcome of the sexual encounter. A comprehensive approach addressing both psychosexual and purely organic aspects is important. Physicians from any specialty should keep this perspective in mind when treating a patient with ED. A series of basic sexual recommendations are listed below that the physician should convey to all patients to help improve the quality of their sexual relations. This is the main goal of treatment, in addition to improving ED. Convey to the patient that he has an erection problem, but that it does not make him impotent or diminish his value as a person or as a man. This implies challenging the traditional model of sexual prowess. Although an erection is an important variable in male sexuality, it is not the only variable, and it is possible to have a satisfactory sex life without an erection. Encourage flexible and spontaneous sexual relations, where sensuality and tenderness play an important role, where there are no excessive and unrealistic expectations. The partner will usually have to take part in the treatment process. Explore and combat negative myths that are commonly linked to ED: * ED does not necessarily imply that the couple has an emotional conflict. * ED, even if due to a predominantly psychological cause, does not imply that the patient has a deep psychological disorder. * ED does not necessarily imply that the man has lost sexual interest for his partner or is having extramarital sexual relations. * In principle, only the excitation phase is affected by ED. The man can still feel desire and sensual pleasure. Intervene on lifestyle by making the patient see the importance of stress and excess work on sexuality. To have satisfactory sexual relations, a certain emotional climate needs to be cultivated: a relaxed atmosphere, no time pressures, not being exhausted. This is difficult to achieve with many current lifestyles, but it is essential to stress the importance of devoting time to oneself and to the relationship with the partner, and the impact this has on general health. Convey from the start that the patient and his partner must cultivate a climate of tolerance of frustration ( things do not always go well, there may be ups and down in treatment ) and a certain sense of humor, which will make things easier. Regardless of the etiology, any patient with this disorder develops a series of dysfunctional mechanisms. Basically, an excess of self-observation and a lack of attention toward erotic stimuli, together with a series of negative expectations, will lead the patient to evaluate constantly his erectile function and contribute to aggravating the problem and distorting the couple s sexual communication. To break this vicious circle, it can be recommended to the couple if considered appropriate based on their history to vary the dynamics of their sexual relationship slightly, giving

6 more emphasis to nongenital caressing with a nonevaluative attitude, in which cultivating sensuality is the most important goal. This is one of the basic resources of sexual therapy, and it is useful to break the routines of self-observation that may have been created. Lifestyle modification: Quitting smoking is recommended because of its importance as a cardiovascular risk factor and for general health. 19 Although it may be useful in patients with early detumescence, quitting smoking alone does not appear to reverse ED in older men. 20 Reduction of alcohol intake should be recommended, 21 although it may not reverse ED. 22 Regular exercise may help reduce the risk of ED. 4 Reduction of excess weight, dietary fat intake, and in general, any behavioral change that promotes an improvement in physical and mental well-being is likely to have a positive effect on sexual function. 22 Drugs: In patients who are taking a medication associated with ED, a trial without this agent or switching to another drug that causes fewer EDrelated side effects should be attempted whenever possible. 4,22 Treatment of associated medical conditions: Treatment and optimal control of medical conditions associated with ED (diabetes, hypertension, dyslipidemia, and so on) is essential but may not be sufficient to control ED. Etiologic treatments A therapeutic intervention with curative intention may be performed in certain cases. These patients are usually young subjects who have a complicated psychogenic etiology, pelvic or perineal trauma, or an underlying hormonal cause. In these cases, treatment should be performed in the secondary care setting. Sex therapy. Sex therapy is indicated in cases of ED that are psychogenic in origin or that have significant psychogenic components. This is a specialized form of psychotherapy, which should be carried out by physicians or psychologists specialized in sexology. The methods used are described in more detail in another article within this supplement entitled Specific aspects of erectile dysfunction in sexology. Revascularization surgery. Revascularization surgery has a curative intention when ED is an arterial cause or is the consequence of pelvic or perineal trauma in a young subject without cardiovascular risk factors. Both diagnosis and treatment of this condition require a highly specialized setting. Hormone therapy. Hormone therapy is indicated when hormonal disorders are the cause of ED, and it should be managed by a specialist. Symptomatic treatments Most patients with ED will benefit from symptomatic treatments, specifically those that may be used regardless of the cause of ED. These are safe and effective treatments that are classified, based on the difficulty of their management, as first-, second-, and third-line treatments. Primary care physicians who are not specialists in ED may prescribe first-line treatments, but second- and third-line treatments should only be reserved for specialists who have greater knowledge of the disease and the capacity to respond to potential immediate or late complications. First-line treatments. Oral drugs: Sildenafil citrate, owing to its proven efficacy and safety, is currently considered one of the drugs of choice for initial treatment of ED. 23,24 Sildenafil is a potent selective inhibitor of phosphodiesterase type 5 (PDE5). It restores the natural response of the body to sexual stimulation by inducing smooth muscle relaxation in the corpus cavernosum, permitting an erection to be obtained and maintained. 25,26 Prior sexual desire and stimulation are necessary to re-establish erection. The onset of its therapeutic effect occurs min after administration, and the ability to achieve an erection persists for 4 5 h. Ingestion of high-fat foods may delay the onset of action. Sildenafil does not interact with alcohol; however, consumption of large amounts of alcohol can impair sexual function. For therapeutic trials, patients are administered a first dose of 50 mg of sildenafil. If this dose is ineffective, a second dose of 50 mg can be repeated on a different day. If the second dose is still ineffective, a third, fourth, and fifth dose of 100 mg can be attempted. The maximum dose is 100 mg per day. If the 50-mg dose is effective, the effectiveness of a 25-mg dose may be tested. Sildenafil is effective for 61 87% of patients with ED, 23,25 33 compared with 8 53% in placebotreated patients. The number needed to treat (NNT) to achieve an erection is 1.8 (95% CI ). 34 After 6 y of experience, sildenafil has shown to be effective for the treatment of ED in diabetes, hypertension, heart disease, radical prostatectomy, spinal cord injury, multiple sclerosis, depression, radiotherapy, spina bifida, dialysis, and transplant recipients. 23,25 33 The most common side effects are facial flushing, headache, dyspepsia, rhinitis, and vision S31

7 S32 disturbances. Side effects are more frequent with increasing doses and are usually mild to moderate in intensity. The number of discontinuations due to side effects is low and similar to that occurring with placebo. Priapism was not observed in any of the clinical studies. Treatment with sildenafil did not produce a higher incidence of acute myocardial infarction or angina in either clinical trials or postmarketing studies. 35 The major contraindications of sildenafil are concomitant treatment with nitrates or nitric oxide donating drugs (including amyl nitrite poppers), patients in whom sexual activity is inadvisable (those with unstable angina, severe heart failure, recent infarction), and patients who are allergic or intolerant to the drug. Tadalafil and vardenafil are two new oral drugs recently released in Spain for the treatment of ED. Because these drugs are so new, no consensus has been reached on the possible role they have in clinical practice. Both are potent and selective PDE5 inhibitors, thus acting through the same mechanism of action as sildenafil. No head-to-head comparative studies of these drugs have been published. Limited experience with these drugs shows that they may have similar clinical efficacy of sildenafil; however, more efficacy data are needed. Some differences can be observed in the selectivity profile of tadalafil that may influence its safety data, and also the pharmacokinetic profile, which may offer a longer therapeutic window for most patients. Data, again, are needed. Sublingual apomorphine is another oral drug available for treatment of ED. Apomorphine is a dopaminergic agonist that acts centrally by increasing the signal sent from brain centers (hypothalamus) through the spinal cord and spinal centers to the penis, enhancing smooth muscle relaxation and consequently erection. Apomorphine is administered sublingually. The tablet typically dissolves within 10 min and is unaffected by the ingestion of food. An erectile response may occur within approximately 20 min of sexual stimulus. Treatment begins at 2 mg and should be increased to 3 mg if there is no response, or there is an inadequate response after 2 doses. The dose can be repeated every 8 h. In phase III clinical trials of apomorphine, a positive response was seen in approximately 45% of subjects treated with 2 mg and approximately 50% of subjects receiving 3 mg. Postmarketing experience is limited, and thus efficacy data are not available in specific patient populations, such as patients with spinal cord injury, multiple sclerosis, radical prostatectomy, pelvic surgery, or diabetes. The most frequent side effects are nausea and headache. Fainting (syncope), which is preceded by prodromes (eg, sweating or dizziness), may also occur. Concurrent alcohol intake may cause an increase in the incidence and extent of hypotension. Treatment with apomorphine is contraindicated in patients in whom sexual activity is inadvisable (those with unstable angina, severe heart failure, recent infarction) and in patients who are allergic or intolerant to the drug. 36 The clinical use of apomorphine has been largely disappointing owing to its lack of efficacy at the recommended doses. It is no longer considered a true alternative to sildenafil, and its use is limited to patients in whom sildenafil is contraindicated. Vacuum devices and constriction rings: Vacuum devices may be useful in patients with ED related to various causes. Although they may limit spontaneity and affect ejaculation, a low incidence of side effects and low cost are important considerations. Patient satisfaction rates are high, and complications are generally minimal; however, they are infrequently used. When the initial erection is satisfactory, yet the problem is premature detumescence, constriction rings may be used. They are applied at the base of the penis, where they block venous return, thereby maintaining the erection. As with vacuum devices, they can be used only for a short period not exceeding 30 min, owing to the need for oxygenation of penile smooth muscle. 37 Second-line treatments. When first-line treatments fail or cannot be used, a more aggressive level of therapy is needed. In second-line treatments, the physician must possess sufficient training and, as previously mentioned, the capacity to respond in the event of immediate or late complications. Treatments with intraurethral or topical drugs are not mentioned because they are currently unavailable in Spain, and therefore only intracavernous administration of vasoactive drugs is discussed. Alprostadil is a prostaglandin (PGE 1 ) that acts by relaxing smooth muscle. It is administered by intracavernous injection, which the patient self-injects after a period of training. When used as monotherapy, alprostadil has an overall efficacy of over 70% and very few side effects, although some of them require immediate action. Immediate side effects include pain after injection, which may require discontinuing or changing treatment, and prolonged erection (over 4 h), which may require pharmacological reversal and, in extreme cases, surgical shunting. Fibrosis of the corpora cavernosa, usually related to poor injection

8 technique, may occur as a late complication and may resolve with treatment discontinuation. There is a high dropout rate over time. However, close monitoring of patients in a self-injection program reduces the number of dropouts. 38 Papaverine is a nonspecific inhibitor of phosphodiesterases. It is used in combination with PGE1 and/or phentolamine, and reduces the side effects of PGE and benefits patients who are nonresponders to PGE1 alone. Phentolamine is a nonspecific alpha-blocker that inhibits the contraction of smooth muscle, thus enhancing its relaxation. It is used in combination with the two previous drugs, and enhances efficacy synergistically. There are other drugs for intracavernous injection, but they are not available in Spain and are not discussed here. Despite the effectiveness of these drugs, the risk of serious adverse effects, such as priapism, and the requirement that they be prescribed by a specialist make their use inadvisable in the primary care setting. Third-line treatments. When previous treatments have failed, more aggressive therapy (surgery) is required. These treatments are reserved for urologists/andrologists who are specialized in ED. Revascularization surgery: There are two types of revascularization surgeries: 1. Venous: Although used by some as nonspecific treatment in cases of venous leakage, because of the poor results its usefulness is currently questioned. 2. Arterial: The indication for arterial revascularization was previously described in the section on specific treatments. Penile prosthesis: Penile prostheses represent the last treatment option, not because of the lack of efficacy, but because of the aggressiveness of treatment. The satisfaction rate in patients implanted with the most recent generations of prostheses is higher than 90%, and the major drawbacks, including infection and mechanical failure, are currently below 5%. 39 It is important to stress that implantation of a penile prosthesis does not imply any action on the orgasmic or ejaculatory capacity, or sexual desire of the patient; however, these are increased with the ability to obtain an erection. Penile prosthesis, especially the three-piece hydraulic prosthesis, restores a nearly natural physiological erection. However, it should be remembered that it is a mechanical device inserted inside the penis, which must be inflated and deflated for use. Referral criteria In summary, the cases in which nonspecific firstline treatments should not be attempted because the diagnosis of the patient needs to be further investigated through appropriate collaboration of the specialists involved are listed below: 1. Penile diseases. 2. Young men with a history of pelvic or perineal trauma. 3. Patients requiring vascular or neurological diagnosis. 4. Patients with intermediate or high cardiovascular risk in whom sexual activity is inadvisable. 5. Complicated endocrinopathies. 6. Complicated psychiatric or psychosexual problems. 7. When the patient or his physician wishes to perform additional studies to establish a pathophysiologic diagnosis. 4 Decision and referral algorithms are shown in Appendices C and D, which may serve as a guide for all healthcare professionals who manage ED. References 1 Feldman HA et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: Althof SE. Quality of life and erectile dysfunction. Urology 2002; 59: NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: Guideline for the investigation and management of erectile dysfunction. Alberta Medical Association, , Edmonton, AB, June 2001, p 9. 5 Martin-Morales A et al. Prevalence and independent risk factors for erectile dysfunction in Spain: results of the Epidemiologia de la Disfuncion Erectil Masculina Study. J Urol 2001; 166: , discussion Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin N Am 1995; 22: McCulloch DK et al. The prevalence of diabetic impotence. Diabetologia 1980; 18: Fedele D et al. Erectile dysfunction in type 1 and type 2 diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici. Int J Epidemiol 2000; 29: Nathan DM, Singer DE, Godine JE, Perlmuter LC. Non-insulindependent diabetes in older patients. Complications and risk factors. Am J Med 1986; 81: DeWire DM. Evaluation and treatment of erectile dysfunction. Am Fam Physician 1996; 53: Jensen J et al. The prevalence and etiology of impotence in 101 male hypertensive outpatients. Am J Hypertens 1999; 12: Cuellar de Leon AJ et al. [Prevalence erectile dysfunction in patients with hypertension]. Med Clin (Barc) 2002; 119: Rosen MP et al. Cigarette smoking: an independent risk factor for atherosclerosis in the hypogastric-cavernous arterial bed of men with arteriogenic impotence. J Urol 1991; 145: S33

9 S34 14 Keene LC, Davies PH. Drug-related erectile dysfunction. Adverse Drug React Toxicol Rev 1999; 18: Rosen RC et al. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: Rosen RC et al. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 1999; 11: Miller TA. Diagnostic evaluation of erectile dysfunction. Am Fam Physician 2000; 61: , Ralph D, McNicholas T. UK management guidelines for erectile dysfunction. BMJ 2000; 321: Jeremy JY, Mikhailidis DP. Cigarette smoking and erectile dysfunction. J R Soc Health 1998; 118: Derby CA et al. Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology 2000; 56: Jardin A, Wagner G, Khouri Sea. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A, Wagner G, Khouri S, Giuliano F, Padma-Nathan H, Rosen R (eds). Erectile Dysfunction. Health Publication Ltd: Plymouth UK, 2000, pp Greiner KA, Weigel JW. Erectile dysfunction [see comments]. Am Fam Physician 1996; 54: Goldstein I et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 1998; 338: Morales A et al. Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res 1998; 10: Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 1996; 78: Eardley I et al. Sildenafil (VIAGRA [R] ), a novel oral treatment with rapid onset of action for penile erectile dysfunction [abstract]. Br J Urol 1997; 79(Suppl 4): Buvat J et al. Sildenafil (VIAGRAt), an oral treatment for erectile dysfunction: a 1-year, open-label, extension study [abstract]. J Urol 1997; 157: 204, abstract Lue T. Sildenafil study group: a study of sildenafil, a new oral agent for treatment of male erectile dysfunction. J Urol 1997; 157(Suppl): Rendell MS et al. Sildenafil for treatment of erectile dysfunction in men with diabetes. JAMA 1999; 281: Derry F et al. Sildenafil (Viagra) a double blind, placebocontrolled, single dose, two-way crossover study in men with erectile dysfunction caused by traumatic spinal cord injury. J Urol 1997; 157(Suppl): Quirk F et al. Effect of sildenafil (VIAGRAt) on quality-of-life parameters in men with broad-spectrum erectile dysfunction. J Urol 1998; 159: 260, abstract Hatzichristou DG. Sildenafil citrate: lessons learned from 3 years of clinical experience. Int J Impot Res 2002; 14(Suppl 1): S43 S Guay AT, Perez JB, Jacobson J, Newton RA. Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors. J Androl 2001; 22: Brotons Munto F et al. Manejo de las disfuncion erectil en atencio primaria. JANO Med Humanidades 1998; 55: Arruda AM, Mahoney DW, Nehra A, Pellikka PA. Cardiovascular effects of sildenafil citrate (Viagra) during exercise in patients with known or probable coronary artery disease. Presented at the Third World Congress on the Aging Male, February 7 10, 2002, Berlin, Germany. 36 Altwein JE, Keuler FU. Oral treatment of erectile dysfunction with apomorphine SL. Urol Int 2001; 67: Cookson MS, Nadig PW. Long-term results with vacuum constriction device. J Urol 1993; 149: Rodriguez Vela L et al. Tratamiento de la disfuncion erectil mediante farmacoterapia intracavernosa. Actas Urol Esp 1998; 22: Mulhall JP, Ahmed A, Branch J, Parker M. Serial assessment of efficacy and satisfaction profiles following penile prosthesis surgery. J Urol 2003; 169:

10 Appendix A International Index of Erectile Function (IIEF) Patient initials Identification No. Date Are you sexually active (defined as sexual activity with partner or manual stimulation)? Yes & If yes, please complete the questionnaire regarding your sexual activity (mark only one box for each question) Over the past 4 weeks No & NO SEXUAL ACTIVITY NEVER OR NEVER A FEW TIMES (LESS THAN SOMETIMES (ABOUT HALF THE MOST TIMES (MORE THAN OR 1. How often were you able to get an erection during sexual activity? 2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration? 3. When you attempted sexual intercourse, how often were you able to penetrate your partner? 4. During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner? DID NOT ATTEMPT INTERCOURSE EXTREMELY DIFFICULT VERY DIFFICULT DIFFICULT SLIGHTLY DIFFICULT NOT DIFFICULT 5. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? NO ATTEMPTS 1 2 ATTEMPTS 3 4 ATTEMPTS 5 6 ATTEMPTS 7 10 ATTEMPTS 11 OR MORE ATTEMPTS 6. How many times have you attempted sexual intercourse?

11 DID NOT ATTEMPT INTERCOURSE NEVER OR NEVER A FEW TIMES (LESS THAN SOMETIMES (ABOUT HALF THE MOST TIMES (MORE THAN OR 7. When you attempted sexual intercourse, how often was it satisfactory to you? NO INTERCOURSE NO ENJOYMENT AT ALL NOT VERY ENJOYABLE FAIRLY ENJOYABLE HIGHLY ENJOYABLE VERY HIGHLY ENJOYABLE 8. How much have you enjoyed sexual intercourse? NO SEXUAL ACTIVITY NEVER OR NEVER A FEW TIMES (LESS THAN SOMETIMES (ABOUT HALF THE MOST TIMES (MORE THAN OR 9. When you had sexual stimulation or intercourse, how often did you ejaculate? 10. When you had sexual stimulation or intercourse, how often did you have the feeling of orgasm or climax? NO SEXUAL ACTIVITY NEVER OR NEVER A FEW TIMES (LESS THAN SOMETIMES (ABOUT HALF THE MOST TIMES (MORE THAN OR 11. When you had sexual stimulation or intercourse, how often did you ejaculate? 12. When you had sexual stimulation or intercourse, how often did you have the feeling of orgasm or climax? The following questions refer to sexual desire, defined as a feeling that includes wanting to have a sexual experience (for example, masturbation or intercourse), thinking about having sex, or feeling frustrated due to lack of sex.

12 NEVER OR NEVER A FEW TIMES (LESS THAN SOMETIMES (ABOUT MOST TIMES (MORE THAN OR 13. How often have you felt sexual desire? VERY LOW OR NONE AT ALL LOW MODERATE HIGH VERY HIGH 14. How would you rate your level of sexual desire? VERY DISSATISFIED MODERATELY DISSATISFIED EQUALLY SATISFIED AND DISSATISFIED MODERATELY SATISFIED VERY SATISFIED 15. How satisfied have you been with your overall sex life? 16. How satisfied have you been with your sexual relationship with your partner? VERY LOW OR NONE AT ALL LOW MODERATE HIGH VERY HIGH 17. How do you rate your confidence that you could get and keep an erection? Sexual intercourse ¼ penetration of the partner; sexual activity ¼ intercourse, caressing, foreplay, or masturbation; ejaculate ¼ the ejection of semen from the penis (or the feeling of semen ejecting from the penis); sexual stimulation ¼ includes situations such as caressing or foreplay prior to intercourse, looking at erotic photos, and so on.

13 Appendix B Sexual Health Inventory for Men (SHIM) Name of patient: Date of evaluation: Instructions for patient Sexual health is an important part of the emotional and physical well-being of an individual. ED is a very common medical condition that affects sexual health. Fortunately, there are several treatment options for this condition. This questionnaire was prepared to help you and your doctor to identify ED, should this be your case. If so, your doctor will advise you on the most appropriate treatment. Each question has several possible answers. Circle the answer that best describes your situation. Please make sure that you choose only one answer for each question. Over the last 6 months: 1. How do you rate your confidence that you could get an erection? Very low 1 Low 2 Moderate 3 High 4 Very High 5 2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration? No sexual activity 0 Almost never or never 1 A few times (less than half the time) 2 Sometimes (about half the time) 3 Most times (much more than half the time) 4 Almost always or always 5 3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner? Did not attempt sexual intercourse 0 Almost never or never 1 A few times (less than half the time) 2 Sometimes (about half the time) 3 Most times (much more than half the time) 4 Almost always or always 5 4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? Did not attempt sexual intercourse 0 Extremely difficult 1 Very difficult 2 Difficult 3 Slightly difficult 4 Not difficult 5 5. When you attempted sexual intercourse, how often was it satisfactory to you? Did not attempt sexual intercourse 0 Almost never or never 1 A few times (less than half the time) 2 Sometimes (about half the time) 3 Most times (much more than half the time) 4 Almost always or always 5 Score: If your score is less than or equal to 21, you are showing signs of erectile dysfunction. Your doctor can show you several treatment options that can improve your situation.

14 Appendix C S39 Decision Algorithm for Patients With Erectile Dysfunction Appendix D Referral Algorithm for Patients With Erectile Dysfunction