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International Journal of Impotence Research (2004) 16, S26–S39 & 2004 Nature Publishing Group All rights reserved 0955-9930/04 $30.00 www.nature.com/ijir

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

FB Brotons1*, JC Campos2, R Gonzalez-Correales3, A Martı´n-Morales4, I Moncada5 and JM Pomerol6

1Vila-real II Health Center, Castellon, Spain; 2Villamarxant Health Center, Valencia, Spain; 3Piedrabuena Health Center, Ciudad Real, Spain; 4Department of , Carlos Haya University Hospital, Malaga, Spain; 5Department of Urology, Gregorio Maranon University General Hospital, Madrid, Spain; and 6Department of , Fundacio´n 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 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 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 (, revascularization , 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. International Journal of Impotence Research (2004) 16, S26–S39. doi:10.1038/sj.ijir.3901240

Keywords: erectile dysfunction

Key aspects in the care of a patient with specialists. ED may also be an indicator for other erectile dysfunction: practical guide 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 Erectile dysfunction (ED) is one of the most frequent his partner.2 Taking these factors into consideration chronic health problems in men older than 40 y of with the current availability of safe and effective age1 and therefore is one of the most frequent treatments should prompt physicians to proactively reasons for consultation of family physicians and 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 sufficient for *Correspondence: FB Brotons, Vila-real II Health Center, satisfactory and does not include 3 Castellon, Spain. disorders of , , or . E-mail: [email protected] To rule out temporary disorders, the patient must Core document on erectile dysfunction FB Brotons et al S27 experience ED for at least 3 months,4 except in cases  Psychogenic ED: caused by central blockade of the of ED secondary to trauma or surgery. erectile mechanism without physical .  ED of mixed etiology: caused by a combination of physical and psychological factors. In the Prevalence vast majority of ED cases due to physical causes, a psychological component is also pre- sent. 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: Risk factors and causative diseases 17%; moderate: 25%; severe: 10%). The Epidemiology of Male Erectile Dysfunction (EDEM) study5 conducted on 2476 Spanish men The major causes of ED are listed in Tables 1–3. In between the ages of 25 and 70 y found some degree of most cases, the underlying cause of ED is a chronic ED in 12.1% of men (mild: 5.2%; moderate: 5%; severe: health problem or an adverse drug effect. The major 1.9%). Based on the census of the male population, the risk factors for ED are discussed in the following estimated prevalence of ED in Spain is 1.5–2 million sections. men. Of men aged 40–70 y, 17.7% are affected by ED, a lower prevalence than that reported in the MMAS. 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 Etiology considered an inevitable consequence of age be- cause 68% of men between 60 and 70 y of age did not have erection problems in the EDEM study.5 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 Diabetes. Diabetes is the endocrine disease most ED into the following categories:3,6 commonly associated with ED, and the probability of developing ED is three times higher in treated  Organic ED: organic causes may be secondary to diabetic men compared with nondiabetic men.1 vascular injury (the most common cause), neuro- Anywhere from 25 to 75% of diabetic men will genic, hormonal, or local. develop ED.1,7–9 It has been observed that 15% of

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 Spinal cord surgery Rectal amputation

CNS: central nervous system; hCG: human chorionic gonadotropin.

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S28 Table 2 Major drug-related causes of ED

Drugs with hormonal action Psychotropic drugs Antihypertensive drugs

Decrease or block the action of testosterone: Antipsychotics and neuroleptics: Sympathomimetics: clonidine, antiandrogens, estrogens, anabolic drugs, phenothiazines, thioxanthenes, thioridazines, methyldopa, reserpine, guanethidine steroids, spironolactone, ketoconazole, butyrophenones b-Adrenergic blockers: propranolol, digoxin, clofibrate, cimetidine Antidepressants: tricyclic antidepressants, pindolol, atenolol, metoprolol Increase prolactin levels: cimetidine, tetracyclic antidepressants, MAOIs, SSRIs Diuretics: spironolactone, thiazides metoclopramide, phenothiazines, , Anxiolytics: endorphins, tricyclic antidepressants, methyldopa

MAOIs: monoamine oxidase inhibitors; SSRIs: selective serotonin reuptake inhibitors.

Table 3 Some psychological and sexual causes of ED severe and 5% was moderate.12 Furthermore, high blood pressure, smoking, diabetes mellitus, and Partner conflicts hyperlipidemia were more frequent in subjects with Self-image problems Low self-esteem ED than in the general population. Social or work environment problems Smoking. Smoking has been shown to be asso- Factors related to sexual upbringing or education ciated with ED independent of smoking-related Highly restricted sexual upbringing 1,13 Erroneous sexual beliefs chronic diseases. Sexual traumas in childhood or first experiences in childhood Secondary to prescribed medications. Approxi- Excessive fear of or sexually transmitted diseases Other sexual and disorders mately 25% of ED cases have been associated with 14 drug use (Table 2). Sexual identity problems problems Secondary to recreational drug use. Both the abuse Sexual desire disorders of alcohol and of other drugs (cocaine, heroin) has Performance anxiety and spectator role been associated with ED.1 Psychiatric disorders 1 Anxiety Mood disorders. In the MMAS, 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.

healthy men have an altered glucose tolerance 10 curve. The pathophysiologic mechanisms in- Diagnosis volved in the development of ED in diabetics are vascular, neuropathic, or due to gonadal dysfunc- tion. These data suggest that ED should be considered a highly prevalent health problem, which makes it advisable that both primary and secondary Cardiovascular disease. Epidemiological studies physicians participate in patient care to optimize have demonstrated that the presence of heart diagnosis and treatment. Investigation of erectile disease, high blood pressure, peripheral vascular function, particularly in men with risk factors for disease, and decreased high-density lipoprotein ED (hypertension, diabetes, heart disease, and (HDL)-cholesterol is associated with ED.1 The pre- so on), should be a systematic practice of both valence of ED in hypertensive patients ranges from family physicians and other specialists. All men 15–47%,1,11,12 depending on associated diseases with the aforementioned risk factors should be and the presence or absence of pharmacological questioned in a natural and opportune manner treatment. A study on the prevalence of ED in about erectile function. A simple way to ask hypertensive patients in the autonomous commu- the patient is to use the following question: ‘Some nity of Valencia was conducted on a sample of 507 patients, such as diabetics, experience sexual hypertensive men and results found an ED preva- problems. Has this happened to you?’ Specific lence of 46% (95% CI 42–51), of which 6% was questionnaires such as the International Index of

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S29 Erectile Function (IIEF) and the Sexual Health 4. Is the quality of erection currently sufficient for Inventory for Men (SHIM) may present additional the patient to have sexual intercourse with his tools. partner? The IIEF15 is a simple and easy-to-administer test 5. Quality of erection in other situations: Does the with good sensitivity and specificity. The IIEF has patient have nocturnal or morning , been translated and validated in several languages, erections with , erotic images, or including European Spanish. It consists of 15 another partner? questions that assess male sexual function in five 6. Is sexual desire normal, diminished, or absent? domains: erectile function, orgasmic function, sex- 7. Does the patient have normal, premature, or ual desire, intercourse satisfaction, and overall delayed ejaculation or anejaculation? satisfaction. It has been shown that the erectile 8. What are the patient’s and partner’s expectations? function domain, which includes six questions Is the partner willing to cooperate? Does the (maximum score of 30), provides a reliable measure- couple have a reasonable good relationship? How ment for classifying the severity of ED as mild, knowledgeable are they about sexual function? moderate, or severe. This questionnaire is usually 9. Does the patient’s partner have a sexual function reserved to standardize the diagnoses in epidemio- disorder (hypoactive sexual desire, orgasmic logical studies, grade the severity of ED, and disorder, or )? quantify the impact of different treatments for ED (Appendix A). Medical history (Refer to Tables 1–3) A shortened version of the IIEF, the SHIM,16 has been developed to provide a more rapid 1. Presence of chronic diseases, hypertension, per- diagnostic tool for ED. It consists of five questions ipheral vascular disease, endocrine disorders, (#5, 15, 4, 12, and 7 from the IIEF) and also has and so on. high sensitivity and specificity. It has also been 2. Pharmacological treatments that the patient is translated and validated in European Spanish. The currently receiving that may be associated with principal use for the SHIM is as a screening test ED. for subjects with risk factors for ED. Subjects with 3. (tobacco, alcohol, drugs). a score of 21 or lower are diagnosed with ED 4. Presence of mood disorders (depression, anxiety). (Appendix B). 5. Abdominal or pelvic trauma or surgery. After a patient has been diagnosed with ED, a Social history. Stressful situations such as a thorough medical history should be taken to change in social status, divorce, death of spouse, determine the most likely cause, differentiating loss of job, family problems, and so on may between a predominantly organic or psychogenic influence ED.17 cause (Table 4). The following sections should be included. Physical examination. When the etiology of ED has Sexual history not been established in a patient, the physical examination should focus on ruling out the follow- 1. Duration: How long has the patient had this ing causes: problem: months or years? 2. Form of onset: How did it start? Was it insidious,  Vascular diseases: measurement of blood pressure progressive, or abrupt? and heart rate, palpation of peripheral pulses, 3. Type of course: Did the problem worsen progres- presence of peripheral vascular bruits (abdominal, sively or intermittently, with good and bad femoral). periods?  Neurological diseases: the superficial anal reflex (assessed by touching the perianal skin and noting contraction of the external anal sphincter mus- cles) and bulbocavernous reflex (performed by Table 4 Differential diagnosis of organic and psychogenic ED placing a finger in the rectum and noting its contraction when the glans is squeezed); Characteristics Organic ED Pyschogenic ED normal reflexes indicate the integrity of sacral nerve roots. Age 450 y o40 y  Genital disorders: examination of the penis (pre- Onset Gradual Sudden Duration 41y o1y sence of fibrous plaques suggesting Peyronie’s Occurrence Persistent Situational disease, presence of phimosis, and so on) and Course Constant Variable scrotal content (examination of size and consis- Extracoital erection Poor Rigid tency of testes). Psychosexual problems Secondary Long history Partner problems Secondary At start  Endocrine diseases: palpation of neck (goiter), Anxiety and fear Secondary Primary breasts (gynecomastia), testicles, and secondary sexual characteristics.

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S30  When prostate gland disease should be excluded A series of basic sexual recommendations are owing to the age of the patient or before the start of listed below that the physician should convey to all treatment with testosterone, digital rectal exam- patients to help improve the quality of their sexual ination should be performed to assess the size, relations. This is the main goal of treatment, in symmetry, and consistency of the prostate gland.18 addition to improving ED.

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

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S31 more emphasis to nongenital caressing with a Hormone therapy. Hormone therapy is indicated nonevaluative attitude, in which cultivating sen- when hormonal disorders are the cause of ED, and it suality is the most important goal. This is one of should be managed by a specialist. the basic resources of sexual therapy, and it is useful to break the routines of self-observation that may have been created. Symptomatic treatments Lifestyle modification: Quitting smoking is recom- mended because of its importance as a cardiovas- Most patients with ED will benefit from sympto- cular risk factor and for general health.19 Although it matic treatments, specifically those that may be may be useful in patients with early detumescence, used regardless of the cause of ED. These are safe quitting smoking alone does not appear to reverse and effective treatments that are classified, based on ED in older men.20 Reduction of alcohol intake the difficulty of their management, as first-, second-, should be recommended,21 although it may not and third-line treatments. Primary care physicians reverse ED.22 who are not specialists in ED may prescribe first-line Regular exercise may help reduce the risk of ED.4 treatments, but second- and third-line treatments Reduction of excess weight, dietary fat intake, and should only be reserved for specialists who have in general, any behavioral change that promotes an greater knowledge of the disease and the capacity to improvement in physical and mental well-being is 22 respond to potential immediate or late complica- likely to have a positive effect on sexual function. tions. Drugs: In patients who are taking a associated with ED, a trial without this agent or switching to another drug that causes fewer ED- First-line treatments. Oral drugs: Sildenafil citrate, related side effects should be attempted whenever owing to its proven efficacy and safety, is currently possible.4,22 considered one of the drugs of choice for initial Treatment of associated medical conditions: treatment of ED.23,24 Treatment and optimal control of medical condi-  Sildenafil is a potent selective inhibitor of tions associated with ED (diabetes, hypertension, phosphodiesterase type 5 (PDE5). It restores the dyslipidemia, and so on) is essential but may not be natural response of the body to sufficient to control ED. by inducing smooth muscle relaxation in the corpus cavernosum, permitting an erection to be obtained and maintained.25,26 Prior sexual desire Etiologic treatments and stimulation are necessary to re-establish erection. The onset of its therapeutic effect occurs 30–60 min after administration, and the ability to A therapeutic intervention with curative intention achieve an erection persists for 4–5 h. Ingestion of may be performed in certain cases. These patients high-fat foods may delay the onset of action. are usually young subjects who have a complicated Sildenafil does not interact with alcohol; how- psychogenic etiology, pelvic or perineal trauma, ever, consumption of large amounts of alcohol can or an underlying hormonal cause. In these cases, impair sexual function. treatment should be performed in the secondary  For therapeutic trials, patients are administered a care setting. 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 Sex therapy. Sex therapy is indicated in cases of still ineffective, a third, fourth, and fifth dose of ED that are psychogenic in origin or that have 100 mg can be attempted. The maximum dose is significant psychogenic components. This is a 100 mg per day. If the 50-mg dose is effective, the specialized form of psychotherapy, which should effectiveness of a 25-mg dose may be tested. be carried out by physicians or psychologists  Sildenafil is effective for 61–87% of patients with specialized in . The methods used are ED,23,25–33 compared with 8–53% in placebo- described in more detail in another article within treated patients. The number needed to treat this supplement entitled ‘Specific aspects of erectile (NNT) to achieve an erection is 1.8 (95% CI 1.5– dysfunction in sexology’. 2.3).34 After 6 y of experience, sildenafil has shown to be effective for the treatment of ED in Revascularization surgery. Revascularization sur- diabetes, hypertension, heart disease, radical gery has a curative intention when ED is an arterial prostatectomy, spinal cord injury, multiple sclero- cause or is the consequence of pelvic or perineal sis, depression, radiotherapy, spina bifida, dialy- trauma in a young subject without cardiovascular sis, and transplant recipients.23,25–33 risk factors. Both diagnosis and treatment of this  The most common side effects are flush- condition require a highly specialized setting. ing, headache, dyspepsia, rhinitis, and vision

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S32 disturbances. Side effects are more frequent with tatectomy, pelvic surgery, or diabetes. The most increasing doses and are usually mild to moderate frequent side effects are nausea and headache. in intensity. The number of discontinuations due Fainting (syncope), which is preceded by prodromes to side effects is low and similar to that occurring (eg, sweating or dizziness), may also occur. Con- with placebo. Priapism was not observed in any of current alcohol intake may cause an increase in the the clinical studies. Treatment with sildenafil did incidence and extent of hypotension. not produce a higher incidence of acute myocar-  Treatment with apomorphine is contraindicated dial infarction or angina in either clinical trials or in patients in whom sexual activity is inadvisable postmarketing studies.35 (those with unstable angina, severe heart failure,  The major contraindications of sildenafil are recent infarction) and in patients who are allergic concomitant treatment with nitrates or nitric or intolerant to the drug.36 oxide–donating drugs (including amyl nitrite poppers), patients in whom sexual activity is The clinical use of apomorphine has been largely inadvisable (those with unstable angina, severe disappointing owing to its lack of efficacy at the heart failure, recent infarction), and patients who recommended doses. It is no longer considered a are allergic or intolerant to the drug. true alternative to sildenafil, and its use is limited to patients in whom sildenafil is contraindicated. Tadalafil and vardenafil are two new oral drugs recently released in Spain for the treatment of ED. Vacuum devices and constriction rings: Vacuum Because these drugs are so new, no consensus has devices may be useful in patients with ED related to been reached on the possible role they have in various causes. Although they may limit spontane- clinical practice. ity and affect ejaculation, a low incidence of side effects and low cost are important considerations.  Both are potent and selective PDE5 inhibitors, Patient satisfaction rates are high, and complica- thus acting through the same mechanism of action tions are generally minimal; however, they are as sildenafil. infrequently used. When the initial erection is  No head-to-head comparative studies of these satisfactory, yet the problem is premature detumes- drugs have been published. Limited experience cence, constriction rings may be used. They are with these drugs shows that they may have similar applied at the base of the penis, where they block clinical efficacy of sildenafil; however, more venous return, thereby maintaining the erection. As efficacy data are needed. with vacuum devices, they can be used only for a short period not exceeding 30 min, owing to the  Some differences can be observed in the selectiv- 37 ity profile of tadalafil that may influence its safety need for oxygenation of penile smooth muscle. data, and also the pharmacokinetic profile, which may offer a longer therapeutic window for most Second-line treatments. When first-line treatments patients. Data, again, are needed. fail or cannot be used, a more aggressive level of therapy is needed. In second-line treatments, the Sublingual apomorphine is another oral drug physician must possess sufficient training and, as available for treatment of ED. previously mentioned, the capacity to respond in  Apomorphine is a dopaminergic agonist that acts the event of immediate or late complications. centrally by increasing the signal sent from brain Treatments with intraurethral or topical drugs are centers (hypothalamus) through the spinal cord not mentioned because they are currently unavail- and spinal centers to the penis, enhancing smooth able in Spain, and therefore only intracavernous muscle relaxation and consequently erection. administration of vasoactive drugs is discussed.  Apomorphine is administered sublingually. The Alprostadil is a prostaglandin (PGE1) that acts by tablet typically dissolves within 10 min and is relaxing smooth muscle. unaffected by the ingestion of food.  An erectile response may occur within approxi-  It is administered by intracavernous injection, mately 20 min of sexual stimulus. which the patient self-injects after a period of  Treatment begins at 2 mg and should be increased training. to 3 mg if there is no response, or there is an  When used as monotherapy, alprostadil has an inadequate response after 2 doses. The dose can overall efficacy of over 70% and very few side be repeated every 8 h. effects, although some of them require immediate  In phase III clinical trials of apomorphine, a positive action. response was seen in approximately 45% of subjects  Immediate side effects include pain after injection, treated with 2 mg and approximately 50% of which may require discontinuing or changing subjects receiving 3 mg. Postmarketing experience treatment, and prolonged erection (over 4 h), which is limited, and thus efficacy data are not available in may require pharmacological reversal and, in specific patient populations, such as patients with extreme cases, surgical shunting. Fibrosis of the spinal cord injury, multiple sclerosis, radical pros- corpora cavernosa, usually related to poor injection

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S33 technique, may occur as a late complication and Referral criteria may resolve with treatment discontinuation.  There is a high dropout rate over time. However, close monitoring of patients in a self-injection In summary, the cases in which nonspecific first- program reduces the number of dropouts.38 line treatments should not be attempted because the diagnosis of the patient needs to be further investi- Papaverine is a nonspecific inhibitor of phospho- gated through appropriate collaboration of the diesterases. specialists involved are listed below:  It is used in combination with PGE1 and/or 1. Penile diseases. phentolamine, and reduces the side effects of 2. Young men with a history of pelvic or perineal PGE and benefits patients who are nonresponders trauma. to PGE1 alone. 3. Patients requiring vascular or neurological diag- nosis. Phentolamine is a nonspecific alpha-blocker that 4. Patients with intermediate or high cardiovascular inhibits the contraction of smooth muscle, thus risk in whom sexual activity is inadvisable. enhancing its relaxation. 5. Complicated endocrinopathies.  It is used in combination with the two previous 6. Complicated psychiatric or psychosexual pro- drugs, and enhances efficacy synergistically. blems. 7. When the patient or his physician wishes to There are other drugs for intracavernous injection, perform additional studies to establish a patho- but they are not available in Spain and are not physiologic diagnosis.4 discussed here. Despite the effectiveness of these drugs, the risk of Decision and referral algorithms are shown in serious adverse effects, such as priapism, and the Appendices C and D, which may serve as a guide for requirement that they be prescribed by a specialist all healthcare professionals who manage ED. make their use inadvisable in the primary care setting.

Third-line treatments. When previous treatments References have failed, more aggressive therapy (surgery) is required. These treatments are reserved for urolo- 1 Feldman HA et al. Impotence and its medical and psychoso- gists/andrologists who are specialized in ED. cial correlates: results of the Massachusetts Male Aging Study. Revascularization surgery: There are two types of J Urol 1994; 151: 54–61. revascularization : 2 Althof SE. Quality of life and erectile dysfunction. Urology 2002; 59: 803–810. 1. Venous: Although used by some as nonspecific 3 NIH Consensus Conference. Impotence. NIH Consensus treatment in cases of ‘venous leakage’, because of Development Panel on Impotence. JAMA 1993; 270: 83–90. 4 Guideline for the investigation and management of erectile the poor results its usefulness is currently ques- dysfunction. Alberta Medical Association, 1630008, Edmonton, tioned. AB, June 2001, p 9. 2. Arterial: The indication for arterial revasculariza- 5 Martin-Morales A et al. Prevalence and independent risk tion was previously described in the section on factors for erectile dysfunction in Spain: results of the Epidemiologia de la Disfuncion Erectil Masculina Study. specific treatments. J Urol 2001; 166: 569–574, discussion 574–575. Penile prosthesis: Penile prostheses represent the 6 Benet AE, Melman A. The epidemiology of erectile dysfunc- tion. Urol Clin N Am 1995; 22: 699–709. last treatment option, not because of the lack of 7 McCulloch DK et al. The prevalence of diabetic impotence. efficacy, but because of the aggressiveness of treat- Diabetologia 1980; 18: 279–283. ment. The satisfaction rate in patients implanted 8 Fedele D et al. Erectile dysfunction in type 1 and type 2 with the most recent generations of prostheses is diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici. Int J Epidemiol 2000; 29: 524–531. higher than 90%, and the major drawbacks, includ- 9 Nathan DM, Singer DE, Godine JE, Perlmuter LC. Non-insulin- ing infection and mechanical failure, are currently dependent diabetes in older patients. Complications and risk 39 below 5%. It is important to stress that implanta- factors. Am J Med 1986; 81: 837–842. tion of a penile prosthesis does not imply any action 10 DeWire DM. Evaluation and treatment of erectile dysfunction. on the orgasmic or ejaculatory capacity, or sexual Am Fam Physician 1996; 53: 2101–2108. 11 Jensen J et al. The prevalence and etiology of impotence in desire of the patient; however, these are increased 101 male hypertensive outpatients. Am J Hypertens 1999; 12: with the ability to obtain an erection. 271–275. Penile prosthesis, especially the three-piece hy- 12 Cuellar de Leon AJ et al. [Prevalence erectile dysfunction in draulic prosthesis, restores a nearly natural physio- patients with hypertension]. Med Clin (Barc) 2002; 119: 521–526. logical erection. However, it should be remembered 13 Rosen MP et al. Cigarette smoking: an independent risk factor that it is a mechanical device inserted inside the for atherosclerosis in the hypogastric-cavernous arterial bed of penis, which must be inflated and deflated for use. men with arteriogenic impotence. J Urol 1991; 145: 759–763.

International Journal of Impotence Research Core document on erectile dysfunction FB Brotons et al S34 14 Keene LC, Davies PH. Drug-related erectile dysfunction. 28 Lue T. Sildenafil study group: a study of sildenafil, a new oral Adverse Drug React Toxicol Rev 1999; 18: 5–24. agent for treatment of male erectile dysfunction. J Urol 1997; 15 Rosen RC et al. The International Index of Erectile Function 157(Suppl): 181. (IIEF): a multidimensional scale for assessment of erectile 29 Rendell MS et al. Sildenafil for treatment of erectile dysfunction. Urology 1997; 49: 822–830. dysfunction in men with diabetes. JAMA 1999; 281: 16 Rosen RC et al. Development and evaluation of an abridged, 421–426. 5-item version of the International Index of Erectile Function 30 Derry F et al. Sildenafil (Viagra) a double blind, placebo- (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J controlled, single dose, two-way crossover study in men with Impot Res 1999; 11: 319–326. erectile dysfunction caused by traumatic spinal cord injury. 17 Miller TA. Diagnostic evaluation of erectile dysfunction. Am J Urol 1997; 157(Suppl): 181. Fam Physician 2000; 61: 95–104, 109–110. 31 Quirk F et al. Effect of sildenafil (VIAGRAt) on quality-of-life 18 Ralph D, McNicholas T. UK management guidelines for parameters in men with broad-spectrum erectile dysfunction. erectile dysfunction. BMJ 2000; 321: 499–503. J Urol 1998; 159: 260, abstract 998. 19 Jeremy JY, Mikhailidis DP. Cigarette smoking and erectile 32 Hatzichristou DG. Sildenafil citrate: lessons learned from 3 dysfunction. J R Soc Health 1998; 118: 151–155. years of clinical experience. Int J Impot Res 2002; 14(Suppl 1): 20 Derby CA et al. Modifiable risk factors and erectile dysfunction: S43–S52. can lifestyle changes modify risk? Urology 2000; 56: 302–306. 33 Guay AT, Perez JB, Jacobson J, Newton RA. Efficacy and safety 21 Jardin A, Wagner G, Khouri Sea. Recommendations of the 1st of sildenafil citrate for treatment of erectile dysfunction in a International Consultation on Erectile Dysfunction. In: Jardin population with associated organic risk factors. J Androl 2001; A, Wagner G, Khouri S, Giuliano F, Padma-Nathan H, Rosen R 22: 793–797. (eds). Erectile Dysfunction. Health Publication Ltd: Plymouth 34 Brotons Munto F et al. Manejo de las disfuncion erectil UK, 2000, pp 709–726. en atencio primaria. JANO Med Humanidades 1998; 55: 22 Greiner KA, Weigel JW. Erectile dysfunction [see comments]. 42–46. Am Fam Physician 1996; 54: 1675–1682. 35 Arruda AM, Mahoney DW, Nehra A, Pellikka PA. Cardiovas- 23 Goldstein I et al. Oral sildenafil in the treatment of erectile cular effects of sildenafil citrate (Viagra) during exercise in dysfunction. N Engl J Med 1998; 338: 1397–1404. patients with known or probable coronary artery disease. 24 Morales A et al. Clinical safety of oral sildenafil citrate Presented at the Third World Congress on the Aging Male, (VIAGRA) in the treatment of erectile dysfunction. Int J Impot February 7–10, 2002, Berlin, Germany. Res 1998; 10: 69–74. 36 Altwein JE, Keuler FU. Oral treatment of erectile dysfunction 25 Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildenafil, with apomorphine SL. Urol Int 2001; 67: 257–263. a novel effective oral therapy for male erectile dysfunction. 37 Cookson MS, Nadig PW. Long-term results with vacuum Br J Urol 1996; 78: 257–261. constriction device. J Urol 1993; 149: 290–294. 26 Eardley I et al. Sildenafil (VIAGRA[R]), a novel oral treatment 38 Rodriguez Vela L et al. Tratamiento de la disfuncion erectil with rapid onset of action for penile erectile dysfunction mediante farmacoterapia intracavernosa. Actas Urol Esp 1998; [abstract]. Br J Urol 1997; 79(Suppl 4): 66. 22: 291–319. 27 Buvat J et al. Sildenafil (VIAGRAt), an oral treatment for 39 Mulhall JP, Ahmed A, Branch J, Parker M. Serial assessment of erectile dysfunction: a 1-year, open-label, extension study efficacy and satisfaction profiles following penile prosthesis [abstract]. J Urol 1997; 157: 204, abstract 793. surgery. J Urol 2003; 169: 1429–1433.

International Journal of Impotence Research 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 & No & If yes, please complete the questionnaire regarding your sexual activity (mark only one box for each question) Over the past 4 weeks

NO SEXUAL ALMOST A FEW TIMES SOMETIMES MOST TIMES ALMOST ACTIVITY NEVER OR (LESS THAN (ABOUT HALF (MORE THAN ALWAYS NEVER HALF THE THE TIME) HALF THE OR TIME) TIME) ALWAYS

1. How often were you able to 01 2 345 get an erection during sexual activity? 2. When you had erections 01 2 345 with sexual stimulation, how often were your erections hard enough for penetration? 3. When you attempted sexual 01 2 345 intercourse, how often were you able to penetrate your partner? 4. During sexual intercourse, 01 2 345 how often were you able to maintain your erection after you had penetrated your partner?

DID NOT ATTEMPT EXTREMELY VERY DIFFICULT SLIGHTLY NOT INTERCOURSE DIFFICULT DIFFICULT DIFFICULT DIFFICULT

5. During sexual intercourse, 01 2 345 how difficult was it to maintain your erection to completion of intercourse?

NO ATTEMPTS 1–2 ATTEMPTS 3–4 5–6 7–10 11 OR ATTEMPTS ATTEMPTS ATTEMPTS MORE ATTEMPTS

6. How many times have you 01 2 345 attempted sexual intercourse? DID NOT ATTEMPT ALMOST A FEW TIMES SOMETIMES MOST TIMES ALMOST INTERCOURSE NEVER OR (LESS THAN (ABOUT HALF (MORE THAN ALWAYS NEVER HALF THE THE TIME) HALF THE OR TIME) TIME) ALWAYS

7. When you attempted sexual 01 2 345 intercourse, how often was it satisfactory to you?

NO INTERCOURSE NO NOT VERY FAIRLY HIGHLY VERY ENJOYMENT ENJOYABLE ENJOYABLE ENJOYABLE HIGHLY AT ALL ENJOYABLE

8. How much have you 01 2 345 enjoyed sexual intercourse?

NO SEXUAL ALMOST A FEW TIMES SOMETIMES MOST TIMES ALMOST ACTIVITY NEVER OR (LESS THAN (ABOUT HALF (MORE THAN ALWAYS NEVER HALF THE THE TIME) HALF THE OR TIME) TIME) ALWAYS

9. When you had sexual 01 2 345 stimulation or intercourse, how often did you ejaculate? 10. When you had sexual 01 2 345 stimulation or intercourse, how often did you have the feeling of orgasm or climax?

NO SEXUAL ALMOST A FEW TIMES SOMETIMES MOST TIMES ALMOST ACTIVITY NEVER OR (LESS THAN (ABOUT HALF (MORE THAN ALWAYS NEVER HALF THE THE TIME) HALF THE OR TIME) TIME) ALWAYS

11. When you had sexual 01 2 345 stimulation or intercourse, how often did you ejaculate? 12. When you had sexual 01 2 345 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. ALMOST NEVER A FEW TIMES SOMETIMES MOST TIMES ALMOST OR NEVER (LESS THAN (ABOUT (MORE THAN ALWAYS OR HALF THE HALF THE HALF THE ALWAYS TIME) TIME) TIME)

13. How often have you felt 12 3 45 sexual desire?

VERY LOW OR LOW MODERATE HIGH VERY HIGH NONE AT ALL

14. How would you rate your 12 3 45 level of sexual desire?

VERY MODERATELY EQUALLY MODERATELY VERY SATISFIED DISSATISFIED DISSATISFIED SATISFIED AND SATISFIED DISSATISFIED

15. How satisfied have you 12 3 45 been with your overall sex life? 16. How satisfied have you 12 3 45 been with your sexual relationship with your partner?

VERY LOW OR LOW MODERATE HIGH VERY HIGH NONE AT ALL

17. How do you rate your 12 3 45 confidence that you could get and keep an erection?

Sexual intercourse ¼ penetration of the partner; sexual activity ¼ intercourse, caressing, , 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. 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 Very low Low Moderate High Very High confidence that you could 1 2 3 4 5 get an erection?

2. When you had erections No sexual activity Almost never or A few times Sometimes Most times Almost with sexual stimulation, never (less than half (about half the (much more always or how often were your the time) time) than half the always erections hard enough for time) penetration? 0 1 2 3 4 5

3. During sexual intercourse, Did not attempt Almost never or A few times Sometimes Most times Almost how often were you able to sexual intercourse never (less than half (about half the (much more always or maintain your erection the time) time) than half the always after you had penetrated time) your partner? 0 1 2 3 4 5

4. During sexual intercourse, Did not attempt Extremely Very difficult Difficult Slightly Not difficult how difficult was it to sexual intercourse difficult difficult maintain your erection to 0 1 2 3 4 5 completion of intercourse?

5. When you attempted sexual Did not attempt Almost never or A few times Sometimes Most times Almost intercourse, how often was sexual intercourse never (less than half (about half the (much more always or it satisfactory to you? the time) time) than half the always time) 0 1 2 3 4 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. Core document on erectile dysfunction FB Brotons et al S39 Appendix C

Decision Algorithm for Patients With Erectile Dysfunction

Appendix D

Referral Algorithm for Patients With Erectile Dysfunction

International Journal of Impotence Research