Erectile Dysfunction



Fig. 5.1
The Princeton Consenus Recommendations for the management of erectile dysfunction and cardiovascular and cardiovascular disease (DeBusk et al. (2000), Kostis et al. (2005), Nehra et al. (2012); Source: www.​imop.​gr)






5.4.2.5 Sexual Counselling for Individuals with Cardiovascular Disease and Their Partners


Cardiac rehabilitation programs typically neglect the role of sexual function. Health professionals approach management of these disorders from a disease-centered perspective, which often fails to integrate the patient’s needs and perspectives (Hatzichristou and Tsimtsiou 2005). The trajectory, however, of a cardiovascular event and the comorbid ED may demand continuous adjustment from both patients and their partners as they adapt to the chronicity of heart disease. In turn, patients frequently complain about lack of sensitivity or awareness on the part of their physicians. Recently, a joint position statement from the American Heart Association and the European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions has been published (Steinke et al. 2013), in order to address the barriers for successful sexual counselling interventions in CV patients and emphasize the significant value of including sexual counselling content in healthcare providers’ educational programs. The document includes recommendations for sexual activity in patients with congenital heart disease, coronary artery disease, angina and MI, coronary artery bypass surgery, cardiac transplantation and left ventricular assist device, heart failure, implantation of cardioverter-defibrillator, and stroke (Steinke et al. 2013).



5.4.3 The Relationship of Benign Prostatic Hyperplasia (BPH) and ED


BPH-associated lower urinary tract symptoms (LUTS) are the most common non-vascular risk factor for ED. Community-based and clinical studies demonstrate a strong and consistent association between LUTS and ED, suggesting that elderly men with LUTS should be evaluated for ED and vice versa (Gacci et al. 2011).


5.4.3.1 LUTS Is a Strong Predictor of ED


According to the first published study in men with LUTS due to BPH (Rosen et al. 2003), the overall prevalence of ED was 49 %; severity of LUTS was a strong predictor of erectile dysfunction with odds ratio 8.90 (95 % CI: 6.85–11.55). Presence of severe LUTS, as well as changing LUTS severity category (from mild to moderate, or moderate to severe LUTS), had a greater impact on ED than aging by 10 years. Results from the large EpiLUTS study in 2,954 men revealed that 24.8 % had reduced or no sexual activity because of LUTS (Wein et al. 2009). In a systematic review of 12 studies that used both the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) as assessment tools, the overall prevalence of coexistent LUTS and ED of any severity was 71–80 % among men seeking treatment for LUTS. In the 2011 US National Health and Wellness Survey, a cross-sectional, self-administered online survey in men ≥40 years old, the prevalence of ED alone and ED/BPH (ED/BPH) was 24.6 and 4.9 %, respectively (Foster et al. 2013). Overall, 37.3 % of men with ED and 74.6 % with ED/BPH reported moderate-severe urinary (IPSS ≥8). About 23 % of either group reported currently using ED medication, compared to 31.1 % with ED/ BPH; BPH medication was used by 51.7 % of men (Foster et al. 2013). These findings suggest that ED in patients with BPH-associated LUTS is underdiagnosed and undertreated.


5.4.3.2 The Interplay of the Four Common Pathophysiologic Mechanisms


It has been well established that ED and BPH share common pathophysiologic mechanism. Actually, four mechanisms have been proposed, and available data support interplay between those mechanisms in both comorbidities. The four pathophysiologic mechanisms of BPH-associated LUTS and ED are shown in Fig. 5.2 and can be summarized as follows (Gacci et al. 2011; Giuliano et al. 2013):

A303416_1_En_5_Fig2_HTML.gif


Fig. 5.2
Common pathophysiologic mechanisms of erectile dysfunction and benign prostatic hyperplasia (Gacci et al. (2011); Source: www.​impo.​gr)


1.

Alteration of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway. Production of NO synthase (NOS) and NO in the corpora cavernosa, the prostate, and the bladder is reduced in the presence of vascular risk factors, decreasing the level of smooth muscle relaxation of the corpora cavernosa, the bladder neck, and urethra and may stimulate prostatic smooth muscle cell proliferation that results in increased outlet resistance (Giuliano et al. 2013).

 

2.

Enhancement of RhoA–rho-kinase (ROCK) contractile signalling. The ROCK pathway is a major mechanism regulating calcium sensitivity and, hence, contraction of smooth muscle. Increased smooth muscle tone, observed in LUTS and ED, exerts its effects via rho-kinase (Chang et al. 2005).

 

3.

Autonomic adrenergic hyperactivity. Autonomic nervous system hyperactivity is well known to be associated with ED, but is also associated with BPH/LUTS in humans, as a significant association between increased sympathetic tone and the level of LUTS has been observed (McVary et al. 2005).

 

4.

Pelvic atherosclerosis. Risk factors for vascular disease and ED (e.g., hypertension, smoking, diabetes, and hypercholesterolemia) have been proposed to contribute to LUTS by reducing pelvic arterial blood flow and, thus, resulting in smooth muscle loss from the bladder, prostate fibrosis, and increased urethral resistance. Actually, pelvic atherosclerosis may also induce autonomic nervous system hyperactivity, reduce NOS expression, and upregulate rho-kinase (Gacci et al. 2011).

 


5.4.3.3 The Need for Common Management of ED, LUTS, and CVD


The necessity for common management of ED and LUTS is well established, and urologists may diagnose and manage both conditions appropriately (Kirby et al. 2013). Factors that potentially increase the risk of benign prostatic hyperplasia and lower urinary tract symptoms include obesity, diabetes, and lack of physical activity (Parsons 2007). Furthermore, the metabolic syndrome is associated with the risk predictors for clinical progression of BPH in men with moderate to severe lower urinary tract symptoms (Kwon et al. 2013). However, patients with BPH-associated LUTS have a considerably higher prevalence of CVD than the general population in old age. Several studies have documented that CV risk factors are also risk factors for BPH. On the other hand, BPH may be an insidious risk factor for CVD by causing nocturia-induced sleep disturbances, blood pressure variability, increased sympathetic activity, and non-dipping BP variations (Karatas et al. 2010).

On the other hand, as ED and CVD share risk factors, a common prevention strategy has been proposed (Hatzichristou and Tsimtsiou 2005). Currently, the evidence recommends that ED patient education should aim at increasing exercise, reducing weight to achieve a body mass index less than 30 kg/m(2), and stopping smoking to improve or restore erectile function. When comorbidities are present, lifestyle modifications may include precise glycemic control in diabetic men and the use of pharmacologic therapies for hypertension and depression, which are less likely to cause sexual side effects (Glina et al. 2013).

As all common risk factors for ED and BPH are risk factors for CVD, the optimal clinical practice would integrate a common prevention and management strategy for all three conditions (Fig. 5.3). Such clinical practice is further endorsed by data showing that waist circumference – as a main sign of the metabolic syndrome – is positively associated with prostate volume, serum prostate-specific antigen, and IPSS (Lee et al. 2012). Furthermore, statins have a beneficial effect on erectile function (La Vignera et al. 2012), while a retrospective cohort study has suggested that the use of statins may delay the development of LUTS by 6.5–7 years (St Sauver et al. 2011).

A303416_1_En_5_Fig3_HTML.gif


Fig. 5.3
Modifiable risk factors to prevent and treat CVD-ED-LUTS (Parsons (2007), Glina et al. (2013); Source: www.​impo.​gr)


5.4.3.4 BPH Therapies and ED


Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5–9 %, while decreased circulating dihydrotestosterone (DHT) in diminished sexual desire and/or orgasm (Gacci et al. 2011; Gur et al. 2013). Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship (Traish et al. 2011).

A systematic review of 33 randomized controlled trials and cohort studies showed that minimally invasive surgeries for BPH have comparable effects to those of TURP on erectile function (Frieben et al. 2010). From a technical perspective, the comparative effects of bipolar versus monopolar TURP on overall sexual function have been investigated in an international, multicentre double-blind RCT using a true bipolar system and IIEF. No difference was found between the two arms of the trial in relation to any aspect of the sexual function (Mamoulakis et al. 2013).


5.4.3.5 The Role of PDE5i in LUTS


Several randomized controlled trials on PDE5i have demonstrated significant improvements in both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by the one or both conditions, without significant adverse events. A recent meta-analysis showed that the use of PDE5i was associated with a significant improvement of the IIEF score (+5.5; p < 0.0001) and the International Prostate Symptom Score (IPSS) (−2.8; p < 0.0001), but not the maximum flow rate compared to placebo. On the other hand, combination of PDE5i and alpha-1 adrenergic blockers improved the IIEF score (+3.6; p < 0.0001), IPSS score (−1.8; p = 0.05), and Q(max) (+1.5; p < 0.0001) at the end of the study as compared with alpha-blockers alone (Gacci et al. 2012).

Thus, evidence and our everyday clinical practice suggest that PDE5i can improve LUTS as alpha-blockers do, in addition to the erectile function improvement.


5.4.4 Drug-Induced Erectile Dysfunction


ED is a common side effect of medication and should be interpreted with caution. Several drug categories have been associated with ED, including beta-adrenoreceptor antagonists, digoxin, thiazide diuretic, older antipsychotics and risperidone, selective serotonin reuptake inhibitors (SSRIs) and venlafaxine, lithium, gabapentin, carbamazepine, as well as antiandrogens (U 2010). However, two drug categories are the most widely used and associated with ED: antihypertensives and antidepressants. Although ED treatments are efficacious in such patients, strategies to prevent ED are absent. Regarding antihypertensives, sexually related side effects may not only compromise the patient’s and partner’s quality of life, but may also lead to withdrawal or poor compliance with severe consequences: abnormal blood pressure and associated life-threatening morbidity. Unfortunately, only a minority of the existing clinical practice guidelines (CPGs) for the treatment of hypertension consider ED or other sexual issues to be either an adverse outcome or a factor to consider in treatment (Karavitakis et al. 2011). This is partly due to the lack of randomized trials assessing the effects of switching to currently available antidepressant agents with lower rates of adverse sexual effects, the role of psychological or mechanical interventions or of techniques such as “drug holidays” (Taylor et al. 2013). From a clinical practice point of view, the only way to identify the effect of a drug is to order a drug holiday, if indicated: in other words, if erectile function is restored when the prescribed medication is interrupted for some period of time, this easily leads to the conclusion that ED was drug induced. In such case, a change of the prescribed drug to one with similar action without sexual side effects may be worthy. In cases that this is not feasible, the following aspects should be discussed with the physician who prescribed the drug:



  • Dose reduction, if indicated.


  • Dose schedule after sexual activity.


  • Scheduling a drug holiday periodically, e.g., a 2-day drug holiday each week (usually weekends) of an antidepressant, may restore sexual function without the drug losing its efficacy.


5.4.5 Urological Surgery and ED: What Kind of Information Should Be Provided to Patients?


From a urologist’s perspective, ED associated with other urological diseases or treatments is of major interest, particularly post-radical prostatectomy ED, as well as penile surgery-associated ED.


5.4.5.1 Nerve-Sparing Radical Prostatectomy and Rehabilitation Program: A Fairy Tale?


According to the Merriam Webster dictionary, fairy tale is defined as a story in which improbable events lead to a happy ending. Is preservation of erectile function a fairy tale? In order to give an evidence-based answer, two distinct questions have to be addressed: if the nerve-sparing surgery preserves potency in most men and if rehabilitation programs are able to restore erections.


Nerve-Sparing Radical Prostatectomy: Myth or Reality?

Many issues regarding radical prostatectomy and erectile function (EF) remain under discussion (Hatzichristou 2012). Post-radical prostatectomy ED prevalence varies in different studies between 25 and 75 % (Sanda et al. 2008). Given that there are no randomized prospective, well-designed head-to-head, comparative studies to show that the outcome in erectile function (EF) is significantly different between open and laparoscopic or robotic radical prostatectomy (Salonia et al. 2012b), the International Consultation for Sexual Medicine Committee statement recommends: “Patients should be given individualised outcomes based on surgical technique, patient and surgeon factors, thus including accurate data on erectile function recovery from their own patient population” (Mulhall et al. 2010). This last aspect, which seems polemic against a certain type of behavior, actually allows clinicians to bypass the errors of the scientific literature, eventually providing patients with more realistic expectations (Hatzichristou 2012). Therefore, a comprehensive discussion with the patient about the true prevalence of postoperative erectile dysfunction (ED), the concept of spontaneous or pharmacologically assisted erections, and the difference between “back to baseline” EF and “erections adequate enough to have successful intercourse,” clearly emerge as key issues in ultimately understanding ED prevention and promoting satisfactory postoperative recovery of erectile function. Patient factors (including age, baseline EF, and comorbid conditions), cancer location (unilateral vs bilateral nerve-sparing), technical aspects (i.e., intra- vs inter- vs extrafascial technique), surgical approach (i.e., open, laparoscopic, and robot-assisted RP), and surgeon factors (i.e., surgical volume and surgical skill) represent the primary parameters contributing to EF recovery (Salonia et al. 2012b).


Rehabilitation Program: Is It Time to Forget About It?

There has been a lot of discussion in the literature regarding the use of penile rehabilitation to ensure cavernous oxygenation, but the results of the well-designed studies are discouraging. Despite the great number of possible rehabilitation approaches proposed, these approaches should be regarded only as strategies, since incontrovertible evidence for their effectiveness in improving natural EF recovery is limited. Conversely, numerous effective therapeutic options are available for treating post-radical prostatectomy ED (Salonia et al. 2012b).

Regarding rehabilitation programs, two double-blind studies have found no difference between nightly vs on-demand use of vardenafil or sildenafil after nerve-sparing radical prostatectomy (Montorsi et al. 2008; Pavlovich et al. 2013). A goal-oriented treatment paradigm has been recently proposed for our daily practice, where any chosen treatment may actually induce erections that allow sexual intercourse (Fode et al. 2013). Such treatments should be offered as early as possible, to minimize the potential adverse effects regarding both low tissue oxygenation and detrimental psychological effects. The authors stated that “One must be very careful not to repeat the statement that penile rehabilitation regimens improve erectile function after radical prostatectomy so many times that it becomes a truth, even without the proper scientific backing” (Fode et al. 2013).


5.4.5.2 Nerve-Sparing Radical Cystectomy: Is It Feasible?


Cystectomy permanently deteriorates the erectile capacity; results of the newly applied nerve-sparing procedure (NS) are still questioned as limited data are available. In one study, 12 patients (57.8 %) had spontaneous complete tumescence and five patients (21 %) had partial tumescence using PDE5i (Hekal et al. 2009). In contrast, all patients who underwent non-nerve-sparing cystectomy did not improve even with sildenafil and used alprostadil intracavernosal injection postoperatively. In another study, cystectomy was performed with a prostatic capsule- and seminal-sparing approach. A total of 20/21 (95 %) were sexually active following prostate-sparing cystectomy and orthotopic neobladders (Thorstenson et al. 2009). The recent first report on penile rehabilitation post-nerve-sparing radical cystectomy in a small group of patients has shown positive results (Hekal et al. 2011), but the experience from similar programs after radical prostatectomy does not support enthusiasm (Fig. 5.4).

A303416_1_En_5_Fig4_HTML.gif


Fig. 5.4
Individuals’ responses to sexual symptoms: a bio-psychosexual conceptual framework (Adapted from Kirana et al. (2009); Source: www.​impo.​gr)


5.4.5.3 Peyronie’s Disease: Grafting Procedures Are Not Friendly to Erectile Function


Peyronie’s disease is associated with ED, having also major negative impact in the patient’s quality of life (Levine 2013). In the largest, single-center study, a total of 1,001 patients with PD were evaluated retrospectively and 58.1 % reported preoperative ED, while penile color Doppler ultrasound revealed some degree of penile vascular disease in 76.8 %: mixed vascular disease in 41.1 %, cavernosal disease in 23.2 %, and arterial disease in 12.5 % of the patients (Kadioglu et al. 2011).

Regarding postoperative ED, it is clear that the risk of erectile dysfunction seems to be greater for penile lengthening procedures, compared to plication/tunica excision procedures (Hatzimouratidis et al. 2012). The risk of new ED with plication/tunica excision techniques is 0–13 %, compared to 5–53 % for grafting techniques (Hatzimouratidis et al. 2012). Furthermore, diminished sensation is reported in 4–21 % for plication/tunica excision, with limited data for grafting procedures (Levine and Burnett 2013).

Patients should be aware of grafting major drawbacks before surgery. The use of grafts harvested from the patient seems to cause potential complications of healing, scarring, and possible lymphedema. Synthetic grafting is not recommended, due to the potential risk of infection localized inflammation, fibrosis, and reaction to the presence of the synthetic material. Finally, allografts and xenografts (including processed pericardium from a bovine or human source, porcine intestinal submucosa, and porcine skin) have also moderate long-term results. The recurrence of penile curvature, penile length loss, and the new-onset of ED are not uncommon. In one study, although the 6-month postoperative follow-up showed excellent resolution or significantly less penile curvature, this figure significantly decreased in the 5-year follow-up: 50 % in dermal graft, 87 % in Tutoplast graft group, and 76 % in Stratasis graft group patients. Based on IIEF-5 scores, progression of ED was observed and more than 65 % of patients were dissatisfied with the outcome of graft surgery at 5 years (Chung et al. 2011). In patients with Peyronie’s disease and ED that are nonresponders to erectogenic pharmacotherapy, penile prosthesis implantation is the first-line treatment option. However, responders to pharmacotherapy may also be regarded as candidates for corporoplasty, but not for grafting surgery due to the poor outcome (Mulhall et al. 2005).

Based on the above, all proposed guidelines recommend tunica plication procedures for curvature <60° and absence of extreme deformities (hourglass, hingle), while the anticipated loss of length would be less than 20 % of total erect or stretched length. Importantly, what has clearly emerged in the literature is that these men should have strong sexually induced rigidity preoperatively, in order to reduce the likelihood of postoperative ED (Hatzimouratidis et al. 2012; Levine and Burnett 2013).


5.4.5.4 Penile Fracture: Conservative Treatment Leads to ED


Penile fracture is a rare condition in western world; however, the incidence in the Western and Southern Asia countries is higher due to a tradition that involves bending the top part of the erect penis while holding the lower part of the shaft in place, until a click is heard and felt (Taqaandan) (Al Ansari et al. 2013; Zargooshi 2009). In the largest published study in 373 patients, surgical treatment restored erectile function in 98.6 %, while conservative treatment in 20 % (Zargooshi 2009). Other series has shown similar results for surgery, but erectile function in the conservative treatment group was higher (up to 50 %) (Bar-Yosef et al. 2007; Gamal et al. 2011). Penile nodules are the most common postoperative complication, without any impact of erectile function. Despite the fact that dorsal vein tears may mimic penile fracture (Bar-Yosef et al. 2007), surgical exploration is mandatory in every case suspicious for penile fracture in order to preserve potency.


5.4.5.5 Hypospadias Repair: High Incidence of Erectile Dysfunction and Premature Ejaculation


Hypospadias repair is also associated with ED. In a single-center study, 119 patients who underwent hypospadias repair 20–35 years ago responded to questionnaires on penile appearance and sexual life; 8.9 % with glanular hypospadias, 50 % with distal hypospadias, and 72.2 % with proximal hypospadias reported mild ED. Furthermore, it is extremely disappointing that 83.2 % of all patients complained about premature ejaculation and all patients treated for proximal hypospadias reported impaired sexual quality of life (Chertin et al. 2013). Such data clearly show not only the high incidence of erectile dysfunction and premature ejaculation in hypospadias repair surgery and the necessity for appropriate parents’/patients’ counselling before surgery but also the urgent need for the development of new, erection-preventive surgical techniques for the condition.


5.4.5.6 Urethroplasty: Pelvic Fracture and Not Surgery Is the Cause of ED


In a recent meta-analysis of 36 retrospective studies of anterior urethroplasty results, with a total of 2,323 patients, de novo ED was rare, with an incidence of 1 %. Τransient ED was resolved within a 6–12- month period in 86 % of cases (Goel et al. 2013). Transperineal bulboprostatic anastomosis for posterior urethral strictures after pelvic structures has not a major effect on erectile function, as the incidence of preoperative ED in such cases is about 85 % (Fu et al. 2013). Three factors are significant and independent predictors of ED after pelvic fractures: diastasis of pubic symphysis, lateral displacement of prostate, and long urethral gap with odds ratios of 15.9, 6.9, and 2.0, respectively (Koraitim 2013). Appropriate patients’ counselling regarding the likelihood of developing transient or permanent ED following urethroplasty procedures is advised.



5.5 Principles in ED Management



5.5.1 The Problem of Limited Treatment Seeking of Men with ED


Despite major advances in ED management, many patients remain untreated, as they don’t feel comfortable to talk to a physician. The first step, therefore, is to make our patients talk about their problem. However, we should keep in mind that sexual dysfunctions are not always associated with increased bother or dissatisfaction, a condition that influences treatment-seeking behavior (Evangelia et al. 2010). Many patients have difficulty discussing their sexual problems or concerns with a physician. It is the responsibility of the physician to both develop a relationship of trust and intimacy with the patient and analytically discuss all key elements necessary for adequate treatment. The acronym “TALK,” which has been proposed in order to help people ask for help, refers also to what every patient with a sexual problem may consider in his/her appointment with the expert:



  • Trust your doctor.


  • Ask about your sexual problem.


  • Learn available treatment options.


  • Keep your partner involved.


5.5.2 A Conceptual Framework to Explain Treatment-Seeking and Outcome Behavior


Individuals’ responses to symptoms are not limited to common health behaviors, such as treatment-seeking or problem identification. In reality, patients respond to symptoms and treatment regimens within the context of life goals, priorities, health issues, partners’ demands, and other personal concerns that make up their sexual well-being. Based on a previously described model (Hatzichristou 2008; Kirana et al. 2009), a conceptual framework has been developed for better understanding the process from sexual symptom identification to sexual health outcome as occurring in a series of linked phases.


Phase 1: Experience of a New Sexual Problem

A symptom may have different characteristics, including frequency and severity.


Phase 2: Distress

To elicit behavioral responses from a man, ED needs to be perceived as a source of distress. Cognitive appraisal will determine the patient’s perception of ED that is influenced by beliefs and convictions (e.g., sexual myths) about the cause and significance, as well as by anticipated consequences and outcomes. Finally, affective response refers to the impact that ED may have on the individual’s emotions, affect, and mood. If ED causes fear or anxiety and the patient does not seek medical advice, it may result in depression.


Phase 3: Assessment of Available Resources

Individuals’ assessment of the availability and potential effectiveness of available sexual healthcare resources (urological societies may play a key role raising awareness on the condition) will determine the likelihood of treatment seeking for ED. Of even greater importance is the patient’s perception of their availability and effectiveness. Among the potential resources to be considered are the following:



  • Formal resources (i.e., availability of sexual health services, andrological clinics)


  • Informal resources (i.e., partner, friends)


  • Subjective resources (i.e., coping style, previous experiences with healthcare/urological services)

If the individual perceives himself to have access to the required formal or informal resources, then an intention to take action may be evident.


Phase 4: Objective Response

This is the behavioral phase in the process and typically results in the individual choosing between one or more of the following actions:



  • Help seeking (visit a general practitioner or a urologist)


  • Self-care (e.g., via Internet)


  • Avoidance (learn how to live without sex)


Phase 5: Outcome

In the final phase, the patient assesses the outcome of the process, defined as the reduction of symptom distress. According to this model, the outcome of the process should not be defined solely on the basis of objective criteria (e.g., IIEF) but also on the level of sexual satisfaction or reduction in subjective distress achieved. In situations where the patient is satisfied with the outcome (e.g., restoration of erection by using pharmacotherapy), the process may be terminated. Conversely, if there is no satisfactory outcome, the individual may reinitiate the process again. This will likely include reassessment of the level of subjective distress, evaluation of available resources, and selection of an alternative health behavior, e.g., discontinuing PDE5i treatment or visiting another urologist for second opinion.

In conclusion, this model reminds us Jung’s quote: “The shoe that fits one person pinches another.” Keeping this model in our mind, it helps us to better understand our patients in our everyday clinical practice and guides us to identify the best treatment option on individual basis.


5.5.3 Discussing ED in a Urology Office


Sexual health problems are often neglected in clinical practice (Tsimtsiou et al. 2006). Many patients have difficulty discussing their sexual problems or concerns with a physician, as they experience a sense of frustration, confusion, embarrassment, or distress; moreover, patients often feel that physicians are reluctant, disinterested, or unskilled in sexual problem management. On the other hand, clinicians are often reluctant to ask about sexual issues due to their negative attitude towards sexual issues and concerns, time constraint, as well as a growing knowledge gap between developments in Sexual Medicine and clinical skills of practicing physicians (Athanasiadis et al. 2006; Parish and Rubio-Aurioles 2010; Shabsigh et al. 2009).

Talking about sexual problems, the urologist should keep in mind to abide by the following (Hatzichristou et al. 2010):



  • Create an atmosphere of sensitivity and respect.


  • Be culturally sensitive.


  • Respect every individual’s sexual preferences.


  • Consider status of relationship.


  • Present evidence-based treatment options.


  • Organize a close follow-up program.


5.5.4 Differentiating Primary from Secondary ED and Organic from Psychogenic ED


ED is classified in two major subtypes (Porst et al. 2013): (1) primary (lifelong) ED, defined as ED that occurs from the beginning of sexual activities, and (2) secondary (acquired) ED, defined as ED that occurs after a period of normal sexual life in which erectile function used to be intact.

For clinical purposes, sexual dysfunctions are classified into three types according to their etiology (Hatzichristou et al. 2010): type I, psychogenic; type II, organic; and type III, mixed (Table 2). Types II and III differ as for the absence or presence of significant mental (cognitive) or emotional (affect) distress; in type II, resolution of the main symptom will adequately diminish mental and/or emotional distress, while in type III complementary psychotherapy is indicated. It should be emphasized, however, that in most patients with organic ED, the negative psychological impact significantly contributes to exacerbating the severity of ED.

Sexual history is the most helpful tool in order to differentiate psychogenic from organic ED. Table 3 provides an overview of such specific aspects that may be useful.


5.5.5 Defining the Severity of ED


ED is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance (Hatzimouratidis et al. 2010). Two questions to the patients reflect this definition:

(a)

Are you able to get an erection of adequate rigidity for penetration?

This question reflects the problems initiating the erectile process (e.g., neural or arterial insufficiency). In order to explore further the severity of the problem, the use of manual assistance in order to achieve penetration has to be explored.

 

(b)

Are you able to maintain the erection till ejaculation?

This question reflects the problems in maintaining good quality, rigid erection in order to complete sexual performance (e.g., venoocclusive dysfunction). In cases where the erectile maintenance capacity is limited, questions regarding “when and how” erection is lost will follow: “Do you lose your erections before, during, or after penetration?” Typically psychogenic cases lose their erection just in the attempt of vaginal penetration, while patients with venoocclusive dysfunction (excluding severe cases) are able to penetrate, but they lose their erection within a few minutes after penetration.

 

Clinically, severity distinguished in mild, moderate and severe as follows:



  • Mild ED reflects a sexual history where patients report sexual intercourse, but they complain of difficulties in achieving adequate rigidity and occasionally sustaining capability. They are usually able to have sexual intercourse more than half of the times.


  • Moderate ED reflects a sexual history where patients report inadequate rigidity and/or sustaining capability and occasional sexual intercourse with manual assistance for penetration.


  • Severe ED reflects a sexual history where patients are unable to have sexual intercourse due to the quality of their erections.


5.5.6 Questionnaires and Scales for the Everyday Clinical Practice


In supplementation to the sexual history, the IIEF or Sexual Health Inventory for Men (SHIM) questionnaires can also be used, as well as the Sexual Encounter Profile (SEP), especially in order to compare pre- and posttreatment erectile function. In order to facilitate the detection of men with androgen deficiency, the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire is indicated.


5.5.6.1 Brief Sexual Symptom Checklist for Men (BSSC-M) and Women (BSSC-M)


Screening checklists can provide a valuable resource in identifying and assessing sexual problems. To facilitate initial identification of a sexual problem, two brief screening checklists have been developed by the ICSM committee on diagnosis (Hatzichristou et al. 2004). This brief checklist consists of four simple questions, and it is suitable for use in office settings, as it takes 1 min to be completed. It addresses the patient’s level of satisfaction with sexual function, the duration of the sexual problem, the type/s of sexual problems experienced, as well as the willingness of the person to discuss the problem with a healthcare provider. Three of the four questions are common for men and women, while the fourth question (type of problem) is specific for gender. BSSC has been used in the literature, however, validation data are lacking.


5.5.6.2 International Index of Erectile Function (IIEF)


The IIEF is the most widely used self-reported inventory to provide standardized measurement of erectile function in five domains of sexual function in men: erection, orgasm, desire, satisfaction, and overall satisfaction. The IIEF was initially developed for use in the clinical trials for the approval of sildenafil (Rosen et al. 1997). Psychometric validation for IIEF (test-retest reliability, construct validity, and treatment responsiveness) has been well established (Rosen et al. 2002). A systematic review of more than 60 studies found the IIEF scale to be highly robust in different ethnic and geographic populations, as well as sensitive to treatment effects across a variety of treatment agents (Rosen et al. 2002).

IIEF scale allows characterization of the ED severity, using a scoring system from 1 to 30 in the erectile function domain (Rosen et al. 1997):



  • Normal erectile function: score 26–30


  • Mild ED: score 17–25


  • Moderate ED: score 11–16


  • Severe ED: score 1–10

Most recently, criteria have been established for defining minimal clinically significant change after treatment in the EF domain of the IIEF (Rosen et al. 2011):



  • Mild ED: 2-point improvement


  • Moderate ED: 4-point improvement


  • Severe ED: 7-point improvement


5.5.6.3 Sexual Health Inventory for Men (SHIM)


A 5-item brief form of the IIEF (IIEF-5), termed also as the Sexual Health Inventory for Men (SHIM), has been developed and validated, along with a diagnostic classification and an ED severity scale (Cappelleri and Rosen 2005; Rosen et al. 1999). The scoring system for SHIM is as follows:



  • Normal erectile function: score 17–21


  • Mild ED: score 12–16


  • Moderate ED: score 8–11


  • Severe ED: score 1–7

It should be noted that the IIEF and SHIM are not intended to supplant clinical evaluation and diagnostic tests; they are though particularly useful instruments in the urological office setting for the initial screening, as well as for the follow-up visits.


5.5.6.4 Sexual Encounter Profile (SEP)


SEP has been extensively used in clinical trials, although it has never been validated. Actually, the regulatory agencies use SEP results to evaluate the efficacy of drugs. SEP questions use the dichotomous answer system: “YES” or “NO.” Data from clinical trials are presented as the mean percentage of participants who answered “yes.” Questions SEP2 and SEP3 have been the primary endpoint in most clinical trials. The complete questionnaire includes the following five questions:



  • SEP 1: “Were you able to achieve at least some erection (some enlargement of the penis)?”


  • SEP 2: “Were you able to insert your penis into your partner’s vagina?”


  • SEP 3: “Did your erection last long enough for you to have a successful intercourse?”


  • SEP 4: “Were you satisfied with the hardness of your erection?”


  • SEP 5: “Were you satisfied with this sexual experience?”

SEP questions are typically used as a diary of sexual attempts, as patients have to complete SEP after every sexual attempt. Practically, SEP questions reflect the typical questions we ask in our office during sexual history taking that provide us valuable qualitative and quantitative information on the patient’s experience with his erectile function.


5.5.6.5 Androgen Deficiency in the Aging Male (ADAM)


Androgen Deficiency in the Aging Male (ADAM) questionnaire has been widely used as a screening tool for detecting men at risk for androgen deficiency. It was shown to have a sensitivity of 88 %, but specificity of 60 % (Morley et al. 2000). Recently, the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire showed statistically significant correlation to the SHIM (p = 0.001) and serum testosterone (p = 0.046) (Mohamed et al. 2010). The qADAM questionnaire consisted the 10 questions of the original ADAM, with “yes” and “no” replaced by a Likert scale of 1–5, in which 5 represented the absence of a given symptom and 1 represented maximal symptoms. The scoring scale is between 10 and 50, with 10 being most symptomatic and 50 being least symptomatic (Mohamed et al. 2010).


5.5.7 Organic Causes of ED


In the clinical practice, ED may be categorized according to the underlying pathophysiology in six major categories (Table 4). Lifelong ED usually is due to either anatomical (phimosis, congenital curve) or hormonal abnormalities (primary hypogonadism), while vasculogenic ED is rare and usually associated with penile or perineal trauma. Secondary ED is often accompanied with comorbidities associated with ED, such as BPH, CV risk factors, and prostate and bladder cancer therapies.


5.5.8 The ICSM Sexual Dysfunction Management Algorithm for Men and Women


Three principles for the clinical evaluation and management of sexual problems have been reported (Hatzichristou et al. 2010): (1) adoption of a patient-centered framework, with emphasis on cultural competence in clinical practice; (2) application of evidence-based medicine in diagnostic and treatment planning; and (3) use of a unified management approach in evaluating and treating sexual problems in both men and women.

Based on the above principles, the International Consultation in Sexual Medicine developed a common, stepwise diagnostic and treatment algorithm, for every sexual dysfunction, in both men and women (Fig. 5.5) (Hatzichristou et al. 2010). The main goal of ICSM-5 is to reveal the underlying etiology and/or indicate appropriate treatment options according to men/couple’s individual needs (patient-centered medicine), using the best available data from population-based research (evidence-based medicine).

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Fig. 5.5
The ICSM algorithm (Hatzichristou et al. (2010); Source: www.​impo.​gr)


5.5.9 The EAU Treatment Algorithm for ED


The primary goal in the management strategy of a patient with ED is to determine its etiology and treat it when possible, and not to treat the symptom alone. Most men with ED will be treated with therapeutic options that are not cause-specific; therefore, treatment strategy depends on efficacy, safety, invasiveness and cost, as well as patient preference (Hatzichristou et al. 2010). Based on the evidence available, the EAU working group on male sexual dysfunction included a treatment algorithm for ED within the recent guidelines report (Hatzimouratidis et al. 2010) (Fig. 5.6). Urologists use the well-known algorithm extensively in their everyday clinical practice. By using this algorithm, the initial effort is to modify any risk factor for ED, as well as to identify any curable cause of ED. First-line treatment options include PDE5i, intracavernosal injections, intraurethral alprostadil, and vacuum devices. In nonresponders, combination of any of the above treatments may be considered, while penile prosthesis implantation remains a gold standard surgical option.

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Fig. 5.6
Treatment of ED


5.6 Diagnostic Approach


The goal of any diagnostic approach is to: (a) increase certainty about presence/absence of a disease, (b) define severity of the disease, (c) monitor clinical course, (d) assess prognosis/risks, and (e) plan treatment. Given that ED is essentially a self-reported condition, diagnostic tests or procedures should not be recommended without controlled clinical data or research evidence supporting their use. A broad array of specialized diagnostic tests has been developed, but their clinical utility is limited only to a small minority of men (Meuleman et al. 2010).


5.6.1 Is the Partner’s Presence in the Office Substantial or Just Time-Consuming?


Partner involvement is rare in the everyday clinical practice, as urologists typically do not invite partners to be present in the office visits. However, clinical experience has shown that the partner’s involvement – even though time-consuming – offers substantial help to easily identify/control potency status, couples’ expectations, treatment results, and satisfaction (Hatzichristou et al. 2010). It is not possible to include the partner on the patient’s first visit, but an effort should be made to include the partner at the second visit. In conclusion, the partner’s presence in the office and further support positively affects the treatment outcome.


5.6.2 What Diagnostic Work-Up Is Mandatory?


Mandatory work-up for ED includes a medical–sexual–psychosocial history, physical examination, and limited laboratory tests (Hatzichristou et al. 2010; Hatzimouratidis et al. 2010). Medical history should also include use of medications. Laboratory tests are recommended only in patients not tested during the last 6 months, while physical examination should not focus exclusively on the genital system.


5.6.2.1 Medical, Sexual, and Psychosocial History


The first step in evaluating ED is always a detailed medical, sexual, and psychosocial history of patients and partners when available. The sexual history must focus on information about previous and current sexual relationships, current relationship status, onset and duration of the erectile problem, as well as previous consultations and treatments. The partner’s sexual health status is also important, as sometimes a sexual problem of the partner may be the cause of ED (e.g., vaginal atrophy and dryness).

Psychological assessment is important in order to identify: (a) potential social problems (e.g., unemployment and its consequences), (b) relationship status and problems (e.g., extramarital relationships), and (c) psychiatric comorbidities. In one study, detectable psychiatric conditions present included depression in 25.2 %, anxiety disorders in 11.7 %, depression-anxiety comorbidity in 6.8 %, and personality disorders in 5.8 % (Mallis et al. 2005). In cases of suspected depression, the use of a 2-question scale for depression is recommended (Whooley et al. 1997):

1.

“During the past month have you often been bothered by feeling down, depressed or hopeless?

 

2.

During the past month have you often felt very little or no interest or pleasure in doing things?”

 

Taking a comprehensive medical history may reveal one of the many common disorders associated with ED. Urologists should screen their patients for symptoms of hypogonadism, LUTS, and prostate cancer. Where indicated, screening questionnaires, such as ADAMS and the IPSS, could very well be utilized.


5.6.2.2 Physical Examination


Physical examination may include basic cardiovascular and neurological assessment, as well as focused detailed examination of the secondary characteristics and genitalia, including DRE. Cardiovascular assessment may include blood pressure, heart rate, peripheral pulses, and waist circumference measurement.

Genital system examination may include penile size, penile plaques and glans lesions, testicular size and consistency, DRE, and bulbocavernosus reflex (glans squeeze results in contraction of anal sphincter), which test the integrity of the sacral spine cord.

A physical examination may reveal unsuspected diagnoses, such as alterations in secondary sexual characteristics, phimosis, Peyronie’s disease, and small testes. Given that penile deformities are difficult to be detected in the flaccid state, an intracavernosal injection test could be considered, either alone or in combination with duplex Doppler penile ultrasonography. A positive test, however, clearly demonstrates to the patient that he has already a treatment option: the intracavernosal injection program.


5.6.2.3 Laboratory Testing


Laboratory testing aims at identifying CV risk factors and hormonal status. Patients may need a fasting glucose or HbA1c and lipid profile if not recently assessed. Hormonal tests include a morning sample of total testosterone; when low testosterone levels are detected, prolactin and luteinizing hormone tests are performed. Thyroid function tests may be performed at the discretion of the physician. Regarding PSA, the latest EAU statement is as follows: “A baseline serum PSA should be offered to all men 40–45 years of age to initiate a risk-adapted follow-up approach with the purpose of reducing prostate cancer mortality and the incidence of advanced and metastatic prostate cancer” (Heidenreich et al. 2013).


5.6.2.4 Is the Basic Diagnostic Evaluation Adequate in Most Cases?


Baseline diagnostic evaluation for erectile dysfunction can identify the underlying pathological condition or erectile dysfunction-associated risk factors in most patients. One study included 1,276 consecutive patients who presented at an andrology outpatient clinic (Hatzichristou et al. 2002). Medical history revealed erectile dysfunction-associated comorbidities in 57 %; blood tests identified previously undiagnosed medical conditions in 6.2 %, while physical examination and the intracavernosal injection test were diagnostic in 13.9 and 2.6 %, respectively. Therefore, in 8 out 10 cases the diagnosis can be based on the patient’s medical and sexual history, physical exam, and mandatory laboratory tests. In the same study, specialized diagnostic procedures identified an underlying vascular pathology in 12.9 %.


5.6.3 Specialized Tests for ED: Is There Evidence for Their Use?


Specialized tests for the diagnosis of the underlying pathophysiology of ED can be used in the following cases: (a) in patients in whom a reversible form of ED is suspected (b) to differentiate between organic and purely psychogenic cases with nocturnal penile tumescence and rigidity testing and (c) to tailor vascular or penile surgery in patients suspicious for arterial disease or venoocclusive dysfunction.

According to the report of the International Consultation in Sexual Medicine, the higher level of evidence (2B) indicates vascular testing, e.g., color Duplex Penile Ultrasonography and Dynamic Infusion Cavernosometry and Cavernosography (DICC) (Meuleman et al. 2010). Two non-vascular tests belong to the same evidence-based category: the Nocturnal Penile Tumescence and Rigidity (NPTR) Test by the RigiscanTM device and the Bulbocavernosus Reflex Latency. Regarding the rest of specialized tests, selective arteriography (loE2B) is considered only for young men with perineal trauma, as well as for the treatment of high-flow priapism; as for MRI, it is a useful tool in cases of penile trauma and prosthesis complications.


5.6.3.1 The Nocturnal Penile Tumescence and Rigidity (NPTR)


NPTR assessment should be done for at least two nights. A functional erectile mechanism is indicated by an erectile event of at least 60 % rigidity recorded on the tip of the penis that lasts for >10 min (Chertin et al. 2013).


5.6.3.2 Intracavernous Injection Test


The intracavernous injection test provides limited information about vascular status. A positive test is a rigid erectile response (unable to bend the penis) that appears within 10 min after the intracavernous injection and lasts for 30 min (Chew and Stuckey 2000). This response indicates a functional, though not necessarily normal, erection, as this erection may coexist with arterial insufficiency and/or venoocclusive dysfunction (Chrysant and Chrysant 2012) (Fig. 5.7).

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Fig. 5.7
Impact of diagnostic procedures in identifying the etiology of erectile dysfunction (Hatzichristou et al. (2002); Source: www.​impo.​gr)


5.6.3.3 Cavernosometry/Cavernosography


Cavernosometry is generally applied in young men – who are already diagnosed to have ED that is mainly organic, in order to precisely diagnose a venoocclusive dysfunction. During cavernosometry arterial inflow to the penis is also assessed. Cavernosography is indicated in those patients who might be candidates for penile vascular surgery to correct a venoocclusive leak and also in men who have Peyronie’s disease with poor rigidity before penile reconstructive surgery for identifying the site of the “leakage” (Glina and Ghanem 2013). Cavernosometry/cavernosography should be performed only after the intracavernosal injection of vasoactive drugs, with redosing when necessary in order to achieve complete smooth muscle relaxation (Hatzichristou et al. 1995). Also the use of a tri-mix solution is important (Seyam et al. 2005). There is evidence that 70 % of patients require a second injection and 30 % require a third injection to induce complete relaxation of the smooth muscle (Mulhall et al. 2001).


5.6.4 Color Duplex Doppler Ultrasonography of the Penis (CDDU): Who, How, Why


CDDU is the most useful test for vascular assessment of erectile mechanism (Fig. 5.8). While providing the least invasive and accurate option for documenting penile hemodynamics, CDDU requires skilled personnel and modern equipment (color Doppler U/S with a real-time image scanner and high-resolution solid-state linear array 7.5–12-MHz frequency transducer specific for small parts) that may be cost-prohibitive in certain settings (Sikka et al. 2013). Such relatively objective vascular testing may help direct appropriate therapy, especially in middle age men without history of CVD; in such cases CDDU may diagnose arterial disease in the corpora cavernosa (a warning for silent coronary artery disease) (Meuleman et al. 2010). Other cases in which CDDU of the penis is, or might be, necessary to complete the evaluation are in young men with primary or secondary ED and a history of pelvic trauma or drug abuse, prior to surgical interventions for treating Peyronie’s disease, in differentiating psychogenic vs organic ED and in medicolegal cases.

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Fig. 5.8
Color Duplex Doppler ultrasonography of the penis (CDDU) (Sikka et al. (2013); Source: www.​impo.​gr)

It is crucial during the test to assess the quality of the erectile response after the intracavernosal injection of vasoactive agents; subjective assessment of rigidity is carried out independently both by the patient and physician. This approach minimizes the false diagnosis of venous leak, which is most common with anxiety usually present under such testing environment (Teloken et al. 2011).


5.6.4.1 CDDU: Normal Parameters


Several parameters have been used to infer the integrity of the arterial inflow, such as peak systolic flow velocity (PSV) and acceleration time (AT) (measured in ms from the start of systole to PSV) within the first 5 min following ICI. PSV < 25 cm/s has a 100 and 95 % specificity in selecting patients with abnormal penile angiography. PSV >35 cm/s is associated with normal angiography and defines normal cavernous arterial inflow. Speel et al. have proposed that AT is more powerful than PSV in diagnosing atherosclerotic ED (Speel et al. 2003); the cutoff point for acceleration time to discriminate between atherosclerotic and nonatherosclerotic erectile dysfunction was determined at an acceleration time of 100 ms or greater. Sensitivity was 66 % and specificity 71 %. There has recently been some evidence that PSV measurements in the flaccid state may have value in predicting cavernosal arterial insufficiency, silent coronary disease, and the clinical response to ICI (Corona et al. 2008). With CDDU the cavernous venoocclusive mechanism can be evaluated in the late postinjection phase (over 5 min following ICI). End-diastolic flow velocity (EDV) and resistance index (RI) may be used to estimate the degree of venoocclusive function. Thus, persisting diastolic blood flow or a low RI, 5 min or more following ICI, reflects persistent high flow rates due to impaired venoocclusion.

The consensus however for the everyday clinical practice remains that a peak systolic blood flow >30 cm/s, an end-diastolic velocity of <3 cm/s, and a resistance index >0.8 are generally considered normal (Glina and Ghanem 2013). Further vascular investigation is unnecessary when a Duplex examination is normal.


5.6.4.2 CAUTION: The False Diagnosis of Vasculogenic ED in Young Men


PSV in young men can be falsely low (Shamloul 2006). It is noteworthy that in a series of normal controls, 30 % had venoocclusive dysfunction, indicating the inability of CDDU to differentiate between a pathological and a functional (anxiety induced incomplete smooth muscle relaxation) cause of venoocclusive dysfunction (Meuleman et al. 1992). Such false-positive results (low specificity) could lead to a serious psychological setback if a young man is informed, erroneously, that his ED is primarily organic, thus requiring lifetime therapy or surgery. In order to control smooth muscle relaxation, in every case with abnormal results, redosing of tri-mix is required (Hatzichristou et al. 1995). After redosing, all parameters are re-recorded (Glina and Ghanem 2013). This protocol is repeated until a maximum of three doses of tri-mix solution. There is evidence that 70 % of patients require a second injection and 30 % require a third injection to induce a complete relaxation of the smooth muscle. In cases of doubt, DICC under the controlled condition of complete smooth muscle relaxation may be utilized to differentiate between these two entities (Haynes et al. 1996).


5.6.5 Referrals


After the availability of PDE5i, general practitioners manage the majority of ED cases. The urologist is typically the referral physician in cases of (a) life-long ED, (b) nonresponders to PDE5i, or (c) penile disorders (anatomical and trauma) (Hatzichristou et al. 2010). In a minority of patients, however, urologists may refer patients for specialized consultation or testing. Reasons for referral either for further consultation or for a specialized test are the following (Hatzimouratidis et al. 2010):



  • Primary/lifelong sexual dysfunction


  • Complicated anatomical deformities (congenital/acquired)


  • Trauma (pelvic, perineal, genital)


  • Endocrinopathies


  • Complex medical problems (comorbidities)


  • Treatment failure


  • Medicolegal cases


  • Patient’s request

It is worth mentioning that sometimes the patient and/or his partner may wish to obtain further diagnostic evaluation for several reasons; most often patients request referral in order to learn the precise etiology of ED (“need to know” referral).


5.6.6 The Seven Steps of the Difficult First Visit


Every effort should be made by the physician to ensure the patient’s privacy, confidentiality, and personal comfort during the patients’ visits. The first visit is crucial in order to establish a physician–patient relationship; offering the patient the opportunity to discuss sexual matters in a nonthreatening manner and making a statement about the confidentiality of the information being discussed are therefore necessary. Independently of our personal opinion and ethics, direct acknowledgment that any sexual problem is a relevant clinical issue and that the physician’s role is not to judge but to help solving it, may substantially help the patient feel comfortable. Lastly, it is also essential to evaluate the patient’s and partner’s values and preferences, especially when the patient comes from a different ethnic/religious background.

In order to be even more practical, the first visit is described step-by-step:



  • Step 1. Identify the sexual problem. Every consultation begins with the typical question of “What brings you here?” As ignorance and knowledge gaps about sexual function and dysfunction are common, very often sexual myths or Internet-based misinformation may easily lead to the development of a sexual concern. The first step therefore is for physicians to discriminate between sexual concerns (e.g., size of the penis) and difficulties (e.g., differences between the couple’s sexual desire) versus dysfunctions (erectile dysfunction) and/or disorders (e.g., congenital penile deviation).


  • Step 2. Duration and severity of ED. By asking about the duration of ED, we indirectly differentiate lifelong from secondary cases. For evaluating severity of ED, a typical question that we may ask is: “Out of the last ten attempts for sexual intercourse, in how many were you able to achieve penetration and ejaculation?” Patients who are able to have intercourse at least sometimes are the ones who can easily get successful treatment. Patients who are seldom or never able to complete sexual intercourse are difficult cases and usually have long-lasting ED (with the exception of occasional failures). Alternatively, the use of IIEF ED domain or SHIM will lead to accurate classification with regard to ED severity.


  • Step 3. Coexistence of other sexual problems. It is well known that ED provokes or coexists with other sexual problems, such as low sexual desire and premature ejaculation. Also, ED may occur due to a sexual problem of the partner (e.g., dry vagina, orgasmic disorders). Of great value at this point is the use of the 3 first questions of the Brief Sexual symptom Checklist for Men (BSSC-M) and Women (BSSC-M). They both consist of four simple questions, with the only difference being the content of question 3a that has to do with men and women reporting different sexual problems according to gender. Question 4 has to do with screening purposes and may be omitted when the screener is used during the interview. However, it is a critical question when the tool is used to assess sexual problems in patients coming to the office complaining about other urological conditions, such as BPH.


  • Step 4. Defining quality of erectile response. Erectile dysfunction is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Therefore, two are the main characteristics of erection: rigidity and maintenance capacity. Rigidity is a key parameter of erectile response. Asking questions such as “Are your erections hard enough to penetrate without any manual assistance?” give you the first piece of information. It should be noticed that there are men, e.g., with arteriogenic ED, who have adequate rigidity for penetration, but complain that their rigidity is “not like it used to be in the past” or that “it takes effort and time to achieve a good/rigid erection.” Both answers are typically seen in patients with arteriogenic ED. On the contrary, excellent rigidity, but losing the erection before or after penetration, is characteristic of venoocclusive dysfunction. Checking the circumstances under which lost of the erection occurs, it may differentiate between structural (neurogenic or arteriogenic) and functional (anxiety-induced) etiology of venoocclusive dysfunction.


  • Step 5. Medical history. Potentially modifiable risk factors, such as cigarette smoking, alcohol abuse, obesity, uncontrolled hypertension, or diabetes, should be addressed at this stage in the process. The potential role of prescription or nonprescription drugs, including psychotropic agents (e.g., SSRIs), cardiovascular drugs, or other iatrogenic causes of sexual dysfunction, should also be addressed. Patients with specific endocrine deficiencies, such as hypogonadism, should be placed on hormone replacement therapy (in the absence of medical contraindications, such as prostate cancer) prior to initiation of direct therapies for sexual dysfunction. A specialist referral is generally indicated in these cases. Additionally, sexual problems in the partner such as a lack of lubrication, hypoactive sexual desire, or pain disorders (e.g., dyspareunia) should be addressed whenever possible.


  • Step 6. Physical examination. Physical exam should include general screening for medical risk factors or comorbidities that are associated with ED, including secondary sexual characteristics, assessment of blood pressure, central and peripheral pulses, basic neurological exam, and particular focus on the genitalia. Never forget that the physical examination is a great opportunity to inform the patient about aspects of their sexual anatomy or physiology, as well as provide reassurance about his body appearance and function (e.g., size of the penis).


  • Step 7. Laboratory test. At the end of the initial assessment, laboratory tests will be asked. Most of ED patients suffer from several comorbidities and usually have adequate lab test results with them. In case of men without medical history and suspicious for organic ED etiology, laboratory testing may be of value in order to unmask undiagnosed comorbidities, such as diabetes mellitus and hyperlipidemia.


  • Step 8. Review results/education. Results of the initial evaluation should be reviewed with the patient and his partner whenever possible, prior to initiating therapy. This review should be used as an opportunity to educate patients on the anatomy and physiology of sexual function and provide appropriate understanding of “what is wrong.” Furthermore, presentation of the available treatment options will allow to identify patient’s preferences and partner’s endorsement of the proposed solution; such discussion is critical, as together with a close follow-up schedule (usually in 3–4 weeks) minimize dropout rate.


5.7 Is It Possible to Cure ED?


Typically, ED is curable in most psychogenic cases; in organic ED, cure is possible in cases of endocrinological etiology and in mild cases through lifestyle modifications and better management of comorbidities. Lastly, urologists pay high attention to a novel treatment the shockwave therapy for vasculogenic ED. Finally, in rare cases of trauma-associated ED, vascular surgery may offer cure potential. The treatment options that offer not symptom relief, but cure, are briefly discussed.


5.7.1 Lifestyle Changes: What Should We Expect?



5.7.1.1 Sex Is a Healthy Habit for Erections (“Use It or Lose It”)


Sexual activity is inversely related to mortality; in one cohort study, mortality risk was 50 % lower in men with high frequency of orgasm than in men with low frequency of orgasm (Davey Smith et al. 1997). In a survey conducted in Finland in men aged 55–75 years, Koskimäki et al. observed that men reporting intercourse less than once per week at baseline had twice the incidence of ED compared to those reporting intercourse once per week (79 vs 33/1,000). The risk of ED was inversely related to the frequency of intercourse and the authors concluded that regular intercourse protects against the development of ED among men aged 55–75 years (Koskimaki et al. 2008). The well-known quote “use it or lose it” has a scientific basis as frequency of intercourse offers – together with nocturnal erections – better oxygenation in the corpora cavernosa.


5.7.1.2 Physical Activity and Weight Loss May Restore ED


Meta-analysis data of randomized controlled studies using the IIEF for measuring the treatment outcome have shown that the exercise and weight loss are improving erectile function (Esposito et al. 2010; Hsiao et al. 2012; Lamina and Agbanusi 2013). Data from five studies indicated significant effect of aerobic training on erectile dysfunction (Lamina and Agbanusi 2013). Even in young men (18–40 years), exercise –defined as ≤1,400 cal/week – is associated with better sexual function (Hsiao et al. 2012).

Overall, especially in men with the aspects of the metabolic syndrome, both clinical and experimental studies have confirmed that combining the exercise with weight loss provides additional benefit to erectile function, likely via reduced metabolic disturbances (e.g., inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (e.g., increased endothelial function) (Hannan et al. 2009).


5.7.1.3 Pharmacotherapy for CV Risk Factors May Improve ED


According to a meta-analysis of six randomized controlled clinical trials with a follow-up of at least 6 weeks of lifestyle modification interventions or pharmacotherapy for CV risk factor reduction, it was found that lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in IIEF-5 score (mean difference, 2.66 with 95 % CI, 1.86–3.47) (Gupta et al. 2011).


5.7.1.4 The Mediterranean Secret: “Beware What You Eat!”


Going through a systematic literature search, one realizes that a dietary pattern which is high in fruit, vegetables, nuts, whole grains, and fish, but low in red and processed meat and refined grains, is more common in subjects without ED. The Mediterranean diet has been proposed as a healthy dietary pattern based on the evidence that greater adherence to this diet is associated with lower all-cause and disease-specific survival (Esposito et al. 2010). In men with type two diabetes, those with the highest adherence to the Mediterranean diet had the lowest prevalence of ED and were more likely to be sexually active. In clinical trials, the Mediterranean diet has been found to be more effective than a control diet in ameliorating or restoring ED in people with obesity or metabolic syndrome (Esposito et al. 2010).

The above data show us the aspects of a prevention strategy for ED (Fig. 5.6).


5.7.2 Low-Intensity Shockwave Therapy: Is It Really “the Cure Therapy”?


Available treatment options for organic ED may help men reduce or control symptoms, but are unable to cure the disease. Low-intensity extracorporeal shockwave therapy (LI-ESWT) has been used in the management of chronic wounds, peripheral neuropathy, and cardiac neovascularization for many years (Gruenwald et al. 2013). Application of the method to the penis has emerged during the last 5 years as a new and promising modality in the treatment of vasculogenic erectile dysfunction (ED). Basic science has provided evidence that LI-ESWT induces cellular microtrauma, which in turn stimulates the release of angiogenic factors and the subsequent neovascularization of the treated tissue (Gruenwald et al. 2013). In a diabetic rat model, low-intensity extracorporeal shockwave therapy ameliorated ED associated with diabetes mellitus by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis (Qiu et al. 2013). These beneficial effects appear to be mediated by recruitment of endogenous mesenchymal stem cells.

In randomized, double-blind, sham-controlled studies in men with ED, the LI-ESWT eliminated the dependence on PDE5i in patients who responded to oral therapy (PDE5i), and 60–75 % were thus able to successfully achieve erections and vaginal penetration (Vardi et al. 2012). Furthermore, 72 % of the nonresponders to oral pharmacotherapy became responders to PDE5i and capable of vaginal penetration after shockwave treatment. Additionally, LI-ESWT resulted in long-term improvement of the erectile mechanism. The feasibility and tolerability of this treatment, coupled with its potential rehabilitative characteristics, make it an attractive new therapeutic option for men with ED.

Multicentered studies with longer follow-up are underway to confirm that LI-ESWT has the potential to improve and permanently restore erectile function by reinstating penile blood flow (Gruenwald et al. 2013).


5.7.3 Vascular Surgery



5.7.3.1 Penile Revascularization: Only for Young Patients with Pure Arteriogenic ED


Penile revascularization procedures concern a highly selected young patient group with circumscribed acquired or congenital vascular abnormalities. The procedure is performed in centers of excellence to young men, who are nonsmokers and nondiabetic and demonstrate perineal trauma-associated isolated arterial stenoses in the absence of generalized vascular disease (Sohn et al. 2013). All types of the described procedures use the internal pudendal artery (which becomes the common penile artery) as the arterial source to penile blood supply:



  • Anastomosis of the IEA to dorsal penile arteries end-to-end or end-to-side (true revascularization)


  • Anastomosis of the IEA to the deep dorsal vein with additional proximal and/or distal vein ligation (venous arterialization)


  • Anastomosis of the IEA to the deep dorsal vein and artery (arterial-venous shunt)

In one study, a ≥5 point increase in the IIEF-5 score was defined as success threshold; at 5 years after surgery, the success rate in this study was 63.6 % (Kayigil et al. 2012). In another study with 70.8 months and definition of success the satisfactory intercourse without additional therapy, patients under 28 years showed a 73 % success rate vs 23 % in the older ones, while nonsmokers had a 57 % success compared to 29 % in smokers (Vardi et al. 2004). A systematic review and meta-analysis of the 25 published studies showed that the results in men younger than 30 years old are better than older ones (odds ratio, 3.7; 95 % confidence interval, 2.2–6.4; p = .001). Venous leak and history of smoking negative influenced success rate (Babaei et al. 2009). Finally, the evaluation of the long-term results in a Center of Excellence with the use of validated instruments showed that in patients with no vascular risk factors and pure cavernous arterial insufficiency, the microvascular arterial bypass surgery provides long-term improvement in erectile function, depression, and overall satisfaction (Munarriz et al. 2009).


5.7.3.2 Surgery for Venoocclusive Dysfunction: Only for Site-Specific Leak


The results of venous ligation surgery for diffuse venous leak have been disappointing; in one study with a follow-up of at least 3 years, only 21.87 % sustained potency without adjunctive therapy (Da Ros et al. 2000). Young patients, however, with site-specific congenital posttraumatic or post-inflammatory leaks may be considered candidates for vein ligation, as crural ligation surgery improves erectile function in most men treated 1 year postoperatively (Flores et al. 2011). New technologies, such as 3D-CT cavernosography, can provide high-resolution images of venous drainage for precise identification the leaking veins (Kawanishi et al. 2011).


5.8 Vacuum Erection Devices


Despite the fact that VED is considered a first-line therapy option for ED of any etiology, erections with these devices are not normal because they provide passive engorgement of the corpora cavernosa. A constrictor ring is placed at the base of the penis to retain blood within the corpora, which has to be removed within 30 min in order to avoid skin necrosis. Also, VEDs are contraindicated in patients with bleeding disorders or on anticoagulant therapy.

Satisfaction rates range between 27 and 94 % (Levine and Dimitriou 2001). Older men with a motivated, interested, and understanding partner report the high satisfaction rates. Most men who discontinue use of VEDs do so within 3 months. The commonest adverse events include pain, inability to ejaculate, petechiae, bruising, and numbness, which occur in <30 % of patients (Lewis and Witherington 1997). VEDs may be the treatment of choice for well-informed older patients who are in long-term partnerships with occasional intercourse attempts or in patients where comorbidity requires noninvasive, drug-free management of ED.


5.9 Phosphodiesterase Type 5 Inhibitors (PDE5i)


Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE-5, which catalyze the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, into its corresponding metabolites (monophosphates) (Andersson 2011). PDE5-Is exert their beneficial effect by producing vasodilation and increased blood flow to the corpora cavernosa of the penis, which facilitate penile erection.

Currently, three PDE5-Is are in clinical use worldwide for on-demand use with indication for ED: sildenafil (25, 50, 100 mg), vardenafil (5, 10, 20 mg), and tadalafil (10, 20 mg). Vardenafil 10 mg is available also in the form of orodispersible tablet (ODT) in a discreet packaging; it is applied on the tongue without the need of water or any other fluid and provides a rapid disintegration within the mouth before swallowing. Tadalafil has been approved for daily application (OAD) in doses of 2.5 and 5 mg as an alternative treatment regimen to on-demand dosing. Recently, this form of treatment has been approved also for the treatment of BPH-associated lower urinary tract symptoms. Two of the PDE5-Is (sildenafil and tadalafil) are also approved with indication pulmonary arterial hypertension.

Four new PDE5 inhibitors (avanafil, udenafil, lodenafil, and mirodenafil) have been investigated in randomized controlled trials (RCTs) and have shown similar efficacy and safety profiles to sildenafil, tadalafil, and vardenafil. Two of them are marketed in European countries; avanafil has been recently approved in the EU (and the USA), and udenafil is marketed in Russia (and Korea); lodenafil is approved only in Brazil and mirodenafil in South Korea.

Jun 30, 2017 | Posted by in UROLOGY | Comments Off on Erectile Dysfunction

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