Committee I

Committee XIII

Male Sexual Dysfunction

Prof. Abdel Rahman M. Zahran, MD Professor of Urology, Faculty of Medicine, Alexandria University

Prof. Ahmed El Taher, MD Professor of Urology, Faculty of Medicine, Assuit University

Prof. Emad A. Salem, MD Professor of Urology, Faculty of Medicine, Zagazig University

Prof. Magdy S. El-Bahnasawy, MD Professor of Urology, Faculty of Medicine, Mansoura University

Ass. Prof. Mohammed Abdel-Rassoul, MD Assistant Professor of Urology, Faculty of Medicine, Cairo University

Ass. Prof. Mamdouh M. El-Hawy MD Assistant Professor of Urology, Faculty of Medicine, Minia University

Ass. Prof. Mamdouh M. El-Hawy MD Assistant Professor of Urology, Faculty of Medicine, Minia University

Dr. Khaled Mohyelden, MD Lecturer of Urology, Faculty of Medicine, Fayoum University

Contents
XIII.1 List of Abbreviations
  • AUA American Urological Association
  • AIPE Arabic Index of Premature Ejaculation
  • BSSM British Society for Sexual Medicine
  • CCH Clostridium Collagenase
  • CDU Color Duplex Ultrasonography
  • ED Erectile Dysfunction
  • EMA European Medicines Agency
  • EUA European Urological Association
  • ISSM International Society of Sexual Medicine
  • IHD Ischaemic Heart Disease
  • NPT Nocturnal penile tumescence
  • PP Penile Prosthesis
  • PE Premature Ejaculation
  • PEDT Premature Ejaculation Diagnostic Tool
  • PSA Prostate-Specific Antigen
  • QoL Quality of Life
  • RP Radical Prostatectomy
  • RT Radiotherapy
  • SCs Stem Cells
  • TA Tunica Albuginea
  • VED Vacuum Erection Device

XIII.2 Abstract

XIII.2.1 Objectives:
To present the contemporary evidence for medical practice in Egypt for the diagnosis and treatment of male patients suffering from sexual dysfunction.
XIII.2.2 Methods:
Our recommendations are based on 4 resource categories;
• Four international guidelines namely European Urological Association [EUA], American Urological Association [AUA], British Society for Sexual Medicine [BSSM], International Society of Sexual Medicine [ISSM];
• A panel of 8 high-caliber urologists and andrologists representing different universities, institutions and private practice in Egypt.
• A systematic literatures search was conducted using PubMed, Embase, and the Cochrane Library for English-language journal articles between January 2000 and January 2020, using the terms, “erectile dysfunction” (ED), “ejaculatory dysfunction”, “low sexual desire”, “Peyronie’s disease” “hypogonadism” and “priapism”.
• Criteria included all pertinent review articles, randomized controlled trials with tight methodological design, cohort studies, and retrospective analyses. We also manually reviewed references from selected articles.

XIII.2.3 Results:
The Egyptian urological guideline for sexual dysfunction reflects the consensus of the authors that was guided by international guideline recommendations, it was modified to suit the Egyptian environment dominated by a rich bioecological environment, specific demographics, social constraints and limited financial resources.

XIII.2.4 Conclusion:
To help guide Egypt practitioners on effectively diagnosing and properly managing men with sexual dysfunction. This approach should not only provide sexual and psychosocial benefits for our patients but also insuring improvement in their quality of lif
XIII.3 Introduction:

Erectile dysfunction (ED) and premature ejaculation (PE) are the two main complaints in male sexual medicine in the Middle East (1-2). Pharmacological therapies have completely changed the diagnostic and therapeutic approach to ED (3,4). The prevalence of ED is 20–90% among patients with different risk factors and medical comorbidities in Arab region countries. The high prevalence of severe ED in patients in this region could be attributed to:
1. The high prevalence of risk factors;
2. The poor control of those risk factors;
3. The delay in seeking medical advice; and
4. The non-compliance with treatment (1-2).
Unfortunately, in Arab countries there are no firm data on the true prevalence of sexual dysfunction. This prompted several investigators in the region to conduct research to identify the magnitude of the current problem (1-2).
This article integrates recent international guidelines with local experience and also highlights the apparent lack of congruency between available treatment and communication, cultural, and gender norms of Middle East populations that may inhibit treatment seeking. We clarified in our recent publication that strategies for diagnosis and treatment should consider the sociocultural-factors that influence diagnosis and treatment seeking and engagement behaviors necessary for successful outcomes. Specifically, the detrimental effects of sexual problems on quality of life and the potential benefits of proper diagnosis and treatment should be more widely communicated in order to diminish the social disgrace associated with sexual problems and their management (5). Information was incorporated into a modified set of Egyptian Guidelines suitable for incorporation based on our socioeconomic limitations while incorporating evidence based rationale. (11) Having said this the best treatment also depends on the circumstances of each individual case and is not uniform so that the guidelines should be taken as an advisory not legally binding document that should be of benefit in case management.

XIII.4 Methodology

XIII.4.1 Resources of Recommendations:

Our recommendations are based on 4 resource categories:
o Four international guidelines and recommendations, namely European Urological Association [EUA], American Urological Association Guidelines [AUA], British Society for Sexual Medicine [BSSM], International Society of Sexual Medicine [ISSM], (6-12).
o Review of several guides, reviews, statements, recommendations, standards (10-14).
o Relevant Egyptian publications.
o A panel of 8 high-caliber urologists and andrologists representing different universities, institutions and private practice in Egypt.

XIII.4.2 Strength of clinical practice recommendation:

All statements were graded according to strength of clinical practice recommendation, reflecting the consensus of the authors and was guided by other international guideline recommendations. They were modified to suit the Egyptian environment dominated by a rich bioecological environment, specific demographics, social constraints and limited financial resources. Statements were graded into strong or weak.
XIII.4.3 Synthesis of Recommendations:
All recommendations related to, erectile dysfunction (ED), ejaculatory dysfunction, low desire, Peyronie’s disease, hypogonadism and priapism were discussed by a panel of 8 expert urologists and andrologists. The committee members are high caliber academics and clinicians who are dealing with sexual dysfunction from different aspects and they represent different regions of Egypt with different sociodemographic characteristics. A systematic literatures search was conducted using PubMed, Embase, and the Cochrane Library for English-language journal articles between January 2000 and January 2020, using the terms, “erectile dysfunction” (ED), “ejaculatory dysfunction”, “low sexual desire”, “Peyronie’s disease” “hypogonadism” and “priapism”. Criteria included all pertinent review articles, randomized controlled trials with tight methodological design, cohort studies, and retrospective analyses. We also manually reviewed references from selected articles. The participant physicians have disclosed no conflict of interest.

XIII.5 Erectile dysfunction:

XIII.5.1 Definition:
Erectile Dysfunction (ED) is defined as the persistent or recurrent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance (15).
XIII.5.2 Epidemiology:
XIII.5.2.1 General population:
Prevalence of ED in the United States, the United Kingdom, Australia, Japan, and Korea were reported to be 52%, 32%, 43%, 26%, and 37%, respectively (16).
XIII.5.2.2 Egypt and Arabic countries:
In cross-sectional office-based studies, El-Sakka showed that ED was very prevalent and ED risk factors were very common. In all, 92.6% of the patients had ED, 50.8% had premature ejaculation, and 7.6% had low sexual desire. Furthermore, 20% of the patients had psychogenic while 80% had organic causes of ED. Of the patients, ≈10% had mild, 40% had moderate and 50% had severe ED (1,2,17).
Shaeer and Shaeer explored epidemiological aspects of male sexuality using an online survey. They found that among Arab-speaking Internet users, the overall prevalence of ED was 45.1%, strongly correlating with various risk factors (18). In another study from Upper Egypt, Zedan et al., showed that of 658 men with ED, 17.3% had hypertension, 21.4% had DM and 40.1% were smokers (19).
In a cross-sectional community-based random sample of Egyptian men, Seyam et al., found that men with complete ED comprised 13.2% of the sample, 26% of men in their 50s, 49% of men in their 60s and 52% of those aged ⩾70 years (20).

XIII.5.3 Pathophysiology:
The pathophysiology of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced and/or psychogenic. ED may affect physical and psychosocial health and may have a significant impact on the quality of life (QoL) of sufferers and their partner’s (21-23). There is increasing evidence that ED can be an early manifestation of coronary artery and peripheral vascular disease (21-23).
XIII.5.4 Diagnostic evaluation:
The diagnostic pathway and treatment of ED have been reported in many studies, but they are not yet well addressed in the Arab region. This provoked several investigators in Arab countries to assess different methods for the diagnosis and treatment of sexual dysfunction among patients in this region (24). The tailored diagnosis of ED not only allows the physician to avoid further costly evaluation, but also saves the patient from unnecessary and sometime invasive diagnostic techniques (24, 25). In general, the following should be obtained in every patient:
15. 1. A detailed medical and psycho-sexual history
16. 2. A thorough physical examination; and
17. 3. Appropriate laboratory tests (complete blood count, fasting glucose, lipid profile, kidney function, testosterone, and others if indicated) (24-27). For a satisfactory and cost-effective treatment, the evaluation methods should answer these inquiries:
18. 1. Whether the cause of ED is organic or psychogenic;
19. 2.The severity and possible reversibility of ED; 20. 3. The patient’s and probably the partner’s goals and expectations (24).
XIII.5.5 Basic work-up.
XIII.5.5.1 Sexual history:
The first step in evaluating ED is always a detailed medical and sexual history of patients and, when available, their partner’s. In this context, taking a comprehensive medical history may reveal one of the many common disorders associated with ED. It is important to establish a relaxed atmosphere during history taking (28). Validated questionnaires may provide an opportunity to initiate a conversation about ED; examples include the Erection Hardness Score (29) and the Sexual Health Inventory for Men (30), IIEF Arabic version (31). Elnashar and his colleague asses the use of IIEF-5 as a diagnostic tool to determine the severity of vasculogenic ED, and they concluded that IIEF-5 cannot be used to diagnose the severity of vascular affection in ED patients (32).
The sexual history must include information about onset and duration of the erectile problem, prior surgeries, medications, family history of vascular disease, and substance use, and previous consultations and treatments. The presence of nocturnal and/ or morning erections suggests a psychogenic component to ED symptoms (33).
XIII.5.5.2 Physical examination:
A thorough physical examination with particular attention to the genital area can sometimes reveal an obvious cause (e.g. micropenis, penile chordee, Peyronie’s plaque, pre-malignant or malignant genital lesions, prostatic enlargement or irregularity/nodularity,). The finding of small soft atrophic testes or gynaecomastia needs endocrine evaluation. Patients with some genetic syndromes, e.g. Kallmann’s or Kleinfelter’s, can present with obvious physical signs of hypogonadism or a distinctive body habitus.
A careful neurological examination should also be conducted. Testing for genital and perineal sensation and the bulbocavernosus reflex is also useful in assessing possible neurogenic ED (6-8,33). Kamel et al., compared penile measurements in normal subjects and patients with ED. The average fully stretched penile length in normal men was 12.9 cm, but was 11.2 cm in patients with ED (significantly different, P < 0.001), although the mean fully stretched penile girths were not statistically different between the groups (34).
A history and physical examination had 95% sensitivity but only 50% specificity in diagnosing organic ED. In many cases, a careful history and physical examination will direct the physician to the most expedient and cost-effective approach, and eliminate the need for unnecessary diagnostic tests (35).
XIII.5.5.3 Laboratory testing:
The routine laboratory investigation should be directed at identifying treatable conditions or previously undetected medical illnesses that might be contributory, e.g. renal insufficiency, DM and endocrine abnormalities (hypogonadism, hyperprolactinaemia) (36,37).
Laboratory evaluation includes fasting blood glucose, HbA1c, lipid profile if they have not recently been assessed, renal function, a complete blood count, urine analysis, should be done in the initial evaluation. Hormonal tests and additional laboratory tests may be considered in selected patients e.g., prostate-specific antigen (PSA), FSH and LH (36,37).
El-Sakka et al. reported a possible association between sexual dysfunction, e.g. ED, premature ejaculation (PE) and low desire, and hypogonadism. They also found that 23.8% of patients had endocrinopathy. There were significant associations between low desire and low testosterone level, hyperprolactinaemia and hypothyroidism (P < 0.05 for each). Furthermore, they investigated the effect of testosterone replacement therapy on the PSA level in hypogonadal men with ED (38,39). Zohdy et al. concluded in their study that obesity is associated with lower total testosterone levels and disturbances of penile haemodynamics (40).
XIII.5.5.4 Specialized diagnostic tests:
Most patients with ED can be managed based on medical and sexual history, physical examination and laboratory investigations; conversely, some patients may need specific diagnostic tests (6-8). XIII.5.5.4.1 Nocturnal penile tumescence (NPT) and rigidity test: Many investigators have advocated the use of NPT studies to differentiate organic from psychologenic ED. The shortcomings associated with various NPT tests, such as false-negative results were documented (41). XIII.5.5.4.2 Intracavernous injection test: The intracavernous injection test gives limited information about the vascular status. A positive test is a rigid erectile response (unable to bend the penis) that appears within ten minutes after the intracavernous injection and lasts for 30 minutes. Overall, the test is inconclusive as a diagnostic procedure and a duplex Doppler study of the penis should be requested, if clinically warranted (42). XIII.5.5.4.3 Duplex ultrasound of the penis: 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. Further vascular investigation is unnecessary if a duplex ultrasound examination is normal. The hemodynamic parameters were measured several times (starting after 5 min from self-stimulation) in the same sitting to obtain the most optimal results (43). El-Sakka and his colleague reported a significant association between increasing severity of ED and increased values of EDV, and decreased values of PSV and RI on penile Doppler ultrasonography and rigidometer tests. In addition, they showed that a low PSV can be used as a screening tool for ischaemic heart disease (IHD) in patients with ED (44). XIII.5.5.4.4 Rigidometer tests: Rigidometry evaluate the minimal axial pressure that can bend the erect penis [39]. El-Sakka investigated the association between the IIEF and axial penile rigidity values in ED patients with or without DM (45). There was a significant association between the overall presence of ED and low axial penile rigidity (46,47). XIII.5.5.4.5 Arteriography and dynamic infusion cavernosometry & cavernosography: Arteriography and dynamic infusion cavernosometry & cavernosography should be performed only in patients who are being considered for vascular reconstructive surgery. Recent data suggested the use of computed tomography angiography in cases of penile artery angioplasty for patients with ED and isolated penile artery stenoses (48).
XIII.5.5.5 Psychiatric assessment:
Whenever clinically indicated, patients with psychiatric disorders should be referred to a psychiatrist who is particularly interested in sexual health. In younger patients (< 40 years) with long-term primary ED, psychiatric assessment may be helpful before any clinical assessment is carried out (49).
Indications for specific diagnostic tests (6-8)
o Primary ED (not caused by organic disease or psychogenic disorder).
o Young patients with a history of pelvic or perineal trauma, who could benefit from potentially curative revascularization surgery or angioplasty
o Patients with penile deformities which might require surgical correction (e.g., Peyronie’s disease, congenital penile curvature
o Patients with complex psychiatric or psychosexual disorders.
o Patients with complex endocrine disorders.
o Specific tests may be indicated at the request of the patient or his partner.
o Medico-legal reasons (e.g., implantation of penile prosthesis to document end stage ED, sexual abuse).
XIII.5.5.6 Recommendations for the diagnosis of ED:


Table XIII:1 Recommendationsfor Diagnosis of ED

Recommendations

Strength Rate
1. Take a comprehensive medical and sexual history in every patient. Strength rating Strong
2. Use a validated questionnaire especially Arabic version (if available) related to ED to assess all sexual function domains and the effect of a specific treatment modality Strong
3. Perform physical examination in the initial assessment of men with ED to identify underlying medical conditions and comorbid genital disorders that may be associated with ED Strong
4. Assess routine laboratory tests, including glucose-lipid profile and total testosterone, to identify and treat any reversible risk factors and lifestyle factors that can be modified. Strong
5. Include specific diagnostic tests in the initial evaluation only in the presence of “Indications for specific diagnostic tests” mentioned above Strong

XIII.5.6 Treatment of ED

XIII.5.6.1 Non-surgical treatment of ED:
Determining an appropriate treatment requires that the man, his clinician, and ideally his partner navigate all of these issues in order to arrive at a treatment choice that is aligned with the man and his partner's priorities and values. In each scenario, the clinician's role is to ensure that the man and his partner have full understanding of the benefits and risks/burdens of the various management strategies. All men, regardless of the decision to treat ED, should be strongly advised to address any underlying medical issues that may contribute to the ED and that constitute independent risk factors for poor health, reduced QoL, and decreased survival. Each man brings to the clinical encounter not only his symptoms, but his degree of distress; his associated health conditions; his partner's concerns and issues of relationship quality; and his sociocultural, educational, and religious context (5).
XIII.5.6.2 Conservative treatment
It remains the initial step for the treatment of ED. This kind of therapy consists of different modalities including: oral treatments, intracavernosal pharmacotherapy, and evolving modalities such as soluble guanylate cyclase activators, stem cells (SCs), and alternative treatments such as herbal treatment and transdermal/topical pharmacotherapy. However, it should be noted that the currently available pharmacotherapy is still far from ideal. One hopes to witness new drugs and technologies that may revolutionize ED treatment in the future, especially in such complex cases as DM and cardiovascular diseases (50).
The interest in PDE5Is as targets for pharmacologic treatment has evolved with the development of selective PDEIs (51). The effectiveness and tolerability of 12 weeks of open-label treatment with sildenafil citrate for erectile dysfunction (ED) associated with a diagnosis of diabetes mellitus and/or hypertension were assessed in clinical practice in three Middle Eastern countries (52). Furthermore, interesting data add to the body of knowledge regarding testosterone level and sexual function and suggested that testosterone level play a role in sexual desire, frequency of nocturnal erection and frequency of intercourse, further approximately 20 % of men with complains of sexual dysfunction have hypogonadism (53). Makhlouf et al shows that both conditions are fairly prevalent in an ED clinic population, and that there is increased likelihood of finding depression among men with hypogonadism (54).
Early treated rats with vardenafil had preserved erection and normal cavernosal structure, ultrastructure and gene expression of iNOS, nNOS, eNOS, and TGF-β1. Clinical application of this result may encourage early administration of PDE5I (55). Recent study had shown that single intracavernosal dose of Botox either 50 or 100 U in my be of benefit in PDE5I non responders in patients with vasculogenic ED (56).
Several studies have established the role of ICI of vasoactive materials as a very common alternative tool in treatment of severe ED particularly in diabetic patients, post-RP, PDE5I non-responders. Further, new studies have denoted the potential future role of intracavernosal treatment for ED in the era of stem cells and gene therapy. ICI of vasoactive material continues to be a highly effective and safe treatment tool for men with wide varieties of ED etiologies. Several experimental and clinical studies are currently investigating new ICI materials. Hopefully in the near future, we might witness evolved molecules and innovative strategies that could help to treat ED patients with different etiologies (57). XIII.5.6.2.1 Recommendations for non-surgical treatment of ED: XIII.5.6.2.1.1 Recommendations for lifestyle modifications

Table XIII:2 Recommendations for Life Style

Recommendations

Strength Rate
Advise for lifestyle modifications, including changes in diet, increased physical activity, stopping smoking, improving overall health at or before treatment of erectile dysfunction. Strong
XIII.5.6.2.1.2 Recommendations for men who are prescribed PDE5Is
Table XIII:3 Recommendations for men who are prescribed PDE5Is

Recommendations

Strength Rate
1. Patients should be informed regarding approved PDE5Is, including discussion of benefits and risks/burdens. Strong
2. Prescribe PDE5Is as first-line therapy. The dose should be titrated to provide optimal efficacy. Strong

XIII.5.6.2.1.3 Recommendations after treatment for prostate cancer by radical prostatectomy (RP) or radiotherapy (RT)
Table XIII:4 Recommendations after treatment for prostate cancer by radical prostatectomy (RP) or radiotherapy (RT)

Recommendations

Strength Rate
Early rehabilitation programs (use of PDE5I and VED) post-RP may improve erectile function. Strong
XIII.5.6.2.1.4 Recommendations for men with Erectile Dysfunction and hypogonadism


Table XIII:5 Recommendations for men with Erectile Dysfunction and hypogonadism

Recommendations

Strength Rate
Patients should be informed that PDE5Is may be more effective if combined with testosterone therapy when indicated. Strong
XIII.5.6.2.1.5 Recommendations for PDE5Is failure in patients with ED

Table XIII:6 Recommendations for PDE5Is failure in patients with ED

Recommendations

Strength Rate
Assess patients for, inadequate/incorrect prescriptions, poor sexual stimulation, and fat meals when not advised. Weak
XIII.5.6.2.1.6 Recommendations for ED treatment with a vacuum erection device (VED)

Table XIII:7 Recommendations for ED treatment with a Vacuum Erection Device (VED)

Recommendations

Strength Rate
Discuss benefits and risks/burdens on the use of VED, especially in in wellinformed older patients with infrequent sexual intercourse and comorbidity requiring non-invasive, drug-free management of ED. Weak
XIII.5.6.2.1.7 Recommendations for the use of ICI therapy

Table XIII:8 Recommendations for men who are prescribed ICI Therapy

Recommendations

Strength Rate
1. An in-office injection test should be performed. Home therapy after positive office ICI test. Strength rating. Weak
2. Alprostadil (PGE1) is the best agent however its cost is a limitation. Weak
XIII.5.6.2.1.8 Recommendations for intracavernosal stem cell therapy.

Table XIII:9 Recommendations for intracavernosal stem cell therapy

Recommendations

Strength Rate
Intracavernosal stem cell therapy should be considered investigational for treatment of ED. Strength rating. Weak
XIII.5.6.3 Surgical treatment for ED
XIII.5.6.3.1 Vascular surgery
XIII.5.6.3.1.1 Surgery for post-traumatic arteriogenic ED The highest success rates are reported in young men (less than 30 years of age) with isolated arterial stenosis after perineal or pelvic trauma (58). Success of these surgeries has been variable and depends on careful patient selection. Penile arteriography is required to establish a penile arterial anatomic defect, and other organic causes of ED (e.g., venous incompetence) that would limit surgical success should be excluded.
According to the current literature, the following inclusion criteria should be met when selecting patients for arterial surgery (59):
o Age less than 55 years,
o Cessation of tobacco smoking,
o Nondiabetic
o Absence of venous leakage
o Radiographic confirmation of focal stenosis of the internal pudendal artery.
o No atherosclerosis
o Usually result from perineal or pelvic trauma
Several Arterial revascularization procedures have been described to create arterial inflow to the corpora, similarly creating an anastomosis of the inferior epigastric artery either to the corpus cavernosum directly or to vascular conduits of the penis such as the dorsal artery (i.e., revascularization), the deep dorsal vein (i.e., arterialization), or the deep dorsal vein with venous ligation (i.e., arterialization with venous reconstruction) (59). Complications of arterial revascularization surgery include glans hyperemia (13%), shunt thrombosis (8%), and inguinal hernias (6.5%) (60).
Previous studies reported outcomes for arterial reconstruction procedures, the most commonly used outcome measure was the percentage of men in different response categories post-surgery. Typically, high response rates (complete or partial) were reported at short intervals post-surgery, with declining rates over time. Overall, there was considerable variability regarding response rates, particularly complete (range 12 to 81.6%) and partial response rates (range 7.7 to 53.3%) (6-8). XIII.5.6.3.1.2 Venous ligation surgery Venous ligation surgery for veno-occlusive dysfunction is no longer recommended because of poor long-term results (61). XIII.5.6.3.1.3 Penile Prosthesis The surgical implantation of a penile prosthesis may be considered in patients who:
1. Are not suitable for different pharmacotherapies or prefer a definitive therapy; and,
2. Do not respond to pharmacological therapies (62).
Men and their partners should be thoroughly counseled regarding the benefits and potential risks of this modality of treatment to ensure appropriate choice of device, realistic post-operative expectations, and high levels of satisfaction (63).
The two currently available classes of penile implants include inflatable (2- and 3-piece) and semirigid devices (malleable, mechanical, soft flexible) (64,65).
There are two main surgical approaches for inflatable penile prosthesis implantation: penoscrotal and infrapubic (64,65). Regardless of the indication, prosthesis implantation has one of the highest satisfaction rates (92-100% in patients and 91-95% in partners) among the treatment options for ED based on appropriate consultation (66). There is sufficient evidence to recommend this approach in patients not responding to less-invasive treatments due to its high efficacy, safety and satisfaction rates (67). There are also currently no head to head studies comparing the different manufacturers’ implants, demonstrating superiority of one implant type over another.
Complications of penile prostheses
The two main complications of penile prosthesis implantation are mechanical failure and infection. Careful surgical techniques with proper antibiotic prophylaxis against Gram-positive and Gramnegative bacteria reduces infection rates to 2-3% with primary implantation in low-risk patients and in high volume centers (68). Higher-risk populations include patients undergoing revision surgery, those with impaired host defenses (immunosuppression, diabetes mellitus, spinal cord injury) or those with penile corporal fibrosis (69).
XIII.5.6.3.2 Recommendations for Surgical management of erectile dysfunction.


Table XIII:10 Recommendations for Surgical management of Erectile Dysfunction

Recommendations

Strength Rate
1. Surgery should be reserved for men in whom less invasive reversible treatment has not succeeded or is contraindicated or undesirable. Strong
2. Arterial revascularization surgery is offered only to select patients with ED who meet strict clinical and radiographic criteria for surgical success. Strength rating. Strong
3. Vascular surgery for veno-occlusive dysfunction is no longer recommended. Strength rating. Strong
4. Use implantation of a penile prosthesis as third-line therapy if other treatments fail or based upon patient preference. Strength rating. Strong

XIII.6 Premature Ejaculation

XIII.6.1 Definition:
The first evidence-based definition of PE considered that ejaculation that always or nearly always occurs prior to or within about one minute of vaginal penetration (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about three minutes or less (acquired PE). In association with the inability to delay ejaculation on all or nearly all vaginal penetrations; and with negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy (70).
Two more PE syndromes have been proposed: ‘Variable PE’ is characterized by inconsistent and irregular early ejaculations, representing a normal variation in sexual performance. ‘Subjective PE’ is characterized by subjective perception of consistent or inconsistent rapid ejaculation during intercourse, while ejaculation latency time is in the normal range or can even last longer. It should not be regarded as a symptom or manifestation of true medical pathology. The addition of these new types may help in overcoming the limitations of each individual definition and it may support a more flexible view of PE for patient stratification, diagnosis and treatment
XIII.6.2 EPIDEMIOLOGY
The overall prevalence of PE ranges between 19.8-25.8%. According to the four PE subtypes, the prevalence rates is 2.3-3.18% (lifelong PE), 3.9-4.8% (acquired PE), 8.5-11.38% (variable PE) and, 5.1-6.4% (subjective PE) (71, 72).
XIII.6.3 Recommendation for Assessment of PE
Recommendations for assessment of PE are in the below table. (71-76)

Table XIII:12 Recommendations for Treatment of PE

Recommendations

Strength Rate
1. Define the subtype of PE and discuss patient’s expectations thoroughly before starting any treatment. Strong
2. Treat the underlying cause (e.g., ED, prostatitis, LUTS, anxiety, hyperthyroidism) as the initial goal for patients with acquired PE . Strong
3. Pharmacotherapy must be considered as the first-line treatment for patients with lifelong PE i.e. dapoxetine. Strong
4. The use of off-label topical anesthetic agents i. e. the lidocaine/prilocaine spray is considered as as a viable alternative to oral treatment with SSRIs. Weak
5. Use psychological/behavioural therapies in combination with pharmacological treatment in the management of acquired PE. Weak
6. Suggest various behavioral techniques in treating variable and subjective PE. Weak
7. Offer Tramadol on-demand as a weak alternative to SSRIs. Weak
8. Offer PDE5Is alone or in combination with other therapies in patients with PE (without ED). Weak

XIII.7 Delayed Ejaculation

XIII.7.1 Definition:
Marked delay in ejaculation or marked infrequency or absence of ejaculation on almost all or all occasions (75-100% of the times) of partnered sexual activity without the individual desiring delay persisting for at least 6 months and causing significant distress to the individual (77).
XIII.7.2 Background:
Multiple terms including delayed ejaculation, anorgasmia, anejaculation, aspermia, retarded ejaculation, inhibited ejaculation or intra-vaginal ejaculatory dysfunction are used in this domain.
Of all the male sexual dysfunctions, DE is the least understood, least common and least studied (78). Lack of consistent definition and overlap with other dysfunctions such as anejaculation or anorgasmia adds to the difficulty of understanding, diagnosis and management. There is currently no single gold standard for diagnosing DE; the history is the keypoint for the diagnosis. Post-coital urine analysis for sperms to exclude retrograde ejaculation is a strong adjunct for the diagnosis. If applicable treatment should be cause-specific. There are different approaches for its management, including psychosexual interventions, drug therapy, and specific measures for patients with SCI and infertile men. Several drugs were used for treatment of DE however no single drug was approved. Currently, no drug has been approved by FDA for DE. Successful drug treatment of DE is still in its infancy (79). For namely spinal cord injuries (SCI) and refractory cases seeking fertility penile vibratory stimulation (PVS) or electo-ejaculation (EE) were applied with good success rates of semen retrieval. Otherwise different epididymal or testicular sperm extraction methods were applied for IVF/ICSI.
XIII.7.3 Recommendations for assessment of DE

Table XIII:13 Recommendations for Assessment of DE

Recommendations

Strength Rate
1. Analyze thoroughly the complaints to exclude misdiagnosed other sexual dysfunctions, stressing on anorgasmia. Strong
2. Perform detailed medical and sexual history to exclude risk factors (medications especially SSRIs, antipsychotics, drug abuse, DM, depression, LUTS, etc). Strong
3. Determine if DE is lifelong or acquired, global or situational. Strong
4. Ask for assessment of intravaginal ejaculatory latency time (IELT) (selfestimated). Weak
5. Include physical examination in the initial assessment of DE to identify hypogonadism or anatomical abnormalities that may be associated with DE or other sexual dysfunctions, particularly erectile dysfunction. Strong
6. Request post-coital first voided urine sample to exclude retrograde ejaculation. Strong
7. Use specific questionnaires, specialized lab tests and radiologic investigation when indicated only . Weak

XIII.7.4 Recommendations for the treatment of DE


Table XIII:14 Recommendations for treatment of DE 09

Recommendations

Strength Rate
1. If acquired DE consider stopping or modifying underlying incriminated drug regimen. Strong
2. Improving erectile function and maximizing stimulation may trigger ejaculation. Weak
3. Psychosexual therapy can be particularly helpful in primary DE. Weak
4. Testosterone replacement in hypogonadal patients may improve DE. Weak
5. Cabergoline and bupropion could be beneficial for some cases of delayed ejaculation . Weak
6. PDE5I treatment significantly improved ejaculation and orgasm. Strong
7. Sympathetic α1 receptor agonists may help ejaculation with variable success rates in non-SCI patients. Weak
8. For fertility issues and patients with SCI, penile vibratory stimulation or electroejaculation help sperm retrieval in high percentage of patients Strong


XIII.8 Peyronie’s Disease

Peyronie’s disease (PD) is a symptomatic disorder characterized by a constellation of penile symptoms and signs, such as penile pain, curvature, shortening, narrowing, hinge deformity, and palpable plaque with subsequent ED. It is believed to occur as a result of aberrant penile wound healing in genetically susceptible individuals, with formation of fibrous inelastic plaque(s) within the bilayerd tunica albuginea (TA). The exact etiology is unknown. Microvascular trauma to the penile shaft associated with penile buckling in the semi-erect state secondary to sexual activity is thought to be the most common inciting event; however, many patients do not recall an incident that preceded symptom onset (6-8, 80-85).
XIII.8.1 EPIDEMIOLOGY
Multiple demographics studies have been performed worldwide and these have indicated a prevalence rate as high as 9% in adult sexually active men (6-8, 80-85). The natural history of PD has been evaluated in only a few level 2 and 3 studies, indicating that spontaneous resolution is uncommon. The published literature has shown a strong association between PD and cardiovascular risk factors and medical comorbidities (6-8, 80-85).
XIII.8.2 PATHOPHYSIOLOGY
The most widely accepted hypothesis on the aetiology consider PD as an accentuated wound-healing disorder occurring in a presumed genetically susceptible man in whom TA responds inappropriately to repeated minor trauma is. A prolonged inflammatory response with overexpression of cytokines and growth factors such as TGF-B result in remodeling of connective tissue into a fibrotic plaque (86-88).
XIII.8.3 PATIENT EVALUATION
Currently there is no international standard for evaluation of or reporting on treatment outcomes for PD. A detailed history should be obtained with specific emphasis on various characteristics of PD, such as disease onset, duration, pain, deformity, and erectile status as well as associated comorbidities such as diabetes mellitus. (6-8, 80-85)
Physical examination should include genital examination, such as plaque size and site, multiplicity as well as assessment of the degree of penile deformity based on clinical assessment and selfphotography. An in-office intracavernosal injection of a vasoactive agent test is recommended before invasive intervention. Penile CDU provides an objective assessment of various PD characteristics especially calcified plaques and vascular flow parameters. Routine use of plain radiography, computed tomography, and magnetic resonance imaging are not recommended.
XIII.8.4 MANAGEMENT OF PD
XIII.8.4.1 Non-operative treatment
Clostridium collagenase (CCH) has been approved by the European Medicines Agency (EMA) and the FDA for the treatment of PD. Although no other drug has been approved for this purpose, however, there is a long list of drugs which were frequently used in the active phase of PD. Those drugs are eventually stabilizing agents rather than true medical lines of treatment. In the Egyptian market CCH is not yet available probably due to its high cost for general use in treatment of PD in this community.
XIII.8.4.2 Operative treatment
Plication surgery should be preferred for men with adequate erectile function (with or without pharmacotherapy), adequate penile length, and minimal to moderate curvature but without the presence of hourglass deformity. Grafting procedures should be offered for men with good erectile function, severe deformity (significant or severe curvature and/or indentation or hourglass deformity), and concern regarding penile length loss. (89-91)
Penile prosthesis should be considered in men with complex penile deformities and refractory erectile dysfunction.
XIII.8.5 Recommendations for evaluation of PD:


Table XIII:15 Recommendations for Evaluation of PD

Recommendations

Strength Rate
1. There is currently no international standard evaluation and treatment for PD and a detailed history should be obtained with specific emphasis on various characteristics of PD, such as onset, duration, course, pain, deformity or ED. Strong
2. Perform physical examination, including assessment of palpable plaques, penile length, extent of curvature (self-photograph, or pharmacological-induced erection). Strong
3. Do not use specific PD questionnaire, ultrasound measurement of plaque size in everyday clinical practice. Weak
4. Proper pre-operative counselling includes the available treatment options and the known benefits and risks of each treatment. Patients’ expectation will reduce post treatment patient dissatisfaction . Weak
XIII.8.6 Recommendations for the non-operative treatment of PD


Table XIII:16 Recommendations for The Non-Operative Treatment of PD

Recommendations

Strength Rate
1. Use conservative treatment in patients not fit for surgery or when surgery is not acceptable to the patient. Weak
2. Intralesional collagenase injection has shown some outcome benefits in PD management Weak
3. Extracorporeal shockwave treatment may only be offered in the active stage of the disease to alleviate penile pain. Do not use extracorporeal shockwave treatment to improve penile curvature and reduce plaque size. Weak
5. Do not use oral treatment with vitamin E and tamoxifen for significant reduction in penile curvature or plaque size . Strong
6. Do not offer other oral treatments in chronic phase of PD (acetyl esters of carnitine, pentoxifylline, colchicine). Weak


XIII.8.7 Recommendations for Surgical treatment
Table XIII:17 Recommendations for Surgical Treatment of PD

Recommendations

Strength Rate
1. Perform surgery only when PD has been stable for at least three months (without pain or deformity deterioration), which is usually the case after twelve months from the onset of symptoms. Strength rating Strong
2. Prior to surgery, assess penile length, curvature severity, erectile function (including response to pharmacotherapy in case of ED) and patient expectations. Strong
3. Use tunical shortening procedures, especially plication techniques, as the first treatment option for PD with adequate penile length, curvature < 60°, absence of special deformities (hour-glass, hinge) and adequate erection Strong
4. Use grafting techniques for patients with PD with less than adequate penile length, curvature > 60º, presence of special deformities (hour-glass, hinge) and adequate erection. Weak
5. Use penile prosthesis implantation, with or without any additional procedure (modelling, plication, relaxing parallel incisions, grafting), in PD patients with ED not responding to pharmacotherapy Strong

XIII.9 Priapism

XIII.9.1 Definition:
Persistent penile erection for more than four hours and not related to sexual stimulation or relieved by ejaculation.
XIII.9.2 Pathophysiology:
Priapism is one of the challenging conditions facing the urologists during diagnostic or therapeutic phase. This is because priapism carries high risk of structural damage to the cavernosal tissue which may lead to permanent ED (92,93).
XIII.9.3 Types of Priapism:

• Ischemic priapism "veno-occlusive"
It is a persistent erection within corpora cavernosa and no or little cavernous arterial flow. The patient typically complains of penile pain and clinical examination reveals a rigid erection.
• Non-ischemic priapism
It is a persistent erection caused by increased cavernous arterial inflow. The patient typically reports an erection that is not fully rigid and is not associated with pain.
• Stuttering (recurrent or intermittent) priapism
It is a distinct condition that characterized by recurrent attacks of painful and prolonged erections. They are often self-limited with intervening periods of detumescence.
• Primary/Secondary
XIII.9.4 Diagnosis
XIII.9.4.1.1 Clinical History:
Should include duration of erection, presence or absence of pain, sickle cell disease and sickle cell crisis, past attacks of priapism, previously used drugs, the status of erectile function before the priapism episode (92,93).
XIII.9.4.1.1.1 Physical examination:
Inspection and palpation of the penis to assess degree tumescence or rigidity, corporal body involvement and tenderness (92,93).
In ischemic priapism, both corpora cavernosae are usually rigid and tender while non-tender, partially tumescent corpora cavernosa suggest a non-ischemic priapism. Abdominal, perineal, and rectal examinations may help in diagnosing pelvic trauma, infection or malignancy, also full neurologic exam maybe needed in patients with spinal cord injury or lesions (92,93).
XIII.9.4.1.2 Laboratory investigations:
Laboratory testing should include a complete blood count, white blood cell differential, and platelet count which may reveal the presence of acute infections or hematologic abnormalities.
Reticulocyte counts and hemoglobin electrophoresis may signify the presence of Sickle cell disease/trait or other hemoglobinopathies. Cavernous blood gas aspiration and analysis allows immediate differentiation between the variants of priapism (92-94).
Clinical History, Physical Examination, Laboratory Investigations and Radiologic Assessment in Different Types of Priapism are shown in below table (95). Table XIII:18 Recommendations for diagnosis of ischemic priapism

Variant

History and clinical examination

Penile blood appearance

Penile blood gas findings

Color Duplex ultrasonography findings

Ischemic priapism

Tender and rigid corpora cavernosa

Corpus cavernosum testing: blood is hypoxic and dark in color

pO2> 30 mmHg pCO2>60 mmHg pH< 7.25

Minimal or absent blood flow

Nonischemic priapism

Perineal or penile trauma; non tender, partially tumescent corpora cavernosa

Corpus cavernosum testing: blood is oxygenated and red

pO2< 90 mmHg pCO2 < 40 mmHg pH=7.4 similar to normal arterial blood)

Blood flow is normal to high in velocity

Stuttering (recurrent) priapism

Similar attacks

Corpus cavernosum testing: blood is hypoxic and dark in color

Blood gases: pO2< 30 mmHg; pCO2>60 mmHg pH < 7.25

Minimal or absent blood flow during acute priapism; normal blood flow otherwise

pCO2, partial pressure of carbon dioxide; pO2, partial pressure of oxygen.
XIII.9.4.1.3 Radiologic assessment:
Color duplex ultrasonography [CDU] of the perineum and penis can assess intracorporeal arterial blood flow. CDU should not be used as an alternative to arterial blood gas testing.
Penile MRI allows good judgment on smooth muscle viability within the corpora after episodes of priapism. It also helps in detecting malignant infiltration and segmental cavernosal thrombosis. Drawbacks of this technique include costs, MRI accessibility of and the time consumption (92,95).
XIII.9.4.1.4 Recommendations for diagnosis of ischemic priapism


Table XIII:19 Recommendations for diagnosis of ischemic priapism

Recommendations

Strength Rate
1. Thorough history taking is important in making the diagnosis, etiology and type of priapism Strong
2. Physical examination of the genitalia, the perineum and the abdomen are mandatory in the diagnosis of priapism . Strong
3. Laboratory investigations should include blood count, white blood count with cell differential, platelet count and coagulation profile Strong
4. Perform color duplex ultrasound of the penis and perineum for the differentiation between ischemic and non-ischemic priapism . Strong
5. In cases of prolonged ischemic priapism, use magnetic resonance imaging of the penis to predict smooth muscle viability Weak
6. Perform selected pudendal arteriogram when embolization is planned for the management of non-ischemic priapism Strong
XIII.9.5 Management of Priapism
XIII.9.5.1 Ischemic Priapism:
XIII.9.5.1.1 Non-surgical management
The first step is cavernosal aspiration of blood with irrigation of the corpora cavernosa, in combination with normal saline or in combination with ICI of an α-adrenergic sympathomimetic agent (92-95). All patients should be monitored by blood pressure assessment and electrocardiogram especially if they are known to have hypertension, coronary artery disease, or other cardiac comorbidities. The patient should be monitored for known systemic adverse effects, including hypertension, headache, reflex bradycardia, tachycardia, palpitations, and cardiac arrhythmia (92-95).
Drugs used ICI treatment include: Epinephrine (adrenaline) 2 ml of 1/100,000 adrenaline solution up to five times over a twenty-minute period, Nor-epinephrine (nor adrenaline) 10–20 mcg [as occasion requires], Ephedrine: 50–100 mg [as occasion requires] and Phenylephrine (preferable agent) 200 μg every three to five minutes with a maximum dosage is 1 mg within one hour (92-95). Lower doses are recommended in children and patients with severe cardiovascular disease.
Administration of α-adrenergic agonists is contraindicated in patients who have malignant or poorly controlled hypertension or are concurrently using monoamine oxidase inhibitors. In these patients, early surgical intervention may be necessary.
For priapism specifically related to SCD, medical therapies such as intravenous hydration, oxygenation, alkalinization, and exchange transfusion maybe performed.
However, these interventions should never precede the first-line treatment for all episodes of ischemic priapism mentioned above. Ischemic priapism of extended durations (typically greater than 48 h) is unlikely to resolve with ICI/irrigation therapy alone, therefore these patients may be counseled to consider more immediate surgical intervention (92-95).
XIII.9.5.1.2 Surgical shunts
There are four subdivisions of shunts: percutaneous distal shunts, open distal shunts, open proximal shunts, and vein anastomoses/shunts (6-12). (Table XIII:20) .
Table XIII:20 Percutaneous distal shunts, open distal shunts, open proximal shunts, and vein anastomoses/ shunts

Distal shunts

Percutaneous distal shunts

Winter (corporoglanular) shunt Large biopsy needle is inserted through glans
Ebbehoj (corporoglanular) shunt #11 blade scalpel is percutaneously passed
T shunt (corporoglanular shunt) Modified Ebbehoj using #10 blade scalpel and introducing the scalpel rotating it inside 90°

Open distal shunt

 Al-Ghorab A 1 cm incision is made distal to coronal sulcus with excision of 5 × 5 mm cone segment of distal tunica albuginea from each corporal body
Burnett ‘snake’ maneuver Modification of Al-Ghorab shunt. A Hegar dilator is used to evacuate ischemic blood through a distal tunical window

Proximal shunts

Open proximal shunt

 Quackels or Sacher (corporospongiosal) shunt In lithotomy position, bulbocavernosus muscle is dissected from corpus spongiosum and 1 cm staggered ellipses of tissue are incised/excised from spongiosal/corporal bodies, and the defects anastomosed together

Corporo saphenous vein or superficial/deep dorsal vein shunts

 Grayhack shunt The saphenous vein is ligated and anastomosed with corpora cavernosa
Barry shunt The superficial or deep dorsal vein is ligated and anastomosed to the corpora cavernosa
XIII.9.5.2 Penile prosthesis (PP)
There are no defined indications for implanting a penile prosthesis in patients with priapism. Priapism episodes may be definitively treated with penile prosthesis implantation, especially in the context of priapism duration exceeding 72 h, where complete ED is likely to ensue (96,97). Early penile prosthesis insertion for acute ischemic priapism is simple and successful. Distal cylinder protrusion through the defective corpora due to previous shunt surgery remains to confound surgical success (96,97). Therefore, recent studies and systematic review have not demonstrated superiority of immediate PP implantation which necessitate high expertise settings with available resources and motivated patients over delayed PP implantation (98,99).
XIII.9.5.3 Recommendations for the Treatment of Ischemic Priapism:


Table XIII:21 Recommendations for The Treatment of Ischemic Priapism

Recommendations

Strength Rate
1. Start management of ischaemic priapism as early as possible (within four to six hours) and follow a stepwise fashion. Strong
2. First, decompress the corpora cavernosa by penile aspiration until fresh red blood is obtained (with or without irrigation). Strong
3. In priapism that persists despite aspiration, proceed to the next step, which is ICI of a sympathomimetic drug Strong
4. Repeated injections and aspiration should occur for at least up to 1 h prior to proceeding with surgical intervention in patients presenting with a priapism of less than24 h Strong
5. Ischemic priapism of extended durations (typically greater than 72h) is unlikely to resolve with ICI therapy alone, therefore, consider more immediate surgical intervention Strong
6. Perform distal shunt surgical procedures first followed by proximal procedures in case of failure Strong
7. Consider insertion of a penile prosthesis only if priapism episode is > 36 hours, or in cases for which all other interventions have failed Strong


XIII.9.5.4 Recommendations for the treatment of non-ischemic priapism


Table XIII:22 Recommendations for The Treatment of non-ischemic priapism

Recommendations

Strength Rate
1. Perform definitive management at the discretion of the treating physician, because non-ischaemic priapism is not an emergency Weak
2. Manage conservatively with the use of site-specific perineal compression as the first step, especially in children. Consider androgen deprivation therapy only in adults Weak
3. Perform superselective arterial embolization, using temporary material Strong
4. Repeat the procedure with temporary or permanent material for recurrent nonischaemic priapism following selective arterial embolization Weak
5. Reserve selective surgical ligation of a fistula as a final treatment option when embolization has failed Weak

XIII.9.5.5 Recommendations for the treatment of Stuttering Priapism

Table XIII:23 Recommendations for the treatment of Stuttering Priapism

Recommendations

Strength Rate
1. Manage each acute episode similar to that for ischaemic priapism Weak
2. Use hormonal therapies (mainly gonadotropin-receptor hormone agonists or antagonists) and/or anti-androgens for the prevention of future episodes in patients with frequent relapses. Do not use them before sexual maturation is reached Weak
3. Initiate treatment with phosphodiesterase type 5 inhibitors only when the penis is in its flaccid state Strong
4. Use digoxin, α-adrenergic agonists, baclofen, gabapentin or terbutaline only in patients with very frequent and uncontrolled relapses Weak
5. Use intracavernous self-injections of sympathomimetic drugs until ischaemic priapism has been alleviated Weak

XIII.10 Conclusions:

It should be emphasized that clinical guidelines present the best evidence available to the experts. However, following guidelines recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account. Guidelines are not mandating and should not be used as a legal standard of care.

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