Erectile Dysfunction

Erectile Dysfunction

1. Erectile Dysfunction

2. Definition The inability to attain and/or maintain an erection sufficient for satisfactory sexual performance and persistent in 3 months. National Institute of Health. JAMA. 1993 Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Faysal A. Yafi , Wayne J. G. et al. 2016

3. Pathophysiology

4. Epidemiology Massachusetts Male Aging Study (MMAS) reported an overall prevalence of 52% ED in non institutionalized men aged 40-70 years in the Boston area; specific prevalence for minimal, moderate, and complete ED was 17.2%, 25.2%, and 9.6%, respectively. 1 European Male Ageing Study (EMAS) reported a prevalence of erectile dysfunction ranging from 6% to 64% depending on different age subgroups and increasing with age, with an average prevalence of 30%. 2 Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61. Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). Corona G, Lee DM, Forti G, O'Connor DB, Maggi M, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Punab M, Silman AJ, Vanderschueren D, Wu FC, EMAS Study Group. J Sex Med. 2010 Apr; 7(4 Pt 1):1362-80.

5. Epidemiology The incidence rate of ED (new cases per 1,000 men annually) was 26 in the long-term data from the MMAS study and 19.2 (mean follow-up of 4.2 years) in a Dutch study. In a cross-sectional real-life study among men seeking first medical help for new-onset ED, one in four patients was younger than 40 years, with almost 50% of the young men complaining of severe ED Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61. This seminal manuscript defines the prevalence of erectile dysfunction.

6. Risk Factor ED shares both unmodifiable and modifiable common risk factors with CVD (e.g., obesity, diabetes mellitus, dyslipidemia, metabolic syndrome, lack of exercise, and smoking) Mild ED emerged as an important indicator of risk for associated underlying disease (CVDs) A number of studies have shown some evidence that lifestyle modification and pharmacotherapy for cardiovascular risk factors may be of help in improving sexual function in men with ED

7. Patophysiology

8. Pathophysiology The penis remains in its flaccid state when the smooth muscle is contracted. The smooth muscle contraction is regulated by a combination of adrenergic (noradrenaline) control, intrinsic myogenic control and endothelium-derived contracting factors (prostaglandin and endothelins ). 1,2 Andersson KE, Wagner G. Physiology of penile erection.  Physiol Rev. 1995;75:191–236.. 1994;151:54–61. Saenz de Tejada I, Kim N, Lagan I, Krane RJ, Goldstein I. Regulation of adrenergic activity in penile corpus cavernosum. J Urol. 1989;142:1117–1121. A seminal paper on cell signalling in the corpora cavernosum .

9. Pathophysiology Upon sexual stimulation, erection occurs after nitric oxide (NO) is released from non-adrenergic noncholinergic (NANC) nerve fibers and acetylcholine is released from parasympathetic cholinergic nerve fibers the result of the ensuing signaling pathways is increased cyclic GMP (cGMP) concentrations, decreased intracellular Ca 2+  levels and smooth muscle cell relaxation. As the smooth muscle relaxes, blood is able to fill the lacunar spaces in the corpora cavernosa , leading to compression of the subtunical venules , thereby blocking the venous outflow ( veno -occlusion). The process is reversed as cGMP is hydrolysed by phosphodiesterase type 5 (PDE5). 1,2 Erectile dysfunction can occur when any of these processes is interrupted. Lue TF, Tanagho EA. Physiology of erection and pharmacological management of impotence. J Urol. 1987;137:829–836. Lue TF. Erectile dysfunction. N Engl J Med. 2000;342:1802–1813. .

10. Classification Primary Organic (most common, 70%) Vascular Hormonal Neurological Medications Primary Psychogenic Mixed psychogenic and organic EAU Guidelines 2019

11. Diagnostic EAU Guidelines 2019

12. Diagnostic Evaluation Basic work-up The first step in evaluating ED is always a detailed medical and sexual history of patients, and partners when available This will make it easier to ask questions about ED and other aspects of the sexual history to explain the diagnosis and therapeutic approach to the patient and his partner It is important to establish a relaxed atmosphere during history-taking EAU Guidelines 2019

13. Clinical Evaluation for ED Hypertension DM Smoking Alcohol Medications Depression, anxiety Hypogonadysm Thyroid dysfunction Uraemia Pelvic surgery / trauma Partner problems Libido Nocturnal erection EAU Guidelines 2019

14. Sexual History The sexual history must include information about: sexual orientation, previous and current sexual relationships, current emotional status, onset and duration of the erectile problem, and previous consultations and treatments The sexual health status of the partner(s) Detailed description of the rigidity and duration of both sexually-stimulated and morning erections and of problems with sexual desire, arousal, ejaculation, and orgasm Validated psychometric questionnaires (IIEF/SHIM), help to assess the different sexual function domains (i.e. sexual desire, EF, orgasmic function, intercourse, and overall satisfaction), as well as the impact of a specific treatment modality. Screen for symptoms of possible hypogonadism (testosterone deficiency), including decreased energy, libido, fatigue, and cognitive impairment, as well as for LUTS EAU Guidelines 2019

15. IIEF-5

16. 5-Item International Index of Erectile Function (IIEF-5). ED Classification according IIEF-5 Score: Severe (5-7), Moderate (8-11), Mild – Moderate (12-16), Mild (17-21), No ED (22-25).

17. Physical Examination Blood pressure Cardiac, thyroid, testicular, prostate examination Penile anatomical abnormalities Gynecomastia Exercise treadmill test (if cardiac risk factors are present) BMI calculation or waist circumference measurment EAU Guidelines 2019

18. Laboratory testing CBC, Blood chemistry Fasting glucose or HbA1C and lipid profile Early morning total testosterone Additional test (optional): ECG prostate-specific antigen (PSA) prolactin LH Ask routine laboratory test to identify and treat any reversable risk factors and lifestyle factors that can be modified. EAU Guidelines 2019

19. ED & Cardiovascular Disease (CVD) Share the same pathophysiology (vasculopathy, endothelial dysfuntion ) Patients with CVD and CVD’s risk factors has increasing risk of having ED ED may be a manifestation of a CVD, even as a sentinel of silent CVD EAU Guidelines 2019

20. Cardiac risk stratification (2 nd & 3 rd Princeton Consensus) EAU Guidelines 2019

21. Indication for specific diagnostic test Young patients with a history of pelvic or perineal trauma (who could benefit from potentially curative vascular surgery.) Patients with penile deformities which might require surgical correction (e.g., Peyronie’s disease, congenital curvature). Patients with complex psychiatric or psychosexual disorders. Patients with complex endocrine disorders. At the request of the patient or his partner. Medico-legal reasons (e.g., implantation of penile prosthesis, sexual abuse). EAU Guidelines 2019

22. Specific Diagnostic Test Include specific diagnostic tests in the initial evaluation of ED in the presence of the indicated conditions EAU Guidelines 2019

23. Summary of Treatment First-Line Treat underlying disease Life style modification PDE5I Vacuum Erection Device Intraurethral Alprostadil Shockwave therapy Second-Line Intracavernous Injection Third-Line Penile prostheses EAU Guidelines 2019

24. ED Management Algorithm EAU Guidelines 2019

25. ED Management Algorithm EAU Guidelines 2019

26. ED Management Algorithm EAU Guidelines 2019

27. ED Management It is important to tailored treatment to patient preference and partner satisfaction 1,2 EAU Guidelines 2019 Campbell- walsh urology, 11 th ed. 2016

28. Treatment Option (First-Line) Identify the “curable” cause of ED Controlled the Underlying conditions such as Diabetes, hypertension, hypercholesterolemia, obstructive urinary symptoms, BPE, CVD, evaluation of antidepressant & antihypertensive currently used It is important to tell the patient “ED can be treated successfully, but it cannot be cured” The only exception was psychogenic ED, post-traumatic arteriogenic ED, hormonal causes  need specific treatment Lifestyle modification Modifiable risk factors (stop smoking, exercise to reduce body weight for obese patient) EAU Guidelines 2019

29. Treatment Option (First-Line) Oral Pharmacotherapy PDE5-I drug Sildenafil Tadalafil Valdenafil Avanafil Please be advised, PDE5I is not an initiator of erection, patient still need sexual stimulation to facilitate erection. EAU Guidelines 2019

30. PDE5 Inhibitor

31. PDE5 Inhibitor EAU Guidelines 2019

32. PDE5 Inhibitor Avanafil 1,2 Latest PDE5I, available in 2013 Recommended starting dose 100 mg, 15 – 30 minutes before sexual intercourse Maximum dosing frequency once a day Mean percentage of successful intercourse Dosage Successful Sexual Intercourse Placebo 50 mg 47% 28% 100 mg 58% 28% 200 mg 59% 28% Wang, R., et al. Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability. J Sex Med, 2012. 9: 2122. https://www.ncbi.nlm.nih.gov/pubmed/22759639 Goldstein, I., et al. A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction. J Sex Med, 2012. 9: 1122. https://www.ncbi.nlm.nih.gov/pubmed/22248153

33. PDE5 Inhibitor EAU Guidelines 2019

34. PDE5 Inhibitor Safety Issue Cardiovascular Safety Sildenafil, Tadalafil, Vardenafil  no increase in myocardial infarction rate It is CONTRAINDICATED in Patient suffered from myocardial infarction, stroke, life threatening arrythmia within the LAST 6 MONTHS Resting hypotension < 90/50 mmHg or hypertension >170/100 mmHg Unstable angina, Angina with sexual intercourse or CHF NYHA IV Nitrates  result in cGMP accumulation and unpredictable blood pressure drop. If patient taken PDE5I, develop angina, nitrate should be postponed base of PDE5I drugs half-life. Co-administrative with other anti hypertensive agent, considered safe Interaction with alpha-blocker orthostatic hypotension EAU Guidelines 2019

35. PDE5 Inhibitor Safety Issue Drugs that inhibit CYP34A(ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) Increase PDE5-I level  lower dose adjustment Drugs that enhance CYP34A (rifampin, phenobarbital, phenytoin, carbamazepine) Decrease PDE5-I level  increase dose adjustment EAU Guidelines 2019

36. Management of non-PDE5I responder Most common causes Failure to use adequate sexual stimulation Inadequate dose Failure to wait an adequate amount of time between taking medication and attempting sexual intercourse (ingestion of high fat meal, before taking drugs) EAU Guidelines 2019

37. Treatment Option (First-Line) Vacuum erection devices (drug free management) Satisfactory is as high as 90%, for patient without bleeding disorder or anticoagulant therapy 1 Adverse event (< 30% patient) Pain Unable to ejaculate Petechiae Bruising Numbness Remove the ring, before 30 minutes after intercourse  Prevent skin necrosis EAU Guidelines 2019

38. Treatment Option (First-Line) Topical/intraurethral Alprostadil Vasoactive agent, topical route (300 ug) or medicated pellet (500 ug) via urethral meatus Intercourse achieved in 30-65.9% patients Provides alternative treatment for intracavernous injection patients, who prefer less invasive even though it is less-efficacious treatment Adverse effect Local pain Penile erythema Dizziness / hypotension UTI EAU Guidelines 2019

39. Treatment Option (First-Line) Shockwave therapy Low-intensity extracorporeal shockwave therapy EAU recent studies showed that LI-SWT could improve the IIEF and Erection Hardness Score of mild ED patient. Still unclear for definitive recommendation EAU Guidelines 2019

40. Treatment Option (Second-Line) Not responding to oral drugs  offered intracavernous injection Intracavernous Alprostadil, dose 5 – 40 ug Erection appears after 5 to 15 minutes Satisfaction rates 87 – 93.5% in patients 80 – 90.3% in partners Complications Penile pain, prolonged erection, priapism Fibrosis EAU Guidelines 2019