I N T I M A C Y A N D S E X U A L I T Y I N L A T E R L I F E

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1 I N T I M A C Y A N D S E X U A L I T Y I N L A T E R L I F E

2 DESPITE THE COMMON COMPLAINT, EACH PATIENT COMES AS AN INDIVIDUAL, WITH UNIQUE EXPECTATIONS My special interest Counseling patients prior to major pelvic surgery with high risk of erectile dysfunction Supporting patients through their journey to regain their sexual function after surgery penile rehabilitation

3 A DOCTOR S PERSPECTIVE ERECTILE DYSFUNCTION Definition: Persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance But.. What does this actually mean to the patient? Does it get hard, and stay hard enough to satisfy the sexual needs of the patient (and the partner)

4 PATIENTS RELUCTANT TO TALK TO THEIR DOCTORS ABOUT ED WHY? 71% 68% 44% Patients believe ED would not be recognized as a medical problem Patients fear that discussing sexuality may embarrass their doctors 44% of men attending urologists have ED but fail to mention it - most are too embarrassed Marwick C. JAMA 1999;281:

5 ASIAN PREVALENCE OF ED Author/Year Region Prevalence of ED (age group in years) Khoo et al./ Malaysia 70.1% in men >50 years of age Quek et al./ Malaysia 41.6% in men >20 years of age Li et al./ Malaysia 59% in men of years of age Masumori et al./ Japan 15% (40 49), 23% (50 59), 39% (60 69), 71% (70 79) Kongkanand et al. / Thailand 7% (40 49), 22% (50 59), 49% (60 69) Moreira et al. / Korea 32% in men of years 1.Khoo et al. J Sex Med 2008;5: Quek et al., J Sex Med 2008;5: Li, et al. BJU Int 2005;96: Masumori et al., Urology 1999;54: Konkanad A. Int J Androl 2000;23: Moreira et al., J Sex Med 2006;3:

6 Predicted increase In prevalence of ED by 2025 North America Europe Asia South & Central America and the Caribbean Africa Oceania Worldwide prevalence will increase from 152 million men in 1995 to 322 million men in Aytac IA et al. BJU Int 1999; 84:

7 Prevalence of co-morbidities (%) ED is linked to serious health problems! No ED ED N=23, *P< High blood pressure Heart trouble or angina* High cholesterol Diabetes* Depression* Any of these Rosen RC, Fisher WA, Eardley I, et al. The multinational men s attitudes to life events and sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Cur Med Res Opin. 2004;20(5):

8 ERECTILE DYSFUNCTION: NARROWING OF BLOOD VESSELS ED manifests earlier than cardiovascular disease because the smaller penile arteries reach critical narrowing, with insufficient blood flow, earlier than larger vessels (Threshold for symptom development is 50% lumen.) Early Late Penile artery 1-2 mm ED Coronary artery 3-4 mm Angina/infarction Carotid artery 5-7 mm Stroke Femoral artery 6-8 mm Claudication Montorsi P, Ravagnani PM, Galli S, et al. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J Cardiol. 2005;96(suppl):19M 23M. 8

9 ERECTILE DYSFUNCTION Cardiovascular risk Men with organic ED should have their cardiac risk factors addressed ED is significantly associated with cardiovascular risk factors. These include: hypertension raised cholesterol (hyperlipidaemia) diabetes smoking There is a degree of cardiac risk associated with sexual activity, so it is crucial to assess the CV risk The risk is small (~1% for myocardial infarction) and low compared with many other risks most patients will encounter (e.g. watching football) Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:28-36; Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol. 1994;151(1):54-61; Chi JS, Kloner RA. Stress and myocardial infarction. Heart. 2003;89:

10 ERECTILE DYSFUNCTION Princeton II evaluation algorithm Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:

11 ERECTILE DYSFUNCTION Diabetes 20-85% of men with diabetes suffer from ED (ranging from mild to complete) ED was three times more common in diabetic men vs nondiabetic men ED occurs earlier in men with diabetes compared with men who do not have diabetes The risk of ED increases: The longer diabetes is present If the condition is inadequately controlled (raised blood glucose and HbA 1C ) 11

12 ERECTILE DYSFUNCTION Prostate Men with enlarged prostates can also suffer from erection problems ED is underdiagnosed in patients consulting urologists for benign prostatic hyperplasia ED is very often seen after radical prostatectomy for prostate cancer 44-75% of patients Hosel CE, Woll EM, Burkart M, et al. Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS). Eur Urol. 2005;47: ; Taher A. Erectile dysfunction after transurethral resection of the prostate: incidence and risk factors. World J Urol. 2004;22: ; Matthew AG, Goldman A, Trachtenberg J, et al. Sexual dysfunction after radical prostatectomy prevalence, treatments, restricted use of treatments and distress. J Urol. 2005;174: ; Brown MW, Brooks JP, Albert PS, et al. An analysis of erectile function after intensity modulated radiation therapy for localized prostate carcinoma. Prostate Cancer Prostatic Dis. 2007;10:

13 ERECTILE DYSFUNCTION Impact on quality of life Men with ED experience low self-esteem, diminished confidence, and relationship problems Partners often have feelings of rejection, unattractiveness, and guilt Improvements in erection hardness with ED oral treatment have shown to improve satisfaction with sex life, love and romance, and overall health An awareness of the impact of ED on quality of life (QoL) can help health care providers: Empathize and communicate effectively with sufferers Appreciate the value of appropriate treatment Althof SE. Quality of life and erectile dysfuntion. Urology. 2002;59: ; Cappelleri JC, Bell SS, Althof SE, et al. Comparison between sildenafil-treated subjects with erectile dysfunction and control subjects on the self-esteem and relationship questionnaire. J Sex Med. 2006;3: ; Speckens AEM, Hengeveld MW, Nijeholt GL, et al. Psychosexual functioning of partners of men with presumed non-organic erectile dysfunction: cause or consequence of the disorder? Arch Sex Behav. 1995;24(2): ; Montorsi F, Padma-Nathan H, Glina S. Erectile function and assessments of erection hardness correlate positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil citrate(viagra ). Urology. 2006;68(suppl 3A):

14 DIAGNOSIS AND TREATMENT OF ERECTILE DYSFUNCTION F E B R U A R Y 2 6,

15 DIAGNOSIS AND TREATMENT OF ED Diagnosis of ED Basic workup includes: Medical history Psychological history Sexual history Physical examination Laboratory tests Medical and psychological histories should be taken for both patients and their partners Wespes E, Amar E, Eardley I, et al. Erectile dysfunction and premature ejaculation. Guidelines on Male Sexual Dysfunction

16 DIAGNOSIS AND TREATMENT OF ED Patient with erectile dysfunction (self-reported) Medical and psychosexual history (use of validated instruments, eg IIEF) Identify other than ED sexual problems Identify common causes of ED Identify reversible risk factors for ED Assess psychosocial status Focused physical examination Penile deformities Prostatic disease Signs of hypogonadism Cardiovascular and neurological issues Laboratory tests Glucose-lipid profile (if not assessed in the past 12 months) Total testosterone (morning sample) If available: bio-available or free testosterone (instead of total) Wespes E, Amar E, Eardley I, et al. Erectile dysfunction and premature ejaculation. Guidelines on Male Sexual Dysfunction. 2012; Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol. 2010;57:

17 DIAGNOSIS AND TREATMENT OF ED Erection Hardness Score The EHS is a robust, validated, single-item patient-reported outcome for evaluating erection hardness Improvements in erection hardness have correlated with a restoration of confidence in the ED patient You can educate sufferers to use the EHS to assess the severity of their ED An expert panel defined the maximum score 4 as the main goal in the treatment of ED EHS 1 EHS 2 EHS 3 EHS 4 Penis is larger but not hard Penis is hard, but not hard enough for penetration Penis is hard enough for penetration, but not completely hard Penis is completely hard and fully rigid Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring response to treatment in clinical practice recommendations of an international study panel. J Sex Med. 2007;4: ; Mulhall JP, Goldstein I, Bushmakin AG, et al. Validation of the erection hardness score. J Sex Med. 2007;4:

18 Clinical approaches to treatment of ED F O O T N O T E S 18

19 DIAGNOSIS AND TREATMENT OF ED First-line treatment: Oral treatment PDE5 inhibitors PDE5 inhibitors are recommended as the preferred pharmacotherapy for ED PDE5i is a class of vasodilators that work on the nitric oxide-cgmp mechanism to help restore natural erectile function in the presence of sexual stimulation Efficacy is defined by rigidity sufficient for vaginal penetration Sildenafil citrate (Viagra) was the first licensed oral medication for ED, receiving marketing authorization in 1998 Vardenafil (Levitra) and tadalafil (Cialis) received marketing authorization in 2003 Wespes E, Amar E, Hatzichristou D, et al. EAU Guidelines on erectile dysfunction: an update. Eur Urol. 2006;49: ; Wright PJ. Comparison of phosphodiesterase type 5 (PDE5) inhibitors. Int J Clin Pract. 2006;60: ; Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring response to treatment in clinical practice recommendations of an international study panel. J Sex Med. 2007;4: ; Rosen RC, Kostis JB. Overview of phosphodiesterase 5 inhibition in erectile dysfunction. Am J Cardiol. 2003;92(suppl):9M-18M; Wespes E, Amar E, Eardley I, et al. Erectile dysfunction and premature ejaculation. Guidelines on Male Sexual Dysfunction

20 Efficacy evaluation during placebo-controlled studies D A T E 20

21 Increase from baseline SILDENAFIL EFFICACY 24-week dose-response study: Ability to achieve erection Percent increase from baseline in response to IIEF Q3: When you attempted sexual intercourse, how often were you able to penetrate your partner? Placebo Sildenafil Sildenafil Sildenafil n= mg n=96 50 mg n= mg n=101 P< % = End point: 4.00, baseline: % = End point: 3.50, baseline: % = End point: 3.20, baseline: % = End point: 2.20, baseline: 2.10 The results were derived from a 24-week, dose-response, placebo-controlled study with 501 patients completing evaluation. Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 338:

22 Increase from baseline SILDENAFIL EFFICACY 24-week dose-response study: Maintenance of erection Percent increase from baseline in response to IIEF Q4: During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner? P< % = End point: 3.9, baseline: % = End point: 3.5, baseline: % = End point: 3.1, baseline: % = End point: 2.1, baseline: Placebo Sildenafil Sildenafil Sildenafil n= mg n=96 50 mg n= mg n=101 The results were derived from a 24-week, dose-response, placebo-controlled study with 501 patients completing evaluation. Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 338:

23 SILDENAFIL EFFICACY Discontinuations Variable 24-week dose-response study number of men (percent) Placebo (n=216) Sildenafil 25 mg(n=102) Sildenafil 50 mg(n=107) Sildenafil 100 mg(n=107) Reason for discontinuation All causes Treatment-related adverse effect Insufficient response Other* 36 (17) 1 (<1) 11 (5) 24 (11) 15 (15) 1 (1) 3 (3) 11 (11) 8 (7) 1 (1) 2 (2) 5 (5) 8 (7) 2 (2) 0 6 (6) Adverse effect** Headache Flushing Dyspepsia Rhinitis Visual disturbance*** 14 (6) 3 (1) 3 (1) 4 (2) 1 (<1) 14 (14) 13 (13) 3 (3) 1 (1) 2 (2) 23 (21) 29 (27) 12 (11) 3 (3) 6 (6) 32 (30) 21 (20) 17 (16) 12 (11) 10 (9) *Other reasons for discontinuation included protocol violations, not returning for follow-up, adverse effects not related to treatment, withdrawal of consent, and other reasons. **The adverse effects listed are those that occurred in 5% or more of any treatment group. ***The visual disturbances reported were changes in the perception of color hue or brightness. Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 338:

24 SILDENAFIL EFFICACY 12-week evaluation of sildenafil in the treatment of ED of various etiologies Objective: To determine the efficacy and safety of fixed-dose sildenafil in patients with ED of various etiologies. Study design: 12-week, double-blind, placebo-controlled, fixed-dose study. Patients: 514 men (ages 19 to 79) with ED and co-morbid conditions including genitourinary procedures, essential hypertension, diabetes mellitus, BPH, depression, or ischemic heart disease. Montorsi F, McDermott TED, Morgan R, et al. Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectie dysfunction of various etiologies. Urology. 1999;53:

25 SILDENAFIL EFFICACY 12-week evaluation of patient/partner satisfaction with sildenafil in the treatment of ED Objective: To assess the efficacy and safety of sildenafil in men with erectile dysfunction and patient and partner satisfaction with treatment using EDITS. Study design: 12-week, multicenter, double-blind, placebo-controlled, parallel-group, flexible-dose study. Patients: 247 men (ages 31 to 81) with ED and co-morbid conditions including essential hypertension, diabetes, hypercholesterolemia, hyperlipidemia, and prostatic hyperplasia. Lewis R, Bennett CJ, Borkon WD, et al. Patient and partner satisfaction with VIAGRA (sildenafil Citrate) treatment as determined by the erectile dysfunction inventory of treatment satisfaction questionnaire. Urology. 2001; 57:

26 Mean scores SILDENAFIL EFFICACY 12-week fixed-dose study: Patient/partner responses to IIEF questionnaire Mean scores at baseline and at the end of doubleblind treatment Almost always/ always 5 Most times 4 Patient responses to IIEF Q3, Q4, Q7 Baseline Placebo, 12 weeks Sildenafil, 12 weeks * *P<.001 compared with placebo * * Sometimes 3 A few times 2 Almost never/ never 1 Did not attempt 0 Q3 Q4 Q7 Ability to maintain erection Ability to achieve erection Intercourse satisfaction Adapted from Lewis R, Bennett CJ, Borkon WD, et al. Patient and partner satisfaction with VIAGRA (sildenafil Citrate) treatment as determined by the erectile dysfunction inventory of treatment satisfaction questionnaire. Urology. 2001; 57:

27 Mean scores SILDENAFIL EFFICACY 12-week fixed-dose study: Patient/partner responses to IIEF questionnaire Partner responses to IIEF Q1, Q2, Q3 Mean scores at baseline and at the end of doubleblind treatment Almost always/ always 5 Most times 4 Baseline *P<.001 compared with placebo Placebo, 12 weeks Sildenafil, 12 weeks * * Sometimes 3 * A few times 2 Almost never/ never 1 Did not attempt 0 Q1 Q2 Q3 Rating of maintained erections Rating of patient s erections Rating of satisfaction with sexual intercourse Adapted from Lewis R, Bennett CJ, Borkon WD, et al. Patient and partner satisfaction with VIAGRA (sildenafil Citrate) treatment as determined by the erectile dysfunction inventory of treatment satisfaction questionnaire. Urology. 2001; 57:

28 SILDENAFIL EFFICACY Analysis of pooled data from sildenafil double-blind studies in ED patients with co-morbidities Objective: To evaluate findings from 11 double-blind, placebo-controlled, flexible-dose (taken as needed) sildenafil studies. Study design: Four-week baseline period and a 12-week, double-blind, placebocontrolled study. Patient: 2,667 patients (ages 23 to 89) with ED and co-morbid conditions including diabetes, ischemic heart disease, peripheral vascular disease, post-radical prostatectomy, hypertension, depression, or concomitant use of antihypertensive or antidepressant medications. Carson CC, Burnett AL, Levine LA, et al. The efficacy of sildenafil citrate (VIAGRA ) in clinical populations: an update. Urology. 2002; 60(suppl 2B):

29 SILDENAFIL EFFICACY Analysis of pooled data from sildenafil double-blind studies in ED patients with co-morbidities Dosage: Patients were randomized to an initial dose of 50 mg sildenafil or matching placebo. Dose could be increased to 100 mg or decreased to 25 mg based on efficacy or tolerability. Efficacy parameters for the 11 pooled studies: Patients were asked to respond to question 3 (achieving an erection) and question 4 (maintaining erections) of the IIEF questionnaire. A global efficacy question (whether treatment improved erections) was asked at the end of treatment. In 6 of the 11 studies, patients were asked to keep an event log of sexual activity. Carson CC, Burnett AL, Levine LA, et al. The efficacy of sildenafil citrate (VIAGRA ) in clinical populations: an update. Urology. 2002; 60(suppl 2B):

30 Mean score SILDENAFIL EFFICACY Results from 11 pooled double-blind studies: Patient responses to IIEF Q3 Overall baseline mean score and least squares mean (+) SE scores at end of treatment for IIEF question 3 (ability to achieve erections) 5.0 Baseline Placebo Sildenafil *P< * * * * * 3.8 * * * n= Organic Mixed PsychogenicMild/moderate Severe 2yr 2 to 5 yr > 5 yr ED etiology ED severity ED duration Adapted from Carson CC, Burnett AL, Levine LA, et al. The efficacy of sildenafil citrate (VIAGRA ) in clinical populations: an update. Urology. 2002; 60(suppl 2B):

31 Mean score SILDENAFIL EFFICACY Results from 11 pooled double-blind studies: Patient responses to IIEF Q4 Overall baseline mean score and least squares mean (+) SE scores at end of treatment for IIEF question 4 (ability to maintain erections) Baseline Placebo Sildenafil* * * * * * 3.7* 3.6* *P< * n= Organic Mixed PsychogenicMild/Moderate Severe 2yr 2 to 5 yr > 5 yr ED etiology ED severity ED duration Adapted from Carson CC, Burnett AL, Levine LA, et al. The efficacy of sildenafil citrate (VIAGRA ) in clinical populations: an update. Urology. 2002; 60(suppl 2B):

32 ENDOTRIAL study EVALUATION OF EFFICACY IN THE TREATMENT OF ED AMONG SILDENAFIL, TADALAFIL, AND VARDENAFIL (ENDOTRIAL STUDY) D A T E 32

33 SILDENAFIL EFFICACY Within-subject mean change from baseline for IIEF: International Index of Erectile Function question 15 a Primary outcome showing statistical equivalence for all four PDE5i (Data for IIEF questions 1-5 not shown) ** ** * * * P =< ** P = Vardenafil 20 mg Tadalafil 20 mg Sildenafil 50 mg Sildenafil 100 mg a Question 15: How do you rate your confidence that you could get and keep an erection? A spontaneous, open-label, randomized, multicenter, crossover study. The protocol consisted of a fourweek washout period, followed by an eight-week treatment period. Data for primary efficacy were available for 77 out of 100 patients. Jannini EA, Isidori AM, Gravina GL, et al. The ENDOTRIAL study: spontaneous, open-label, randomized, multicenter, crossover study on the efficacy of sildenafil, tadalafil, and vardenafil in the treatment of erectile dysfunctionjsm. J Sex Med. 2009;6:

34 THE TIMING FOR SEX ACCORDING TO MEDICATION Parameter Sildenafil, 100 mg Tadalafil, 20 mg Vardenafil, 20 mg Time to maximum effect hours 2 hours 0.9 hours Half-life of drug hours 17.5 hours 3.9 hours

35 General side effects 35 D A T E

36 SILDENAFIL SAFETY Reported adverse reactions Medically important adverse reactions reported during clinical trials or post-marketing surveillance Very common ( 10% of patients) Uncommon ( 0.1% to <1% of patients) Rare ( 0.01% to <0.1% of patients) Incidence not known* Headache Common ( 1% to <10% of patients) Dizziness Visual disorders Visual color distortion Flushing Nasal congestion Dyspepsia Somnolence Hypoaesthesia Conjunctival disorders Eye disorders Lacrimation disorders Vertigo Tinnitus Vomiting Nausea Dry mouth Palpitations Increased heart rate (by investigation) Tachycardia Skin rash Myalgia Chest pain Fatigue Hypersensitivity reactions Atrial fibrillation Myocardial infarction Cerebrovascular accident Hypertension Hypotension Syncope Sudden deafness Epistaxis Transient ischemic attack Unstable angina Ventricular arrhythmia Sudden cardiac death Seizure Seizure recurrence Non-arteritic anterior ischemic optic neuropathy (NAION) Retinal vascular occlusion Visual field defect Priapism Prolonged erection * Reported through post-marketing surveillance so incidence unknown. VIAGRA Summary of Product Characteristics

37 IMPACT OF TREATMENT ON SELF-ESTEEM AND CONFIDENCE IN THE ED PATIENT Men with ED experience low rates of confidence Treatment with a PDE5 inhibitor has been associated with an increase in self-esteem and confidence in patients with ED From both patient and partner perspectives, satisfaction with ED treatment plays a critical role in maintaining long-term therapy for ED Althof SE. Quality of life and erectile dysfunction. Urology. 2002;59: ; Althof SE, Cappelleri JC, Shpilsky A, et al. Treatment responsiveness of the self-esteem and relationship questionnaire in erectile dysfunction. Urology. 2003;61: ; Althof SE, O'Leary MP, Cappelleri JC, et al. Selfesteem, confidence, and relationships in men treated with sildenafil citrate for erectile dysfunction. J Gen Intern Med. 2006; 21: ; McCabe MP, Conaglen H, Conaglen J, et al. Motivations for seeking treatment for ED: the woman s perspective. Int J Impot Res. 2010;22: ; McCullough AR, Barada JH, Fawzy A, et al. Achieving treatment optimization with sildenafil citrate(viagra ) in patients with erectile dysfunction. Urology. 2002;60(Suppl 2B):