CUA GUIDELINE 2015 CUA Practice guidelines for erectile dysfunction A n th o n y F r a n c o is
J .
B e lla ,
M B ,
F R C S C f J a y
C. L e e ,
B é n a rd ,
M D ,
F R C S C f G e r a ld
B .
M D ,
B ro c k ,
F R C S C f S e rg e M D ,
C a r r ie r ,
M D ,
F R C S C f
F R C S C ±
'G reta and John Hansen Chair in M e n's Health Research, A ssistant Professor o f Urology, D epartm ent o f Surgery, University o f O ttaw a, O ttaw a, ON; 'C linical Assistant Professor, University o f Calgary, Calgary, AB; ^Associate Professor, D epartm ent o f Surgery, Urology Division, M cGill University, M ontreal, QC; 'C hair, Division o f Urology, D epartm ent o f Surgery, Université de M o ntréal, M ontreal, QC; ‘ Professor of Surgery, W estern U niversity, London, ON
See related article on page 3 0 .
Cite as: Can U rol Assoc J 2 0 1 5 ;9 ( l- 2 ) :2 3 - 9 . h ttp ://d x .d o i.o r g /1 0 .5 4 8 9 /c u a j.2 6 9 9 Published online February 5 , 2 0 1 5 .
S u m m ary o f recom m endations •
•
•
•
•
Erectile d ysfu n ctio n (ED) is the preferred c lin ic a l term describing the persistent or recurrent in a b ility to achieve and m a in ta in a p e n ile e re ctio n o f s u ffic ie n t rig id ity to p erm it satisfactory sexual a ctivity fo r at least 3 months. The in itia l diagnosis and treatm ent o f ED is most c o m m o n ly perform ed in Canada by prim ary care physicians (PCPs). PCPs, urologists, internists, psychiatrists, and other treat ing healthcare professionals should be encouraged to in i tia te an open d ia log ue o f sexual issues to id e n tify men w ith ED w h o m ay not o therw ise vo lu n te e r th e ir sexual concerns.
•
cardiovascular disease in general, and should be id e n ti fied d u rin g e valuation as they m ay represent the in itia l clin ic a l sign o f generalized e ndothelial disease (vascular insufficiency). Evaluation o f fa m ily history, n ico tin e use, blo od pressure, lip id p rofile, and glucose is required or should be d ocum ented if p re vio u sly perform ed. A ctive managem ent o f ide ntifie d cardiac risk factors should be instituted (i.e., sm oking cessation, b lo o d pressure treat ment). •
Frequently a careful history, physical exam, serum g lu cose or hem oglobin A1C, lip id p ro file and optio na l hor m onal testing fa cilita te the diagnosis o f ED and effective therapy. Patient history can d ifferen tia te ED from other male sexual dysfunctions, in clu d in g ejaculatory disorders (prem ature e ja cu la tio n and other abnorm alities), h yp o gonadism , disorders o f orgasm, and Peyronie's disease. O rganic (physical) causes o f ED are present in most men, but situational or psychosocial co n trib u tin g factors often
Background
p la y a c o n trib u to ry role. A ddressing these issues m ay enhance treatm ent efficacy. U nderlying risk factors associated w ith ED are com m on to
• •
O n ce reversible causes o f ED are ruled out, a trial o f oral m edication is recom m ended as first-lin e therapy, based on trea tm en t e ffica cy, side effe ct p ro file , and m in im a l invasiveness. Specialized testing and referral are generally reserved for cases w here oral first-lin e treatments fail or are not appropriate, o f if greater insight into the etiolog y is desired by the patient/physician. Second-line therapies, although m ore invasive than oral agents, are generally w e ll-tole ra ted and effective. Surgery remains an im p orta nt o ptio n fo r men refractory to m edical m anagem ent, offe ring effective and durable ED treatm ent outcomes.
highly effective, m in im a lly invasive therapeutic agents - most c o m m o n ly oral therap ies using p h o sp h o diesterase ty p e 5 -
E rec tile d y s fu n c tio n (ED ) is a h ig h ly p re v a le n t c o n d itio n ,
(PD E5) inhibitors. S e co n d -lin e self-in jectio n w ith vasoactive
w h ic h a ffects th e p h y s ic a l a n d p s y c h o s o c ia l w e ll-b e in g
agents, v ac u u m erec tio n devices, and surgical approaches
and q u a lity o f life (Q o L ) fo r thousands o f C a n a d ia n m en ,
w ith in flata b le p e n ile prostheses offer ED m a n a g e m e n t w ith
th e ir partners, and fam ilie s. T h e C an a d ian Study o f Erectile
high p o ten tial for p atie n t and p artner trea tm en t satisfaction.
D ysfu n ction id e n tifie d 4 9 .4 % o f m en o ve r 4 0 w ith ED, w ith
M o s t cases o f ED in C an a d a are id e n tifie d a nd e ffec tive ly
oth er studies sh o w in g that 5 % to 2 0 % o f m en h ave m o d er
treated by p rim a ry care physicians (PCPs).4 E vidence-based
ate to severe E D .1’3 C o n te m p o rary trea tm en t options in clu d e
diagn o stic a nd th e ra p e u tic a p p ro ach es, in c lu d in g e ffec tive
CUAJ • January-February 2015 • Volume 9, Issues 1-2 © 2015 Canadian Urological Association
23
Bella et al.
oral agents like the PDE5-inhibitors, has allowed for a shift of ED management from a historical surgical approach to contem porary medical management. Family physicians, urologists, internists, endocrinologists, cardiologists, and other medical specialists are approached by couples with ED requesting treatment more frequently. In many cases longstanding relationships exist between the couple and their treating physician, fostering an im portant therapeu tic alliance w h ich may translate into im proved clin ica l response to the selected treatm ent approach. A sharedcare model for the treatment of ED is a valid concept and also may reflect optim al utilization of healthcare resources in the Canadian healthcare environm ent.4,5 This sharedcare model is one in w hich PCPs in itia lly identify and treat patients w ith ED and refer prim arily those individuals who have incom plete responses or require more invasive or specialized testing and treatment. The com bined experi ence and knowledge of PCPs coupled w ith the diverse ED knowledge of the specialist can ideally result in optim al care for the patient. In the contemporary model of ED care delivery, urologists remain an essential resource for several important reasons: 1. Referral requested for the d iffic u lt-to -tre a t, oralrefractory cases. 2. Second-line intracavernous and intraurethral vasoac tive therapy may be outside of the practice pattern of some PCPs and therefore require urologie care. 3. In som e cases a n a to m ic a l p e n ile d e fo rm ity (Peyronie's disease or post-trauma) may play an important role in the ED and more frequently require operative correction. 4. In a small but definable population (often men with severe vascular disease or poorly controlled diabe tes), a trial of nonsurgical approaches may not suc ceed, requiring surgical options in the difficult-totreat group. 5. Patients w ith congenital venous leak as the cause of their ED require urologie care. These patients are usually young and do not respond to PDE5-inhibitors. 6. Specific tests performed by urologists may be indi cated at the request of the patient or his partner or for medico-legal issues. 7. Ongoing research into the basic and clinical conse quences of ED is performed in urologie laboratories and clinical practices As presented in this document, the Canadian Urological Association (CUA) Guidelines Committee has updated the CUA Erectile Dysfunction Guidelines using a Canadian per spective. Suggestions were based on peer-reviewed literature through 2015, and the ED recommendations from the W orld Health Organization (WHO)-endorsed 2010 International Consultation on Sexual Medicine, the International Society for Sexual Medicine, the Sexual Medicine Society of North
24
America, and evolving research on new approaches to ED management.4,6'7
Global management objectives 1.
To help the patient and partner establish their objec tives of treatment. 2. To select diagnostic tests based on presenting com plaints and goals of therapy. 3. To use diagnostic tests in a cost-effective and mean ingful manner w hich w ould affect choice of treat ment as well as help to identify and disqualify certain contributory health problems. 4. To provide a diagnosis and understanding o f the likely etiology of the ED to the patient and partner. 5. To identify ED etiologies w hich may affect patient morbidity and mortality (if not previously identified), including screening for vascular risk, and facilitate access to the most appropriate healthcare providers for definitive management. 6. To offer treatment choices with comprehensive infor mation on cost, likelihood of success and common side effects. 7. To initiate therapy w ith the least invasive option w hich w ould satisfy the patient and partner goals of treatment. 8. To provide patients w ith information and ongoing support to maximize treatment success. 9. To re-establish the couples' ability to achieve and maintain sexual intimacy in the most natural man ner possible. 10. To choose approaches w hich are reversible when ever possible.
Management approach: Diagnosis
Overview The CUA supports the view that the general framework for the evaluation of patients w ith any type of sexual dysfunc tion should follow the same basic principles.3,4,6The sexual history should ascertain the severity, onset, and duration of the problem, concomitant medical or psychosocial fac tors, and bother to the patient and partner (if applicable). In-person interview is often supplemented w ith question naires or potential web-based methods. The manner of sexual inquiry is important and should reflect a high level of sensitivity and regard for each individual's unique ethnic, cultural, and personal background. 1. D eterm ine that the problem is ED versus other aspects of the sexual response cycle (desire, ejacu lation, orgasm) or from other causes (Peyronie's dis-
CUAJ • January-February 2 0 1 5 • Volume 9 , Issues 1-2
CUA Guidelines on ED
ease, lifestyle factors in c lu d in g illic it drug use, q u a lity
•
N o c tu rn a l p e n ile tu m e s c e n c e te s tin g (N P TR ) (Rigiscan)
•
D y n a m ic in fu s io n c a v e rn o s o g ra p h y and ca ve rn o so m e try (DIC C )
T he p a tie n t (w ith o r w ith o u t th e ir partner) w ill gu id e w h e th e r tre a tm e n t is desired.
•
Penile and p e lv ic a ngiog ra m
Id e n tify w h e th e r a p o te n tia lly reve rsib le cause to the
D iag n o s is h is to ry
o f partners re la tio n sh ip ). 2.
D e te rm in e th e tim in g o f onset, n a tu re o f th e p ro b lem , and s ig n ific a n c e to th e p a rtn e r (if a p p lic a b le ).
3.
ED exists (m edication s), stress, depression, h o rm o n a l a b n o rm a litie s in c lu d in g a ndroge n, th y ro id and p itu itary, to b a cco , excessive a lc o h o l use, drug abuse, and
O b ta in in g a d ia g n o stic h isto ry is th e cornerstone o f the e v a l uation o f sexual d y sfu n ctio n and ED. The history w ill p ro vid e
p a rtn e r-sp e cific issues). Testosterone p ro file is a p p ro priate at the ED diagnosis if hypogo nadism suspected, bu t screening is no t recom m ended fo r all ED patients.
the lik e ly diagnosis in m ost cases.4,6'8 A su p p o rtive healthcare
Establish a lik e ly u n d e rly in g e tio lo g y based on h is to ry , p h y s ic a l exam , and lab te stin g . O b ta in in g o r c o n fir m in g re c e n t b lo o d p re ssu re m e a su re m e n ts,
A m o n o g a m o u s , h e te ro se xu a l re la tio n s h ip s h o u ld n o t be assum ed. P otential e tio lo g ie s fo r sexual d y s fu n c tio n in c lu d e a w id e range o f o rg a n ic and m e d ic a l factors, b u t m u ltip le
lip id p ro file , an d g lu c o s e /H g B A lC are h ig h ly re c om m ended. A c o m m o n ly used schem a is: • V a scu la r
p s y c h o lo g ic a l o r interperson al factors (i.e., a n x ie ty , depres sion, re la tio n s h ip distress) can be causal o r c o n trib u to ry .
4.
•
E ndocrine
• •
N e u ro lo g ic a l S ituationa l
•
End organ (p e n ile d e fo rm ity - P eyronie's disease o r traum a)
•
M ix e d (M ost cases have an u n d e rly in g o rg a n ic cause o r causes; s im ila r ly m o s t m en w i l l s u b s e q u e n tly re p o rt a n x ie ty , stress, and d e p re s s io n as a c o n s e qu e n ce o f ED.)
professiona l a llo w s th e c o u p le to relate th e ir co n ce rn s and express th e ir goals o f tre a tm e n t in an u n h u rrie d m a nner.
General domains o f the history •
•
Sexual desire, re la tio n s h ip issues, stressors at h o m e and w o rk .
•
G e n ita l pa in o r altered shape.
•
Lifestyle factors: sm o kin g , substance use/abuse, seden ta ry lifestyle.
• •
C o m o rb id c o n d itio n s : hypertensio n, p e rip h e ra l vascular disease, diabetes, ob e sity, and renal disease. P elvic surgery, ra d ia tio n o r traum a.
•
M e d ic a tio n s .
•
P sychiatric illness o r c o n d itio n s .
Methodology 1.
H is to ry a n d c lin ic a l q u e s tio n in g (m o s t im p o rta n t c o m p o n e n t o f the ED e v a lu a tio n ).
2.
Focused p hysical e x a m in a tio n (directed at a n a to m ic, va scu la r and neural systems essential fo r erections).
3.
Use o f fo rm a liz e d q u e s tio n n a ire in s tru m e n ts (e.g., Sexual H ealth In ve n to ry fo r M e n [S H IM ], A p p e n d ix h ttp ://jo u rn a ls .s fu .c a /c u a j/in d e x .p h p /jo u rn a l/a rtic le / v ie w /2 6 9 9 /2 0 2 2 ) is re c o m m e n d e d b u t n o t m a n d a to ry, as th e q u estion n a ire s are useful in esta b lish in g b a s e lin e fu n c tio n , ED s e v e rity , e v a lu a te tre a tm e n t response, and in m ost cases q u e s tio n n a ire results do n o t add s ig n ific a n tly to d u ra tio n o f the d o c to r-p a tie n t e n co u n te r.
4.
5. 6.
La b o ra to ry inve stig a tio n s: serum glucose, lip id p ro file , and in se le c t cases h o rm o n a l s c re e n in g (to ta l testo ste ro n e /b io a v a i Ia b le testosterone). C o nsultatio n w ith subspecialists (e n d o c rin o lo g y , psy c h o lo g y , ca rd io lo g y). S p e cia lize d tests: • C o m b in e d in je c tio n and s tim u la tio n test (CIS) • D uplex ultrasound w ith vasoactive penile injection
D e te rm in e sp e cifics related to ED (onset, severity, sig n ific a n c e and situ a tio n s) and desire, aro u sa l, orgasm , and e ja c u la tio n .
Q u e s tio n n a ire s Use o f v a lid a te d q u e s tio n n a ire s m a y be b e n e fic ia l. These to o ls can be p a tie n t s e lf-a d m in is te re d a n d p ro v id e m u ch o f th e a b o v e in fo rm a tio n in an e ffic ie n t n o n -th re a te n in g m anner, w h ile b e in g tim e -s a v in g and c o s t-e ffe c tiv e .6 T here are v a lid a te d in stru m e n ts designe d to e va lu a te sexual and e re c tile fu n c tio n . T he greatest u tility o f these q u e stio n n aires m ay be in e s ta b lish in g a response to th e ra p y and d e te rm in ing o v e ra ll satisfaction w ith d ru g use o ve r a s p e cifie d length o f tim e (i.e., 4 weeks). The m ost c o m m o n q u e s tio n n a ire is th e S H IM (A p p e n d ix -h ttp ://jo u rn a ls .s fu .c a /c u a j/in d e x .p h p / jo u rn a l/a rtic le /v ie w /2 6 9 9 /2 0 2 2 ).9
P h ysical e x a m The aim o f a focused physical e xa m in a tio n in m en w ith ED is to e xa m in e g e n ita l a n a to m y and id e n tify any related a b n o r-
CUAJ • Jonuory-February 2 0 1 5 » Volume 9, Issues 1-2
25
Bella et al.
malities (e.g., Peyronie's plaques), endocrine signs, and pos sible com orbidities (neurological, vascular, and possible life-threatening conditions).10 An association exists between erectile dysfunction and peripheral vascular disease, as well as ED and the potential development of coronary artery dis ease.11 Assessment should include body habitus (secondary sexual characteristics), peripheral circulation (ED is a predic tor of cardiovascular morbidity and mortality, findings con sistent when controlled for confounders), neurological and genitourinary systems.10 Testicular examination is important to ensure testes/testis presence and to examine consistency of the testicle (i.e., atrophy, hypogonadism). The identifica tion of penile deformities may be best achieved in the erect state, but is most com m only examined by stretching the penis to make the Peyronie's plaque(s) more pronounced. The physical examination can also be a source of embarrass ment or discomfort for some patients; therefore, every effort should be made to ensure privacy and personal comfort.
Laboratory testing
O ptional testing such as thyroid-stim ulating hormone (TSH), luteinizing hormone (LH) and follicle-stim ulating hormone (FSH), prolactin, complete blood count (CBC), and urinalysis are considered complementary and not felt to be mandatory in the evaluation of ED in most cases, but are added when dictated by clinical context.3,5,10
Specialized testing
/.
Psychological/psychiatric assessment
These assessments often provide important complementary insight into relationships and situational causes to ED. The lack of widespread availability and cost lim it their use in most cases of ED treatment. The primary goals of psychotherapy are to reduce or eliminate performance anxiety, to understand the context in which men or a couple function sexually, to imple ment psycho-education in order to modify sexual scripts, and to reduce premature discontinuation of pharmacotherapy.3,6,14
2. NPTR Overview The recommendations by the International Society for Sexual Medicine's International Consultation on Sexual Medicine suggest that laboratory tests for men w ith sexual problems may include fasting glucose, lipid profile and, in select cases, a hormone profile. Hormone profiles are used to identify or confirm specific etiologies (e.g., hypogonadism) or to assess the role of potential medical comorbidities or concomitant illnesses.6-12 Assessment for occult diabetes may be performed with a fasting glucose or HbA1c. Although recommended by the W H O consensus panel, the lipid screen is considered an optional component of the Canadian ED assessment but is suggested as a valuable addition to the evaluation and good general practice.2 Hormonal profile screening remains a controversial aspect of the routine evaluation of ED. There is a general guideline agreement that in a man w ith ED and hypoactive desire, incomplete response to PDE5-inhibitor treatment, and in all men with known diabetes (as suggested by 2013 Canadian Diabetes Association guidelines)2 testing and potential treat ment for low levels of testosterone is appropriate. In men w ith normal desire and ED the need for global testing is controversial and currently undetermined. In the appropri ate patient, once treatment w ith exogenous testosterone is initiated, ongoing follow -up is mandatory according to pub lished guidelines.12-13 For men w ith diabetes, the 2013 Canadian Diabetes Association guidelines also support annual review of sexual function and determination of testosterone levels.
26
NPTR is a m inim ally invasive means to measure and record nighttim e erectile events (nocturnal penile tumescence), but has lim ited a va ila b ility in Canada and costs are not covered by most provinces. Nocturnal penile tumescence and rigidity testing using Rigiscan should take place for at least 2 nights, measuring 2 to 5 overnight erections. A functional erectile mechanism is indicated by an erectile event of 60% rigidity recorded on the tip of the penis lasting for 10 minutes. NPTR's greatest utility is in medico-legal cases and in investigative pharmacological studies to assess treatment impact.15
3. Vascular testing A variety of vascular tests exist. Penile duplex cavernous artery flow determination after corporal injection of vaso active agents is commonly performed.16 Use of ultrasound to localize and measure the size and flow through the cav ernous vessels, pre- and post-vasoactive injection allow a more refined assessment of penile circulation. This test is performed less frequently in Canada since the advent of effective oral medications. In cases where indicated, fur ther vascular investigation is unnecessary if duplex ultra sound is normal, as indicated by a peak systolic blood flow >30 cm/sec and a resistance index >0.8. If the ultrasound is abnormal, however, arteriography and dynamic infusion cavernosometry and cavernosography should be performed only in patients who are potential candidates for vascular reconstructive surgery - these tests though are rarely used in current Canadian ED treatment.
CUAJ • Januory-Februory 2015 • Volume 9, Issues 1-2
CUA Guidelines on ED
DICC aims to define how well the penile blood-trapping mechanism (the veno-occlusive mechanism) w orks.17 In brief, dye and fluid are delivered into the penis to induce an erection. Measurement of the rise and fall of intra-penile pressure with radiologic visualization of the veins draining the penis determine whether a competent or incompetent veno-occlusive mechanism exists. The most invasive diagnostic test is an arteriography. It is reserved generally for cases of high-flow priapism or planned vascular bypass. A penile angiogram allows visualization of the penile circulation and directs em bolization for the unusual case of penile injury induced high-flow priapism.
4. Endocrinological tests There is still controversy on the ideal endocrine workup for men w ith EDA6 A m orning total testosterone or bioavailable testosterone is logical in men w ith: decreased sexual interest, delayed ejaculation, reductions History in ejaculate volum e, failu re of Physical and Labs (Glucose, Lipids*, P D E 5-inhibito r treatm ent, and Testosterone*, Profactin*) men w ith ED and d ia b e te s.13 Free testosterone measurements have significant intra-assay vari a b ility w hich lim its their c lin i cal u tility in Canada and is not recommended. Bioavailable tes tosterone is clinically useful and recommended, but is not avail able in all areas o f Canada; as well, patients may incur a cost for a bioavailable testosterone assay. Calculated bioavailable testoster one (which requires a m orning total testosterone, album in and sex-hormone binding globulin) is an acceptable substitute for measured bioavailable testoster one if it is not available or costprohibitive.
Treatment options
Overview Management of ED most often w ill occur concurrently with lifestyle modification and treatment of organic or psychosexual dysfunctions. Patients and partners are made aware of efficacy, risks and benefits of appropriate treatments, taking into consideration preferences and expectations. Oral ther apy failure may often be salvaged by patient re-education on PDE5-inhibitor use and optimization of dosing. Stepwise progression from oral agents through second- and third-line therapies occurs as needed (Fig. 1). 1. Oral therapy (on-demand or daily dosing). Given the differences between oral agents, the choice of
5. Neuro-physiological testing /S u c c e s s fN
This form of testing generally allows us to measure the sacral reflex arc, an indirect measure of the perineal neural integrity, and has lim ited clin ica l a vailability and utility.18
I continue V treatm ent
)
J
Unsuccessful consider third-line therapy
ÇPenile im p la n t M surgery
Fig. 1. Management of erectile dysfunction. f Consider first-line ED treatment for men with ED and Peyronie's disease. ^Optional testing. ICI: intracavernosal injections; VED: vacuum erection device; NTG: nitrates/nitroglycerine; ED: erectile dysfunction.
CUAJ • Jonuary-Februory 2015 • Volume 9, Issues 1-2
27
B e ll a e t a l.
2.
3.
4. 5. 6.
which initiating PDE5-inhibitor you should use may be influenced by several factors, including timing or frequency of intercourse, and interactions with food or alcohol (Table 1).3,6,19'21 Testosterone replacement therapy in men with doc umented hypogonadism is an option. Testosterone may be used alone for hypogonadism, or in combi nation with oral PDE5-inhibitor therapy when ED is present.20-21 Sexual counselling (this may represent a spectrum of approaches from a simple open discussion with the PCP to psychologist, sexual therapists and/or psy chiatrists).3,6 Local therapy (intracavernous or intraurethral agents).2,3,6,22 Vacuum erection device therapy.23 Surgery.3,6,23 a. Penile implant. b. Peyronie's surgical repair. c. Vascular bypass procedure (generally reserved for young men after traumatic arterial penile vas cular injury).
Conclusions 1. 2.
3. 4.
5.
6.
A careful history and physical exam are the essential elements of the ED workup in most cases. Basic screening tests include the identification of car diac risk factors and blood tests. The following tests are recommended: serum fasting glucose, lipids and testosterone (if indicated). A stepwise treatment approach using the least inva sive option is suggested. In some cases where greater detailed information is desired or failure of the initial oral medication is encountered, trials of more invasive second-line treatment or investigations may be appropriate. Surgery should be reserved for men in whom less invasive reversible treatment has not succeeded or is contraindicated. Treatment should be individualized and patient fol low-up should be arranged to assess the efficacy of treatment.
Competing interests: Or. Bella is a member of the advisory boards for Lilly, Actavis, American Medical Systems, and Coloplast. He is also a member of the Speakers' Bureau for Lilly and CUA (accredited CME speaker) and a co-principal investigator and cofounder of the PROPPER (Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration) registry. Dr. Lee is a member of
T able 1. Com parison o f th e properties o f PDE5-inhibitors Tadalafil
Sildenafil
Property
Vardenafil
>TMAX
30-120 minutes (median 60 minutes)
30-360 minutes (median 120 minutes)
30-120 minutes (median 60 minutes)
T
4 hours
17.5 hours
4 hours
Absorption
Fatty meals cause a mean delay in TM AX of 60 minutes
Not affected by food
Fatty meals cause a reduction in CMAX
Available Doses
25 mg, 50 mg, 100 mg PRN
2.5 mg, 5 mg daily 5 mg, 10 mg, 20 mg PRN
10 mg oral dissolvable tablet 2.5 mg, 5 mg, 10 mg, 20 mg PRN
M axim um Dose
100 mg daily
20 mg daily
20 mg daily
Efficacy
Each of the PDE5 inhibitors offers sim ilar efficacy.
1/2
Patients >65 years old Hepatic im pairm ent Renal im pairm ent Concomitant use of potent cytochrome P450 3A4 inhibitors, such as ritonavir and erythromycin
• • • •
Contraindications
• Any patient using organic nitrates either regularly or interm ittently • Known hypersensitivity to any com ponent of the tablet
• Any patient using organic nitrates either regularly or interm ittently • Known hypersensitivity to any com ponent of the tablet
Use w ith alpha blockers
Concomitant use of selective alpha blockers does not present a risk for significant hypotension. There is a potential risk o f significant hypotension when using non-selective alpha blockers.
Side effects (5 most common in order of frequency when compared to placebo)
Headache, flushing, dyspepsia, nasal congestion, alteration in colour vision
Dose adjustments may be needed
Patients >65 years old Hepatic im pairm ent Renal im pairm ent Concomitant use of potent cytochrome P450 3A4 inhibitors, such as ritonavir and erythromycin • Concomitant use o f cimetidine
Patients >65 years old Hepatic im pairm ent Renal im pairm ent Concomitant use of potent cytochrome P450 3A4 inhibitors, such as ritonavir and erythrom ycin
• • • •
• • • •
Headache, dyspepsia, backpain, myalgia, nasal congestion
Please consult the individual product m onographs for additional inform ation.
28
CUAJ • January-February 2015 • Volume 9, Issues 1-2
• Any patient using organic nitrates either regularly or interm ittently • Known hypersensitivity to any com ponent of the tablet
Headache, flushing, rhinitis, dyspepsia, sinusitis
CUA Guidelines on ED
the advisory boards for Abbott and Lilly. He has also received grants from Abbott, Lilly and Actavis and is participating in a clinical trial with Lilly. Dr. Carrier is a member of the advisory boards for Astellas, Eli Lilly Canada, Pfizer Canada, Abbott, Novartis, and Actavis. He is also a member of the Speakers' bureau for Eli Lilly Canada, Pfizer Canada, Abbott, Merck, and Actavis. He is participating in clinical trials with Astellas and Eli Lilly Canada. Dr. Bénard is a member of the advisory boards and part of the Speakers' Bureau for Abbott, Astellas, Pfizer, Lilly, Paladin, and Actavis. He has received payment for talks from Abbott, Astellas, Pfizer, Lilly, Paladin, and Actavis. He also has investments in many pharmaceutical companies through his diversified retirement plan. He is also currently participating in a clinical trial with Allergan. Dr. Brock is a member of the advisory boards and part of the Speakers' Bureau for Lilly, Coloplast, AMS, GSK, Abbott, and Actavis. He has also received payments and grants from these same companies.
10. 11. 12 . 13. 14.
15.
This paper has been peer-reviewed.
16.
References
17.
1. Grover SA, Lowensteyn I, Kaouache M, et al. The prevalence of erectile dysfunction in the primary core setting: Importance of risk factors for diabetes and vascular disease. Arch Intern Med 2006; 166:213-9. http://dx.d 0i.0r g /l 0.1001 /archinte.l 66.2.213 2. Brock G, Harper W; for Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Erectile dysfunction. Can J Diabetes 2013;37:S150-2. http://dx.doi.org/! 0.1016/j.jcjd.2013.01.041 3. Hatzimouratidis K, Amor E, Eardley I, et al. Guidelines on mole sexual dysfunction: Erectile dysfunction and premature ejaculation. £or t/ro/2010;57:804-l 4. http://dx.d 0i.0r g /l 0.1016/j.eururo.2010.02.020 4. Canadian Urological Guidelines Committee. Erectile dysfunction practice guidelines. Can i Urol 2002;9:1583-87. 5. Costa P, Grandmottet G, Mai HD, et al. Impact of 0 first treatment with phosphodiesterase inhibitors on men and partners' quality of sexual life: Results of a prospective study in primary care. J Sex Med 2013:10; 1850-60. http://dx.d 0i.0r g /l 0.1111 /jsm .12186 6. Montorsi F, Adaikan G, Becher E, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2010;7:3572-88. h ttp ://d x.d o i.O rg /1 0 .llll/i.1 7 4 3 -6 1 0 9 .2 0 1 0 .0 2 0 6 2 .x 7. Porst H, Burnett A, Brock G. SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med 2013; 10:130-71. http://dx.d 0i.0r g /l 0.1111/jsm . 12023 8. Brock G. Diagnosing erectile dysfunction could save your patient's life. Can Urol Assoc J2014;8:S151-2. h ttp://dx.doi.org/! 0.5489/cuaj.2311 9. Ramanathan R, Mulhall J, Rao S, et al. Predictive correlation between the International Index of Erectile Function (IIEF) ond Sexual Health Inventory for Men (SHIM): Implicotions for calculating a derived SHIM for clinical use. 7Sex/Hed2007;4:1336-44. http://dx.doi.org/10.! 111 / | . l 743-6109.2007.00576.x
18. 19.
20 . 21 .
22
.
23.
Ghanem HM, Salonia A, Martin-Morales A. SOP: Physical examination and laboratory testing for men with erectile dysfunction. J Sex Med 2013;10:108-10. h ttp ://d x .d o i.o rg /! 0 .1111 /j 17436109.2012.02734.x Jackson G, Nehra A, Miner M, et al. The assessment of vascular risk with erectile dysfunction: the role of the cardiologist ond general physician. IntJ Clin frac 2013;67:1163-72. http://dx.d 0i.0r g /l 0 1 1 1 1 / ijcp.12200 Meuleman EJ, Hatzichristou D, Rosen RC, et al. Diagnostic tests for male erectile dysfunction revis ited. Committee Consensus Report of the International Consultation in Sexual Medicine. J Sex Med 2010;7:2375-81. Morales A, Bella AJ, Chun S, et al. A practical guide to diagnosis, management ond treatment of testos terone deficiency for Canadian physicians. Can Urol Assoc J 2010;4:269-75. Schmidt HM, Munder T, Gerger H, et al. Combination of psychological intervention and phosphodisterase-5 inhibitors for erectile dysfunction: A narrative review and meta-analysis. J Sex Med 2014; 11:1376-91. http://dx.doi.org/! 0.1111 /ism .12520 Nocturnal penile erections. The role of RigiScan in the diagnosis of vascular erectile dysfunction. J Sex Aferf 2010:9;3219-26. Sikka SC, Hellstrom WJ, Brock G, et al. Standardization of vascular assessment of erectile dysfunc tion: Standard operating procedures for duplex ultrasound. J Sex Med 2013;10:120-9. http://dx.doi. org/10.1111/].1743-6109.2012.02825.x Glina S, Ghanem H. SOP: corpus cavernosum assessment (cavernosography/cavernosometry). J Sex Med 2013;10:111-4. http://dx.d 0i.0rg /l0 .1 1 1 1 / j . l 743-6109.2012.02795.x Giuliano F, Rowland Dl. Standard operating procedures for neurophysiologic assessment of male sexual dysfunction. J Sex Med 2013;10:1205-11. http://dx.d 0i.0r g /l 0.1111 /jsm .12164 Smith WB, McCaslin IR, Gokce A, et al. PDE5 inhibitors: Considerations for preference and long-term adherence. IntJ Clin Pract 2013:67:768-80. http://dx.d 0i.0r g /l 0.1111 /ijc p .l 2074 Alhathal N, Elshal AM, Carrier S. Synergistic effect of testosterone and phosphodiesterase-5 inhibitors in hypogonadal men with erectile dysfunction: A systematic review. Can 1/ra/Assoc J 2012;6:269-74. http://dx.d 0i.0r g /l 0.5489/cuaj.l 1291 Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: A systematic review and meta-analysis. Ann Intern Afe/2009;151:650-61. http://dx.doi.org/! 0.7326/0003-4819-1519-200911030-00150 Coombs PG, Heck M, Guhring P, et al. A review of an intracavernosal injection therapy program. BJU Int 2012; 110:1787-91. http://dx.doi.O rg/10.l 111 /j.l 464-410X.2012.11080.x Hellstrom WJ, Montague DK, Moncoda I, et al. Implants, mechanical devices, and vascular surgery for erec tile dysfunction. 7Sex/Mec72010;7:501-23. h ttp ://dx.doi.O rg/10.llll/i.1 743-6109.20 09.01626.x
Correspondence: Dr. Anthony Bella, Room A345, B3 Urology Civic Campus, 1053 Carling Ave., Ottawa ON K1Y 4E9; [email protected]
CUAJ • January-February 2 0 1 5 » Volume 9, Issues 1-2
29
Copyright of Canadian Urological Association Journal is the property of Canadian Urological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
J .
B e lla ,
M B ,
F R C S C f J a y
C. L e e ,
B é n a rd ,
M D ,
F R C S C f G e r a ld
B .
M D ,
B ro c k ,
F R C S C f S e rg e M D ,
C a r r ie r ,
M D ,
F R C S C f
F R C S C ±
'G reta and John Hansen Chair in M e n's Health Research, A ssistant Professor o f Urology, D epartm ent o f Surgery, University o f O ttaw a, O ttaw a, ON; 'C linical Assistant Professor, University o f Calgary, Calgary, AB; ^Associate Professor, D epartm ent o f Surgery, Urology Division, M cGill University, M ontreal, QC; 'C hair, Division o f Urology, D epartm ent o f Surgery, Université de M o ntréal, M ontreal, QC; ‘ Professor of Surgery, W estern U niversity, London, ON
See related article on page 3 0 .
Cite as: Can U rol Assoc J 2 0 1 5 ;9 ( l- 2 ) :2 3 - 9 . h ttp ://d x .d o i.o r g /1 0 .5 4 8 9 /c u a j.2 6 9 9 Published online February 5 , 2 0 1 5 .
S u m m ary o f recom m endations •
•
•
•
•
Erectile d ysfu n ctio n (ED) is the preferred c lin ic a l term describing the persistent or recurrent in a b ility to achieve and m a in ta in a p e n ile e re ctio n o f s u ffic ie n t rig id ity to p erm it satisfactory sexual a ctivity fo r at least 3 months. The in itia l diagnosis and treatm ent o f ED is most c o m m o n ly perform ed in Canada by prim ary care physicians (PCPs). PCPs, urologists, internists, psychiatrists, and other treat ing healthcare professionals should be encouraged to in i tia te an open d ia log ue o f sexual issues to id e n tify men w ith ED w h o m ay not o therw ise vo lu n te e r th e ir sexual concerns.
•
cardiovascular disease in general, and should be id e n ti fied d u rin g e valuation as they m ay represent the in itia l clin ic a l sign o f generalized e ndothelial disease (vascular insufficiency). Evaluation o f fa m ily history, n ico tin e use, blo od pressure, lip id p rofile, and glucose is required or should be d ocum ented if p re vio u sly perform ed. A ctive managem ent o f ide ntifie d cardiac risk factors should be instituted (i.e., sm oking cessation, b lo o d pressure treat ment). •
Frequently a careful history, physical exam, serum g lu cose or hem oglobin A1C, lip id p ro file and optio na l hor m onal testing fa cilita te the diagnosis o f ED and effective therapy. Patient history can d ifferen tia te ED from other male sexual dysfunctions, in clu d in g ejaculatory disorders (prem ature e ja cu la tio n and other abnorm alities), h yp o gonadism , disorders o f orgasm, and Peyronie's disease. O rganic (physical) causes o f ED are present in most men, but situational or psychosocial co n trib u tin g factors often
Background
p la y a c o n trib u to ry role. A ddressing these issues m ay enhance treatm ent efficacy. U nderlying risk factors associated w ith ED are com m on to
• •
O n ce reversible causes o f ED are ruled out, a trial o f oral m edication is recom m ended as first-lin e therapy, based on trea tm en t e ffica cy, side effe ct p ro file , and m in im a l invasiveness. Specialized testing and referral are generally reserved for cases w here oral first-lin e treatments fail or are not appropriate, o f if greater insight into the etiolog y is desired by the patient/physician. Second-line therapies, although m ore invasive than oral agents, are generally w e ll-tole ra ted and effective. Surgery remains an im p orta nt o ptio n fo r men refractory to m edical m anagem ent, offe ring effective and durable ED treatm ent outcomes.
highly effective, m in im a lly invasive therapeutic agents - most c o m m o n ly oral therap ies using p h o sp h o diesterase ty p e 5 -
E rec tile d y s fu n c tio n (ED ) is a h ig h ly p re v a le n t c o n d itio n ,
(PD E5) inhibitors. S e co n d -lin e self-in jectio n w ith vasoactive
w h ic h a ffects th e p h y s ic a l a n d p s y c h o s o c ia l w e ll-b e in g
agents, v ac u u m erec tio n devices, and surgical approaches
and q u a lity o f life (Q o L ) fo r thousands o f C a n a d ia n m en ,
w ith in flata b le p e n ile prostheses offer ED m a n a g e m e n t w ith
th e ir partners, and fam ilie s. T h e C an a d ian Study o f Erectile
high p o ten tial for p atie n t and p artner trea tm en t satisfaction.
D ysfu n ction id e n tifie d 4 9 .4 % o f m en o ve r 4 0 w ith ED, w ith
M o s t cases o f ED in C an a d a are id e n tifie d a nd e ffec tive ly
oth er studies sh o w in g that 5 % to 2 0 % o f m en h ave m o d er
treated by p rim a ry care physicians (PCPs).4 E vidence-based
ate to severe E D .1’3 C o n te m p o rary trea tm en t options in clu d e
diagn o stic a nd th e ra p e u tic a p p ro ach es, in c lu d in g e ffec tive
CUAJ • January-February 2015 • Volume 9, Issues 1-2 © 2015 Canadian Urological Association
23
Bella et al.
oral agents like the PDE5-inhibitors, has allowed for a shift of ED management from a historical surgical approach to contem porary medical management. Family physicians, urologists, internists, endocrinologists, cardiologists, and other medical specialists are approached by couples with ED requesting treatment more frequently. In many cases longstanding relationships exist between the couple and their treating physician, fostering an im portant therapeu tic alliance w h ich may translate into im proved clin ica l response to the selected treatm ent approach. A sharedcare model for the treatment of ED is a valid concept and also may reflect optim al utilization of healthcare resources in the Canadian healthcare environm ent.4,5 This sharedcare model is one in w hich PCPs in itia lly identify and treat patients w ith ED and refer prim arily those individuals who have incom plete responses or require more invasive or specialized testing and treatment. The com bined experi ence and knowledge of PCPs coupled w ith the diverse ED knowledge of the specialist can ideally result in optim al care for the patient. In the contemporary model of ED care delivery, urologists remain an essential resource for several important reasons: 1. Referral requested for the d iffic u lt-to -tre a t, oralrefractory cases. 2. Second-line intracavernous and intraurethral vasoac tive therapy may be outside of the practice pattern of some PCPs and therefore require urologie care. 3. In som e cases a n a to m ic a l p e n ile d e fo rm ity (Peyronie's disease or post-trauma) may play an important role in the ED and more frequently require operative correction. 4. In a small but definable population (often men with severe vascular disease or poorly controlled diabe tes), a trial of nonsurgical approaches may not suc ceed, requiring surgical options in the difficult-totreat group. 5. Patients w ith congenital venous leak as the cause of their ED require urologie care. These patients are usually young and do not respond to PDE5-inhibitors. 6. Specific tests performed by urologists may be indi cated at the request of the patient or his partner or for medico-legal issues. 7. Ongoing research into the basic and clinical conse quences of ED is performed in urologie laboratories and clinical practices As presented in this document, the Canadian Urological Association (CUA) Guidelines Committee has updated the CUA Erectile Dysfunction Guidelines using a Canadian per spective. Suggestions were based on peer-reviewed literature through 2015, and the ED recommendations from the W orld Health Organization (WHO)-endorsed 2010 International Consultation on Sexual Medicine, the International Society for Sexual Medicine, the Sexual Medicine Society of North
24
America, and evolving research on new approaches to ED management.4,6'7
Global management objectives 1.
To help the patient and partner establish their objec tives of treatment. 2. To select diagnostic tests based on presenting com plaints and goals of therapy. 3. To use diagnostic tests in a cost-effective and mean ingful manner w hich w ould affect choice of treat ment as well as help to identify and disqualify certain contributory health problems. 4. To provide a diagnosis and understanding o f the likely etiology of the ED to the patient and partner. 5. To identify ED etiologies w hich may affect patient morbidity and mortality (if not previously identified), including screening for vascular risk, and facilitate access to the most appropriate healthcare providers for definitive management. 6. To offer treatment choices with comprehensive infor mation on cost, likelihood of success and common side effects. 7. To initiate therapy w ith the least invasive option w hich w ould satisfy the patient and partner goals of treatment. 8. To provide patients w ith information and ongoing support to maximize treatment success. 9. To re-establish the couples' ability to achieve and maintain sexual intimacy in the most natural man ner possible. 10. To choose approaches w hich are reversible when ever possible.
Management approach: Diagnosis
Overview The CUA supports the view that the general framework for the evaluation of patients w ith any type of sexual dysfunc tion should follow the same basic principles.3,4,6The sexual history should ascertain the severity, onset, and duration of the problem, concomitant medical or psychosocial fac tors, and bother to the patient and partner (if applicable). In-person interview is often supplemented w ith question naires or potential web-based methods. The manner of sexual inquiry is important and should reflect a high level of sensitivity and regard for each individual's unique ethnic, cultural, and personal background. 1. D eterm ine that the problem is ED versus other aspects of the sexual response cycle (desire, ejacu lation, orgasm) or from other causes (Peyronie's dis-
CUAJ • January-February 2 0 1 5 • Volume 9 , Issues 1-2
CUA Guidelines on ED
ease, lifestyle factors in c lu d in g illic it drug use, q u a lity
•
N o c tu rn a l p e n ile tu m e s c e n c e te s tin g (N P TR ) (Rigiscan)
•
D y n a m ic in fu s io n c a v e rn o s o g ra p h y and ca ve rn o so m e try (DIC C )
T he p a tie n t (w ith o r w ith o u t th e ir partner) w ill gu id e w h e th e r tre a tm e n t is desired.
•
Penile and p e lv ic a ngiog ra m
Id e n tify w h e th e r a p o te n tia lly reve rsib le cause to the
D iag n o s is h is to ry
o f partners re la tio n sh ip ). 2.
D e te rm in e th e tim in g o f onset, n a tu re o f th e p ro b lem , and s ig n ific a n c e to th e p a rtn e r (if a p p lic a b le ).
3.
ED exists (m edication s), stress, depression, h o rm o n a l a b n o rm a litie s in c lu d in g a ndroge n, th y ro id and p itu itary, to b a cco , excessive a lc o h o l use, drug abuse, and
O b ta in in g a d ia g n o stic h isto ry is th e cornerstone o f the e v a l uation o f sexual d y sfu n ctio n and ED. The history w ill p ro vid e
p a rtn e r-sp e cific issues). Testosterone p ro file is a p p ro priate at the ED diagnosis if hypogo nadism suspected, bu t screening is no t recom m ended fo r all ED patients.
the lik e ly diagnosis in m ost cases.4,6'8 A su p p o rtive healthcare
Establish a lik e ly u n d e rly in g e tio lo g y based on h is to ry , p h y s ic a l exam , and lab te stin g . O b ta in in g o r c o n fir m in g re c e n t b lo o d p re ssu re m e a su re m e n ts,
A m o n o g a m o u s , h e te ro se xu a l re la tio n s h ip s h o u ld n o t be assum ed. P otential e tio lo g ie s fo r sexual d y s fu n c tio n in c lu d e a w id e range o f o rg a n ic and m e d ic a l factors, b u t m u ltip le
lip id p ro file , an d g lu c o s e /H g B A lC are h ig h ly re c om m ended. A c o m m o n ly used schem a is: • V a scu la r
p s y c h o lo g ic a l o r interperson al factors (i.e., a n x ie ty , depres sion, re la tio n s h ip distress) can be causal o r c o n trib u to ry .
4.
•
E ndocrine
• •
N e u ro lo g ic a l S ituationa l
•
End organ (p e n ile d e fo rm ity - P eyronie's disease o r traum a)
•
M ix e d (M ost cases have an u n d e rly in g o rg a n ic cause o r causes; s im ila r ly m o s t m en w i l l s u b s e q u e n tly re p o rt a n x ie ty , stress, and d e p re s s io n as a c o n s e qu e n ce o f ED.)
professiona l a llo w s th e c o u p le to relate th e ir co n ce rn s and express th e ir goals o f tre a tm e n t in an u n h u rrie d m a nner.
General domains o f the history •
•
Sexual desire, re la tio n s h ip issues, stressors at h o m e and w o rk .
•
G e n ita l pa in o r altered shape.
•
Lifestyle factors: sm o kin g , substance use/abuse, seden ta ry lifestyle.
• •
C o m o rb id c o n d itio n s : hypertensio n, p e rip h e ra l vascular disease, diabetes, ob e sity, and renal disease. P elvic surgery, ra d ia tio n o r traum a.
•
M e d ic a tio n s .
•
P sychiatric illness o r c o n d itio n s .
Methodology 1.
H is to ry a n d c lin ic a l q u e s tio n in g (m o s t im p o rta n t c o m p o n e n t o f the ED e v a lu a tio n ).
2.
Focused p hysical e x a m in a tio n (directed at a n a to m ic, va scu la r and neural systems essential fo r erections).
3.
Use o f fo rm a liz e d q u e s tio n n a ire in s tru m e n ts (e.g., Sexual H ealth In ve n to ry fo r M e n [S H IM ], A p p e n d ix h ttp ://jo u rn a ls .s fu .c a /c u a j/in d e x .p h p /jo u rn a l/a rtic le / v ie w /2 6 9 9 /2 0 2 2 ) is re c o m m e n d e d b u t n o t m a n d a to ry, as th e q u estion n a ire s are useful in esta b lish in g b a s e lin e fu n c tio n , ED s e v e rity , e v a lu a te tre a tm e n t response, and in m ost cases q u e s tio n n a ire results do n o t add s ig n ific a n tly to d u ra tio n o f the d o c to r-p a tie n t e n co u n te r.
4.
5. 6.
La b o ra to ry inve stig a tio n s: serum glucose, lip id p ro file , and in se le c t cases h o rm o n a l s c re e n in g (to ta l testo ste ro n e /b io a v a i Ia b le testosterone). C o nsultatio n w ith subspecialists (e n d o c rin o lo g y , psy c h o lo g y , ca rd io lo g y). S p e cia lize d tests: • C o m b in e d in je c tio n and s tim u la tio n test (CIS) • D uplex ultrasound w ith vasoactive penile injection
D e te rm in e sp e cifics related to ED (onset, severity, sig n ific a n c e and situ a tio n s) and desire, aro u sa l, orgasm , and e ja c u la tio n .
Q u e s tio n n a ire s Use o f v a lid a te d q u e s tio n n a ire s m a y be b e n e fic ia l. These to o ls can be p a tie n t s e lf-a d m in is te re d a n d p ro v id e m u ch o f th e a b o v e in fo rm a tio n in an e ffic ie n t n o n -th re a te n in g m anner, w h ile b e in g tim e -s a v in g and c o s t-e ffe c tiv e .6 T here are v a lid a te d in stru m e n ts designe d to e va lu a te sexual and e re c tile fu n c tio n . T he greatest u tility o f these q u e stio n n aires m ay be in e s ta b lish in g a response to th e ra p y and d e te rm in ing o v e ra ll satisfaction w ith d ru g use o ve r a s p e cifie d length o f tim e (i.e., 4 weeks). The m ost c o m m o n q u e s tio n n a ire is th e S H IM (A p p e n d ix -h ttp ://jo u rn a ls .s fu .c a /c u a j/in d e x .p h p / jo u rn a l/a rtic le /v ie w /2 6 9 9 /2 0 2 2 ).9
P h ysical e x a m The aim o f a focused physical e xa m in a tio n in m en w ith ED is to e xa m in e g e n ita l a n a to m y and id e n tify any related a b n o r-
CUAJ • Jonuory-February 2 0 1 5 » Volume 9, Issues 1-2
25
Bella et al.
malities (e.g., Peyronie's plaques), endocrine signs, and pos sible com orbidities (neurological, vascular, and possible life-threatening conditions).10 An association exists between erectile dysfunction and peripheral vascular disease, as well as ED and the potential development of coronary artery dis ease.11 Assessment should include body habitus (secondary sexual characteristics), peripheral circulation (ED is a predic tor of cardiovascular morbidity and mortality, findings con sistent when controlled for confounders), neurological and genitourinary systems.10 Testicular examination is important to ensure testes/testis presence and to examine consistency of the testicle (i.e., atrophy, hypogonadism). The identifica tion of penile deformities may be best achieved in the erect state, but is most com m only examined by stretching the penis to make the Peyronie's plaque(s) more pronounced. The physical examination can also be a source of embarrass ment or discomfort for some patients; therefore, every effort should be made to ensure privacy and personal comfort.
Laboratory testing
O ptional testing such as thyroid-stim ulating hormone (TSH), luteinizing hormone (LH) and follicle-stim ulating hormone (FSH), prolactin, complete blood count (CBC), and urinalysis are considered complementary and not felt to be mandatory in the evaluation of ED in most cases, but are added when dictated by clinical context.3,5,10
Specialized testing
/.
Psychological/psychiatric assessment
These assessments often provide important complementary insight into relationships and situational causes to ED. The lack of widespread availability and cost lim it their use in most cases of ED treatment. The primary goals of psychotherapy are to reduce or eliminate performance anxiety, to understand the context in which men or a couple function sexually, to imple ment psycho-education in order to modify sexual scripts, and to reduce premature discontinuation of pharmacotherapy.3,6,14
2. NPTR Overview The recommendations by the International Society for Sexual Medicine's International Consultation on Sexual Medicine suggest that laboratory tests for men w ith sexual problems may include fasting glucose, lipid profile and, in select cases, a hormone profile. Hormone profiles are used to identify or confirm specific etiologies (e.g., hypogonadism) or to assess the role of potential medical comorbidities or concomitant illnesses.6-12 Assessment for occult diabetes may be performed with a fasting glucose or HbA1c. Although recommended by the W H O consensus panel, the lipid screen is considered an optional component of the Canadian ED assessment but is suggested as a valuable addition to the evaluation and good general practice.2 Hormonal profile screening remains a controversial aspect of the routine evaluation of ED. There is a general guideline agreement that in a man w ith ED and hypoactive desire, incomplete response to PDE5-inhibitor treatment, and in all men with known diabetes (as suggested by 2013 Canadian Diabetes Association guidelines)2 testing and potential treat ment for low levels of testosterone is appropriate. In men w ith normal desire and ED the need for global testing is controversial and currently undetermined. In the appropri ate patient, once treatment w ith exogenous testosterone is initiated, ongoing follow -up is mandatory according to pub lished guidelines.12-13 For men w ith diabetes, the 2013 Canadian Diabetes Association guidelines also support annual review of sexual function and determination of testosterone levels.
26
NPTR is a m inim ally invasive means to measure and record nighttim e erectile events (nocturnal penile tumescence), but has lim ited a va ila b ility in Canada and costs are not covered by most provinces. Nocturnal penile tumescence and rigidity testing using Rigiscan should take place for at least 2 nights, measuring 2 to 5 overnight erections. A functional erectile mechanism is indicated by an erectile event of 60% rigidity recorded on the tip of the penis lasting for 10 minutes. NPTR's greatest utility is in medico-legal cases and in investigative pharmacological studies to assess treatment impact.15
3. Vascular testing A variety of vascular tests exist. Penile duplex cavernous artery flow determination after corporal injection of vaso active agents is commonly performed.16 Use of ultrasound to localize and measure the size and flow through the cav ernous vessels, pre- and post-vasoactive injection allow a more refined assessment of penile circulation. This test is performed less frequently in Canada since the advent of effective oral medications. In cases where indicated, fur ther vascular investigation is unnecessary if duplex ultra sound is normal, as indicated by a peak systolic blood flow >30 cm/sec and a resistance index >0.8. If the ultrasound is abnormal, however, arteriography and dynamic infusion cavernosometry and cavernosography should be performed only in patients who are potential candidates for vascular reconstructive surgery - these tests though are rarely used in current Canadian ED treatment.
CUAJ • Januory-Februory 2015 • Volume 9, Issues 1-2
CUA Guidelines on ED
DICC aims to define how well the penile blood-trapping mechanism (the veno-occlusive mechanism) w orks.17 In brief, dye and fluid are delivered into the penis to induce an erection. Measurement of the rise and fall of intra-penile pressure with radiologic visualization of the veins draining the penis determine whether a competent or incompetent veno-occlusive mechanism exists. The most invasive diagnostic test is an arteriography. It is reserved generally for cases of high-flow priapism or planned vascular bypass. A penile angiogram allows visualization of the penile circulation and directs em bolization for the unusual case of penile injury induced high-flow priapism.
4. Endocrinological tests There is still controversy on the ideal endocrine workup for men w ith EDA6 A m orning total testosterone or bioavailable testosterone is logical in men w ith: decreased sexual interest, delayed ejaculation, reductions History in ejaculate volum e, failu re of Physical and Labs (Glucose, Lipids*, P D E 5-inhibito r treatm ent, and Testosterone*, Profactin*) men w ith ED and d ia b e te s.13 Free testosterone measurements have significant intra-assay vari a b ility w hich lim its their c lin i cal u tility in Canada and is not recommended. Bioavailable tes tosterone is clinically useful and recommended, but is not avail able in all areas o f Canada; as well, patients may incur a cost for a bioavailable testosterone assay. Calculated bioavailable testoster one (which requires a m orning total testosterone, album in and sex-hormone binding globulin) is an acceptable substitute for measured bioavailable testoster one if it is not available or costprohibitive.
Treatment options
Overview Management of ED most often w ill occur concurrently with lifestyle modification and treatment of organic or psychosexual dysfunctions. Patients and partners are made aware of efficacy, risks and benefits of appropriate treatments, taking into consideration preferences and expectations. Oral ther apy failure may often be salvaged by patient re-education on PDE5-inhibitor use and optimization of dosing. Stepwise progression from oral agents through second- and third-line therapies occurs as needed (Fig. 1). 1. Oral therapy (on-demand or daily dosing). Given the differences between oral agents, the choice of
5. Neuro-physiological testing /S u c c e s s fN
This form of testing generally allows us to measure the sacral reflex arc, an indirect measure of the perineal neural integrity, and has lim ited clin ica l a vailability and utility.18
I continue V treatm ent
)
J
Unsuccessful consider third-line therapy
ÇPenile im p la n t M surgery
Fig. 1. Management of erectile dysfunction. f Consider first-line ED treatment for men with ED and Peyronie's disease. ^Optional testing. ICI: intracavernosal injections; VED: vacuum erection device; NTG: nitrates/nitroglycerine; ED: erectile dysfunction.
CUAJ • Jonuary-Februory 2015 • Volume 9, Issues 1-2
27
B e ll a e t a l.
2.
3.
4. 5. 6.
which initiating PDE5-inhibitor you should use may be influenced by several factors, including timing or frequency of intercourse, and interactions with food or alcohol (Table 1).3,6,19'21 Testosterone replacement therapy in men with doc umented hypogonadism is an option. Testosterone may be used alone for hypogonadism, or in combi nation with oral PDE5-inhibitor therapy when ED is present.20-21 Sexual counselling (this may represent a spectrum of approaches from a simple open discussion with the PCP to psychologist, sexual therapists and/or psy chiatrists).3,6 Local therapy (intracavernous or intraurethral agents).2,3,6,22 Vacuum erection device therapy.23 Surgery.3,6,23 a. Penile implant. b. Peyronie's surgical repair. c. Vascular bypass procedure (generally reserved for young men after traumatic arterial penile vas cular injury).
Conclusions 1. 2.
3. 4.
5.
6.
A careful history and physical exam are the essential elements of the ED workup in most cases. Basic screening tests include the identification of car diac risk factors and blood tests. The following tests are recommended: serum fasting glucose, lipids and testosterone (if indicated). A stepwise treatment approach using the least inva sive option is suggested. In some cases where greater detailed information is desired or failure of the initial oral medication is encountered, trials of more invasive second-line treatment or investigations may be appropriate. Surgery should be reserved for men in whom less invasive reversible treatment has not succeeded or is contraindicated. Treatment should be individualized and patient fol low-up should be arranged to assess the efficacy of treatment.
Competing interests: Or. Bella is a member of the advisory boards for Lilly, Actavis, American Medical Systems, and Coloplast. He is also a member of the Speakers' Bureau for Lilly and CUA (accredited CME speaker) and a co-principal investigator and cofounder of the PROPPER (Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration) registry. Dr. Lee is a member of
T able 1. Com parison o f th e properties o f PDE5-inhibitors Tadalafil
Sildenafil
Property
Vardenafil
>TMAX
30-120 minutes (median 60 minutes)
30-360 minutes (median 120 minutes)
30-120 minutes (median 60 minutes)
T
4 hours
17.5 hours
4 hours
Absorption
Fatty meals cause a mean delay in TM AX of 60 minutes
Not affected by food
Fatty meals cause a reduction in CMAX
Available Doses
25 mg, 50 mg, 100 mg PRN
2.5 mg, 5 mg daily 5 mg, 10 mg, 20 mg PRN
10 mg oral dissolvable tablet 2.5 mg, 5 mg, 10 mg, 20 mg PRN
M axim um Dose
100 mg daily
20 mg daily
20 mg daily
Efficacy
Each of the PDE5 inhibitors offers sim ilar efficacy.
1/2
Patients >65 years old Hepatic im pairm ent Renal im pairm ent Concomitant use of potent cytochrome P450 3A4 inhibitors, such as ritonavir and erythromycin
• • • •
Contraindications
• Any patient using organic nitrates either regularly or interm ittently • Known hypersensitivity to any com ponent of the tablet
• Any patient using organic nitrates either regularly or interm ittently • Known hypersensitivity to any com ponent of the tablet
Use w ith alpha blockers
Concomitant use of selective alpha blockers does not present a risk for significant hypotension. There is a potential risk o f significant hypotension when using non-selective alpha blockers.
Side effects (5 most common in order of frequency when compared to placebo)
Headache, flushing, dyspepsia, nasal congestion, alteration in colour vision
Dose adjustments may be needed
Patients >65 years old Hepatic im pairm ent Renal im pairm ent Concomitant use of potent cytochrome P450 3A4 inhibitors, such as ritonavir and erythromycin • Concomitant use o f cimetidine
Patients >65 years old Hepatic im pairm ent Renal im pairm ent Concomitant use of potent cytochrome P450 3A4 inhibitors, such as ritonavir and erythrom ycin
• • • •
• • • •
Headache, dyspepsia, backpain, myalgia, nasal congestion
Please consult the individual product m onographs for additional inform ation.
28
CUAJ • January-February 2015 • Volume 9, Issues 1-2
• Any patient using organic nitrates either regularly or interm ittently • Known hypersensitivity to any com ponent of the tablet
Headache, flushing, rhinitis, dyspepsia, sinusitis
CUA Guidelines on ED
the advisory boards for Abbott and Lilly. He has also received grants from Abbott, Lilly and Actavis and is participating in a clinical trial with Lilly. Dr. Carrier is a member of the advisory boards for Astellas, Eli Lilly Canada, Pfizer Canada, Abbott, Novartis, and Actavis. He is also a member of the Speakers' bureau for Eli Lilly Canada, Pfizer Canada, Abbott, Merck, and Actavis. He is participating in clinical trials with Astellas and Eli Lilly Canada. Dr. Bénard is a member of the advisory boards and part of the Speakers' Bureau for Abbott, Astellas, Pfizer, Lilly, Paladin, and Actavis. He has received payment for talks from Abbott, Astellas, Pfizer, Lilly, Paladin, and Actavis. He also has investments in many pharmaceutical companies through his diversified retirement plan. He is also currently participating in a clinical trial with Allergan. Dr. Brock is a member of the advisory boards and part of the Speakers' Bureau for Lilly, Coloplast, AMS, GSK, Abbott, and Actavis. He has also received payments and grants from these same companies.
10. 11. 12 . 13. 14.
15.
This paper has been peer-reviewed.
16.
References
17.
1. Grover SA, Lowensteyn I, Kaouache M, et al. The prevalence of erectile dysfunction in the primary core setting: Importance of risk factors for diabetes and vascular disease. Arch Intern Med 2006; 166:213-9. http://dx.d 0i.0r g /l 0.1001 /archinte.l 66.2.213 2. Brock G, Harper W; for Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Erectile dysfunction. Can J Diabetes 2013;37:S150-2. http://dx.doi.org/! 0.1016/j.jcjd.2013.01.041 3. Hatzimouratidis K, Amor E, Eardley I, et al. Guidelines on mole sexual dysfunction: Erectile dysfunction and premature ejaculation. £or t/ro/2010;57:804-l 4. http://dx.d 0i.0r g /l 0.1016/j.eururo.2010.02.020 4. Canadian Urological Guidelines Committee. Erectile dysfunction practice guidelines. Can i Urol 2002;9:1583-87. 5. Costa P, Grandmottet G, Mai HD, et al. Impact of 0 first treatment with phosphodiesterase inhibitors on men and partners' quality of sexual life: Results of a prospective study in primary care. J Sex Med 2013:10; 1850-60. http://dx.d 0i.0r g /l 0.1111 /jsm .12186 6. Montorsi F, Adaikan G, Becher E, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2010;7:3572-88. h ttp ://d x.d o i.O rg /1 0 .llll/i.1 7 4 3 -6 1 0 9 .2 0 1 0 .0 2 0 6 2 .x 7. Porst H, Burnett A, Brock G. SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med 2013; 10:130-71. http://dx.d 0i.0r g /l 0.1111/jsm . 12023 8. Brock G. Diagnosing erectile dysfunction could save your patient's life. Can Urol Assoc J2014;8:S151-2. h ttp://dx.doi.org/! 0.5489/cuaj.2311 9. Ramanathan R, Mulhall J, Rao S, et al. Predictive correlation between the International Index of Erectile Function (IIEF) ond Sexual Health Inventory for Men (SHIM): Implicotions for calculating a derived SHIM for clinical use. 7Sex/Hed2007;4:1336-44. http://dx.doi.org/10.! 111 / | . l 743-6109.2007.00576.x
18. 19.
20 . 21 .
22
.
23.
Ghanem HM, Salonia A, Martin-Morales A. SOP: Physical examination and laboratory testing for men with erectile dysfunction. J Sex Med 2013;10:108-10. h ttp ://d x .d o i.o rg /! 0 .1111 /j 17436109.2012.02734.x Jackson G, Nehra A, Miner M, et al. The assessment of vascular risk with erectile dysfunction: the role of the cardiologist ond general physician. IntJ Clin frac 2013;67:1163-72. http://dx.d 0i.0r g /l 0 1 1 1 1 / ijcp.12200 Meuleman EJ, Hatzichristou D, Rosen RC, et al. Diagnostic tests for male erectile dysfunction revis ited. Committee Consensus Report of the International Consultation in Sexual Medicine. J Sex Med 2010;7:2375-81. Morales A, Bella AJ, Chun S, et al. A practical guide to diagnosis, management ond treatment of testos terone deficiency for Canadian physicians. Can Urol Assoc J 2010;4:269-75. Schmidt HM, Munder T, Gerger H, et al. Combination of psychological intervention and phosphodisterase-5 inhibitors for erectile dysfunction: A narrative review and meta-analysis. J Sex Med 2014; 11:1376-91. http://dx.doi.org/! 0.1111 /ism .12520 Nocturnal penile erections. The role of RigiScan in the diagnosis of vascular erectile dysfunction. J Sex Aferf 2010:9;3219-26. Sikka SC, Hellstrom WJ, Brock G, et al. Standardization of vascular assessment of erectile dysfunc tion: Standard operating procedures for duplex ultrasound. J Sex Med 2013;10:120-9. http://dx.doi. org/10.1111/].1743-6109.2012.02825.x Glina S, Ghanem H. SOP: corpus cavernosum assessment (cavernosography/cavernosometry). J Sex Med 2013;10:111-4. http://dx.d 0i.0rg /l0 .1 1 1 1 / j . l 743-6109.2012.02795.x Giuliano F, Rowland Dl. Standard operating procedures for neurophysiologic assessment of male sexual dysfunction. J Sex Med 2013;10:1205-11. http://dx.d 0i.0r g /l 0.1111 /jsm .12164 Smith WB, McCaslin IR, Gokce A, et al. PDE5 inhibitors: Considerations for preference and long-term adherence. IntJ Clin Pract 2013:67:768-80. http://dx.d 0i.0r g /l 0.1111 /ijc p .l 2074 Alhathal N, Elshal AM, Carrier S. Synergistic effect of testosterone and phosphodiesterase-5 inhibitors in hypogonadal men with erectile dysfunction: A systematic review. Can 1/ra/Assoc J 2012;6:269-74. http://dx.d 0i.0r g /l 0.5489/cuaj.l 1291 Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: A systematic review and meta-analysis. Ann Intern Afe/2009;151:650-61. http://dx.doi.org/! 0.7326/0003-4819-1519-200911030-00150 Coombs PG, Heck M, Guhring P, et al. A review of an intracavernosal injection therapy program. BJU Int 2012; 110:1787-91. http://dx.doi.O rg/10.l 111 /j.l 464-410X.2012.11080.x Hellstrom WJ, Montague DK, Moncoda I, et al. Implants, mechanical devices, and vascular surgery for erec tile dysfunction. 7Sex/Mec72010;7:501-23. h ttp ://dx.doi.O rg/10.llll/i.1 743-6109.20 09.01626.x
Correspondence: Dr. Anthony Bella, Room A345, B3 Urology Civic Campus, 1053 Carling Ave., Ottawa ON K1Y 4E9; [email protected]
CUAJ • January-February 2 0 1 5 » Volume 9, Issues 1-2
29
Copyright of Canadian Urological Association Journal is the property of Canadian Urological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
