OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
NACE – Emerging Challenges in Primary Care: 2014 OAB - 1
Emerging Challenges In Primary Care: 2014
!
Faculty
OAB Made Simple for the Primary Care Provider (PCP):
How to Identify, When to Treat and When to
Refer
Matt T. Rosenberg, MD Medical Director of Mid-Michigan Health Centers
Jackson, MI Section Editor of
Urology, International Journal of Clinical
Practice
Louis Kuritzky, MD Clinical Assistant
Professor Department of
Community Health & Family Medicine
University of Florida Gainesville, FL
Pamela Ellsworth, MD Professor of Urology
Department of Urology UMass Memorial Medical
Center/University of Massachusetts Medical
School Worcester, MA
² Pamela Ellsworth, MD - Speaker/Advisory Board – Pfizer, Allergan - Advisory Board – Astellas
² Louis Kuritzky, MD - No relevant relationships to disclose
² Matt T. Rosenberg, MD - Speaker/Consultant – Astellas, Horizon, Pfizer - Speaker – Forest, Ortho-McNeil - Consultant – Easai, Ferring, Lilly, Bayer
FACULTY DISCLOSURES
2
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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PRE-TEST QUESTIONS OAB/LUTS
3
On a scale of 1 to 5, please rate how confident you would be in the diagnosis and management
of a patient with OAB.
1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident
4
PRE-TEST QUESTION 1 OAB
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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1. OAB is less prevalent than chronic sinusitis 2. An 80 year old patient should know that it is normal
to get up several times per night to empty their bladder
3. At least 50% of symptomatic patients are offered medical treatment for their symptoms of OAB
4. Understanding volume voided is a helpful point of distinction when evaluating LUTS symptoms for OAB
PRE-TEST QUESTION 2 OAB
Mary is a 80 year old patient who admits during her yearly exam that she wears a diaper “just in case” she can’t make it to the bathroom in time. Which of
the following is true regarding OAB?
5
When you tell Mary she may have OAB, she asks about the evaluation. Which is test is not
recommended by the AUA in the initial evaluation of OAB in the uncomplicated patient?
1. Urinalysis 2. Bladder ultrasound 3. Voiding diary 4. Genital exam
PRE-TEST QUESTION 3 OAB
6
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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After an appropriate evaluation you discuss treatment options with Mary. Which of the following statements regarding
expectations of OAB therapy is false?
1. It is appropriate to tell the patient that urinary urgency may be reduced with the correct therapy
2. It may take titration or changes in the pharmacologic therapy before an adequate response in attained
3. Therapeutic efficacy is enhanced with the combination of behavioral therapy and pharmacologic therapy as opposed to either alone
4. The risk of urinary retention in the male increases with longer duration on pharmacologic therapy for OAB
PRE-TEST QUESTION 4 OAB
7
Mary is very interested in efficacy but wants to limit side effects. Which of the following is true regarding OAB
pharmacologic therapy with either an antimuscarinic or a beta 3 adenergic agonist?
1. Both classes have a high rate of dry mouth 2. The efficacy of the antimuscarinic medications are higher
than the beta 3 adrenergic agonist medication 3. The efficacy of the beta 3 adrenergic agonist medication is
higher than the antimuscarinic medication 4. One agent blocks contraction while the other stimulates
relaxation
PRE-TEST QUESTION 5 OAB
8
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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PRE-TEST QUESTIONS LUTS
9
On a scale of 1 to 5, please rate how confident you would be with diagnosing and treating lower
urinary tract symptoms in men.
1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident
10
PRE-TEST QUESTION 1 LUTS
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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Fred presents to the clinic complaining of urgency, frequency and decreased stream. Which of the following
is true regarding his symptom complex?
1. The cause is always the prostate or bladder 2. Such symptoms are a normal part of aging 3. The source of the symptoms can be prostate,
bladder or other 4. The best way to determine the cause is performing
urodynamics
11
PRE-TEST QUESTION 2 LUTS
In addition to his urinary symptoms, Fred mentions some problems with his “love life”. Which of the
following is true regarding the relationship between Erectile Dysfunction(ED) and Benign Prostatic
Hyperplasia (BPH)? 1. There is no relationship as they occur independent of
each other 2. They are only seen in the elderly male 3. The severity of one is inversely related to the severity
of the other 4. They share many of the same co-morbidities 5. BPH predicts cardiac risk, whereas ED does not
12
PRE-TEST QUESTION 3 LUTS
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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With an appropriate evaluation you diagnose Fred with BPH. He is worried that his problem could get
worse. Which of the following is NOT a risk factor for progression of BPH?
1. Age 2. Urine flow rate (Qmax) 3. Prostate volume 4. Diabetes 5. Post void residual
13
PRE-TEST QUESTION 4 LUTS
Instead of Fred having urinary obstruction you recognize that he has overactive bladder (OAB).
Which of the following is/are considered appropriate therapy for OAB?
1. Alpha blockers 2. Phosphodiesterase 5 inhibitors 3. 5 alpha reductase inhibitors 4. Beta 3 agonists or antimuscarinics
14
PRE-TEST QUESTION 5 LUTS
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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LEARNING OBJECTIVES OAB
After participating in this educational activity, clinicians should be better able to:
1. Recognize the role of simple questioning for identifying patients with overactive bladder (OAB)
2. Discuss the essential components of the evaluation of the patient with OAB symptoms
3. Develop a management plan for patients with OAB that emphasizes the incorporation of behavioral therapy and setting appropriate expectations, optimizes efficacy and minimizes side effects to improve patient compliance and adherence with pharmacologic therapy
4. Describe the role of recently approved second line therapies, third line therapies and future therapies in patients with OAB who are unsatisfied with antimuscarinic therapy 15
DEFINITION OF OAB
OAB is syndrome or symptom complex defined as: “Urgency, with or without urgency incontinence, usually with frequency and nocturia”
Urgency is the key symptom of OAB
Urgency is defined as “a sudden compelling desire to void, which is difficult to defer”
Abrams P, et al. Urology. 2003;61:37-49. Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546. 16
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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PREVALENCE OF OAB SYMPTOMS
Coyne S, et al. Urology. 2011;77:1081-1087.
1 in 3 US adults ≥40 years of age reported symptoms of OAB at least “sometimes”
Age (years)
Resp
onde
nts
(%)
17
Stewart WF, et al. World J Urol. 2003;20(6):327-336. Pleis JR, Coles R. Summary health statistics for U.S. adults: National Health Interview Survey, 1998. Vital Health Stat 10. 2002;209:1-113. Centers for Disease Control and Prevention/National Center for Health Statistics. Vital and Health Statistics. Hyattsville, MD: U.S. Department of Health and Human Services; 1997. DHHS Publication No. (PHS) 97-1522. «http://www.cdc.gov/nchs/data/series/sr_10/sr10_194.pdf».
Overactive Bladder Chronic Sinusitis
Arthritic Symptoms
Hay Fever/Allergic Rhinitis Heart Disease
Asthma
Chronic Bronchitis Diabetes
Ulcer
0 10 20 30 40Millions
OAB & OTHER DISORDERS
18
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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To cope with symptoms of OAB, many patients
employ elaborate behaviors aimed at hiding and managing urine loss
Rosenberg MT. Curr Urol Rep. 2008. Abrams et al. Am J Manag Care. 2000 Jul;6(11 Suppl):S580-S590. Ricci JA, et al. Clin Ther. 2001;23:1245-1259.
Restrict fluid intake
Carry extra clothes in case of wetting accident
Try to urinate on a schedule
Bathroom mapping
Wear dark, baggy clothes to hide wet
spots or wear diapers
Use diapers or other
absorbent products
COPING STRATEGIES
19
² 33.3 million US adults are said to have OAB ² Less than 50% will discuss with healthcare
provider ² Only a minority will be diagnosed and offered
treatment ² A smaller proportion will stay on therapy
Stewart WF et al. World J Urol. 2003;20:327-336. Rovner E, Wein A. Curr Urol Rep. 2002;3:434-438. Milsom I et al. BJU Int. 2001;87:760-766. Benner J et al. J Urol. 2009;181:2591-2598. Rosenberg M et al. Cleve Clinic J Med. 2007;74:S21-S29. Goepel M et al. Eur Urol. 2002;41:234-239. Dmochowski RR et al. Curr Med Res Opin. 2007;23:65-76.
OAB IS PREVALENT, UNDIAGNOSED AND UNDERTREATED
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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The Reality is We Can Do Better in the Identification
and Treatment of OAB
21
The answer is education and communication
Unfortunately, if we don’t understand the disease, we may not identify it
even to refer, let alone treat!!!!!!
WHY IS OAB UNDERDIAGNOSED AND UNDERTREATED?
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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Rosenberg MT. Curr Urol Rep. 2008;9:428-432.Yu YF, et al. Value Health. 2005;8:495-505.
IDENTIFYING OAB TAKES A VILLAGE
23
PATIENTS DON’T DISCUSS BLADDER ISSUES WITH THE PROVIDER
² Embarrassment ² Fear of invasive procedures or need for
surgery ² Perception of lack of available and effective
treatment
Ricci JA, et al. Clin Ther 2001;23:1245–1259. Milsom I, et al. BJU Int 2001;87:760–766. 24
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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² I have had this problem and did not know who to talk to
² My previous doctor told me it was part of aging
² It became a problem only when my diaper overflowed
² I thought it was normal as my sister and mother had this
² You mean going to the bathroom every hour is not normal?
² I am too embarrassed
MacDiarmid S, Rosenberg, M. Curr Med Res Opin. 2005; 21:1413-1421.
WHAT DO PATIENTS SAY?
25
THE UROLOGIST AND THE UROGYNECOLOGIST ROLE IN THE PARTNERSHIP
² Identification and initial evaluation of OAB starts in the office of the PCP
² There is a significant amount of medically related LUTS
² The diagnosis of OAB does not require an extensive or complicated evaluation
Stewart WF, et al. World J Urol. 2003;20:327-336. Darkov T, et al. Pharmacotherapy. 2005;25:511-519. Ailinger RL, et al. J Comm Health Nurs. 2005;22:135-142. Rosenberg M et al. Cleve Clinic J Med. 2007;74:S21-S29. 26
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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POTENTIAL MISCONCEPTIONS IN OAB
² OAB is a natural part of aging ² Diagnosis and treatment of genitourinary
disease is to be determined by a specialist
² Diagnosis and treatment is outside the realm of the PCP setting
MacDiarmid S, Rosenberg, M. Curr Med Res Opin. 2005;21(9):1413-1421. 27
WHAT DO DOCTORS SAY?
² No time ² Treatments are not all that effective ² If it was a problem for the patient, he or she
would bring it up ² Your bladder/penis/kidney won’t kill you, your
heart will, so I need to focus
MacDiarmid S, Rosenberg, M. Curr Med Res Opin. 2005;21(9):1413-1421. 28
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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NOT SO! ² What is the outcome of an elderly patient
falling and breaking a extremity?
² What is one of the primary drivers for nursing home admission?
Brown et al. J Am Geriatr Soc. 2000;48:721-725. 29
Current Thinking Is a Myth
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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REALITIES OF OAB MANAGEMENT
² The PCP is the first line of contact ² Diagnosis and treatment is within the realm of
the PCP setting
² Current treatments offer significant improvement of patient symptoms and patient quality of life
31
What we have here is a
failure to communicate. Initially stated by the Warden in Cool Hand Luke
repeated by Jackie Gleason in Smokey and the Bandit And now just shamelessly used by me for lecturing amusement
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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WHAT DOES THE PCP NEED?
² Keep It Simple
33
WHAT DOES THE PCP NEED?
² Keep It Simple
² Keep It Effective
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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WHAT DOES THE PCP NEED?
² Keep It Simple
² Keep It Effective
² Keep Us From Harming Our Patients
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IT ALL COMES DOWN TO “NORMAL”
² How many times a day does a normal person need to urinate?
² What is the normal volume of urine voided per micturition?
² Is it normal for older people to get up during the night to use the bathroom?
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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What are the normal functions of the bladder?
37
² Normal Function - Storage capacity (300 – 500 ml of fluid)
• Adequate low pressure urinary storage (bladder) • Adequate outlet resistance (sphincter)
- Empty to completion (minimal residual) • Adequate bladder contraction • Absence of outlet obstruction
² Abnormal Function (failure to store or empty) - Voiding frequently small amounts - Uncontrollable urge (urgency) - Incomplete emptying - Hesitancy, poor stream Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds.
Campbell-Walsh Urology. 9th ed. Philadelphia, PA: W. B. Saunders/Elsevier; 2007:1973-1985.
FUNCTION OF THE BLADDER
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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What are the normal functions of the prostate?
39
² Normal Function - Does not grow (enlarge) into the urethra thereby
allowing unobstructed flow - It is intimately associated with the continence
mechanism - Produces fluid for seminal emission
² Abnormal Function (failure of flow) - Obstruction of urinary flow (“obstruction” “retention”) - Sphincteric damage /usually surgical - (“stress
incontinence”)
Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds. Campbell-Walsh Urology. 9th ed. Philadelphia, PA: W. B. Saunders/Elsevier; 2007:1973-1985.
FUNCTION OF THE PROSTATE
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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LOWER URINARY TRACT SYMPTOMS (LUTS): BLADDER OR PROSTATE?
Storage (bladder) Voiding (prostate) Urgency Hesitancy
Frequency Poor flow/weak stream Nocturia Intermittency
Urge incontinence Straining to void Stress incontinence Terminal dribble Mixed incontinence Prolonged urination
Overflow incontinence Urinary retention
Chapple CR, et al. Eur Urol. 2006;49:651-658. 41
It is all about VOLUME VOIDED
and FLOW
Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496. 42
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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Guess What Happens When You Understand
What is Normal?
43
Guess What Happens When You Understand
What is Normal? ² Your patients will understand what is normal, and
subsequently, what is abnormal
44
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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Guess What Happens When You Understand
What is Normal? ² Your patients will understand what is normal, and
subsequently, what is abnormal ² You recognize when you have something to fix
45
Treat or Refer
LUTS
Focused HPE UA/PSA Blood Sugar
Desires Treatment?
Watchful Wai@ng
Treat for BPH Con@nue Meds
Assess and Treat OAB/SI
Con@nue Meds
Refer
Unlikely OAB/BPH/SI
Likely OAB/BPH/SI
No
Yes Provisional BPH Provisional OAB/SI
Effec@ve
Ineffec@ve
Effec@ve
Ineffec@ve
Modified from Rosenberg MT, Staskin DR, Kaplan SA, et al. Int J Clin Pract. 2007;61(9):1535-1546.
THE LUTS ALGORITHM Key:
LUTS – lower urinary tract symptoms HPE – history, physical examination UA – urinalysis PSA – prostate specific antigen BPH – benign prostatic hyperplasia OAB – overactive bladder SI – stress incontinence
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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DEFINING LUTS
Frequency • Patient considers that he/she voids too
often by day • Normal is < 8 times per 24 hours
Nocturia • Waking to urinate during sleep hours • Considered a clinical problem if
frequency is greater than twice a night
Urgency • Sudden compelling desire to pass urine that is difficult to defer
UUI • Involuntary leakage accompanied by, or immediately preceded by, urgency
OAB “Wet” • OAB with UUI
OAB “Dry” • OAB without UUI
Warning Time • Time from first sensation of urgency to voiding
Abrams P, et al. Neurourol Urodyn. 2002;21:167-78; Wein A, et al. J Urol. 2006;175:S5-10; Zinner N, et al. Int J Clin Pract. 2006;60:119-26; Wein AJ. Am J Manag Care. 2000;6:S559-64.
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SIMPLE QUESTIONS THE PCP CAN ASK
Abrams P, et al. Neurourol Urodyn. 2002;21:167-78; Wein A, et al. J Urol. 2006;175:S5-10;Zinner N, et al. Int J Clin Pract. 2006;60:119-26; Wein AJ. Am J Manag Care. 2000;6:S559-64.
² Do you have a sudden urge to void and can barely make it to the bathroom?
² Do you wear a pad or diaper? ² Can you sit through a movie without going to
the bathroom? ² Do you leak urine? ² Do you get up at night?
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OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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THE EVALUATION OF LUTS
² Medical and surgical history ² Medications ² Focused physical examination ² Voiding diary ² Labs ² Urodynamics, cystoscopy, and diagnostic
renal and bladder ultrasound not necessary in initial workup of uncomplicated patients
49 Gormley EA, et al. American Urological Association (AUA) Guideline. AUA Web site. 2012. http://www.auanet.org/content/media/OAB_guideline.pdf. Accessed March 21, 2014.
EXAMPLES IN THE MEDICAL AND SURGICAL HISTORY THAT MAY CAUSE LUTS
² Diabetes (new onset or poorly controlled) - Causing polyuria/polydipsia
² Congestive heart failure - Nighttime fluid mobilization
² Recent Surgery - Catheterization during surgery, immobilization,
constipation from pain medications
A recent onset of the symptoms may provide a clue to the etiology
50
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
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MEDICATIONS AS A CAUSE OF LUTS
Sedatives Confusion, secondary incontinence
Alcohol, Caffeine, Diuretics Diuresis
Anticholinergics Impair contractility, voiding difficulty, overflow incontinence
α – Agonists Increased outlet resistance, voiding difficulty
ß - Blockers Decreased urethral closure, stress incontinence
Calcium-Channel Blockers Reduce bladder smooth muscle contractility
ACE Inhibitors Induce cough, stress urinary incontinence
First generation antihistamines
Increase outlet resistance
Cholinesterase inhibitors Precipitate urge incontinence
Opioids Direct effect, constipation
Wyman JF, et al. Int I Clin Pract. 2009;63:1177-1191. Newman DK. Nurse Pract. 2009;34:33-45. 51
THE FOCUSED PHYSICAL EXAMINATION
² Abdominal – Tenderness, masses, distension
² Neurological – Mental and ambulatory status, neuromuscular function
² Genitourinary – Meatus and testis – Vaginal mucosal integrity, urethral mobility, bladder
prolapse ² Rectal
– Tone – Prostate size, shape, nodules and consistency
Rosenberg MT, Newman DK, Tallman CT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29. 52
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LABORATORY TESTS
² Urinalysis – Infection, blood – The urine is not an adequate screener for diabetes since the blood
sugar must be above 180 mg/dl before it spills into the urine
² A random or fasting blood sugar – Diabetes
² Prostate specific antigen – Prostate specific not cancer specific but can be used in screening – Excellent as a surrogate marker for prostate size
§ PSA is more accurate than a DRE when estimating prostate size § A PSA of 1.5 ng/ml equates to a prostate volume of at least 30
grams(ml)
Rosenberg MT, Staskin DR, Kaplan SA, et al. Int J Clin Pract. 2007;61,9,1535-1546. Bosch J, et al. Eur Urol. 2004;46:753-759 Roerborn CG, et al. Urology. 1999;53;381-9. 53
THE PURPOSE OF THE VOIDING DIARY
² Identifies voiding frequency and voided volume ² Differentiates behavioral vs LUTS pathology
- Voiding frequently § excessive volume(behavioral) § small amounts as a result of always being in a rush (behavioral) § small amounts (OAB)
² Alerts patients to habits /opportunities to modify ² Can monitor effect of treatment
Wyman JF, et al. Int J Clin Pract. 2009; 63(8):1177-91 54
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THE POST VOID RESIDUAL (PVR) IS ONLY NEEDED IN SELECT PATIENTS
² The fear of patients going into retention when treated for OAB leaves many patients untreated
² If PVR residual is less than 50 ml, causing retention when treating OAB is extremely unlikely - FACT: most PCPs will not have bladder scanner and will not
want to catheterize a patient - FACT: most PCPs will have access to a ultrasound unit and
can order a post void residual
² Use common sense, if you are treating the patient for voiding too frequently (OAB) and they have not voided in 6 – 8 hours or have a sense to void but cannot, have them contact you
Rosenberg MT. Curr Opin Urol. 2008;9(6):428-32. Rosenberg MT, Staskin DR, Kaplan SA, et al. Int J Clin Pract. 2007;61(9):1535-1546. 55
INDICATIONS FOR REFERRAL
² History of recurrent urinary tract infections or other infection
² Pelvic irradiation ² Microscopic or gross hematuria ² Prior genitourinary surgery ² Elevated prostate-specific antigen ² Abnormal genital exam ² Suspicion of neurological cause of symptoms ² Meatal stenosis ² History of genitourinary trauma ² Pelvic pain ² Uncertain diagnosis or patient choice
Rosenberg MT, Staskin DR, Kaplan SA, et al. Int J Clin Pract. 2007;61(9),1535-1546 56
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TREATMENT NOW CAN BE EMPIRIC
² No identifiable etiology ² No reversible causes ² Is patient bothered enough for treatment?
- No, watchful waiting - Yes, consider algorithm
§ Weak flow – think Prostate § Poor voiding volumes – think Bladder § Incontinence – think Bladder/Outlet
Rosenberg MT. Cur Uro 2008;9:428–432. 57
Treat or Refer
LUTS
Focused HPE UA/PSA Blood Sugar
Desires Treatment?
Watchful Wai@ng
Treat for BPH Con@nue Meds
Assess and Treat OAB/SI
Con@nue Meds
Refer
Unlikely OAB/BPH/SI
Likely OAB/BPH/SI
No
Yes Provisional BPH Provisional OAB/SI
Effec@ve
Ineffec@ve
Effec@ve
Ineffec@ve
Modified from Rosenberg MT, Staskin DR, Kaplan SA, et al. Int J Clin Pract. 2007;61(9):1535-1546.
THE MALE (OR PROSTATE) DILEMMA
Key: LUTS – lower urinary tract symptoms HPE – history, physical examination UA – urinalysis PSA – prostate specific antigen BPH – benign prostatic hyperplasia OAB – overactive bladder SI – stress incontinence
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TREATMENT GUIDELINES FOR OAB
Kirby M, et al. Int J Clin Pract. 2006;60:1263-1271.Burgio K, et al. J Am Geriatr Soc. 2000;48:370-374 .
² Behavioral treatment ² Pharmacologic management ² Referral for specialist management/surgery
59
Gormley EA, et al. American Urological Association (AUA) Guideline. AUA Web site. 2012. http://www.auanet.org/content/media/OAB_guideline.pdf. Accessed March 21, 2014.
BEHAVIORAL THERAPY FOR OAB
Behavioral Therapy for OAB
Bladder training
Educa:on reinforcement
Pelvic floor exercises
Biofeedback
Diaries
Timed voiding
Fluid/Dietary management
No matter what the treatment course, behavioral modification should be offered to every patient
Soda T, et al. J Urol. 2010; 184: 1000-1004 60
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HABIT CHANGES: MANAGING BLADDER HEALTH
Technique
Lifestyle Modification
Diet, fluid, bowel, and weight management Smoking cessation
Timed/ Prompted Voiding
Urination at a fixed interval that avoids the symptom Useful for urgency and urinary incontinence not associated with frequency Good option in patients with cognitive impairment
Wyman JF, et al. Int J Clin Pract. 2009;63:1177-91. Wagg AS, et al. BJU Int. 2007;99:502-9. Lucas MG, et al. Eur Urol 2012;62(6):1130-42.
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HOW TO PERFORM PELVIC FLOOR MUSCLE EXERCISES
² Explain location of perineal muscles (anal area)
² Contract perineal muscles, squeezing upward through the pelvis
² Sit or stand with your legs apart, don’t hold your breath ² Hold the contraction for 10 seconds, then gradually relax ² Repeat at least 5 times, increase to 30-40 per day in
groups of 10 ² Relaxation is as important as contraction for muscle
rehabilitation
² Use exercises to control symptoms - eg, during urge episode, not during urination
Harv Womens Health Watch. www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2011/ January/how-to-perform-kegel-exercises.
The exercises can be performed anywhere 62
OAB Made Simple for the Primary Care Provider (PCP): How to Identify, When to Treat and When to Refer
NACE – Emerging Challenges in Primary Care: 2014 OAB - 32
–100
–80
–60
–40
–20
0
Mea
n R
educ
tion
in U
I, %
Behavioral Therapy
Combined Therapy
Drug Therapy
Combined Therapy
P < .05 P = .001
–57.5%
–88.5%
–72.7%
–84.3%
ADDITIVE EFFECT OF COMBINING BEHAVIORAL AND DRUG THERAPY
Burgio KL, et al. J Am Geriatr Soc. 2000;48:370-374. 63
PHARMACOLOGIC MANAGEMENT
² 8 antimuscarinics, 6 are oral and 2 are topical
² 1 beta-3 adrenergic agonist ² Choice is based of efficacy, dose flexibility,
adverse event profiles, drug interactions and patient preference
² Trying several medications before referral is appropriate
64
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Antimuscarinics ACH
NE
M3 muscarinic receptor
Detrusor smooth muscle
(relaxation) Norepinephrine
β3 AR
β3 agonist
–
+
Acetylcholine
(contraction)
RECEPTOR PATHWAYS FOR OAB TREATMENT
Takeda M, et al. J Pharmacol Sci. 2010;2110:121-127. Fowler CJ, et al. Nat Rev Neurosci. 2008;8:453-466. 65
ANTIMUSCARINICS – IMMEDIATE RELEASE
Drug Brand Name Dose Dosing Oxybutynin IR Ditropan 5 mg 1 – 3 times per
day Tolterodine IR Detrol 1 -2 mg Twice per day Trospium Chloride Sanctura 20 mg Twice per day
Physcians’ Desk Reference. 64st ed. Montvale, NJ: Thomson PDR; 2010. 66
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ANTIMUSCARINICS – EXTENDED RELEASE extended release medications have a better tolerability than their
immediate release counterparts
Drug Brand Name Dose Dosing Darifenacin Enablex 7.5 mg, 15 mg Daily Fesoterodine Toviaz 4 mg, 8 mg Daily Oxybutynin ER Ditropan XL 5 – 30 mg Daily Oxybutynin TDS Oxytrol 3.9 mg Twice per week Oxybutynin 10% gel
Gelnique 100 mg Daily
Solifenacin Vesicare 5 mg, 10 mg Daily Tolterodine ER Detrol LA 2, 4mg Daily Trospium Chloride Sanctura XR 60 mg Daily
Physcians’ Desk Reference. 64st ed. Montvale, NJ: Thomson PDR; 2010. 67
COMMON SIDE EFFECTS OF ANTIMUSCARINICS
² Dry Mouth ² Constipation ² Headaches ² Blurred vision
Clinicians should manage constipation and dry mouth before abandoning effective antimuscarinic therapy. Balance of efficacy and tolerability should be considered and discussed with each patient.
Steers WD. Urol Clin North Am. 2006;33:475-482. Erdam N, et al. Am J. Med 2006;119(suppl 1):29-36. Gormley EA, et al. American Urological Association (AUA) Guideline. AUA Web site. 2012. http://www.auanet.org/content/media/OAB_guideline.pdf. Accessed March 21, 2014. 68
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CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS FOR ANTIMUSCARINICS
² Contraindications- - Urinary or gastric retention - Uncontrolled narrow-angle glaucoma
² Warnings & Precautions – - Angioedema of face, lips, tongue and/or larynx - Clinically significant bladder outlet obstruction - Decreased gastrointestinal motility - Treated narrow angle glaucoma - May have CNS effects i.e., somnolence - Use with caution in patients with myasthenia
gravis Physicians’ Desk Reference. 64st ed. Montvale, NJ: Thomson PDR; 2010. Oelke M, et al. Eur Urol. 2013;64(1):118-140. 69
BETA-3 ADRENERGIC AGENTS
Drug Brand Name Dose Dosing Mirabegron Myrbetriq 25 mg, 50 mg Daily
Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 70
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COMMON SIDE EFFECTS OF MIRABEGRON
² Hypertension ² Nasopharyngitis ² Urinary Tract Infections ² Headaches
Balance of efficacy and tolerability should be considered and discussed with each patient.
Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 71
CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS FOR MIRABEGRON
² Contraindications – NONE ² Precautions & Warnings –
- Not recommended for use in severe uncontrolled hypertensive patients
- Use with caution in patients with urinary retention or bladder outlet obstruction
- Use with caution in patients taking antimuscarinic drugs for overactive bladder
- Caution with use in patients taking drugs metabolized by CYP2D6 as mirabegron is a moderate inhibitor of CYP2D6
Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 72
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FOLLOW UP ON THE PATIENT TREATED FOR OAB
² Review the patient after 2 – 4 weeks - Be prepared to titrate as studies show > 50 % will
increase dose if given the option - Be prepared to try different agent or class
² Consider checking PVR to ensure volume not increasing significantly in the complex patient - Studies on medication usage in males show safety
and minimal increase in post void residual over time of follow up
- The risk of urinary retention (although low) is highest during the first 30 days of treatment
Chapple CG, Rosenberg MT, Brenes FJ. Brit J Urol. 2009;104(7):960-7. Rosenberg MT, Staskin DR, Kaplan SA, et al. Int J Clin Pract. 2007;61(9):1535-1546. Martin-Merino E, et al. J Urol. 2009; 182(4):1442-8. Rosenberg M, Newman DK, Tallman CT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29. Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 73
HIGH DISCONTINUATION RATE FOR PATIENTS ON OAB THERAPY
*Cumulative incidence of discontinuation was determined using the Kaplan-Meier method.
Gopal M, et al. Obstet Gynecol. 2008;112:1311-1318.
Study Design: UK study. Overall drug discontinuation for all women prescribed anticholinergic medications (N=29,369). Unadjusted cumulative incidence of discontinuation (95% CI).
Months to Discontinuation
Dis
cont
inua
tion
Rat
e (%
) Fr
om
Ant
icho
liner
gics
for
OA
B (9
5% C
I)*
Adapted from Gopal et al.
74
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IMPROVING PATIENT ADHERENCE BY ADDRESSING EXPECTATIONS
² Effects on urgency ² Limiting incontinence ² Decreasing nocturia ² Improved quality of life ² Tolerability of medication
Rosenberg MT. Cur Uro 2008, 9:428–432. DeCastro J, et al. Am J Med. 2008;121:S27-S33. 75
OPTIONS FOR THE UNSATISFIED PATIENT
² Sacral Nerve Stimulation ² Percutaneous Tibial Nerve Stimulation ² Onabotulinum Toxin A
Gormley EA, et al. American Urological Association (AUA) Guideline. AUA Web site. 2012. http://www.auanet.org/content/media/OAB_guideline.pdf. Accessed March 21, 2014
76
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TAKE HOME MESSAGE
² Overactive bladder doesn’t take your life — it steals it from you
² The untreated 85% is in the PCP office ² OAB can be diagnosed and treated in the
primary care office efficiently, effectively and safely
77
• Be willing to discuss his/her symptoms
• Make recommended lifestyle changes
• Adhere to prescribed medication
• Diagnose OAB
• Set realistic patient expectations/goals • Provide initial treatment of OAB • Refer appropriate patients
• Treat refractory or complicated OAB • Educate PCPs to better manage OAB
Rosenberg MT. Curr Urol Rep. 2008;9:428-432.Yu YF, et al. Value Health. 2005;8:495-505.
TREATING OAB TAKES A VILLAGE
78
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POST-TEST QUESTIONS OAB
79
1. OAB is less prevalent than chronic sinusitis 2. An 80 year old patient should know that it is normal
to get up several times per night to empty their bladder
3. At least 50% of symptomatic patients are offered medical treatment for their symptoms of OAB
4. Understanding volume voided is a helpful point of distinction when evaluating LUTS symptoms for OAB
POST-TEST QUESTION 1 OAB
Mary is a 80 year old patient who admits during her yearly exam that she wears a diaper “just in case” she can’t make it to the bathroom in time. Which of
the following is true regarding OAB?
80
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When you tell Mary she may have OAB, she asks about the evaluation. Which is test is not
recommended by the AUA in the initial evaluation of OAB in the uncomplicated patient?
1. Urinalysis 2. Bladder ultrasound 3. Voiding diary 4. Genital exam
POST-TEST QUESTION 2 OAB
81
After an appropriate evaluation you discuss treatment options with Mary. Which of the following statements regarding
expectations of OAB therapy is false?
1. It is appropriate to tell the patient that urinary urgency may be reduced with the correct therapy
2. It may take titration or changes in the pharmacologic therapy before an adequate response in attained
3. Therapeutic efficacy is enhanced with the combination of behavioral therapy and pharmacologic therapy as opposed to either alone
4. The risk of urinary retention in the male increases with longer duration on pharmacologic therapy for OAB
POST-TEST QUESTION 3 OAB
82
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Mary is very interested in efficacy but wants to limit side effects. Which of the following is true regarding OAB
pharmacologic therapy with either an antimuscarinic or a beta 3 adenergic agonist?
1. Both classes have a high rate of dry mouth 2. The efficacy of the antimuscarinic medications are higher
than the beta 3 adrenergic agonist medication 3. The efficacy of the beta 3 adrenergic agonist medication is
higher than the antimuscarinic medication 4. One agent blocks contraction while the other stimulates
relaxation
POST-TEST QUESTION 4 OAB
83
On a scale of 1 to 5, please rate how confident you would be in the diagnosis and management
of a patient with OAB.
1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident
84
POST-TEST QUESTION 5 OAB
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POST-TEST QUESTION 6 OAB Which of the statements below describes your
approach to diagnosing and treating patients with OAB?
1. I do not diagnose or treat patients with OAB, nor do I plan to this year.
2. I did not diagnose or treat patients with OAB before this course, but as a result of attending this course I’m thinking of managing them now.
3. I do diagnose and treat patients with OAB and I now plan to change my treatment methods based on completing this course.
4. I do diagnose and treat patients with OAB and this course confirmed that I don’t need to change my treatment methods. 85
Faculty
Emerging Challenges In Primary Care: 2014
!
Evaluating and Treating LUTS in the Primary Care Setting
Matt T. Rosenberg, MD Medical Director of Mid-Michigan Health Centers
Jackson, MI Section Editor of
Urology, International Journal of Clinical
Practice
Louis Kuritzky, MD Clinical Assistant
Professor Department of
Community Health & Family Medicine
University of Florida Gainesville, FL
Pamela Ellsworth, MD Professor of Urology
Department of Urology UMass Memorial Medical
Center/University of Massachusetts Medical
School Worcester, MA
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LEARNING OBJECTIVES LUTS
After participating in this educational activity, clinicians should be better able to: 1. Understand that lower urinary tract symptoms in a male
could be caused by medical issues, the bladder or the prostate and that a simple history and physical can help delineate the problem
2. Recognize that erectile dysfunction (ED) and BPH share many of the same co-morbidities.
3. Discuss the different classes of medications available for OAB and BPH
4. Recognize the risk factors for progression of BPH
87
DAVID – 65 Y/O MALE WITH DM
² 65 yr old obese male with type 2 DM ² At the encouragement of his wife he admits that he has
some issues“down there” - Urinary urgency, a poor stream, frequency and nocturia - Poor erections (“not hard enough”) - Symptoms for many years that he thought was a natural part
of aging ² Meds – metformin, lisinopril and atorvastatin ² Physical exam – contributory only for obesity ² Labs
- HgA1C – 6.7% - PSA – 2.8 ng/dl - Urinalysis - normal
88
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WHAT ARE THE CLUES?
² 65 yr old obese male with type 2 DM ² At the encouragement of his wife he admits that he has
some issues“down there” - Urinary urgency, a poor stream, frequency and nocturia - Poor erections (“not firm enough”) - Symptoms for many years that he thought was a natural part
of aging ² Meds – metformin, lisinopril and atrovastatin ² Physical exam – contributory only for obesity ² Labs
- HgA1C – 6.7% - PSA – 2.8 ng/ml - Urinalysis - normal
89
FUNCTION OF THE PROSTATE
NORMAL FUNCTION ABNORMAL FUNCTION
² Produces fluid for seminal emission
² Does not grow into the urethra thereby allowing unobstructed flow
² Obstruction of urinary flow
² Poor function seen as failure to void
90 Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.
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NATURAL HISTORY OF PROSTATE GROWTH
² A common condition as men age - By sixth decade: > 50% have some degree of hyperplasia - By eighth decade: > 90% will have hyperplasia
² ±10% will require surgical or medical intervention ² A 55-year–old man who is experiencing symptoms,
has a PSA of 1.5 ng/ml and a 30 mL prostate volume can expect his prostate to approximately double in size over the next 15 years.
91 McVary KT, et al. J Urol. 2011;185(5):1793-1803. Roehrborn C, et al. J Urol. 2000;163(1):13–20.
RISK EVALUATION OF BPH-LUTS PROGRESSION
Five risk factors 1. Total prostate volume ≥31 mL 2. PSA ≥1.6 ng/mL 3. Age ≥62 Not usually evaluated by the PCP 4. Qmax <10.6 mL/s 5. PVR ≥39 mL
92
PVR, post-void residual; Qmax, maximum flow rate. Crawford ED, et al. Urology. 2006;175(4):1422-1427. Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
Baseline Factors as Predictors
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ASSESSMENT: DRE VS. PSA
² There is a strong and clinically useful relationship between serum PSA and prostate volume.
² Digital rectal examination (DRE) is quite inaccurate in estimating the correct prostate size when compared to either transrectal ultrasound (TRUS) or other imaging modalities.
93 Roehrborn CG. Int J Impot Res. 2008;20 Suppl 3:S19-26.
FUNCTION OF THE BLADDER
NORMAL FUNCTION ABNORMAL FUNCTION
² Storage capacity of 300 – 500 ml of fluid
² Empty to completion after a gentle urge
² Voiding frequently of small amounts (less than capacity)
² Uncontrollable urge (urgency) to empty
² Incomplete emptying ² Poor function seen
as failure to store or empty
94 Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.
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DEFINITION OF OAB
OAB is syndrome or symptom complex defined as: “Urgency, with or without urgency incontinence, usually with frequency and nocturia”
Urgency is the key symptom of OAB
Urgency is defined as “a sudden compelling desire to void, which is difficult to defer”
Abrams P, et al. Urology. 2003;61:37-49. Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546. 95
USING SYMPTOMS TO DISTINGUISH THE ORIGIN OF THE PROBLEM
96
Urine Storage
Urgency
Frequency
Urgency incontinence
Nocturia
Urine Voiding
Hesitancy
Weak stream
Intermittent
Straining
Kapoor A. Can J Urol. 2012;19 Suppl 1:10-17. Abrams P, et al. Neurourol Urodyn. 2002;21:167-178.
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DIFFERENTIATING THE ETIOLOGY OF LUTS?
² Weak flow – think prostate ² Voiding small amounts – think bladder ² Leakage of urine – think bladder or sphincter ² Good flow, normal volume – think too much
fluid production and evaluate accordingly
97
It is all about volume and flow
Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.
OAB AND BPH CAN COEXIST
98
BPH OAB
Rosenberg MT, et al. Int J Clin Pract. 2007;61,9,1535-1546.
LUTS
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BACK TO DAVID
Upon questioning David’s symptoms are consistent with BPH-LUTS. Which would you
consider to be the three most prevalent co-morbid conditions associated with BPH-LUTS?
1. Heart disease, diabetes, arthritis 2. Hypertension, high cholesterol, ED 3. Diabetes, pain, depression 4. Digestive tract disorders, allergies, arthritis
99
COMMON COMORBIDITIES IN BPH-LUTS
Comorbidity with BPH-LUTS (N = 6,909)
%
Hypertension 53 High cholesterol 45 Erectile or other sexual dysfunction
36
Digestive tract disorder 21 Arthritis 20 Heart disease/Heart failure 18 Diabetes 17 Depression/Anxiety/Sleep disorder
16
Allergies/cold/flu/congestion 15 General pain/inflammation 11
100 Roehrborn CG, et al. BJU Int. 2007;100(4):813-819.
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Lee RK and Chung D, et al. BJU Int. 2012;110(4):540-545. Parsons JK. Curr Bladder Dysfunct Rep. 2010;5(4):212-218. Robert G. Curr Opin Urol. 2011;21(1):42-48. Roehrborn CG. BJU Int. 2006;97(S2):7-11. Rosen R. Eur Urol. 2003;44(6):637-649. Shabsigh R, et al. BMC Urol. 2010;10:18. Woo HH, et al. Med J Aust. 2011;195(1):34-39.
LINKING LUTS-BPH AND ED 101 LUTS-BPH
Risk Factors Comorbidities • Increasing LUTS severity
or symptom worsening • Increasing serum
dihydrotestosterone • Enlarged prostate; >30 mL • Inflammation • Elevated IPSS • Refractory to treatment • Poor flow • Genetics • History of AUR • High waist
circumference • Increasing age • PSA >1.5 ng/dL • PVR >50 mL • Increasing bother • Reduced physical activity
• Cardiovascular disease
• Diabetes/Disrupted glucose homeostasis
• Erectile dysfunction • Metabolic syndrome • Obesity
ED Risk Factors Comorbidities
• Increasing age • Smoking • High waist
circumference
• Cardiovascular disease
• Depression • Diabetes • Hypercholesterolemia • Lower urinary tract
symptoms • Metabolic syndrome • Obesity
22.3
19.2
15.3
21.1
18.3
13.2
18.9
15.8
10.3
14.912.4
7.5
0
10
20
30
50-59 Years 60-69 Years 70-79 Years
NoMildModerateSevere
LUTS-BPH AND ED AND DIRECTLY RELATED
102
N=10,636 men who had been sexually active within the last 4 weeks. IIEF, International Index of Erectile Function. McVary KT. BJU Int. 2006;97:23-28.
Worse Erectile
Function
Better Erectile
Function Age Effect
Mea
n IIE
F Er
ectil
e
Func
tion
Dom
ain
LUTS Effect LUTS Effect LUTS Effect
LUTS Severity
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BPH-LUTS AND ED COMMON PATHOPHYSIOLOGIC MECHANISMS
103 cGMP, cyclic guanosine monophosphate; NO, nitric oxide; ROCK, Rho-associated protein kinase. Gacci M, et al. Eur Urol. 2011;60(4):809-825.
Reduced NO–cGMP signaling
Increased RhoA–ROCK signaling
Autonomic hyperactivity
Pelvic atherosclerosis
FUNCTIONAL CONSEQUENCES AT TISSUE LEVEL
(corpora cavernosa, prostate, urethra, and
bladder functional alterations)
• Reduced function of nerves and endothelium
• Altered smooth muscle relaxation or contractility
• Arterial insufficiency, reduced blood flow, and hypoxia-related tissue damage
BPH-LUTS ED
Comorbidities Hypertension, Metabolic Syndrome, Diabetes, etc.
Chronic inflammation Steroid hormone unbalance
² Lower Urinary Tract Symptoms (LUTS) can be of urologic origin, which includes the prostate and bladder, or can be medical in nature
² A comprehensive history, physical and lab evaluation will generally provide the needed clues
WHAT TO KEEP IN MIND IN THE EVALUATION OF LUTS
Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. 104
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EXAMPLES IN THE MEDICAL OR SURGICAL HISTORY THAT CAN CAUSE OR CONFOUND LUTS
² Poorly controlled diabetes causing polyuria/polydipsia
² Antihypertensive diuretics can frequency and urgency whereas some cold medications (e.g., α-agonists) can cause urinary retention or hesitancy
² Nocturia associated with CHF ² Recent surgery causing immobilization or
constipation ² Poor urinary hygiene
105
Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Burgio KL, et al. Int J Clin Pract. 2013;67(6):495-504.
The temporal relationship may offer a clue
A FOCUSED PHYSICAL EXAMINATION
² Abdominal – Tenderness, masses, distension
² Neurological – Mental and ambulatory status, neuromuscular
function
² Genitourinary – Meatus and testes
² Rectal – Tone – Prostate size, shape, nodules and consistency
106 Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496.
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LABORATORY TESTS ² Urinalysis
- Infection, blood, crystals - The urine is not an adequate screener for diabetes since the
blood sugar must be above 180 mg/dl before it spills into the urine
² A random or fasting blood sugar - Diabetes
² Prostate specific antigen - Prostate specific not cancer specific but can be used in
screening - Excellent as a surrogate marker for prostate size
§ PSA is more accurate than a DRE when estimating prostate size § A PSA of 1.5 ng/ml equates to a prostate volume of at least 30
grams(ml)
107 Rosenberg MT, et al. Int J Clin Pract. 2007;61,9,1535-1546. Bosch J, et al. Eur Urol. 2004;46(6):753-759. Roerborn CG, et al. Urology. 1999;53;581-589.
OPTIONAL TESTS
² International Prostate Symptom Score (IPSS)
² Voiding Diary
² Post Void Residual (PVR)
² Urine Flow Rate (Qmax)
108 Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496.
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INTERNATIONAL PROSTATE SYMPTOM SCORE (IPSS)
109 McVary KT, et al. J Urol. 2011;185(5):1793-1803. Available at http://www.urospec.com/uro/Forms/ipss.pdf
THE PURPOSE OF THE VOIDING DIARY
² Identifies voiding frequency and voided volume ² Differentiates behavioral vs LUTS pathology
- Voiding frequently § excessive volume(behavioral) § small amounts as a result of always being in a rush
(behavioral) § small amounts (OAB)
² Alerts patients to habits /opportunities to modify ² Can monitor effect of treatment
Wyman JF, et al. Int J Clin Pract. 2009; 63(8):1177-91 110
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POST-VOID RESIDUAL
² FACTS - 50 ml or less represents adequate emptying
- 200 ml or more is consistent with clinically significant inadequate emptying
² WHEN TO CHECK - Clinical suspicion
- Refractory to therapy for BPH
- Prior to pharmacologic treatment of OAB
111 Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-96.. AUA Guidelines available at: http://www.auanet.org/education/guidelines/benign-prostatic-hyperplasia.cfm .
URINE FLOW RATE
112
It is all about the “arc” of the void
Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496.
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LUTS AND INDICATIONS FOR REFERRAL
² Suspicion of neurologic cause of symptoms ² History of recurrent UTI or other infection ² Findings or suspicion of urinary retention ² Abnormal prostate exam (nodules) ² Microscopic or gross hematuria ² History of genitourinary trauma ² Prior genitourinary surgery ² Uncertain diagnosis ² Meatal stenosis ² Elevated PSA ² Pelvic pain
113 Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.
THE NEXT STEP
114 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
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THE NEXT STEP: STEP 1
115 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
STEP 1: INFORMED SURVEILLANCE .
If the patient has symptoms but no bother and no complications
Patients who opt for this may benefit from:
² Education and reassurance ² Lifestyle changes (exercise, weight
management) ² Fluid management ² Bladder training: timed and complete voiding ² Medication modification ² Validation: LUTS:BPH significant QoL impact
116 Yap T, et al. Curr Opin Urol. 2010;20:20-27. Burgio KL, et al. Int J Clin Pract. 2013;67(6):495-504.
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THE NEXT STEP: STEP 2
117 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
RATIONALE FOR ALPHA-BLOCKER OR PDE5I THERAPY
118
Alpha-blockers
PDE5is
Dynamic component Rapidly relieve symptoms by
inhibiting contraction of prostate smooth muscle
Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496. Roehrborn CG. Rev Urol. 2009;11(Suppl 1):S1-8. Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):1595-605.
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STEP 2: ALPHA BLOCKERS (AB)
Single medication therapy with an AB is appropriate
for the symptomatic patient who has identified bother and has a PSA of < 1.5 ng/ml
² Generally fast acting, relieving symptoms
within hours ² Does not affect progression of prostate
growth
119 Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496.
STEP 2: ALPHA – BLOCKERS Non - Uroselective Uroselective
Terazosin 1, 2, 5, 10 mg daily Tamsulosin 0.4 mg daily
Doxazosin 1, ,2, 4, 8 mg daily Alfuzosin 10 mg daily
Silodosin 8 mg daily
120
Potential side effects (decreased incidence with uroselective agents) ² Asthenia, fatigue, dizziness ² Postural hypotension ² Congestion, rhinitis, cough ² Abnormal ejaculation ² Edema ² Headache
Physician’s Desk Reference, 64 ed. Montvale, NJ:Thomson PDR; 2010. Lepor H. Rev Urol. 2007;9:181-190. Roehrborn CG. Rev Urol. 2009;11(Suppl 1):S1-8.
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STEP 2: PHOSPHODIESTERASE 5
INHIBITORS(PDE5I)
² It is believed that the PDE5i increase the signaling of the
NO/cGMP pathway, which reduces smooth muscle tone in the lower urinary tract
² It is not believed that use of a PDE5i will reduce progression of prostate growth
121 Roehrborn CG, et al. J Urol. 2008;180(4):1228-1234. Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
Monotherapy with a PDE5-I is appropriate for the symptomatic patient who has identified bother and has a PSA of < 1.5 ng/ml. The potential favorable impact of
this therapy on male sexual function should be considered
STEP 2: PHOSPHODIESTERASE TYPE 5 INHIBITORS
Medication Dose Indication
Tadalafil 2.5 mg per day ED
Tadalafil 5.0 mg per day BPH and ED
Common side effects: headache, back pain, myalgia, dizziness, flushing and dyspepsia. Contraindicated in patients who use nitrates. Patients should not use tadalafil if sex is inadvisable due to cardiovascular status.
122 Roehrborn CG, et al. J Urol. 2008;180(4):1228-1234. Oelke M, et al. Eur Urol. 2013;64(1):118-140. Nehra A, et al. Mayo Clin Proc. 2012;87(8):766-778. Cialis (product insert). Indianapolis, IN; Eli Lilly and Company, 2011.
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PDE-5 Inhibitors
Pharmacokinetics
1. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020895s036lbl.pdf); 2. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021400s011lbl.pdf); 3. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021368s012lbl.pdf); 4. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202276s001lbl.pdf);
Parameters Available doses, mg Tmax, hours T½, hours
Sildenafil1 25, 50, 100 1 4
Vardenafil2 5, 10, 20 1 4-5
Tadalafil3 2.5, 5, 10, 20 2 17.5
Avanafil4 50, 100, 200 0.5-0.75 5
123
TADALAFIL IN BPH-LUTS ONCE-DAILY DOSING
N=427 men who completed a 12-week, placebo-controlled, dose-finding study assessing once-daily tadalafil for BPH-LUTS. HRQoL, health-related quality of life. Donatucci CF, et al. BJU Int. 2011;107:1110-1116.
Tot
al IP
SS C
hang
e F
rom
Bas
elin
e
IPSS
-HR
QoL
Cha
nge
Fr
om B
asel
ine
124
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ADVERSE EVENTS WITH TADALAFIL ONCE-DAILY VS ON-DEMAND DOSING
Adverse Event 5 mg
Once Dailya N=238
5/10/20 mg On Demandb
N=1173
Headache 2.1% 15.8%
Dyspepsia 3.8% 11.8%
Nasopharyngitis 5.9% 11.4%
Back pain 5.0% 8.2%
Influenza-like illness 2.5% 3.2%
Discontinuation due to adverse events possibly related to the study drug
0.8% 3.1%
a24-month extension trial of tadalafil 5 mg once daily for erectile dysfunction. bPooled 24-month extension trial data from five 8- or 12-week studies examining on-demand tadalafil for erectile dysfunction. Montorsi F, et al. Eur Urol. 2004;45:339-344; Porst H, et al. J Sex Med. 2008;5;2160-2169. 125
WHAT ABOUT PDE5IS AND ABS?
² Recent studies show benefit of PDE5i/AB combination therapy over AB monotherapy - Improvement in IPSS - No added benefit in urodynamic parameters
² Concerns over hemodynamics effects of combination therapy not demonstrated
126 Bechara A, et al. J Sex Med. 2008;5:2170–2178. Giuliano F, et al. Urology. 2006;67:1199–1204. Liguori G, et al. J Sex Med. 2009;6:544–552. Kaplan SA, et al. Eur Urol. 2007;51:1717–1723. Gacci M, et al. Eur Urol. 2012;61(5):994-1003.
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PDE-5 INHIBITORS AND Α-BLOCKERS Effects on IPSS, Erectile Dysfunction, and Flow Rate
These studies examined the PDE-5 inhibitors tadalafil, sildenafil, and vardenafil, and the α-blockers alfuzosin and tamsulosin. Gacci M, et al. Eur Urol. 2012;61:994-1003.
Kaplan et al, 2007
Bechara et al, 2008
Liguori et al, 2009
Gacci et al, 2012
Overall
Source IPSS Mean Differences
-6 -4 -2 0 2
Tuncel et al, 2009
α-blocker + PDE-5 inhibitor
α-blocker alone
IIEF Score Mean Differences
0 6 8 10 12
α-blocker + PDE-5 inhibitor
4 2
Qmax Mean Differences
-2 0 2 4 6
α-blocker + PDE-5 inhibitor
α-blocker alone
Compared with α-blockers alone, the combination regimens significantly improved IPSS (P=0.05), IIEF scores (P<0.0001), and Qmax (P<0.0001)
127
THE NEXT STEP: STEP 3A
128 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
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RATIONALE FOR COMBINING AB/PDE5I WITH ANTIMUSCARINIC/BETA - 3
129
Alpha-blockers
PDE5s
Dynamic component Rapidly relieve symptoms
Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496. Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
Antimuscarinics
Blocks contraction of detrusor
Beta 3 Agonists
Facilitates bladder storage
+
STEP 3A: ADDITION OF AN ANTIMUSCARINIC OR BETA-3 AGONIST
If the patient has symptoms of both obstruction and irritation as well as bother
² In multiple studies the addition of an antimuscarinic to an α-blocker was more efficacious in reducing voiding frequency, nocturia, or IPSS compared to α-blockers or placebo alone.
² Not yet studied - β3 agonists+ α-blocker - β3 agonist + PDE5i - Antimuscarinic + PDE5i
130 Oelke M, et al. Eur Urol. 2013;64(1):118-140. Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
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ANTIMUSCARINICS – IMMEDIATE RELEASE
Drug Brand Name Dose Dosing Oxybutynin IR Ditropan 5 mg 1 – 3 times per
day Tolterodine IR Detrol 1 -2 mg Twice per day Trospium Chloride Sanctura 20 mg Twice per day
Physcians’ Desk Reference. 64st ed. Montvale, NJ: Thomson PDR; 2010. 131
ANTIMUSCARINICS – EXTENDED RELEASE
extended release medications have a better tolerability
than their immediate release counterparts Drug Brand Name Dose Dosing Darifenacin Enablex 7.5 mg, 15 mg Daily Fesoterodine Toviaz 4 mg, 8 mg Daily Oxybutynin ER Ditropan XL 5 – 30 mg Daily Oxybutynin TDS Oxytrol 3.9 mg Twice per week Oxybutynin 10% gel
Gelnique 100 mg Daily
Solifenacin Vesicare 5 mg, 10 mg Daily Tolterodine ER Detrol LA 2, 4 mg Daily Trospium Chloride Sanctura XR 60 mg Daily
Physcians’ Desk Reference. 64st ed. Montvale, NJ: Thomson PDR; 2010. 132
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COMMON SIDE EFFECTS OF ANTIMUSCARINICS
² Dry Mouth ² Constipation ² Headaches ² Blurred vision
Clinicians should manage constipation and dry mouth before abandoning effective antimuscarinic therapy. Balance of efficacy and tolerability should be considered and discussed with each patient.
Steers WD. Urol Clin North Am. 2006;33:475-482. Erdam N, et al. Am J. Med 2006;119(suppl 1):29-36. Gormley EA, et al. American Urological Association (AUA) Guideline. AUA Web site. 2012. http://www.auanet.org/content/media/OAB_guideline.pdf. Accessed March 21, 2014.
133
CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS FOR ANTIMUSCARINICS
² Contraindications- - Urinary or gastric retention - Uncontrolled narrow-angle glaucoma
² Warnings & Precautions – - Angioedema of face, lips, tongue and/or larynx - Clinically significant bladder outlet obstruction - Decreased gastrointestinal motility - Treated narrow angle glaucoma - May have CNS effects i.e., somnolence - Use with caution in patients with myasthenia gravis
Physicians’ Desk Reference. 64st ed. Montvale, NJ: Thomson PDR; 2010. Oelke M, et al. Eur Urol. 2013;64(1):118-140. 134
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BETA-3 ADRENERGIC AGONISTS
Drug Brand Name Dose Dosing Mirabegron Myrbetriq 25 mg, 50 mg Daily
Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 135
COMMON SIDE EFFECTS OF MIRABEGRON
² Hypertension ² Nasopharyngitis ² Urinary Tract Infections ² Headaches
Balance of efficacy and tolerability should be considered and discussed with each patient.
Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 136
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CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS FOR MIRABEGRON
² Contraindications – NONE ² Precautions & Warnings –
- Not recommended for use in severe uncontrolled hypertensive patients
- Use with caution in patients with urinary retention or bladder outlet obstruction
- Use with caution in patients taking antimuscarinic drugs for overactive bladder
- Caution with use in patients taking drugs metabolized by CYP2D6 (i.e., metoprolol or desipramine) as mirabegron is a moderate inhibitor of CYP2D6
Myrbetriq™ (mirabegron) prescribing information, Astellas Pharma US, Inc. June 2012. 137
THE NEXT STEP: STEP 3B
138 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
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RATIONALE FOR COMBINING AB/PDE5I WITH 5ARI
139
5-alpha-reductase inhibitors (5ARIs)
Static component Arrest disease progression
Alpha-blockers
PDE5s
Dynamic component Rapidly relieve symptoms
Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496. Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
STEP 3B: ADDING A 5 ALPHA REDUCTASE
INHIBITOR (5ARI)
² Prostate growth may result in symptom progression, AUR and surgery
² Prostate growth is stimulated by dihydrotestosterone (DHT) with is converted from testosterone by the 5-alpha reductase enzyme
² Decreasing DHT may induce prostatic epithelial apoptosis and atrophy which can lead to approximately 18% – 28% reduction in prostate size and approximately a 50% reduction in PSA levels after 6 - 12 months
140 Naslund MJ, et al. Clin Ther. 2007;29(1):17-25. Rosenberg MT, et al. Int J Clin Pract. 2010; 64(4):488-496.
The addition of a 5ARI is appropriate for the symptomatic patient with BPH-LUTS who has identified
bother and has a PSA of 1.5 ng/ml or greater
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5 ARIS
Drug Dosage
Finasteride Dutasteride
5 mg daily 0.5 mg daily
Potential side effects ² Diminished ejaculatory volume ² Erectile dysfunction ² Decreased libido ² Gynecomastia ² Increase risk of high-grade prostate cancer *
* Conflicting data in the literature Physicians’ Desk Reference. 64th ed. Montvale, NJ: Thomson PDR; 2010. Andriole G, et al. J Urol. 2004;172(4 Pt 1):1399-1403. Thompson, IM, et al. N Engl J Med. 2013;369(7):603-610.
141
COMBINATION THERAPY
² Starting with combination therapy may allow immediate symptom relief from the AB or a PDE51 while facilitating prostate reduction from the 5ARI
² Two prolonged studies (MTOPS and CombaT) using a AB and a 5ARI have shown that combination therapy is better than either monotherapy alone
² One 26 week study showed that use of tadalafil with finasteride was better than finasteride alone
142
Crawford ED, et al. Urology. 2006;175:1422-1427. Roehrborn CG, et al. Eur Urol. 2009;55(2): 461-471. Kaplan S. J Urol. 2006;175(1):217-220. Roehrborn CG, et al. 28TH Annual EAU Congress; Milan, Italy; 15-19 March 2013
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α-BLOCKER PLUS 5 ARI OUTPERFORMS MONOTHERAPY
IPSS = Interna@onal Prostate Symptom Score LOCF = last observa@on carried forward
IPSS -‐ Adjusted Mean Change From Baseline (LOCF)
Tamsulosin (n = 1582) Dutasteride (n = 1592) Combina:on (n = 1575)
-‐6.3 P<0.001 Combina:on vs Tamsulosin
P<0.001 Combina:on vs Dutasteride
Roehrborn CG, et al. Eur Urol. 2010;57(1):123-31.
-‐3.8
-‐8
-‐7
-‐6
-‐5
-‐4
-‐3
-‐2
-‐1
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
Treatment month
Chan
ge (u
nits)
-‐5.3
143
PDE5I PLUS 5 ARI OUTPERFORMS MONOTHERAPY
Roehrborn CG, et al. 28TH Annual EAU Congress; Milan, Italy; 15-19 March 2013
IPSS Total Score— LS Mean Changes at 4, 12,and 26 Weeks
144
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EARLY VS DELAYED COMBINATIONS 5-ARI and α-Blocker
aClinical progression, defined as the occurrence of AUR or prostate surgery during the 12 months after first prescription fill. bDelayed combination therapy, initiation of a 5-ARI >30 days and <180 days after initial α-blocker treatment. cEarly combination therapy, initiation of an α-blocker and a 5-ARI on the same day, or a 5-ARI within 30 days of initial α-blocker treatment OR, odds ratio. N=13,551 men ≥50 years of age and treated for BPH-LUTS with a 5-ARI and an α-blocker. Morlock R, et al. Clin Ther. 2013;35:624-633.
Better Outcomes With Delayed Combination Therapyb
Better Outcomes With Early Combination Therapyc
1.0 0.0 3.0 2.0 5.0 4.0 7.0 6.0
Clinical Progressiona
AUR
Surgery
Total Costs
All Patients Patients with PSA values Patients with 1.5< PSA value <10 All Patients Patients with PSA values Patients with 1.5< PSA value <10 All Patients Patients with PSA values Patients with 1.5< PSA value <10 All Patients Patients with PSA values Patients with 1.5< PSA value <10
OR=1.70 OR=1.82
OR=2.33
OR=1.82
OR=1.54 OR=1.96
OR=1.75 OR=2.50
OR=3.45
OR=1.79 OR=1.75
OR=2.63
145
THE NEXT STEP: STEP 4
146 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
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STEP 4: REFERRAL
For the patient with symptoms and bother who is
refractory to therapy
² “Alarm symptoms” or “red flags” ² Failure to respond in a reasonable amount
of time - Alpha blockers, PDE5is, antimuscarinics and β3
agonists should work quickly - 5 ARIs work slowly
147 Rosenberg MT, et al. Current Urology Reports. 2013 Dec;14(6):595-605.
SUMMARY
² The cause of LUTS-BPH can be medical, the prostate or the bladder
² A simple evaluation in the office of the PCP can elicit the cause in most cases
² There appears to be a shared pathophysiology that underlies benign prostatic hyperplasia (BPH) and erectile dysfunction (ED)
² The treatment of LUTS-BPH should occur in a step-wise fashion that depends on symptom severity, sexual function and risk factors
148
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POST-TEST QUESTIONS LUTS
149
Fred presents to the clinic complaining of urgency, frequency and decreased stream. Which of the following
is true regarding his symptom complex ?
1. The cause is always the prostate or bladder 2. Such symptoms are a normal part of aging 3. The source of the symptoms can be prostate,
bladder or other 4. The best way to determine the cause is performing
urodynamics
150
POST-TEST QUESTION 1 LUTS
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In addition to his urinary symptoms, Fred mentions some problems with his “love life”. Which of the
following is true regarding the relationship between Erectile Dysfunction(ED) and Benign Prostatic
Hyperplasia (BPH)? 1. There is no relationship as they occur independent of
each other 2. They are only seen in the elderly male 3. The severity of one is inversely related to the severity
of the other 4. They share many of the same co-morbidities 5. BPH predicts cardiac risk, whereas ED does not
151
POST-TEST QUESTION 2 LUTS
With an appropriate evaluation you diagnose Fred with BPH. He is worried that his problem could get
worse. Which of the following is NOT a risk factor for progression of BPH?
1. Age 2. Urine flow rate (Qmax) 3. Prostate volume 4. Diabetes 5. Post void residual
152
POST-TEST QUESTION 3 LUTS
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Instead of Fred having urinary obstruction you recognize that he has overactive bladder(OAB). Which of the following is/are considered appropriate therapy
for OAB?
1. Alpha blockers 2. Phosphodiesterase 5 inhibitors 3. 5 alpha reductase inhibitors 4. Beta 3 agonists or antimuscarinics
153
POST-TEST QUESTION 4 LUTS
On a scale of 1 to 5, please rate how confident you would be with diagnosing and treating lower
urinary tract symptoms in men.
1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident
154
POST-TEST QUESTION 5 LUTS
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Which of the statements below describes your approach to participating in diagnosing and treating lower urinary tract
symptoms in men? 1. I do not participate in the diagnosis and treatment of lower
urinary tract symptoms in male patients, nor do I plan to this year.
2. I did not participate in the diagnosis and treatment of lower urinary tract symptoms in male patients before this course, but as a result of attending this course I’m thinking of doing this now.
3. I do participate in the diagnosis and treatment of lower urinary tract symptoms in male patients and I now plan to change my treatment methods based on completing this course.
4. I do participate in the diagnosis and treatment of lower urinary tract symptoms in male patients and this course confirmed that I don’t need to change my methods.
155
POST-TEST QUESTION 6 LUTS
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