Approach to Lower Urinary Tract Symptoms (LUTS) in Males Dr Ho Siew Hong Consultant Urologist S H Ho Urology and Laparoscopy Centre Gleneagles Hospital

What is LUTS ? Symptoms described by patient or care-giver 3 groups a. Storage b. Voiding c. Post micturition International Continence Society, American Urological Association, European Urological Association

Symptoms described by patient or care-giver

3 groups a. Storage b. Voiding c. Post micturition

LUTS Storage day time frequency, nocturia, urgency, incontinence Voiding slow, splitting, intermittent, hesistancy, straining, terminal dribbling Post micturition sensation of incomplete voiding, post micturition dribbling

Storage day time frequency, nocturia, urgency, incontinence

Voiding slow, splitting, intermittent, hesistancy, straining, terminal dribbling

Post micturition sensation of incomplete voiding, post micturition dribbling

Causes of LUTS in males Bladder Prostate Urethra Infection Stone Enlargement Stricture Malignancy Neurogenic Drugs

Bladder

Prostate

Urethra

Infection

Stone

Enlargement

Stricture

Malignancy

Neurogenic

Drugs

Anatomy of BPH Normal BPH Prostate Bladder Urethra Hypertrophied detrusor muscle Obstructed urinary flow

Epidemiology of BPH: histological prevalence around the world Adapted from Roehrborn CG, McConnell JD. Etiology, Pathophysiology, Epidemiology, and Natural History of BPH. In: Walsh P, editor. Campbell’s Urology. 8th ed. Philadelphia: WB Saunders Co. 2002. p. 1308 Prevalence (%) 100 80 60 40 20 0 20–29 30–39 40–49 50–59 60–69 70–79 80–89 Age (years) Average Linear average

Risk of AUR versus other diseases (60 year old male) 10-year cumulative risk (%) 20 15 10 5 0 AUR Hip fx Hip fx Diabetes Stroke MI (women) (men) Jacobsen S. Urology 2001;58(6A):5

IPSS / AUA Symptom Score

Estimate size of prostate, Exclude nodule Detect hematuria, pyuria Creatinine

Watchful waiting Regular monitoring to avoid the need for therapy Physicians and patients can see if the symptoms improve or deteriorate Watchful waiting is often more suitable for those with low symptom scores which are less bothersome and have a low risk of progression

Regular monitoring to avoid the need for therapy

Physicians and patients can see if the symptoms improve or deteriorate

Watchful waiting is often more suitable for those with low symptom scores which are less bothersome and have a low risk of progression

Alpha-blockers Doxasozin (Cardura™) Terazosin (Hytrin™) Alfuzosin (Xatral) R educ es smooth muscle tone of muscle around the bladder neck and the prostate which is under symphathetic nerve control mediated by receptors do not reduce prostate size may delay the occurrence of AUR and BPH-related surgery, they do not reduce the overall risk

Doxasozin (Cardura™)

Terazosin (Hytrin™)

Alfuzosin (Xatral) R educ es smooth muscle tone of muscle around the bladder neck and the prostate which is under symphathetic nerve control mediated by receptors do not reduce prostate size may delay the occurrence of AUR and BPH-related surgery, they do not reduce the overall risk

Alpha-blocker tolerability Majority of side effects are minor and mild Common alpha-blocker adverse events include dizziness/malaise abnormal ejaculation headache asthenia postural hypotension palpitations nausea/gastrointestinal effects nasal congestion Walsh PC et al. Campbell’s Urology, 7th Edition. Philadelphia: WB Saunders Co., 1998; Flomax SmPC; Hytrin SmPC; Cardura SmPC; Xatral SmPC

Majority of side effects are minor and mild

Common alpha-blocker adverse events include

dizziness/malaise

abnormal ejaculation

headache

asthenia

postural hypotension

palpitations

nausea/gastrointestinal effects

nasal congestion

Alpha blockers and PDE 5 Inhibitors Warning label in Viagra Similar in Cialis and Levitra May cause a BP change of 7mm Hg if consumed within 4 hours of each other Avoid PDE 5 I within 4 hours of consuming alpha blockers

Warning label in Viagra

Similar in Cialis and Levitra

May cause a BP change of 7mm Hg if consumed within 4 hours of each other

Avoid PDE 5 I within 4 hours of consuming alpha blockers

5 alpha reductase inhibitor Finasteride (Proscar TM ) inhibitor of type 2 Dutasteride (Avodart TM ) inhibitor of both type 1 and type 2 Avodart TM is 2.5x more potent against type 2 isoenzyme than finasteride Structural compression Testosterone DHT + Androgen receptor 5 alpha reductase Prostate Tissue

Finasteride (Proscar TM )

inhibitor of type 2

Dutasteride (Avodart TM )

inhibitor of both type 1 and type 2

Avodart TM is 2.5x more potent against type 2 isoenzyme than finasteride

Primary endpoint: Mean change in IPSS from baseline Roehrborn et al . J Urol (In Press) -7 -6 -5 -4 -3 -2 -1 0 0 3 6 9 12 15 18 21 24 Treatment month Adjusted mean change in IPSS from baseline (ITT, LOCF) p<0.001 combo vs . tam p<0.001 combo vs . dut Tamsulosin -4.8 -4.5 -4.4 -4.3 -4.5 -4.4 -4.7 -4.5 Dutasteride -2.8 -3.4 -4.0 -4.2 -4.8 -4.9 -5.0 -4.9 Combination -4.8 -4.8 -5.4 -5.6 -6.0 -6.0 -6.2 -6.2

Secondary endpoint: Mean change in Qmax from baseline Roehrborn et al . J Urol (In Press) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 0 6 12 18 24 Treatment month Adjusted mean change in Qmax (mL/sec) from baseline (ITT, LOCF) p<0.001 combo vs . tam p<0.006 combo vs . dut 1.2 0.9 1.1 0.9 Tamsulosin Dutasteride 1.5 1.8 1.9 1.2 Combination 2.0 2.0 2.3 2.4

Drug-related adverse events Roehrborn et al . J Urol (In Press) 1.0% 1.2% 1.4% 1.6% 1.7% 1.8% 2.4% 3.4% 4.2% 7.4% Combination (n=1610) 1.0% 0.6% 1.8% 0.7% 1.3% 0.3% 0.5% 2.8% 0.6% 6.0% Dutasteride (n=1623) 0.3% Breast tenderness 0.3% Nipple pain 0.8% Breast enlargement 1.7% Dizziness 0.9% Loss of libido 0.8% Semen volume decreased 0.8% Ejaculation failure 1.7% Altered (decreased) libido 1.1% Retrograde ejaculation 3.8% Erectile dysfunction Tamsulosin (n=1611)

Is combination therapy for every patient? Individualized treatment Efficacy of treatment v/s side effects Convenience Cost Surgery is still an option

Individualized treatment

Efficacy of treatment v/s side effects

Convenience

Cost

Surgery is still an option

Surgery Surgery may be recommended for patients who fail to respond to medical treatment or as first-line therapy TURP ( transurethral resection of the prostate) the most common surgical treatment the ‘gold standard’ of surgical procedures most patients experience symptom improvement, but postoperative complications (e.g. retrograde ejaculation) may occur Benign Prostatic Hyperplasia: Diagnosis and Treatment, Clinical Practice Guideline, No. 8, US Department of Health and Human Services, Publication No. 94-0582, February 1994

Surgery may be recommended for patients who fail to respond to medical treatment or as first-line therapy

TURP ( transurethral resection of the prostate)

the most common surgical treatment

the ‘gold standard’ of surgical procedures

most patients experience symptom improvement, but postoperative complications (e.g. retrograde ejaculation) may occur

Postoperative complications Retrograde ejaculation (>70%) Urinary incontinence (1%) Bladder neck contracture (1–2%) Urethral strictures (2–20%) Erectile dysfunction (10–20%) Repeat surgery (2%) Bleeding , transfusion (<5%) Transurethral resection syndrome ( <1 %) Benign Prostatic Hyperplasia: Diagnosis and Treatment, Clinical Practice Guideline, No. 8, US Department of Health and Human Services, Publication No. 94-0582, February 1994 Mebust et al. J Urol 1989;141:243

Retrograde ejaculation (>70%)

Urinary incontinence (1%)

Bladder neck contracture (1–2%)

Urethral strictures (2–20%)

Erectile dysfunction (10–20%)

Repeat surgery (2%)

Bleeding , transfusion (<5%)

Transurethral resection syndrome ( <1 %)

Other surgical options Plasma kinetic TURP - isotonic solution - decreases risk of TUR syndrome - better hemostasis, shorter duration of wash out Laser prostatectomy - ablation, resection - less bleeding, better hemostasis

Plasma kinetic TURP - isotonic solution - decreases risk of TUR syndrome - better hemostasis, shorter duration of wash out

Laser prostatectomy - ablation, resection - less bleeding, better hemostasis

What about the storage symptoms? TRABECULATION FREQUENCY NOCTURIA

Management of Storage symptoms Up to 50% of patients have day time frequency and nocturia Maybe main symptoms in many situations Storage symptoms increases in aging bladder Generally improves with obstruction relief (alpha blockers or reductase inhibitors), but may take a long time

Up to 50% of patients have day time frequency and nocturia

Maybe main symptoms in many situations

Storage symptoms increases in aging bladder

Generally improves with obstruction relief (alpha blockers or reductase inhibitors), but may take a long time

Role of Anti-cholinergics in LUTS with significant storage symptoms Detrusitol, Ditropan (Oxybutinin) Used in conjunction with alpha-blockers in suspected prostatomegaly Single agent therapy in suspected Overactive bladder - younger persons (<50 years old)

Detrusitol, Ditropan (Oxybutinin)

Used in conjunction with alpha-blockers in suspected prostatomegaly

Single agent therapy in suspected Overactive bladder - younger persons (<50 years old)

Anti-cholinergic caution Generally, side-effects are minimal with selective anti-cholinergic agents Dry mouth, constipation, mild giddiness Risk of urinary retention in elderly men with untreated prostatomegaly

Generally, side-effects are minimal with selective anti-cholinergic agents

Dry mouth, constipation, mild giddiness

Risk of urinary retention in elderly men with untreated prostatomegaly

Take home message Etiology of LUTS in males – mix bag BPH / prostatomegaly predominates in older men BPH can be effectively managed by the family physician Management of storage symptoms are just as important

Etiology of LUTS in males – mix bag

BPH / prostatomegaly predominates in older men

BPH can be effectively managed by the family physician

Management of storage symptoms are just as important

Thank you