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MEDICAL MANAGEMENT OF LUTS/BPH 
& 
RECENT ADVANCES 
Bikash Bk. Thapa 
MS – General Surgery
Introduction
Component of BOO 
• A dynamic (physiologic, reversible) component 
– related to the tension of prostatic smooth muscle 
in...
Association of BOO 
• Voiding Dysfunction 
– BPO- muscle hypertrophies- decompensation- reduced 
expression of connexin 43...
Pathogenesis 
• Hormonal 
• Dysregulation of stromal growth factors 
• Reawakening of embryonic process 
• Decrease cell d...
Role of Androgen
New Hypothesis 
• BPH is caused by malfunction of the valves in the 
internal spermatic vein manifesting as varicocele 
– ...
Summary
Diagnosis 
• History 
• Assessment of symptoms and QOL 
• Physical Examination 
• Urine Analysis 
• Uroflowmetry 
• PVR 
•...
Severity Index
Current treatment options 
• Conservative treatment 
• Alpha blockers 
• 5-alpha-reductase inhibitors (5ARIs) 
• Combinati...
Goal of treatment 
• Relieving LUTS 
• Decreasing BOO 
• Improving bladder emptying 
• Ameliorating overactive bladder act...
Efficacy index
Watchful waiting 
• Patient selection 
• Education, 
• Reassurance, 
• Periodic monitoring, 
• Lifestyle advice
Watchful waiting 
• Patient selection 
• Education, 
• Reassurance, 
• Periodic monitoring, 
• Lifestyle advice
Life Style Advice 
• Reduction in fluid intake 
• Avoidance of moderation of caffeine and alcohol 
• Double voiding techni...
Treatment Goals of Medical Therapy
Alpha – Blocker 
1a, 1b, 1d
Pharmacotherapy 
• Non selective alpha blockers 
– Phenoxybenzamine 
• Selective short acting (alpha 1) 
– Prazosin, Alfuz...
Drug Saftey 
• Asthenia 
• Diziness 
• Nasal congestion 
• Postural hypertension 
• Co-medication 
• anejaculation 
• Intr...
α-blockers should be offered to men with 
moderate to severe LUTS. 
• a1-adrenoceptor antagonists can result in a 
16–25% ...
5 alpha Reductase inhibitor 
Dutasteride 
Finasteride 
Type II 5AR 
Testosterone DHT 
Dutasteride 
Prostate 
volume 
reduc...
Clinical role of dual inhibition remains 
unclear 
Reduce LUTS (IPSS) by approximately 15-30%, 
Decrease prostate volume...
Proscar Long-Term Efficacy and Safety Study (PLESS)
Combination Therapy & 
Short term Efficacy 
• In the Veterans Affairs Cooperative Study, 1229 men with BPH (mean peak 
uri...
• PREDICT trial in which 1095 men were randomly 
assigned to doxazosin, finasteride, or both for one 
year 
– Doxazosin wa...
Combination Therapy & 
Long Term Efficacy
Medical Therapy of Prostatic Symptoms (MTOPS) trial, in which 3047 men with 
BPH were randomly assigned to receive doxazos...
CombAT vs MTOPS 
Clinical progression CombAT MOPTS 
Overall risk of disease 
progression % 
66 44 
Symptomatic 
progressio...
Anticholinergic and OAB with BPH 
• 75% of clinical BPH have concomitant urodynamic detrusor 
overactivity 
• In concomita...
Anitcholinergic agents
Anticholinergic - M1 , M3 receptor 
• Adverse effect 
– Dry mouth (up to 16%), 
– Constipation(up to 4%), 
– Micturition d...
Alpha blocker n Anticholinergic 
• Reducing voiding frequency, nocturia, or IPSS 
compared to α-blockers or placebo alone....
Plant Extract- Phytotherapy 
• Have anti-inflammatory, antiandrogenic, or oestrogenic 
effects 
• Decrease sexual hormone ...
Phytotherapeutic agents
Conclusion from systemic reviews 
• The plant extract beta-sitosterol improved symptoms 
• Cernilton, which is prepared fr...
Desmopression (v1, v2 receptor) 
• Desmopressin significantly reduced nocturnal 
diuresis by approximately 0.6-0.8 ml/min ...
• headache, nausea, diarrhoea, abdominal pain, 
dizziness, dry mouth, and hyponatraemia. 
• Peripheral oedema (2%) and hyp...
Practical Consideration 
• Desmopressin should be taken once daily before sleeping. 
• desmopressin treatment should be in...
Nitric Oxide 
cGMP 
activate protein kinases, ion 
channels, and cGMP-binding 
phosphodiesterases 
Calcium depletion 
Smoo...
Newer Agents 
Phosphodiesterase inhibitors 
mean Qmax increase 3.7-4.3 mLs or 24-38% 
reduced IPSS by approximately 17-35%
Side Effects of PDE5 inhibitors 
• Headache, flushing, dizziness, dyspepsia, nasal 
congestion, myalgia, 
• Hypotension, s...
New Trials 
• Several new drugs are currently under clinical investigation 
(phase II-III trials) of which none has been l...
Is bladder diary recommended?
USG is recommended for the 
anatomical evaluation of Prostate
Evaluation of upper urinary tract
Is long-term therapy with a1-adrenoceptor 
antagonists recommended? 
Approximately 18, 64, and 36–80% of patients 
withdre...
What urodynamic test is recommended for men 
undergoing surgical treatment for BPH?
What foods and dietary habits are 
recommended for patients with BPH?
Is a reduced alcohol intake recommended 
in patients with BPH
What treatments are recommended for 
urinary retention by BPH?
What therapeutic strategies are 
recommended to avoid sexual dysfunction 
as an adverse event?
Referal for Surgical therapy 
• Symptom assessment 
• Duration of therapy 
• Disease progression 
• Complication 
• Follow...
AUA GUIDELINES
References 
• JUA clinical guidelines for benign prostatic 
hyperplasia 
• EUA guidelines for LUTS 
• AUA Guidelines 
• Ca...
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
Medical management of bph
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Medical management of bph

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Approach and management of Benign enlargement of Prostate and recent advances

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Medical management of bph

  1. 1. MEDICAL MANAGEMENT OF LUTS/BPH & RECENT ADVANCES Bikash Bk. Thapa MS – General Surgery
  2. 2. Introduction
  3. 3. Component of BOO • A dynamic (physiologic, reversible) component – related to the tension of prostatic smooth muscle in the prostate, prostate capsule, and bladder neck • A fixed (structural) component – related to the bulk of the enlarged prostate impinging upon the urethra
  4. 4. Association of BOO • Voiding Dysfunction – BPO- muscle hypertrophies- decompensation- reduced expression of connexin 43- impairs synchronise contraction-contractile dysfunction • Storage Dysfunction – cycle of urine storage and voiding causes repeated bladder distension, raised intravesical pressure, ischemia, reperfusion – Impaired vesical blood flow results in oxidative stress, with free radicals causing damage to the urothelium, nerves, and smooth muscle.
  5. 5. Pathogenesis • Hormonal • Dysregulation of stromal growth factors • Reawakening of embryonic process • Decrease cell death • Genetic susceptibiltiy
  6. 6. Role of Androgen
  7. 7. New Hypothesis • BPH is caused by malfunction of the valves in the internal spermatic vein manifesting as varicocele – Elevated venous pressure causes hypertrophy and exposure to high concentration of free testosterone causes hyperplaisa of prostate • Involvement of adrenergic nerves in prostatic hyperplasia. • Cytokines derived from inflammatory cells also induce epithelial growth factors
  8. 8. Summary
  9. 9. Diagnosis • History • Assessment of symptoms and QOL • Physical Examination • Urine Analysis • Uroflowmetry • PVR • PSA • Prostate Ultrasound • Case Sensitive and Elective – bladder diary, pressure-flow studies, serum creatinine measurements,and ultrasonography of the upper urinary tract.
  10. 10. Severity Index
  11. 11. Current treatment options • Conservative treatment • Alpha blockers • 5-alpha-reductase inhibitors (5ARIs) • Combination therapy • Phytotherapy • Minimally invasive techniques • Surgery
  12. 12. Goal of treatment • Relieving LUTS • Decreasing BOO • Improving bladder emptying • Ameliorating overactive bladder activity • Reversing renal insufficiency • Preventing disease progression
  13. 13. Efficacy index
  14. 14. Watchful waiting • Patient selection • Education, • Reassurance, • Periodic monitoring, • Lifestyle advice
  15. 15. Watchful waiting • Patient selection • Education, • Reassurance, • Periodic monitoring, • Lifestyle advice
  16. 16. Life Style Advice • Reduction in fluid intake • Avoidance of moderation of caffeine and alcohol • Double voiding technique • Urethral stripping • Distraction- mind out of bladder n toilet • Bladder retraining- Hold on • Optimising drugs • Treatment of constipation
  17. 17. Treatment Goals of Medical Therapy
  18. 18. Alpha – Blocker 1a, 1b, 1d
  19. 19. Pharmacotherapy • Non selective alpha blockers – Phenoxybenzamine • Selective short acting (alpha 1) – Prazosin, Alfuzosin, Indoramin • Selective long acting (alpha1, all three type) – Terazosin, Doxazosin, Alfuzosin SR • Partially subtype (alpha 1a) – Tamsulosin, Sildosin • Partially subtype ( alpha 1d) – Naftopidil, Tamsulosin
  20. 20. Drug Saftey • Asthenia • Diziness • Nasal congestion • Postural hypertension • Co-medication • anejaculation • Intraoperative floppy iris syndrome – Miosis, iris billowing, iris prolapse
  21. 21. α-blockers should be offered to men with moderate to severe LUTS. • a1-adrenoceptor antagonists can result in a 16–25% (2.0–2.5 mL/s) increase in maximum flow rate and a 30–40% (4–6 point) reduction in the average IPSS.
  22. 22. 5 alpha Reductase inhibitor Dutasteride Finasteride Type II 5AR Testosterone DHT Dutasteride Prostate volume reduced Type I 5AR Bartsch G et al. Eur Urol. 2000;37:367380.
  23. 23. Clinical role of dual inhibition remains unclear Reduce LUTS (IPSS) by approximately 15-30%, Decrease prostate volume by 18-28% and Increase Qmax by 1.5-2.0 ml/s PSA dec by 50% Dec hematuria Inc apoptotic index of stromal and epithelial cell Dec detrusor pressure at Qmax
  24. 24. Proscar Long-Term Efficacy and Safety Study (PLESS)
  25. 25. Combination Therapy & Short term Efficacy • In the Veterans Affairs Cooperative Study, 1229 men with BPH (mean peak urinary flow rate of 10.5 mL/sec) were randomly assigned to placebo, finasteride (5 mg/day), terazosin (10 mg/day), or both for one year Terazosin lowered the symptom score and increased the peak urinary flow rate when compared with placebo. Finasteride alone was no better than placebo. The combination of finasteride and terazosin was no better than terazosin alone.
  26. 26. • PREDICT trial in which 1095 men were randomly assigned to doxazosin, finasteride, or both for one year – Doxazosin was more effective than finasteride or placebo for urinary symptoms and flow rate, but again, the combination was no more effective than doxazosin alone
  27. 27. Combination Therapy & Long Term Efficacy
  28. 28. Medical Therapy of Prostatic Symptoms (MTOPS) trial, in which 3047 men with BPH were randomly assigned to receive doxazosin, (4 to 8 mg/day), finasteride (5 mg/day), combination therapy, or placebo
  29. 29. CombAT vs MTOPS Clinical progression CombAT MOPTS Overall risk of disease progression % 66 44 Symptomatic progression % 64 41 AUR % 81 68 Urinary incontinence % 65 26 BPH related surgery % 67 71
  30. 30. Anticholinergic and OAB with BPH • 75% of clinical BPH have concomitant urodynamic detrusor overactivity • In concomitant BPH and DO, 65% have inadequate symptoms control • 19% have persistent OAB symptoms after TURP • Recurrence of OAB symptoms after TURP in long term mean follow up of 12.6 years .
  31. 31. Anitcholinergic agents
  32. 32. Anticholinergic - M1 , M3 receptor • Adverse effect – Dry mouth (up to 16%), – Constipation(up to 4%), – Micturition difficulties (up to 2%) – Nasopharyngitis (up to 3%), – And dizziness (up to 5%). – Disorientiation, hallucination, convulsion – hyperthermia • Contraindications – Myasthenia gravis – Glaucoma – Significant bladder outflow obstruction – Urinary retention – Severe ulcerative colitis – Gastrointestinal obstruction – Hypethyroidism – CAD – CCF
  33. 33. Alpha blocker n Anticholinergic • Reducing voiding frequency, nocturia, or IPSS compared to α-blockers or placebo alone. • Reduce urgency urinary incontinence episodes as well as urgency and significantly increased QoL
  34. 34. Plant Extract- Phytotherapy • Have anti-inflammatory, antiandrogenic, or oestrogenic effects • Decrease sexual hormone binding globulin (SHBG) • Inhibit aromatase, lipoxygenase, growth-factor stimulated proliferation of prostatic cells • Α-adrenoceptors, 5α-reductase, muscarinic cholinoceptors, dihydropyridine receptors, or vanilloid receptors • Improve detrusor function • Neutralize free radicals .
  35. 35. Phytotherapeutic agents
  36. 36. Conclusion from systemic reviews • The plant extract beta-sitosterol improved symptoms • Cernilton, which is prepared from the rye grass pollen, Secale cereale, has been evaluated in four clinical trials – It improved symptoms, but did not affect urinary flow rates or residual urine or prostate volume. • Pygeum africanum is an extract of bark from an African plum tree. – In a meta-analysis of 18 randomized controlled trials, active treatment improved symptoms two times more frequently than placebo and increased peak urinary flow rates 23 percent
  37. 37. Desmopression (v1, v2 receptor) • Desmopressin significantly reduced nocturnal diuresis by approximately 0.6-0.8 ml/min (-40%) • Decreased the number of nocturnal voids by approximately 0.8-1.3 (-40%) • Extended the time until the first nocturnal void by approximately 1.6 hours • Reduced night-time urine volume as well as the percentage of urine volume excreted at night
  38. 38. • headache, nausea, diarrhoea, abdominal pain, dizziness, dry mouth, and hyponatraemia. • Peripheral oedema (2%) and hypertension (5%)
  39. 39. Practical Consideration • Desmopressin should be taken once daily before sleeping. • desmopressin treatment should be initiated at a low dose (0.1 mg/day) • The maximal daily dose recommended is 0.4 mg/day. • Patients should avoid drinking fluids at least 1 hour before using desmopressin until 8 hours thereafter. • In men aged 65 years or older, desmopressin should not be used if the serum sodium concentration is below the normal value. • In all other men aged 65 years or older, serum sodium concentration should be measured at day 3 and 7 as well as after 1 month and, if serum sodium concentration has remained normal, every 3-6 months subsequently.
  40. 40. Nitric Oxide cGMP activate protein kinases, ion channels, and cGMP-binding phosphodiesterases Calcium depletion Smooth muscle relaxation guanylyl-cyclase PDE5 hydrolyses PDE- INHIBITORS
  41. 41. Newer Agents Phosphodiesterase inhibitors mean Qmax increase 3.7-4.3 mLs or 24-38% reduced IPSS by approximately 17-35%
  42. 42. Side Effects of PDE5 inhibitors • Headache, flushing, dizziness, dyspepsia, nasal congestion, myalgia, • Hypotension, syncope, tinnitus, conjunctivitis, or altered vision (blurred, discoloration). • Priapism or acute urinary retention is considered minimal.
  43. 43. New Trials • Several new drugs are currently under clinical investigation (phase II-III trials) of which none has been licensed for male LUTS so far. These new drugs target: – the prostate, e.g. gonodotrophin-releasing hormone antagonists, oestrogen receptor antagonists, • Chlormadinone/allylesternol • Zanoterone/Flutamide – apoptosis-inducing agents, vaccines, vitamin D agonists, or androgen replacement therapies; – the bladder, e.g. β3-adrenoceptor agonists; – the nervous system, e.g. neuromuscular blocking agents, tachykinin receptor antagonists.
  44. 44. Is bladder diary recommended?
  45. 45. USG is recommended for the anatomical evaluation of Prostate
  46. 46. Evaluation of upper urinary tract
  47. 47. Is long-term therapy with a1-adrenoceptor antagonists recommended? Approximately 18, 64, and 36–80% of patients withdrew from the studies after2, 3, and >4 years, respectively.
  48. 48. What urodynamic test is recommended for men undergoing surgical treatment for BPH?
  49. 49. What foods and dietary habits are recommended for patients with BPH?
  50. 50. Is a reduced alcohol intake recommended in patients with BPH
  51. 51. What treatments are recommended for urinary retention by BPH?
  52. 52. What therapeutic strategies are recommended to avoid sexual dysfunction as an adverse event?
  53. 53. Referal for Surgical therapy • Symptom assessment • Duration of therapy • Disease progression • Complication • Follow up • Cost effectiveness
  54. 54. AUA GUIDELINES
  55. 55. References • JUA clinical guidelines for benign prostatic hyperplasia • EUA guidelines for LUTS • AUA Guidelines • Campbell Urology- 9th edn

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