Benign Prostatic Hyperplasia

Introduction

Benign Prostatic Hyperplasia (BPH) is a histologic condition of proliferation of smooth muscle and epithelial cells in prostatic transition zone.

• The prevalence increases with age, affecting approximately 42% of men between the ages of 51 and 60 years and 82% of men between the ages of 71 and 80 years.
• BPH may progresses to benign prostatic enlargement (BPE) and subsequent bladder outlet obstruction (BOO), leading to lower urinary tract symptoms (LUTS).

Lower tract urinary symptoms (LUTS) may include

• Storage symptoms: daytime frequency, urgency, nocturia and incontinence
• Voiding symptoms: weak stream, dribbling, dysuria, straining

Symptoms can significantly impact quality of life.

• Complications include acute urinary retention, urinary tract infection, bladder calculi and renal insufficiency.

Treatment Principles

The severity of reported BPH symptoms guides selection of treatment.

• Validated severity and bother scores exist, such as the American Urological Association Symptom Index (AUA-SI), BPH Impact Index, or International Prostate Symptom Score (IPSS), to quantitatively grade the severity and bother of LUTS.

Nonpharmacological Management

Offer watchful waiting for men with LUTS due to BPH which are not significantly bothered by their symptoms.

Suggest limiting fluid intake in evening, avoiding excess alcohol, avoiding caffeine and increasing physical activity.

Consider altering medications that may be aggravating symptoms, if appropriate.

• E.g. Anticholinergic drugs, diuretics, testosterone replacement

Pharmacological Management

α-Adrenergic Blockers

• Works by reducing smooth muscle contractions in the urethra and surrounding tissues.
• Nonspecific α-adrenergic blockers (e.g. doxazosin and terazosin) also lower blood pressure significantly.
• Newer agents such as tamsulosin, silodosin and alfuzosin are more α₁-selective and may have less associated hypotension.
• Can improve symptoms within 48 hours (full effect in 4-6 weeks) and also improve urinary flow rates.
  
• Intraoperative floppy iris syndrome is a concern with α-blockers, especially tamsulosin. This increases the technical difficulty of cataract surgery and increases the incidence of complications such as posterior capsule rupture, iris trauma and vitreous loss.
  
• Other adverse effects include retrograde ejaculation, erectile dysfunction, nasal congestion, hypotension, dizziness and tachycardia.

5α-Reductase Inhibitors

• 5α-reductase inhibitors (e.g. dutasteride and finasteride) do not immediately reduce LUTS and should be reserved for use in men with large prostate volume (more than 40 g). At least 6 months of therapy is usually needed for clinical benefit. Prostate size may be reduced by about 25% during this interval.
• The most common adverse effects are erectile dysfunction, decreased libido, decreased ejaculate and decreased semen count.
• Usage of 5α-reductase inhibitors may be associated with a delayed diagnosis of prostate cancer and a more advanced histological stage of cancer at the time of diagnosis.
  

The MTOPS trial and CombAT trial found that combination therapy with an alpha blocker and 5-alpha reductase inhibitor provided a greater improvement in LUTS compared to monotherapy.

Phosphodiesterase Type 5 Inhibitors

• May be considered for patients with comorbid BPH and erectile dysfunction.
  
• Tadalafil 5 mg once daily.
• Reported adverse effects with PDE5 inhibitors are relatively rare, with the more commonly reported effects consisting of headache, flushing, dyspepsia, nasal congestion, back pain, myalgias, and sinusitis.
• They should be avoided in patients receiving nitrates for ischaemic heart disease or those with poor cardiac function.

Anticholinergic (antimuscarinic) Agents

• An appropriate and effective treatment alternative for management of LUTS secondary to BPH in men without an elevated postvoid residual and when LUTS are predominantly storage symptoms (frequency, urgency, and incontinence).
• Examples are tolterodine, oxybutynin, darifenacin, solifenacin and trospium.

Beta-3 Agonist

• Mirabegron may be used in men with mainly bladder storage symptoms (frequency, urgency, and incontinence).

Surgery

Surgery is preferred in men with severe symptoms and in those with moderate symptoms who have not adequately responded to medical options.

• The options range from minimally invasive therapies (e.g. prostatic urethral lift, transurethral needle ablation) to the more invasive transurethral resection of the prostate, and enucleation prostatectomy in select cases.

Supplements

There is conflicting evidence about the efficacy of saw palmetto plant extract (Serenoa repens) in relieving LUTS.

• Serenoa repens for benign prostatic hyperplasia, 2002
  
• Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review, 2012
  

Though the exact mechanism(s) by which saw palmetto works is uncertain, available evidence supports a possible additive or synergistic effect with 5α-reductase inhibitors, which impair the conversion of testosterone to dihydrotestosterone (DHT).

Pygeum, pumpkin seed (beta-sitosterol) and rye pollen are other natural products that have shown some improvement in BPH symptoms.

External Links

• Reliability and validity of the International Prostate Symptom Score in a Malaysian population, 2001
  
• The MTOPS Study: New Findings, New Insights, and Clinical Implications for the Management of BPH, 2006
  
• Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial, 2012
  
• Combination treatment with tamsulosin and dutasteride for benign prostatic hyperplasia, 2012
  
• Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE), 2016
  
• Drugs for benign prostatic hypertrophy, 2018