benign%20prostatic%20hyperplasia
BENIGN PROSTATIC HYPERPLASIA
Benign prostatic hyperplasia (BPH) is a histopathological diagnosis characterized by epithelial cell & smooth muscle cell proliferation in the transition zone of the prostate leading to a non-malignant enlargement of the gland, which may result in lower urinary tract symptoms, including voiding and storage symptoms.
It is commonly called enlarged prostate.
The exact cause of BPH is still not well understood.

Benign%20prostatic%20hyperplasia Treatment

Principles of Therapy

  • The primary treatment goals are to reduce LUTS, prevent complications, prevent or delay disease progression and improve prostate-related QoL

Pharmacotherapy

Alpha Blockers

  • Also known as alpha-adrenergic antagonists or alpha-adrenergic receptor (alpha-adrenoreceptor) antagonists
  • Act on the smooth muscle tone within the prostate and the bladder neck and produce symptomatic relief within weeks
  • Bind to and inhibit type 1 alpha-adrenergic receptor and thus inhibit smooth muscle contraction
  • May also regulate prostate growth by inducing apoptosis in the epithelial and stromal smooth muscle cells without affecting the rate of cell proliferation
  • Do not alter the natural progression of BPH
  • Have similar efficacy and choice is influenced by its adverse effects and ease of use
  • Used for patients with symptomatic BPH regardless of prostate size 
    • May also be given to patients with primary symptoms of bladder outlet obstruction, small prostate and/or PSA ≤1.5 ng/mL

Selective Long-acting Alpha-1 Adrenergic Antagonists

  • Alfuzosin (slow-release)
  • Doxazosin
  • Terazosin

Selective Short-acting Alpha-1 Adrenergic Antagonists

  • Alfuzosin
  • Prazosin

Partially Subtype (Alpha-1a)-selective Adrenergic Antagonists

  • Silodosin
  • Tamsulosin

5-alpha Reductase Inhibitors (5-ARIs)

  • Inhibit 5-alpha reductase, an isoenzyme that metabolizes testosterone to dihydrotestosterone (DHT) in the prostate gland, liver and skin, resulting in inhibition of the conversion of testosterone to DHT and reduction of serum and tissue DHT levels
  • Induce apoptosis of prostate epithelial cells causing reduction in prostate size and decreasing circulating PSA levels after 6-12 months of therapy
  • Reduce prostate volume, risk of progression to urinary retention and prostatic surgery
  • Indicated for patients with significant obstruction and prostate volume >40 mL
  • Have slow onset of action (3-6 months) and therefore appropriate only for long-term treatment (years)
  • Monotherapy with 5-ARIs is safe and effective based on systematic reviews

Dutasteride

  • Meta-analysis of four randomized controlled trials showed improvement of symptom score and maximum flow rate while decreasing prostate volume, episodes of urinary retention and the need for surgical intervention

Finasteride

  • An azasteroid that inhibits type-2 isoform of 5-alpha reductase which is responsible for the conversion of testosterone to DHT and has anti-androgenic properties
  • It causes regression of the enlarged prostate to improve symptoms
  • Data on clinical efficacy persists with long-term treatment (≥6 months)
  • A trial wherein men were treated daily with 5 mg Finasteride showed improvements in symptom scores, maximal urinary flow rates and prostate volume were maintained for >4 years
  • May also suppress gross hematuria associated with BPH

Phosphodiesterase Type 5 (PDE5) Inhibitor

  • Selectively inhibits PDE5 and increases cyclic guanosine monophosphate (cGMP) which cause smooth muscle relaxation
    • Smooth muscle cells of the prostate and bladder contain PDE5
  • Considered in patients with history of erectile dysfunction (ED) and LUTS secondary to BPH or in patients who failed alpha-adrenergic antagonists or 5-alpha reductase inhibitors
    • Consistently reduces LUTS associated with BPH
  • Has rapid onset of action and fewer side effects, enhances sexual function and improves QoL

Tadalafil

  • A double-blind, placebo-controlled, multicenter study randomized 281 participants who showed significant improvement in the QoL assessment of both irritative and obstructive symptoms and in the International Prostate Symptom Score (IPSS) score

Anticholinergic Agents

  • Relax bladder smooth muscle by reducing the muscarinic effect of acetylcholine on the smooth muscle
  • Used as alternative monotherapy for patients with irritative symptoms (frequency, nocturia and urgency with or without incontinence) related to overactive bladder (OAB) and without elevated PVR
  • Placebo-controlled trials showed reduced sensations of urgency, decreased episodes of frequency and urgency incontinence, and increased voided volume
  • Please see Overactive Bladder disease management chart for full Dosage Guidelines

Darifenacin

  • Selective M3 receptor antimuscarinic which has greater selectivity for the muscarinic receptors of the bladder
  • Used in the management of urinary frequency, urgency and incontinence in detrusor instability

Fesoterodine

  • Well absorbed, not affected by food, and is metabolized by both the CYP2D6 and CYP3A4 enzyme systems
  • Used for the treatment of OAB with urinary urgency, frequency and/or urge incontinence
  • A pilot study was made for the use of Fesoterodine in the management of OAB and showed a reduction in the IPSS, IPSS irritative sub score, and mean number of nocturia events 7 months after follow up, as well as increase in the QoL

Oxybutynin

  • Increases bladder capacity by diminishing bladder muscle contractions
  • Used in urinary incontinence, urgency and frequency in the urinary bladder due to neurogenic bladder disorders (eg multiple sclerosis, spina bifida or idiopathic detrusor instability)

Solifenacin

  • Selective M3 receptor antagonist
  • Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency in patients with overactive bladder syndrome (OBS)

Tolterodine

  • In one study, the extended-release formulation improved bladder variables among patients who took immediate-release formulation or other anticholinergics

Trospium

  • Quaternary amine, classified as smooth muscle relaxant
  • Has limited ability to cross blood-brain barrier and has less impact on cognitive dysfunction
  • Used for the treatment of OAB with urinary frequency, urgency and incontinence and nocturia

Beta-3 Adrenergic Agonist

  • Increases the capacity of the bladder to relax the smooth muscles during the storage phase of urinary bladder filled-void cycle
  • Please see Overactive Bladder disease management chart for full Dosage Guidelines

Mirabegron

  • First in class beta-3 adrenergic agonist for the treatment of OAB
  • Used in the management of urinary frequency, urgency, and incontinence in OBS related to BPH
  • It improves OAB symptoms for which antimuscarinic agents are insufficient
  • Study revealed that it is safe to utilize because of its low and mild incidences of side effects

Combined Treatments Containing Alpha-1 Adrenergic Antagonist and 5-alpha Reductase Inhibitors

  • Advantage of having rapid onset of symptomatic relief by an alpha-1 adrenergic antagonist and prevention of BPH progression by a 5-ARI 
  • Used in patients with LUTS associated with demonstrable prostatic enlargement who are at a significant risk of progression and/or PSA >1.5 ng/mL
  • Used only for long-term treatment (>12 months)
  • Can be an option for patients with prostate volume >30 mL and unresponsive to maximal dose of alpha-1 adrenergic antagonist monotherapy
  • Discontinuation of alpha-1 adrenergic antagonist may be considered after 6-9 months of successful combination therapy

Dutasteride and Tamsulosin

  • The 4-year CombAT study provided an evidence of its efficacy among patients with larger prostate
  • It revealed a significant decrease in the IPSS compared with either monotherapy

Finasteride and Doxazosin

  • Based from the Medical Therapy of Prostatic Symptoms trial (MTOPS), this combination is more effective than either monotherapy in improving urinary symptoms in men with medium (25 to <40 mL) and large (>40 mL) prostates in long-term treatment

Combination Treatments Containing Alpha-1 Adrenergic Antagonist and Anticholinergic Agents

  • Can be considered in patients with persistent symptoms of BPH who have irritative symptoms (eg OAB) without an elevated PVR urine volume (≥180 mL)
  • Combination treatment improves QoL and is more effective in reducing urgency urinary incontinence, voiding frequency, nocturia or IPSS compared with alpha-1 adrenergic antagonist alone

Alternative Medications

  • Herbal medications used as a dietary supplement in the treatment of BPH:
    • Saw palmetto
      • The most popular herbal remedy for BPH
      • From the berry of the plant Serenoa repens
    • Extracts from African plum tree (Pygeum africanum), rye grass pollen (Secale cereale), stinging nettle root (Urtica dioica), South African star grass (Hypoxis rooperi) and pumpkin seed oil (Cucurbita peponis)
    • Beta-sitosterol, a plant sterol, which is found in some dietary supplements marketed for prostate health

Non-Pharmacological Therapy

  • Clinical studies support proper nutrition, avoidance of constipation, weight loss, and regular physical activity as beneficial in improving and preventing urinary symptoms

Watchful Waiting

  • Recommended with yearly follow-up of patients with mild BPH symptoms when other conditions have been excluded
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