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.
Etiology is unknown but due to its similarity to the embryonic morphogenesis of the prostate has led to the hypothesis that BPH may be the result of "reawakening" in adulthood of embryonic induction processes.

Principles of Therapy

The primary treatment goal is to reduce lower urinary tract symptoms (LUTS), improve prostate-related quality of life, & prevent or delay disease progression

Pharmacotherapy

Alpha Blockers

  • Also known as alpha-adrenergic antagonists or alpha-adrenergic receptor antagonists
  • Act on the smooth muscle tone w/in the prostate & the bladder neck & produces symptomatic relief w/in weeks
  • Bind to & inhibit type 1 alpha-adrenergic receptor & thus inhibit smooth muscle contraction
  • May also regulate prostate growth by inducing apoptosis in the epithelial & stromal smooth muscle cells w/o affecting the rate of cell proliferation
  • Have similar efficacy & choice is influenced by its adverse effects & ease of use

Selective long-acting alpha-1 adrenergic antagonists:

  • Alfuzosin (slow-release)
  • Doxazosin
  • Terazosin

Selective short-acting alpha-1 adrenergic antagonists:

  • Alfuzosin

Partially subtype (alpha-1a)-selective adrenergic antagonists:

  • Silodosin
  • Tamsulosin

5-α Reductase Inhibitors

  • Inhibits 5-α reductase, an isoenzyme that metabolizes testosterone to dihydrotestosterone (DHT) in the prostate gland, liver & skin, that blocks its conversion & reduces the serum & tissue dihydrotestosterone (DHT)
  • Reduces prostate volume, risk of progression to urinary retention & prostatic surgery
  • Monotherapy w/ 5α-reductase inhibitors (5-ARIs) are safe & effective based on systematic reviews

Dutasteride

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

Finasteride

  • An azasteroid that inhibits type-2 isoform of 5-α reductase, which is responsible for the conversion of testosterone to dihydrotestosterone & has anti-androgenic properties
  • It causes regression of the enlarged prostate to improve symptoms
  • Data on clinical efficacy persists w/ long-term treatment (≥6 months)
  • A trial treated daily w/ 5 mg Finasteride showed improvement in symptoms scores, maximal urinary flow rates & prostate volume were maintained for years
  • May also suppress gross hematuria associated w/ benign prostatic hyperplasia (BPH)

Combined Treatments Containing Alpha1-adrenoreceptor Blocker & 5α-Reductase Inhibitor

Used in patients w/ lower urinary tract symptoms (LUTS) associated w/ demonstrable prostatic enlargement who are at a significant risk of progression

  • Dutasteride & Tamsulosin
    • The four year CombAT study provided an evidence of its efficacy among patients w/ larger prostate
    • It revealed a significant decrease in the International Prostate Symptom Score (IPSS) compared w/ either monotherapy
  • Finasteride & 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 w/ medium (25 to <40mL) & large (>40 mL) prostates in long-term treatment

Phosphodiesterase Type 5 Inhibitors

  • Selectively inhibits phosphodiesterase type 5 & increases cyclic guanosine monophosphate (cGMP) which causes smooth muscle relaxation
    • Smooth muscle cells of the prostate & bladder contain phosphodiesterase type 5 inhibitors
  • Considered in patients w/ history of erectile dysfunction (ED) &  lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), or in patients who failed alpha-adrenergic antagonists or 5-alpha reductase inhibitors
    • Consistently reduces  lower urinary tract symptoms (LUTS) associated w/ benign prostatic hyperplasia (BPH)
  • Offers conventional therapies such as rapid onset of action, fewer side effects, enhanced sexual function & improved quality of life (QoL)

Tadalafil

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

Anticholinergic Agents

  • Relaxes bladder smooth muscle by reducing the muscarinic effect of acetylcholine on the smooth muscle
  • Used as alternative monotherapy for patients w/ irritative symptoms (frequency, urgency, & incontinence) related to overactive bladder (OAB) & without elevated post void residuals (PVR)
  • Also used in combination therapy w/ alpha-adrenergic agents for patients w/ persistent symptoms of benign prostatic hyperplasia (BPH) who have irritative symptoms w/o elevated post void residuals (PVR)
  • Placebo-controlled trials showed reduced sensations of urgency, decreased episodes of frequency & urgency incontinence, & 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 & incontinence in detrusor instability

Fesoterodine

  • Well absorbed, not affected by food, & is metabolized by both the CYP2D6 & CYP3A4 enzyme systems
  • Used for the treatment of overactive bladder w/ urinary urgency, frequency &/or urge incontinence
  • A pilot study was made for the use of Fesoterodine in the management of overactive bladder (OAB) & showed a reduction in the International Prostate Symptom Score (IPSS), International Prostate Symptom Score (IPSS) irritative sub score, & mean number of nocturia events 7 months after follow up, as well as increased in the quality of life (QoL)

Oxybutynin

  • Increases bladder capacity by diminishing bladder muscle contractions
  • Used in urinary incontinence, urgency & 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 &/or increased urinary frequency & urgency in patients w/ overactive bladder syndrome (OBS)

Tolterodine

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

Trospium

  • Quaternary amine, classified as smooth muscle relaxant
  • Has limited ability to cross blood-brain barrier & has less impact on cognitive dysfunction
  • Used for the treatment of overactive bladder w/ urinary frequency, urgency & incontinence & 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

Mirabegron

  • First in class beta-3 adrenergic agonist for the treatment of overactive bladder
  • Used in the management of urinary frequency, urgency, & incontinence in overactive bladder syndrome (OBS) related to blood pressure (BP)
  • It improves overactive bladder (OAB) symptoms for which antimuscarinic agents are insufficient
  • Study revealed that it is safe to utilize because of its low & mild incidences of side effects
  • In 2014, a systematic review of 44 randomized trials including 27,000 patients revealed, 50 mg of Mirabegron was efficacious as that of other antiocholinergics in reducing the frequency & episodes of urinary incontinence w/ less dry mouth as its effect
  • Please see Overactive Bladder Disease Management Chart for full Dosage Guidelines

Alternative Medications

  • Herbal medications used as a dietary supplement in the treatment of benign prostatic hyperplasia (BPH):
    • Saw palmetto
      • The most popular herbal remedy for benign prostatic hyperplasia (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) & pumpkin seed oil (Cucurbita peponis)
    • Beta-sitosterol, a plant sterol found in some dietary supplements marketed for prostate health

Non-Pharmacological Therapy

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

Watchful Waiting

  • This is recommended w/ yearly follow-up w/ mild benign prostatic hyperplasia (BPH) symptoms when other conditions have been excluded
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