Pharmacotherapy of Benign Prostatic Hyperplasia

Pharmacotherapy of Benign Prostatic Hyperplasia

1. Definition, pathophysiology & the rationale for medical therapy

• Benign prostatic hyperplasia (BPH) is a histological diagnosis — hyperplasia of the stromal and epithelial (glandular) elements of the transition zone of the prostate — that occurs to a variable degree in almost all ageing men and may obstruct urinary outflow by compressing the prostatic urethra (G&G 14e Ch.49, p.994).
• The clinical syndrome it produces is lower urinary tract symptoms (LUTS), conventionally divided into voiding/obstructive symptoms (weak stream, hesitancy, intermittency, straining, incomplete emptying, terminal dribbling) and storage/irritative symptoms (frequency, urgency, nocturia, urge incontinence). This voiding-vs-storage split underpins the choice between α₁-blockers/5-ARIs and antimuscarinics/β₃-agonists (AUA BPH Guideline 2021, Statements 10, 13, 19–20).
• BPH-related bladder-outlet obstruction has two pharmacologically separable components (KDT 8e Ch.21, pp.326–7):
  • a static (anatomical) component — the bulk of the enlarged adenoma physically narrowing the urethra; this is androgen (DHT)-dependent and is the target of 5α-reductase inhibitors.
  • a dynamic (functional) component — active smooth-muscle tone of the prostatic capsule, stroma and bladder neck, mediated by α₁-adrenoceptors; this is the target of α₁-blockers and accounts for ~40% of urethral resistance in BPH.
• The development of BPH is mediated by the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase type II within prostatic cells (G&G 14e Ch.49, p.994, citing Wilson 1980). DHT is the dominant intraprostatic androgen and the proximate growth signal — this is the molecular basis for 5-ARI therapy.
• BPH is one of the two testosterone-dependent diseases of men >40 years (the other being prostate cancer) (G&G 14e Ch.49, p.996).
• Goals of medical therapy: relieve bothersome LUTS, improve flow rate and quality of life, and — for agents that act on the static component — prevent disease progression (acute urinary retention [AUR] and the need for BPH-related surgery) (AUA Guideline 2021, Statement 14).

1.1 Treatment-decision framework (when to use which drug)

• Watchful waiting / lifestyle for mild, non-bothersome symptoms (AUA Guideline 2021 reserves drugs for moderate-to-severe, bothersome LUTS — Statement 10).
• α₁-blocker — first-line for rapid symptomatic relief of voiding symptoms regardless of prostate size; onset within days (AUA Statement 10).
• 5-ARI — for men with demonstrable prostatic enlargement (prostate volume >30 g on imaging, PSA >1.5 ng/mL, or palpable enlargement on digital rectal exam); slow onset (~6 months) but disease-modifying (AUA Statements 13, 14).
• Combination (α₁-blocker + 5-ARI) — for larger glands and men at risk of progression (AUA Statement 18, Strong, Grade A).
• Antimuscarinic or β₃-agonist (± α₁-blocker) — for predominant storage LUTS (AUA Statements 19–20).
• Tadalafil 5 mg daily — for LUTS/BPH especially with comorbid erectile dysfunction (AUA Statement 17).