Pharmacotherapy of Benign Prostatic Hyperplasia

Introduction & rationale for medical therapy

• Benign prostatic hyperplasia (BPH) is a histological hyperplasia of stromal and epithelial elements of the prostatic transition zone that occurs in nearly all ageing men and can obstruct urinary outflow by compressing the prostatic urethra; the clinical syndrome it produces is lower urinary tract symptoms (LUTS).
• Symptom split — LUTS divide into voiding/obstructive symptoms (weak stream, hesitancy, intermittency, straining, terminal dribbling) and storage/irritative symptoms (frequency, urgency, nocturia, urge incontinence) — this split underpins the choice between α₁-blockers/5-ARIs and antimuscarinics/β₃-agonists.
• Two separable components — Outlet obstruction has a static (anatomical) component — the bulk of the DHT-dependent adenoma narrowing the urethra (target of 5α-reductase inhibitors) — and a dynamic (functional) component — α₁-adrenoceptor-mediated smooth-muscle tone of the capsule, stroma and bladder neck (target of α₁-blockers), accounting for ~40% of urethral resistance.
• Androgen dependence — BPH development is driven by conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase type II within prostatic cells; DHT is the dominant intraprostatic androgen and proximate growth signal. BPH is one of the two testosterone-dependent diseases of men >40 yr (the other being prostate cancer).
• Goals of therapy — Relieve bothersome LUTS, improve flow rate (Qmax) and quality of life, and — for static-component agents — prevent progression (acute urinary retention [AUR] and the need for BPH surgery). Drugs are reserved for moderate-to-severe, bothersome LUTS; mild non-bothersome disease is managed by watchful waiting/lifestyle.