Medical Management of BPH

Omar S. Akhtar,Urology Registrar

What is BPH?● Benign prostatic hyperplasia (BPH), also known as is

a histologic diagnosis characterized by proliferation of the cellular elements of the prostate

● Per se, it is not the enlargement of the prostate, but the Bladder Outlet Obstruction (BOO) secondary to it that is the cause of worry

● These may include, recurrent infections, back-pressure changes, leading to renal insufficiency, gross haematuria, etc.

Presentation● Incomplete emptying● Frequency● Intermittency● Urgency● Weak stream● Straining● Nocturia

Medical Management● Goals: reduce symptoms

Management Strategy● Essential word: BOTHER● AUA-SI score <8, or AUA-SI score >/= 8,

with NO BOTHER: WATCHFUL WAITINGo Re-examine: annually

● Those with AUA-SI >8: treat, treat, treat

Medication Types● Alpha-blockers - Selective/Non-selective● 5-Alpha reductase inhibitors● Phosphodiesterase inhibitors

Mechanisms of Action

Alpha Blockers● Significant contribution to LUTS from smooth

muscle tension in the bladder neck, urethra, prostate stroma

● Mediated by alpha-adrenergic receptors● Three subtypes: A-1a, A-1b, A-1c● A-1a, is most abundant in prostate tissue● Drugs targeting blockade of A-1a, are used for

BPH

Alpha Blockers - Types● Nonselective alpha-blockers - phenoxybenzamine● Selective short-acting alpha-1 blockers - prazosin,

alfuzosin, indoramin● Selective long-acting alpha-1 blockers - terazosin,

doxazosin, slow-release (SR) alfuzosin.● Partially subtype (alpha-1a)–selective agents –

tamsulosin (Urimax), silodosin (Silodal)

Alpha Blockers - Effects● AUA-SI score fall of 4-6 over 6 months● In pts with mild LUTS, may be discontinued after 6

months, with severe LUTS, may require long-term therapy

● Alpha blockers tend to show effect fast● Must be individualised, due to side-effects● CAUTION: young males, elderly pts with hypotension,

large prostates (>59 gms)● Does NOT decrease the likelihood of AUR!!!

5-Alpha Reductase Enzyme Inhibitors● Enzyme used to activate Testosterone, reducing it to

active form (DHT)● Two main types - Type 1, liver, skin and Type 2, prostate● Blockade of Type 2 - 5-Alpha-reductase, leads to

decreased prostatic growth, prostate involution, apoptosis

● Finasteride (Type 2 Inhibitor), Dutasteride (Type 1 & 2 Inhibitor), are two examples

5-Alpha Reductase Inhibitors - Effect● Both finasteride and dutasteride actively reduce DHT

levels > 80%● Improve symptoms, ● Reduce the incidence of urinary retention (PLESS)● Decrease the likelihood of surgery ● Adverse effects: sexual in nature (decreased libido,

erectile dysfunction, ejaculation disorder)● Reduce PSA levels by 50% in 1 year, important when

monitoring pts

PDE Inhibitors, Alternatives● PDE inhibitors (Sildenafil) were shown to

improve LUTS secondary to BPH● Evidence for their use in combination or

alone, is lacking● Recent guidelines have not advocated their

use● AUA 2010 Guideline states: ‘No dietary

supplement, combination phytotherapeutic agent or other nonconventional therapy is recommended for the management of LUTS secondary to BPH.’ (Page 16)

Combination Therapy - CombAT trial is underway: it has shown that for prostates of 30-58 gms, with LUTS, combination therapy:● improved symptoms, ● urinary flow, ● QOL better than monotherapy with either drug, although not in men who had a prostate volume of 58 mL or more

So where does this leave us?● Key word: BOTHER● If there is BOTHER, then TREAT● Indications for Surgery - go for it● Conservative: for small prostates,

start with alpha-blockers, selective A-1a blockade x 6 months

● For larger prostates, start with combination therapy, Dutas + Alpha-Blockade