Benign prostatic hyperplasia: Treat or wait?

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Applied Evidence

Benign prostatic hyperplasia: Treat or wait?

J Fam Pract. 2008 July;57(7):454-463

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References

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Where nocturia is a particular problem, diuretics timed to minimize night-time urine production, daytime naps, and use of antidiuretic hormones (although contraindicated in patients with congestive heart failure) may be appropriate.^24,25 Notably, in the context of combined bladder outlet obstruction and detrusor overactivity validated by urodynamic studies, there are recent studies identifying a role for anticholinergics.^26,27

Medical therapy before surgery

Medical therapy has supplanted surgery as the primary therapeutic tool for BPH-related lower urinary tract symptoms.⁴ a-Adrenergic antagonists decrease prostatic and urethral smooth muscle tone, induce tissue apoptosis through tumor growth factor-beta signaling, and increase detrusor muscle vascular supply, while 5-a reductase inhibitors block conversion of testosterone to dihydrotestosterone and reduce prostate volume ( TABLE ).^{4,14,15,28-40}

FAST TRACK

How much symptoms interfere with work, social life, sleep, sexual function, and travel, are more important than the symptoms, per se

a-Adrenergic blockers. Nonselective a-adrenergic blockers include terazosin, doxazosin, and alfuzosin. Their greater selectivity for nonprostatic peripheral vasculature a-1_B receptors than for prostatic a-1_A receptors account for their potential to cause orthostatic hypotension. A fourth agent, tamsulosin, is mostly selective for the prostatic a-1_A receptor and does not have a clinically significant effect on blood pressure.³⁰

At therapeutic doses, these drugs have comparable efficacy in lowering IPSS scores, increasing urine flow rates, and improving symptoms.⁴ Potential side effects include asthenia, headache, dizziness, and peripheral edema. Early postural hypotension and later rebound hypertension on withdrawal are primarily seen with terazosin and doxazosin, which require titration and tapering over 2 to 3 weeks when being introduced or eliminated. The uroselectivity of alfuzosin, as well as new dosing formulations, have helped reduce hypotensive side effects.^28,29 Like tamsulosin, it can be started and stopped directly.

TABLE
Medical therapies for BPH at a glance^{4,14,15,28-40}

TYPE OF THERAPY	ACTIVITY	EFFICACY IN CLINICAL TRIALS	SIDE EFFECTS	INDICATIONS	NUMBER NEEDED TO TREAT*
a-Adrenergic blockers Nonselective Terazosin Doxazosin Alfuzosin Selective Tamsulosin	Decrease prostatic and urethral smooth muscle tone Induce tissue apoptosis by increasing tumor growth factor-ß Increase detrusor muscle vascular supply	Comparable efficacy in lowering IPSS scores 4 to 6 points and increasing urine flow rates Show clinical change as early as 48 hours after initiation Minimal impact on prostate volume	Potential side effects include asthenia, headache, dizziness, and peripheral edema Early postural hypotension and rebound hypertension on withdrawal are seen with terazosin and doxazosin, requiring titration and tapering over 2 to 3 weeks when introduced or eliminated Alfuzosin is preferentially concentrated at prostatic sites^28,29 and does not require titration or tapering Doxazosin has been associated with increased risks of congestive heart failure in men with cardiac risk factors in the ALLHAT trial;¹⁴ this concern reasonably extends to terazosin, which shares hypotensive effects Tamsulosin and alfuzosin are associated with rhinitis and ejaculatory dysfunction, but fewer cardiovascular effects³⁰	Patients with LUTS secondary to BPH	Terazosin 4.0 (to achieve >10% improvement in Boyarsky score, an older measure comparable to the IPSS)³¹ Doxazosin 13.7 (for the prevention of clinical progression)³² Alfuzosin 5.8 (to achieve =3 points improvement in IPSS)³³ Tamsulosin 4.5 (to achieve =25% increase in AUA score)³⁴
5- a Reductase inhibitors Dutasteride Finasteride	Block conversion of testosterone to dihydrotestosterone, thereby reducing prostate volume¹⁴	Decrease prostate volume (20%-30%) Lower IPSS scores 3 to 4 points Increase urine flow rates and decrease urinary retention and need for surgery (50%) vs placebo¹⁵ Clinical effects gradually appear over 3 to 6 months³⁵	Decreased libido Erectile dysfunction Ejaculation disorders Lowers PSA levels by as much as half¹⁵ Finasteride may reduce the prevalence of prostate cancer almost 25% vs placebo³⁶	Patients with significantly enlarged prostates >40 mL³⁵	Dutasteride mild-to-moderate symptoms : 10 (to achieve 2-point improvement in AUA-SS) severe symptoms: 6.3 (to achieve 2-point improvement in AUA-SS)^37,38 Finasteride 15.0 (for the prevention of clinical progression)³²
Combination therapy with a-Adrenergic blockers and 5-a reductase inhibitors		MTOPS study compared placebo, doxazosin, finasteride, and combination therapy on clinical progression measures of BPH³² Significant symptom score improvements by all drug treatments, but clear superiority in the combination group Combination therapy and finasteride significantly reduced urinary retention and need for surgery; doxazosin did not	Side effects similar to those of each drug alone vs placebo Abnormal ejaculation, peripheral edema, and dyspnea were more frequent in patients taking both drugs	Patients with larger glands and higher PSA values at greatest risk for progression; thresholds not yet clear⁴	Combination of doxazosin + finasteride 8.4 (for the prevention of clinical progression)³²
Phytotherapy Saw palmetto	Unknown; possible antiandrogen effects	Short-term improvement of nocturia and peak urinary flow comparable with finasteride suggested by metaanalyses of trials (n=~3000 patients) lasting from 1 month to 1 year³⁹ Double-blind, randomized, 1-year trial (n=225) vs placebo detected no significant difference in LUTS, flow rates, prostate size, residual volumes, QOL measures, or serum PSA⁴⁰	Identified drug interactions and side effects have been minimal	Not recommended by AUA or EAU guidelines	N/A
*Number needed to treat (NNT) values should not be regarded as points of efficacy comparison since they are not consistently based on head-to-head trials, are derived from different patient populations, and may refer to different efficacy end points as well as different lengths of follow-up.
AUA-SS, American Urological Association symptom score; BPH, benign prostatic hyperplasia; EAU, European Association of Urology; IPSS, International Prostate Symptom Score; LUTS, lower urinary tract symptoms; N/A, not available; PSA, prostate-specific antigen; QOL, quality of life.