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Canadian Urological Association Journal logoLink to Canadian Urological Association Journal
. 2012 Oct;6(5 Suppl 2):S130–S132. doi: 10.5489/cuaj.12231

Benign prostatic hyperplasia and lower urinary tract symptom guidelines

Claus Roehrborn 1,✉
PMCID: PMC3481951  PMID: 23092776

Abstract

Lower urinary tract symptoms (LUTS) are very common in men, with incidence increasing with age. Several clinical practice guidelines are available as decision-making aids for men with LUTS and the recommendations are based on the presumed etiology of the symptoms (due to obstruction, overactive bladder or a combination of the two). This review presents the various pharmacologic treatment options and summarizes key clinical trial data supporting their use.

Lower urinary tract symptoms (LUTS) are very common in men, with an increase in prevalence correlating with increasing age in a linear manner.1 Approximately 50% of men over the age of 50 have histological benign prostatic hyperplasia (BPH) and approximately 25% of men over 50 have moderate-to-severe LUTS. Clearly, not all men with BPH develop LUTS. In addition, not all men with LUTS have BPH as the underlying cause.

For clinicians who treat LUTS in men, there are several relevant clinical practice guidelines that are available to help guide management decisions. This review will focus on the guideline recommendations with respect to pharmacotherapies, and include highlights of the key clinical trial evidence supporting the inclusion of these therapies among the recommended management options.

What are the most recent, relevant guidelines?

The most recent evidence-based recommendations in this field are the 2012 Guidelines on the Management of Male LUTS, published by the European Association of Urology (EAU).2 The American Urological Association (AUA) and the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) published guidelines for BPH and male LUTS, respectively, in 2010.3,4 Finally, the recommendations of the International Scientific Committee (ISC) on the Evaluation and Treatment of Lower Urinary Tract Symptoms in Older Men were published in 2009.5

Pharmacologic options

Each of the published guidelines mentioned above recommend the use of several different pharmacotherapies for the treatment of LUTS, depending on the clinical situation. Figure 1 shows the algorithm presented in the ISC recommendations (2009).5 The following is a review of the recommended pharmacologic treatment options. Surgical interventions are addressed in another section of this supplement.

Fig. 1.

Fig. 1

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Algorithm for the treatment of lower urinary tract symptoms in men.

Antimuscarinics

Antimuscarinics can be used to treat men with symptoms consistent with overactive bladder (OAB) and no bladder outlet obstruction (BOO), or those with mixed symptoms suggestive of combined BOO and OAB pathology. The data supporting this recommendation are primarily from studies investigating tolterodine. For example, in a post-hoc analysis of men with BOO and confirmed detrusor overactivity included in two studies, there was a significant reduction in frequency of urgency-related micturition.6 However, at present there is a lack of prospective data from longer-term studies for the use of antimuscarinics in patients at risk (i.e., larger glands and higher residual urine at baseline).

Alpha-blockers

The evidence base is much more compelling for the use of alpha-blockers for men with BOO. For those men with smaller prostates and/or low prostate-specific antigen (PSA), the guidelines recommend monotherapy with an alpha-blocker as the primary pharmacotherapy. There are several such agents approved for this indication;7–11 these agents appear to have similar efficacy, but do have some differences in terms of tolerability and safety profiles.

The mechanism of action (MOA) of the alpha-blockers for BOO is modulation of contraction of the smooth muscle in the prostate, bladder base and neck, and urethra. Yet, these agents do not address the underlying prostate growth. Over time, the prostatic enlargement can progress to an extent where alpha-blockade has limited or no effect on symptoms.

Combination alpha-blockers +5-ARa

The pharmacotherapy that does have a direct impact on prostate size is antagonism of 5-alpha-reductase (5-AR). For men with larger prostate volumes and/or high PSA, each of the guidelines recommends combination therapy with an alpha-blocker and a 5-AR antagonist (e.g., dutasteride, finasteride). Antagonism of 5-AR has been shown to reduce retention even when used alone.12 However, there are better outcomes when the 5-AR antagonist is combined with an alpha-blocker, as observed in the Medical Therapy of Prostatic Symptoms (MTOPS) and Combination of Avodart and Tamsulosin (CombAT) studies.12,13 In both studies, there were also higher incidences of adverse events in the combination arm versus either agent as monotherapy.

Combination antimuscarinics + alpha-blockers

For patients with mixed OAB and BOO, the combination of an antimuscarinic and an alpha-blocker has been shown to be more beneficial than alpha-blockade alone.14–17 Fixed-dose combinations of these agents are in development.

PDE-5 Inhibition

PDE-5 inhibitors (e.g., tadalafil) are not currently recommended in any published guideline, but the evidence suggests that they soon will be. The proposed MOA of these agents for the treatment of LUTS is a beneficial effect on smooth-muscle relaxation, smooth muscle and endothelial cell proliferation, nerve activity, and tissue perfusion.18 Research among men with or without erectile dysfunction (ED) and LUTS has shown that tadalafil has a beneficial effect on LUTS independent of the drug’s benefit on ED.19–23 Indeed, a head-to-head comparison of tadalafil with the alpha-blocker tamsulosin showed similar improvements of LUTS due to BPH with each agent.23

Conclusions

Male LUTS are extremely common. They are often associated with histological BPH, prostate enlargement, and measurable obstruction. For many reasons, measures of these conditions do not correlate highly at baseline. However, there are strong correlations between some baseline measures and changes or outcomes over time, which are clinically useful and allow for differentiated treatment assignments. The AUA, EAU, NICE and International Consultation on Urologic Disease (ICUD) guidelines all provide evidence-based treatment algorithms. The newest drug class (PDE-5 inhibitors, e.g., tadalafil) is not yet incorporated into any guidelines (although they are discussed as emerging therapies in the 2012 EAU guidelines, they will likely be included during ICUD sessions during the Société Internationale d’Urologie congress in autumn 2012).

Footnotes

Competing interests: Dr. Roehrborn is an ongoing paid consultant with Neo Tract, NxThera, Afferent, Astellas, GlaxoSmithKline, and Eli Lilly.

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