Recent clinical trials have shown that combination therapy using an alpha-receptor antagonist and an antimuscarinic is more effective than either agent alone in improving quality of life and objective urodynamic variables in men with bladder outflow obstruction. There appear to be no negative effects on bladder function. The mode of action of this combination is unknown but presumed to be an antimuscarinic reduction in detrusor overactivity and the alpha-receptor antagonist reduced outflow tract resistance. We have shown with in vitro experiments that in smooth muscles influencing outflow tract resistance (prostate, trigone) there is a profound contractile synergy between adrenergic and muscarinic pathways. We propose the hypothesis that both arms of the combination therapy reduce contractile tone of the outflow tract and that their simultaneous attenuation has a disproportionately large effect on outflow tract resistance. Our data from trigone muscle suggest that adrenergic and muscarinic receptor activation increase the intracellular [Ca(2+)] but the adrenergic pathway also operates through Ca(2+)-sensitisation of the contractile apparatus, primarily through a PKC-dependent pathway.

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Benign prostatic hyperplasia (BPH) is common in men older than age 50, and the symptoms occurring from bladder outlet obstruction (BOO) commonly overlap with lower urinary tract symptoms (LUTS) experienced in overactive bladder (OAB). Anticholinergics are often withheld from men with BOO. This article reviews seven randomized controlled trials (RCTs) and a meta-analysis study examining anticholinergic use in men with LUTS associated with OAB and BPH. There is growing evidence that anticholinergics are a suitable, safe treatment in men with persistent LUTS associated with BOO, refractory to α -blockers. Only four of 750 men treated with anticholinergics in the seven RCTs reviewed had acute urinary retention. Further well-designed, placebo-controlled RCTs are required to assess the effi cacy and long-term safety outcomes of combination therapy. However, it appears feasible to effectively use adjunctive anticholinergic therapy in men with LUTS/BPH and no signifi cant increase in postvoid residual volume.

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