Beta 3 Adrenoreceptor Agonist for the Management of Lower Urinary Tract Symptoms in Men With Benign Prostatic Hyperplasia: A Systematic Review.

"Conflict of Interest: SJK, a member of the Editorial Board of International Neurourology Journal, is the second author of this article. However, she played no role whatsoever in the editorial evaluation of this article or the decision to publish it. Except for that, no potential conflict of interest relevant to this article was reported."

"The finding of our review, however, are not consistent with those of previous report of OAB patients. While B3AR agonist can improve the patient-important outcomes within group (before and after treatment), it does not appear to have additional effects on urological symptom scores and QoL compared to current standard BPH treatment such as AB or anticholinergic. Although B3AR agonist therapy with PDE5I showed statistical improvement on urological symptom scores or QoL compared to PDE5I monotherapy, it must be due to the difference of pharmacologic profile. B3AR agonist may reduce frequency of voiding compared to AB or PDE5I monotherapy, but the effect estimates may be clinically trivial. For safety profile, B3AR agonist does not appear to increase adverse event rate as well as acute urinary retention rate. However, one RCT compared B3AR agonist combination therapy with AB to AB monotherapy reported 3 serious cardiovascular adverse events (1 acute myocardial infarction, 1 angina pectoris, 1 cerebral infarction). Although post hoc analysis reported the effects of mirabegron in men with OAB (not only in men with BPH), we believe that our review is the most recent evidence for the use of B3AR agonists in men with BPH. The major limitation of current evidence for B3AR agonists is the heterogeneous definition of BPH among the included studies. For example, Yamanishi et al. [] included men aged 50–89 years with LUTS. Therefore, a proportion of included participants may not have been patients with BPH, even if their mean prostatic volume was over 30 mL. Additionally, further studies are needed to provide assurance of long-term effectiveness and safety of beta 3 agonists as the elderly are more likely to take the B3AR agonist as a combination therapy with conventional BPH in clinical practice. As most studies in this review only included Asian men, there are also limitations in generalizing the results. Almost all studies were sponsored by pharmaceutic companies, raising concerns about conflicts of interest and publication bias that can overestimate the effect size. Even though the authors performed a comprehensive search without any publication or language restrictions, it is possible that additional studies may have been conducted but not yet published. Particularly, some negative studies may have been published in unindexed journals or only presented at local conferences, which can deviate from our search and lead to potential publication biases. Finally, only 1 study was double-blinded, while the others were open-blinded. There is a consistent need for greater methodological rigor and transparency reporting. Fund/Grant Support: This study was supported by Center of Evidence Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea."