**2. Ambiguous Mechanisms of LUTS Related to BPH**

Prevalence of LUTS generally increases with age. A large cross-sectional population-based study from the Asia-Pacific region reported LUTS prevalence to be higher in men than women [5]. More men had voiding symptoms (45.3%) than women (31.3%) [5], and the phenomenon could be attributed to BPH. Interestingly, the epidemiologic study showed more storage symptoms (49.9%) in men than voiding symptoms (45.3%). This could be attributed to BOO, which is capable of reducing bladder blood flow and subsequently causes chronic bladder ischemia, as reported by various epidemiologic and clinical studies [6–8]. BOO is also associated with repeated episodes of prolonged detrusor ischemia in pigs with an artificially implanted ring around urethra [9]. BOO causes a reduction in acetylcholine esterase staining nerves in detrusor muscle and expression of hypoxia-inducible factor 1 alpha, a cellular marker of hypoxia [10,11]. Moreover, experimentally, BOO has been shown to exhibit elevated cystometric voiding pressure, reduced urine flow rates, generated bladder hyperactivity, and increased bladder detrusor hypertrophy [12,13]. Further, BOO related bladder ischemia also causes denervation supersensitivity, leading to a fundamental reorganization of the detrusor's electrical activity and C-fiber mediated micturition reflexes [13–16]. BOO with high bladder pressure could also induces adaptive change of bladder wall, including detrusor muscle hypertrophy, bladder wall fibrosis and reduced bladder compliance [17]. Therefore, besides the preconceived voiding symptoms, BPH also causes varied storage symptoms related to bladder response to BOO. In addition, the prevalence of prostatitis-like symptoms in a community-based study was 11.5% and 8.5% in younger (<50 years) and older (≥50 years) men, respectively [18]. This study also measured irritative and obstructive voiding symptom severity (score, 0 to 10), where men with prostatitis-like symptoms showed significantly higher urinary symptom score. Prostatic inflammation is believed to play an important role in the BPH pathogenesis and progression [19,20]. In brief, most BPH related LUTS arises from BPE/BOO, prostatic inflammation, and bladder response to BPE/BOO. Therefore, it is difficult to distinguish the specific etiology of male LUTS through clinical practice. Although the exact mechanism underlying BPH related LUTS is unknown, its treatment should probably be tailored according to the cause of LUTS.
