3 In this paradigm of clinical BPH, the dynamic component of BOO was mediated by the tension of prostate smooth muscle via α-adrenoceptors. The static component of BOO was attributed to the anatomic obstruction resulting from bulk enlargement of the prostate, which was under the regulation

of androgens. Because the proliferative process of BPH involved both smooth muscle and epithelial hyperplasia,4 it was reasonable to assume that both histologic elements contributed to the underlying pathophysiology of BOO and the disease.5 Inhibitors,research,lifescience,medical Beginning in the 1990s, the first multicenter, randomized, doubleblind, placebo-controlled studies confirmed the clinical effectiveness of α-blockade6 and androgen deprivation therapy7 for the treatment of BPH. In these studies, Inhibitors,research,lifescience,medical α-blockade and androgen deprivation therapies were achieved using selective long-acting α1-blockers and 5α-reductase inhibitors (5ARIs), respectively. The agents represented a significant advancement over the drugs used in the early

1970s to achieve α-blockade and androgen deprivation, due primarily to better drug tolerance and ease of administration. The amelioration of side effects was a fundamental step forward because the pharmacologic improvement of quality of life via improvement of lower urinary tract symptoms (LUTS) mandated drugs with exceptionally Inhibitors,research,lifescience,medical favorable tolerability. The Veterans Affairs (VA) Cooperative Trial8 was the first study to compare the effectiveness of α-blockers, 5ARIs, the combination of these drugs, and placebo in a cohort of men with Inhibitors,research,lifescience,medical clinical BPH. The study demonstrated that effectiveness (symptom improvement and increase in peak urinary flow rate) was only observed in the α-blockade and combination arms. There were no significant differences in efficacy between placebo and the 5ARI groups or the α-blocker and combination groups. These studies were interpreted to show that in men designated as having clinical BPH, 5ARIs exhibit no effectiveness

and simply act as a placebo. A second Inhibitors,research,lifescience,medical multicenter study using a different α-blocker confirmed the results of the VA Cooperative Trial.9 How does one resolve the apparent contradiction of the literature as it relates to 5ARIs? The answer is quite simple. All of the phase III BPH studies enrolled the XAV-939 in vivo subset of men with exceptionally large ADP ribosylation factor prostates, whereas the VA Cooperative Trial8 and the Prospective European Doxazosin and Combination Therapy (PREDICT) trial9 enrolled all men with clinical BPH. 5ARIs exhibit clinical effectiveness only in men with “large” prostates, which represents a relatively small subset of men classified as having clinical BPH; therefore, only those studies enrolling men with “large” prostates demonstrated the clinical effectiveness of 5ARIs.