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  • In an effort to determine

    2022-11-17

    In an effort to determine if one 5ARI was more effective than the other, the Enlarged Prostate International Comparator Study (EPICS) [17] compared treatment with finasteride and dutasteride in 1630 men over the age of 50 and concluded that after one year of treatment, both groups had statistically similar reductions in prostate volume; improvements in the International Prostate Symptom Score (IPSS) were greater with dutasteride than finasteride, but were not statistically significant. A list of key randomized monotherapy trials and results are shown in Table 2A. Effects of 5ARIs in symptomatic relief of BPH-LUTS are presumed to be a result of a reduction in prostate volume [18], so relief requires more time (up to several months) than with the faster acting alpha-blockers, which are thought to work by relaxing the smooth muscle in the prostate and dibromide receptor neck (working within 1–2 weeks) [14]. Therefore, an argument can be made for combination therapy, wherein an alpha-blocker provides rapid relief of symptoms and a 5ARI provides for a long-term reduction in prostate volume and lessens the risk of progression to AUR and/or surgery. A number of studies have examined the effectiveness of combination therapy. The Prospective European Doxazosin and Combination Therapy (PREDICT) [14] and the Medical Therapy of Prostate Symptoms (MTOPS) [19] trials examined the efficacy of treatment with finasteride and alpha-blocker doxazosin either alone or in combination. In the one-year PREDICT trial it was initially determined that doxazosin alone was more effective in improving urinary symptoms than finasteride alone or a combination of the two. Further secondary analysis suggested that the addition of finasteride was more effective in men with larger (>40cm3) prostates, as found in the PLESS, but the PREDICT trial was not designed to take this parameter into account [14]. Analysis of the longer MTOPS trial concluded that finasteride alone or in combination with doxazosin consistently resulted in clinically significant TPV reduction regardless of baseline prostate size [19], [20], [21]. There is still some debate as to the value of using combination therapy and adding a 5ARI in patients with smaller prostates, as opposed to the use of an alpha-blocker alone. The dual 5ARI dutasteride has also been studied in combination with an alpha-blocker. The Combination of Avodart® and Tamsulosin (CombAT) [22] study concluded that dutasteride alone or in combination with the alpha-blocker tamsulosin was significantly more effective than tamsulosin alone in reducing the risk of AUR or eventual surgery. Combination therapy significantly reduced the risk of clinical progression of BPH, but apocrine glands should be noted that there was no placebo arm of this study due to ethical considerations. In a meta-analysis of four studies using randomized controlled data and a total of 10,215 patients, it was determined that at a follow-up time of ≥4 years, combinational therapy with either 5ARI and an alpha-blocker was superior to monotherapy, notably in men with moderately enlarged prostates (starting at 25ml) and significantly better in men with moderate (25–39ml) or large prostates (≥40ml) [23]. Taking another approach, the Symptom Management After Reducing Therapy (SMART) [24] trial demonstrated that dutasteride and tamsulosin can be used together for six months to obtain rapid relief of symptoms, after which time the alpha-blocker can be discontinued and relief maintained using only the 5ARI. Table 2B lists selected combination therapy trials. Overall, drug-related adverse events with treatment tended to be low in these studies with the most common being dizziness (alpha-blockers) and sexual dysfunction (5ARIs) [18]. Based on the current evidence presented in these numerous and various trials, the conclusion can be drawn that the use of 5ARIs, either as monotherapy or in combination with an alpha-blocker, is effective for the treatment of BPH-LUTS in preventing disease progression and the need for invasive surgery. Whether or not there is an additional benefit from the dual 5AR inhibition offered by dutasteride over finasteride or whether there is a difference in long-term adverse outcomes has not been determined [13].