In symptomatic LUTS/BPH patients with large prostates, 5-ARI monotherapy can provide significant symptom relief and prevent progression to AUR and the need for surgery when compared to placebo. A measure of effectiveness of intended treatment “50% rule” applies to the PSA reduction after 3-6 months of 5-ARI treatment as stated in Statement 2.63, 64 The efficacy of 5-ARIs for the treatment of BPH is likely linked to the decrease of conversion of testosterone to dihydrotestosterone (DHT) in the serum and prostatic tissue. Despite both having the ability to bind testosterone receptors in the prostate cells, DHT is more potent than testosterone. By inhibiting the conversion of testosterone to DHT, 5-ARIs will lead to a decrease in transcription and translation of growth signals to the prostatic cell, leading to an increase in apoptosis and atrophy of prostatic tissue. This mechanism will lead to a mean prostate volume reduction ranging from 17.9-21% after 12 and 24 months of medication use, respectively.162, 163 Lower doses of 5-ARIs used for hair loss (typically 1 mg) will also cause PSA reductions of 40% after 48 weeks of using the medication.164 The two isoenzymes responsible for the conversion of testosterone into DHT are 5-alpha reductase enzymes types I and II. These isoenzymes are the targets of the two approved 5-ARIs, finasteride and dutasteride. Finasteride exclusively inhibits the isoenzyme type II while dutasteride can inhibit both types I and II. By blocking both isoenzymes, dutasteride can have a more pronounced reduction in DHT levels in the serum and prostatic tissues of up to 95%, while blocking only the type II isoenzyme, finasteride can lead to a reduction in testosterone activity up to 70%. Dutasteride has a faster onset of clinical effect when compared to finasteride. Although dutasteride has a pronounced DHT reduction when compared to placebo, both dutasteride and finasteride showed significant symptom improvements in patients with BPH.143, 165, 166 Although there are differences in the ability to reduce DHT in the serum and prostatic tissue, studies show no differences in prostate volume reduction, AUA-SI, and Qmax between finasteride and dutasteride. Both medications are an option for monotherapy to treat BPH.167 When considering monotherapy treatment of BPH with 5-ARIs, clinicians and patients should discuss the relationship of prostate volume and PSA levels. Studies have shown that the prostate volume reduction is greater with larger prostates.168 The traditional 40 cc prostate volume cut-off has been challenged by several large studies that used a 30 cc cut-off with significant results, making it reasonable to reduce the prostate volume cut-off to 30 cc when using 5-ARIs.169 Studies with patients on 5-ARI treatment have shown prostate volume reduction, IPSS improvements, decreased risk of AUR, and increase in Qmax are similar in those with pretreatment prostate volumes between 30-40 cc.170, 171 In assessing the volume, the use of dedicated prostate images or reviewing previous cross-sectional images are appropriate for prostate volume assessment. If no dedicated prostate images are available, clinicians should be aware of the inaccuracy of DRE for prostate volume assessment; however, a large palpable prostate may be enough to qualify men for treatment with 5-ARIs. There is usually a correlation between prostate volume and PSA, and higher levels of PSA can be a surrogate for prostate volume. Populational studies have shown strong association between PSA and prostate volume.172 A PSA threshold >1.6 ng/mL has a specificity of 70% for detecting men (without evidence of prostate cancer) with prostates >40 cc.172 Even though 5-ARIs are usually used for patients with PSA >1.5 ng/mL, clinicians do not need to order a PSA if the goal is only to determine eligibility for 5-ARIs. LUTS/BPH can be progressive and could lead to complications such as AUR and the need for BPH-related surgeries. In a large prospective, double-blinded, placebo-controlled trial, men treated with 5-ARIs had a 55% reduced risk of needing surgery, and a 57% reduced risk in developing AUR compared to placebo.173 The findings of this trial suggest that in patients with large prostates and LUTS/BPH, the use of 5-ARIs could alter the natural course of the disease and reduce complications of BPH progression such as AUR and surgery.