Although infrequently reported in clinical trials, rhinitis and ejaculatory dysfunction are known side effects of tamsulosin and alfuzosin.30,41 a1-Blockers have recently been reported as possibly having an association with intraoperative floppy iris syndrome (IFIS), a surgical condition that has been observed during phacoemulsification cataract surgery.42 The etiology of this syndrome is unknown. Patients undergoing cataract surgery who are taking a1-blockers should inform their surgeons, who should be prepared for possible modifications to the surgical technique. The benefit of stopping a1-blocker therapy prior to cataract surgery has not been established.43-45
FAST TRACK
Combination a-blocker and 5-a reductase inhibitor therapy is appropriate for patients with larger glands (>40 mL)
5-a Reductase inhibitors. Finasteride and dutasteride are comparable in efficacy and have been shown to decrease prostate volume (20%-30%), lower IPSS ratings 3 to 4 points, increase urine flow rates, and decrease urinary retention and the need for surgery (50%) when compared with placebo.15 Their clinical effect appears gradually over 3 to 6 months, and they are most beneficial when prostate volume exceeds 40 mL.35
Decreased libido (6%), ED (8%), and ejaculatory disorders (4%) are the main side effects of these drugs, as is their lowering of PSA levels by as much as half.15 This latter effect may prompt checking PSA velocities and free:total PSA ratios as a part of prostate cancer screening. Additionally, finasteride may reduce the prevalence of prostate cancer almost 25% compared with placebo, but more high-grade tumors may be associated with its use.36 The reason for this difference and its clinical importance require further study.36,46,47
Combination therapy. Combination therapy with a-adrenergic blockers and 5-a reductase inhibitors has increased due to results from the long-term (4.5 years) Medical Therapy of Prostatic Symptoms (MTOPS) study.32 It compared the efficacy of placebo, doxazosin, finasteride, and combination therapy on clinical progression measures of BPH. These were defined as an increase of 4 points on the IPSS, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infections. All drug treatments significantly improved symptom scores, but the combination was clearly superior.32 Additionally, combination therapy and finasteride significantly reduced urinary retention and the need for surgery, whereas doxazosin did not.
The number needed to treat (NNT) for the prevention of a single instance of clinical progression over a 4-year period was 8.4 for combination therapy, compared with 13.7 for doxazosin monotherapy and 15.0 for finasteride monotherapy (TABLE).32
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Surgery, especially TURP, remains the standard, but is associated with increased ejaculatory dysfunction
A secondary analysis, conducted to establish the NNT for disease progression in patients with larger baseline prostates or higher serum PSA, found that among patients with a PSA level >4.0 ng/mL, the NNT was 4.7 (vs 7.2 for finasteride), and for patients with a prostate volume >40 mL, the NNT was 4.9 (vs 7.2 for finasteride).32 These results suggest that patients with larger glands and higher PSA values, who are at greatest risk for progression, would benefit from combination approaches, although absolute threshold values are not yet clear.4
A combination of an a-adrenergic blocker and an anticholinergic medication may also be used in the treatment of comorbid lower urinary tract symptoms and overactive bladder. A 12-week placebo-controlled trial of a combination of tamsulosin and the anticholinergic tolterodine found significant benefits in terms of IPSS scores, urgency episodes, frequency of micturitions, quality-of-life scores, and patient perception of treatment benefit.48
Phytotherapy. Saw palmetto is derived from the ripe berries of the American dwarf palm (Serenoa repens or Sabal serrulata); retail sales in the United States totaled over $20 million in 2004.49 The mechanism of action is uncertain, but may involve antiandrogen activity. Short-term improvement of nocturia and peak urinary flow comparable with that of finasteride has been suggested by meta-analyses involving almost 3000 patients in trials ranging from 1 month to 1 year.39 However, neither American nor European guidelines recommend its use.4,15,40
A 6-month, double-blind, placebo-controlled trial of urtica dioica (stinging nettle) in 620 BPH patients found a significant improvement in IPSS scores, peak flow rates, and a small but significant reduction in prostate size among patients taking urtica dioica compared with baseline.50
Bothersome symptoms? Consider surgery
Transurethral resection of the prostate (TURP) was the primary surgical approach during most of the 20th century and remains the benchmark. TURP involves removing a portion of the prostate through the urethra.4 When compared with watchful waiting, TURP achieved better outcomes with men most bothered by symptoms at the outset. Watchful waiting was also considered safe, but 24% of this group underwent surgery during the 3 years. There were no increases in urinary incontinence or ED among surgically treated patients.51
