The goals of treating men with LUTS are to improve quality of life with minimal adverse effects and to reduce risk of disease progression.
22-24 If assessment reveals that symptoms are minimally bothersome to the patient, watchful waiting may be appropriate. Continued education, reassurance, ongoing monitoring, and lifestyle modifications should be part of the treatment plan in patients who select watchful waiting. Lifestyle modifications include eating a healthy diet high in fiber, exercising regularly, decreasing fluid intake several hours before going to bed, and decreasing caffeine and alcohol consumption. Primary care physicians can counsel patients on the timing of diuretics, the avoidance of decongestants, and the maintenance of regular bowel function. Many patients are unaware of the anticholinergic effects of most decongestants until after an episode of acute urinary retention; patient education may prevent such an event.
When LUTS are found to be moderate to severe and bothersome, pharmacotherapy should be initiated.
22,25 The first-line treatment for men with predominant voiding symptoms is generally α-adrenergic receptor antagonists (α-blockers), which work by relaxing the smooth muscle tone and increasing the size of the prostatic lumen during urination.
26 Tamsulosin and silodosin are α
1A selective, whereas terazosin, doxazosin, and alfuzosin are nonselective α
1-adrenergic receptor blockers. Treatment response is rapid and should be detectible in 7 to 10 days. The most common adverse effects are dizziness, orthostatic hypotension, and retro-grade ejaculation. The frequency of α-adrenergic receptor antagonists side effects vary depending on the specific drug.
27
If the symptoms are related to a problem with urinary storage, then a trial of anticholinergics may be indicated. However, physicians should use caution when prescribing an anticholinergic medication in men with a history of acute urinary retention or elevated postvoid residual volume greater than 250 mL.
22 Oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin, and trospium are the anticholinergics currently available for the management of OAB.
28,29 Anticholinergics may exert an effect within 1 week but usually achieve their maximal effect after 3 months.
30 The most common adverse effects are dry mouth, dry eyes, and constipation. A major concern regarding the use of anticholinergics in male patients is the risk of urinary retention. However, in the absence of increased postvoid residual volumes, appropriately dosed anticholinergic therapy has shown no greater risk of retention than placebo in randomized controlled trials.
30
The 5α-reductase inhibitors (ARIs) are considered first-line therapy in men with a clinically enlarged prostate and bothersome LUTS. Finasteride and dutasteride are the 2 drugs in this class, and both work by inhibiting the conversion of testosterone to dihydrotestosterone, thereby reducing the size of the prostate by 25%.
31 The most common adverse effects are impotence, decreased libido, decreased volume of ejaculate, and gynecomastia.
32
Available data show that ARIs help prevent the progression of BPE and their ability to reduce the risk for acute urinary retention and the need for surgical intervention is statistically significant.
33 They also usually decrease serum PSA levels by 50% within 6 to 12 months; these levels must therefore be multiplied by 2 when they are monitored for the detection of prostate cancer.
34
In 2013, the US Food and Drug Administration expanded the indications of tadalafil to include LUTS related to BPH.
35 Tadalafil is a type 5 phosphodiesterase (PDE5) inhibitor that has conventionally been used for erectile dysfunction. The PDE5 enzyme is expressed in the bladder, prostate, and urethra. Its inhibition increases smooth muscle relaxation and improves LUTS. Findings of a recent meta-analysis
36 suggested that tadalafil can statistically significantly improve LUTS in men with BPH and can be considered as an alternative treatment option with or without the presence of erectile dysfunction.
In 2012, mirabegron was the first of a new class of β
3-adrenergic agonists approved by the US Food and Drug Administration for the management of OAB.
37 It works by relaxing the detrusor smooth muscle, decreasing afferent signaling from the bladder, improving bladder compliance during filling, and increasing overall bladder capacity. Its most common adverse effects are headache and a mild increase in blood pressure, and it therefore should not be used in patients with uncontrolled hypertension. Mirabegron reduces the number of micturitions and incontinence episodes in a 24-hour period, compared with placebo.
38,39 It also improves OAB symptoms related to BPH without a substantial difference in postvoid residual volumes.
40 Because this drug has been approved for a short period, many questions about how to best implement its use remain unanswered.
Although monotherapy is sufficient for some men, a combination of treatments may be necessary to achieve maximal therapeutic response. Combination therapy with an α-blocker to rapidly reduce LUTS and an ARI to shrink the prostate can be used.
41 The Medical Therapy of Prostate Symptoms and the Combination Avodart and Tamsulosin trials showed that the combination of an α-blocker and an ARI inhibitor prevents progression of BPH better than either agent alone.
41-43 If monotherapy or combination therapy with an α-blocker and an ARI fails to control symptoms to the patient's satisfaction, specialty evaluation is indicated before further treatment.
44 The medical literature supports the use of other combinations of medications for the management of LUTS in specific clinical scenarios. For example, the combination of a PDE5 inhibitor with an α-blocker is significantly more effective than an α-blocker alone in men with LUTS related to BPH.
45 In addition, in men with BPH, a combination of an α-blocker and an anticholinergic can improve quality of life, voiding symptom scores, urinary urgency and frequency, and nocturia better than either agent alone.
46,47 If combination therapy is unsuccessful, surgical intervention may be necessary.