Current Treatment Guidelines
The goal of treatment is to relieve LUTS and slow the clinical progression of BPH while improving patient QOL. The 2010 updated treatment guideline from the AUA recommend that if the patient presents with LUTS, with or without uncomplicated prostate enlargement, and the symptoms are not affecting his QOL, then no further evaluation or treatment is recommended. The patient should be reassured and scheduled for a follow-up appointment with his physician if necessary.[2] SIDEBAR 1 presents a case report of a patient with BPH.
Watchful Waiting
Watchful waiting or active surveillance is recommended for men who begin experiencing mild symptoms related to BPH. The physician and patient should discuss potential treatment options, including benefits and risks associated with each alternative, and identify a choice treatment based on shared decision-making.[2] Additional optional evaluations could also be pursued at this time. In general, watchful waiting is appropriate in patients who are experiencing some symptoms that have not yet begun to affect their daily life.[2]
Lifestyle Modifications
If patients present with bothersome LUTS that begin affecting their QOL, lifestyle modifications should be recommended initially. Common lifestyle modifications and behavior recommendations include nightly fluid restriction, timed bladder voiding, double-voiding techniques, regular physical activity, treatment of constipation, and avoiding caffeine, alcohol, and highly seasoned or irritative foods.[5] These recommendations help to improve symptoms and prevent progression of symptoms to the point of requiring pharmacotherapy or surgery.
Pharmacotherapy
If lifestyle modifications are insufficient in improving QOL, then pharmacotherapy may be indicated in patients who do not have absolute indications warranting surgery.[5] Current oral pharmacotherapy options for managing BPH include alphaadrenergic antagonists (alphablockers), 5-alpha-reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), and phosphodiesterase 5 (PDE5) inhibitors.[6] A summary of the available agents in each class can be found in Table 1.[5,6]
Alpha-Blockers. This class of medications is indicated for the treatment of patients with moderate-to-severe symptomatic BPH regardless of prostate size.[5] Alpha-blockers work by blocking the alpha-adrenoceptors on the smooth muscle of the prostate, prostatic urethra, and bladder neck, leading to decreased muscle tone and reduction in bladder obstruction.[5] All available alphablockers have comparable efficacy when given at appropriate doses and can help to improve urinary flow rate after a few hours or days after administration. The most common class-related adverse events are summarized in Table 1.[5,6]
In particular, intraoperative floppy iris syndrome (IFIS; i.e., poor pupil dilation and sudden constriction) is an ocular adverse event that may occur in those undergoing cataract surgery.[5] Alpha-blocker treatment should be discontinued prior to cataract surgery and restarted once surgery is complete.[5] Orthostatic hypotension with dizziness may also occur due to vasodilation induced by blockage of alpha-adrenergic receptors. Thus, caution should be exercised in those taking antihypertensive agents or with cardiovascular comorbidities. Vasodilatory effects are more commonly seen with doxazosin and terazosin, and are less common with alfuzosin, tamsulosin, and silodosin.[7]
Patients should be counseled to take alfuzosin, tamsulosin, and silodosin with or immediately after the same meal each day, and to swallow the capsule whole without crushing, chewing, or opening the contents.[8–10] Tamsulosin capsule contents may be mixed with a small amount of acidic fruit juice or soft food when necessary, while silodosin should only be mixed with applesauce.[9,10] Doxazosin and terazosin can be taken without regard to meals. In addition, patients should be cautious when stretching or moving suddenly from a sitting to a standing position in order to avoid orthostatic hypotension.[11,12]
5ARIs. These medications (dutasteride, finasteride) are also recommended for patients with moderate-to-severe symptomatic BPH in addition to an enlarged prostate. An enlarged prostate is defined by gland size >25 mL and/or PSA levels >1.5 ng/mL based on clinical trials.[2] 5ARIs have also been shown to decrease both serum dihydrotestosterone (DHT) and PSA levels, improving maximum urinary flow rate and LUTS with no difference in clinical efficacy between agents.[2,13]
A main difference between the two agents is the serum half-life for each, which is 3 to 16 hours for finasteride and 5 weeks for dutasteride.[14,15] This may have implications on medication adherence and persistence of adverse effects, which may last well after the discontinuation of the drug.[13] Another difference is that finasteride is indicated for male pattern hair loss (androgenetic alopecia), while for dutasteride, it is an off-label use. Both finasteride and dutasteride can be administered with or without food.[14,15] In addition, dutasteride capsules must be swallowed whole to avoid irritation of the oropharyngeal mucosa.[15]
MRAs. These agents (tolterodine, fesoterodine) are recommended for patients experiencing BPH with OAB symptoms. Symptoms may include irritative LUTS such as urinary urgency, with or without urge incontinence, often with frequency and nocturia.[2] MRAs were studied in clinical trials as add-on therapy with alpha-blockers or 5ARIs in cases of OAB associated with BPH. Both tolterodine and fesoterodine demonstrated a significant improvement in storage symptoms, with dry mouth being the most common side effect.[16,17] Patients should be counseled to take these agents without regard to meals and swallow the formulations whole.[16,17]
PDE5 Inhibitors. There has been growing interest in the use of PDE5 inhibitors alone or in combination with previously mentioned therapies in men experiencing LUTS, regardless of preexisting erectile dysfunction (ED).[18] Although the most current update of the AUA guideline for BPH management does not mention treatment with PDE5 inhibitors, the 2013 European Association of Urology (EAU) guidelines report that these agents (i.e., tadalafil, sildenafil, and vardenafil) can be utilized to quickly decrease urinary symptoms and also improve ED.[7,18] Tadalafil currently has a labeled indication for BPH and should be administered around the same time each day without regard to meals.[19]
Combination Therapy. Also available on the market is a fixed-dose combination product of dutasteride (5ARI) plus tamsulosin (alpha-blocker), which is approved for the symptomatic management of BPH.[20] Clinical trials have shown that the synergistic effect of the dual mechanisms of action is significantly superior to tamsulosin and dutasteride monotherapy in symptom improvement as well as reducing BPH clinical progression in men with enlarged prostates.[20] Adverse events were consistent with those seen in monotherapy; however, the frequency of these events was shown to be higher. The AUA guideline recommends the use of this combination therapy in men who have moderate-to-severe symptomatic BPH, an enlarged prostate, and reduced urine flow rate and are at risk for disease progression.[7,20]
Recently, there has also been evidence for the combination of PDE5 inhibitors with 5ARI therapy. One study found that tadalafil (PDE5 inhibitor) combined with finasteride (5ARI) led to an improvement in LUTS associated with BPH, regardless of the presence of ED symptoms.[21] However, there is currently no drug combination product containing both medications available on the market in the U.S.
Phytotherapy. Plant-based or herbal medications have also been used for those experiencing mild-to-moderate LUTS.[22] Clinical trials have shown efficacy in the treatment of LUTS; however, many products are not standardized and long-term safety data are not always available.[22] Although a number of clinical trials of these products are ongoing, the most updated AUA guideline currently does not recommend the use of phytotherapy or other alternative medicines for the management of LUTS secondary to BPH.[2] Commonly seen therapy options may include Serenoa repens (saw palmetto), Pygeum africanum (tree bark), Cucurbita pepo (squash), and Urtica dioica (stinging nettle).[2,22] It is important to weigh the risks and possible benefits of utilizing alternative treatment.
Surgical Treatment
The 2010 AUA guideline states that surgical intervention is appropriate for individuals with moderate-to-severe LUTS, acute urinary retention, or other complications due to BPH.[2] Surgery is the most invasive BPH management strategy. Patients usually fail lifestyle modifications and pharmacotherapy management before proceeding to surgery. Patients may elect to pursue surgery as primary treatment, but the physician and patient should discuss the risks versus benefits and weigh other options.
The AUA guideline recognizes transurethral resection of the prostate (TURP), which involves boring a larger passageway through the center of the prostate allowing for better flow of urine, as the benchmark therapy among the surgical options. In addition, an open prostatectomy may be reserved for men with very enlarged prostate glands (volume >80–100 mL), bladder diverticula, or bladder stones.[2]
US Pharmacist. 2016;41(8):36-41. © 2016 Jobson Publishing
