By Raman Unnikrishnan, MD; Nima Almassi, MD; and Khaled Fareed, MD
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(This post is an abridged version of a January 2017 Cleveland Clinic Journal of Medicine article.)
Primary care physicians are uniquely positioned to screen for benign prostatic hyperplasia (BPH) and lower urinary tract symptoms, to perform the initial diagnostic workup and to start medical therapy in uncomplicated cases. Effective medical therapy is available but underutilized in the primary care setting.
This overview covers how to identify and evaluate patients with lower urinary tract symptoms, initiate therapy and identify factors warranting timely urology referral.
Two mechanisms: static, dynamic
BPH is a histologic diagnosis of proliferation of smooth muscle, epithelium, and stromal cells within the transition zone of the prostate, which surrounds the proximal urethra.
Symptoms arise through two mechanisms: static, in which the hyperplastic prostatic tissue compresses the urethra (Figure 1); and dynamic, with increased adrenergic nervous system and prostatic smooth muscle tone (Figure 2). Both mechanisms increase resistance to urinary flow at the level of the bladder outlet. As an adaptive change to overcome outlet resistance and maintain urinary flow, the detrusor muscles undergo hypertrophy. However, over time the bladder may develop diminished compliance and increased detrusor activity, causing symptoms such as urinary frequency and urgency. Chronic bladder outlet obstruction can lead to bladder decompensation and detrusor underactivity, manifesting as incomplete emptying, urinary hesitancy, intermittency (starting and stopping while voiding), a weakened urinary stream and urinary retention.
Figure 1. The static component of benign prostatic hyperplasia and lower urinary tract symptoms, with hyperplasia leading to urethral compression.
Figure 2. The dynamic component of benign prostatic hyperplasia. The bladder outlet and prostate are richly supplied with alpha-1 receptors (their distribution represented by blue dots), which increase smooth muscle tone, promoting obstruction to the flow of urine. Alpha-1 adrenergic blockers counteract this effect.
Most men eventually develop BPH
Autopsy studies have shown that BPH increases in prevalence with age beginning around age 30 and reaching a peak prevalence of 88 percent in men in their 80s. This trend parallels those of the incidence and severity of lower urinary tract symptoms. In the year 2000 alone, BPH was responsible for 4.5 million physician visits at an estimated direct cost of $1.1 billion, not including the cost of pharmacotherapy.
BPH can cause lower urinary tract symptoms that fall into two categories: storage and emptying. Storage symptoms include urinary frequency, urgency and nocturia, whereas emptying symptoms include weak stream, hesitancy, intermittency, incomplete emptying, straining and postvoid dribbling.
History and differential diagnosis
Assessment begins with characterizing the patient’s symptoms and determining those that are most bothersome. Because BPH is just one of many possible causes of lower urinary tract symptoms, a detailed medical history is necessary to evaluate for other conditions that may cause lower urinary tract dysfunction or complicate its treatment.
- Obstructive urinary symptoms can arise from BPH or from other conditions, including urethral stricture disease and neurogenic voiding dysfunction.
- Irritative voiding symptoms such as urinary urgency and frequency can result from detrusor overactivity secondary to BPH, but can also be caused by neurologic disease, malignancy, initiation of diuretic therapy, high fluid intake, or consumption of bladder irritants such as caffeine, alcohol and spicy foods.
- Urinary frequency is sometimes a presenting symptom of undiagnosed or poorly controlled diabetes mellitus resulting from glucosuria and polyuria. Iatrogenic causes of polyuria include the new hypoglycemic agents, canagliflozin and dapagliflozin, which block renal glucose reabsorption, improving glycemic control by inducing urinary glucose loss.
- Nocturia has many possible nonurologic causes including heart failure (in which excess extravascular fluid shifts to the intravascular space when the patient lies down, resulting in polyuria), obstructive sleep apnea, and behavioral factors such as high evening fluid intake. In these cases, patients usually have nocturnal polyuria (greater than one-third of 24-hour urine output at night) rather than only nocturia (waking at night to void).
- Hematuria can develop in patients with BPH with bleeding from congested prostatic or bladder neck vessels; however, hematuria may indicate an underlying malignancy or urolithiasis, for which a urologic workup is indicated.
A general examination should include the following:
- Body mass index. Obese patients are at risk of obstructive sleep apnea, which can cause nocturnal polyuria.
- Abnormal gait may suggest a neurologic condition such as Parkinson disease or function.
- Lower abdomen. A palpable bladder suggests urinary retention.
- External genitalia. Penile causes of urinary obstruction include urethral meatal stenosis or a palpable urethral mass.
- Digital rectal examination can reveal benign prostatic enlargement or nodules or firmness, which suggest malignancy and warrant urologic referral.
- Neurologic examination, including evaluation of anal sphincter tone and lower extremity sensorimotor function.
- Bilateral lower-extremity edema may be due to heart failure or venous insufficiency.
The International Prostate Symptom Score
All men with lower urinary tract symptoms should complete the International Prostate Symptom Score (IPSS) survey, consisting of seven questions about urinary symptoms plus one about quality of life. Specifically, it asks the patient, “Over the past month, how often have you….”
- Had a sensation of not emptying your bladder completely after you finish urinating?
- Had to urinate again less than 2 hours after you finished urinating?
- Found you stopped and started again several times when you urinated?
- Found it difficult to postpone urination?
- Had a weak urinary stream?
- Had to push or strain to begin urination?
- Over the past month, how many times did you most typically get up to urinate from the time you went to bed until the time you got up in the morning?
- If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?
Scores are categorized as mild, moderate and severe. The questionnaire can also be used to evaluate for disease progression and response to treatment over time.
Urinalysis is recommended to assess for urinary tract infection, hematuria, proteinuria or glucosuria.
A fluid diary is useful for patients complaining of frequency or nocturia and can help quantify the volume of fluid intake, frequency of urination and volumes voided. The patient should complete the diary over a 24-hour period, recording the time and volume of fluid intake and each void.
Serum creatinine not recommended
Measuring serum creatinine is not recommended in the initial BPH workup, as men at higher risk of renal failure than those without these symptoms.
Prostate-specifi c antigen (PSA) utility extends to guiding the management of BPH. PSA levels correlate with prostate volume and subsequent growth.
In addition, the risks of developing acute urinary retention or needing surgical intervention rise with increasing PSA. Therefore, men with BPH and an elevated PSA are at higher risk with watchful waiting and may be better served with medical therapy.
If the initial evaluation reveals hematuria, recurrent urinary tract infection, a palpable bladder, abnormal findings on digital rectal examination suggesting prostate cancer, or a history of or risk factors for urethral stricture or neurologic disease, the patient should be referred to a urologist for further evaluation (Table 1). Other patients who should undergo urologic evaluation are those with persistent bothersome symptoms after basic management and those who desire referral.
Patients referred for urologic evaluation may require additional tests for diagnosis and to guide management.
- Postvoid residual volume is easily measured with either abdominal ultrasonography or catheterization and is often included in the urologic evaluation of BPH.
- Uroflowmetry is a noninvasive test measuring the urinary flow rate during voiding and is ecommended during specialist evaluation of men with lower urinary tract symptoms and suspected BPH.
- Urodynamic studies. If the diagnosis of bladder outlet obstruction remains in doubt, urodynamic studies can differentiate obstruction from detrusor underactivity.
- Cystourethroscopy is not recommended for routine evaluation of BPH.
Management strategies for BPH
While BPH is rarely life-threatening, it can significantly detract from a patient’s quality of life. The goal of treatment is not only to alleviate bothersome symptoms, but also to prevent disease progression and disease-related complications.
Understanding the natural history of BPH is imperative to appropriately counsel patients on management options, which include
- Watchful waiting
- Behavioral modification
- Pharmacologic therapy
Though men managed with watchful waiting are at no higher risk of death or renal failure than men managed surgically, population-based studies have demonstrated an overall risk of acute urinary retention of 6.8/1,000 person-years with watchful waiting. Older men with a larger prostate, higher symptom score, and lower peak urinary flow rate are at higher risk of acute urinary retention and progression to needing BPH treatment.
There is evidence that patients progressing to needing surgery after an initial period of watchful waiting have worse surgical outcomes than men managed surgically at the onset. This observation must be considered in counseling and selecting patients for watchful waiting. Ideal candidates include patients who have mild or moderate symptoms that cause little bother. Patients electing watchful waiting warrant annual follow-up including history, physical examination, and symptom assessment with the International Prostate Symptom Score (IPSS) survey.
Behavioral modification should be incorporated into whichever management strategy a patient elects. Such modifications include:
- Reducing total or evening fluid intake for patients with urinary frequency or nocturia.
- Minimizing consumption of bladder irritants such as alcohol and caffeine, which exacerbate storage symptoms.
- Smoking cessation counseling.
- For patients with lower extremity edema who complain of nocturia, using compression stockings or elevating their legs in the afternoon to mobilize lower extremity edema and promote diuresis before going to sleep. If these measures fail, initiating or increasing the dose of a diuretic should be considered.
Drugs for BPH include alpha-adrenergic blockers, 5-alpha reductase inhibitors, anticholinergics, beta-3 agonists, and phosphodiesterase-5 inhibitors.
Alpha-adrenergic receptor blockers
In clinical trials in BPH, alpha-blockers improved the symptom score by 30 percent to 45 percent and increased the peak urinary flow rate by 15 percent to 30 percent from baseline values. These agents have a rapid onset (within a few days) and result in significant symptom improvement. They are all about the same in efficacy (Table 2), with no strong evidence that any one of them is superior to another.
Though rapidly effective in reducing symptoms, alpha-blocker monotherapy may not be the best option in men at higher risk of BPH progression, as discussed below.
Before starting this therapy, patients must be counseled about common side effects such as dizziness, fatigue, peripheral edema, orthostatic hypotension and ejaculatory dysfunction.
To maximize efficacy of alpha-blocker therapy, it is imperative to understand dosing variations among agents. Alpha-blocker therapy should be delayed in patients planning to undergo cataract surgery.
5-Alpha reductase inhibitors
There are also two 5-alpha reductase inhibitors: dutasteride and finasteride. Both agents induce apoptosis of prostatic stroma, with a resultant 20 percent to 25 percent mean reduction in prostate volume.
Finasteride and dutasteride are believed to mitigate the static obstructive component of BPH, with similar improvements in urinary flow rate (1.6–2.2 mL/sec) and symptom score (–2.7 to – 4.5 points) in men with an enlarged prostate. Indeed, data from the MTOPS trial showed that men with a prostate volume of 30 grams or greater or a PSA level of 1.5 ng/mL or greater are most likely to benefit from 5-alpha reductase inhibitors. Maximum symptomatic improvement is seen after 3 to 6 months of 5-alpha reductase inhibitor therapy.
In addition to improving urinary flow and lower urinary tract symptoms, finasteride has been shown to reduce the risk of disease progression in men with prostates greater than 30 grams.
Before starting 5-alpha reductase inhibitor therapy, patients should be counseled about common adverse effects such as erectile dysfunction (occurring in 5-8 percent), decreased libido (5 percent), ejaculatory dysfunction (1-5 percent) and gynecomastia (1 percent).
Given its superior efficacy and benefits in preventing disease progression, combination therapy (the alpha-blocker, doxazosin, and the 5-Alpha reductase inhibitor, finasteride) should be considered for men with an enlarged prostate and moderate to severe lower urinary tract symptoms.
Anticholinergics were historically contraindicated in men with BPH because of concern about urinary retention. However, in men with a postvoid residual volume less than 200 mL, anticholinergics do not increase the risk of urinary retention. Further, greater symptom improvement has been demonstrated with the addition of anticholinergics to alpha-blocker therapy for men with BPH, irritative lower urinary tract symptoms, and a low postvoid residual volume.
An alternative to anticholinergic agents is the beta-3 agonist mirabegron. Mirabegron does not have anticholinergic side effects and is generally well tolerated, though poorly controlled hypertension is a contraindication to its use.
Phosphodiesterase-5 (PDE5) inhibitors, a mainstay in the treatment of erectile dysfunction, have demonstrated significant improvement in lower urinary tract symptoms with an average two-point IPSS improvement on a PDE5 inhibitor compared with placebo.
Tadalafil is the only drug of this class approved by the FDA for the treatment of lower urinary tract symptoms, though other agents have demonstrated similar efficacy.
Dual therapy with a PDE5 inhibitor and an alpha-blocker has greater efficacy than either monotherapy alone; however, caution must be exercised as these agents are titrated to avoid symptomatic hypotension. Lower urinary tract symptoms and sexual dysfunction often coexist; PDE5 inhibitors are appropriate in the management of such cases.
Surgery for BPH
Even with effective medical therapy, the disease will progress in some men. In the MTOPS trial, the four-year incidence of disease progression was 10 percent for men on alpha-blocker or 5-alpha reductase inhibitor monotherapy and 5 percent for men on combination therapy. Between 1 and 3 percent of those in the various treatment groups needed surgery.
A number of effective surgical therapies are available for men with BPH, providing excellent one-year outcomes including a mean 70 percent reduction in IPSS and a mean 12 mL/sec improvement in peak urinary flow. With this in mind, patients whose symptoms do not improve with medical therapy, whose symptoms progress or who simply are interested in surgery should be referred for urologic evaluation.
Full references for this article are included in the unabridged version in the Cleveland Clinic Journal of Medicine. Dr. Unnikrishnan is a former urology resident now practicing in Virginia.