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Evaluation and Medical Management of Benign Prostatic Hyperplasia
Benign prostatic hyperplasia (BPH) is common among aging men. Untreated BPH may lead to complications including urinary tract infection, acute urinary retention, and obstructive nephropathy.
Diagnosing BPH can be challenging because lower urinary tract symptoms are found in conditions other than BPH, and prostate size correlates poorly with symptoms of obstruction. Nonetheless, a careful medical history and physical examination, along with prudent use of diagnostic tests, can yield an accurate diagnosis. We review the evaluation of men with suspected BPH and indications for referral to a urologist for invasive therapy. We also review supporting evidence and treatment considerations for saw palmetto and the 2 major classes of prescription medications, α adrenergic antagonists and 5α-reductase inhibitors.
Mayo Clin Proc. 2005;80(10):1356-1362
AUA-SS = American Urological Association Symptom Score; BPH = benign prostatic hyperplasia; DHT = dihydrotestosterone; DRE = digital rectal examination; ED = erectile dysfunction; LUTS = lower urinary tract symptoms; PSA = prostate-specific antigen
Benign prostatic hyperplasia (BPH) is common in older men. The prostate is about the size of a walnut (20 cm[Angstrom]) in men younger than 30 years, but its size increases gradually, leading to BPH in most men older than 60 years.1,2 Benign prostatic hyperplasia results from the growth of epithelial and stromal cells. Hyperplasia begins in the transition zone of the prostate gland,3 causing urinary outflow resistance. Eventually, this resistance may lead to detrusor dysfunction, bladder trabeculation, and uninhibited bladder contractions.4
There is evidence that BPH progresses when untreated. Rhodes et al5 showed that prostate volumes increase steadily by 1.6% per year. For 6 years, Roberts et al6 monitored 492 men older than 40 years and showed that peak urinary flow rates declined by 2.1% per year. Jacobsen et al7 studied 2115 men older than 40 years who experienced a gradual increase in prostate symptom severity. Furthermore, the 5- year cumulative incidence of acute urinary retention ranged from 1.6% among men aged 40 to 49 years to 10% among men aged 70 to 79 years.8 Other complications of BPH include hypotonie bladder, hematuria from friable prostatic blood vessels, bladder calculi, urinary tract infections, and obstructive nephropathy.4
Diagnosing BPH and determining its clinical prevalence is challenging because diagnostic criteria are not always reliable in men presenting with lower urinary tract symptoms (LUTS). Specifically, prostate size correlates poorly with LUTS,9-11 and numerous conditions other than BPH can cause LUTS.12,13 Nevertheless, criteria such as symptom severity, prostatic enlargement on digital rectal examination (DRE), and abnormal results from uroflow studies with increased postvoid residual urine aid in diagnosis of BPH.14 On the basis of clinical criteria, the Baltimore Longitudinal Study of Aging found that the prevalence of BPH is approximately 25% in men aged 40 to 49 years, 50% in men aged 50 to 59 years, and 80% in men aged 70 to 79 years.1 Notably, the clinical prevalence of BPH generally correlates with autopsy data.1,2,15
Medical management of BPH
This article focuses on the medical management of BPH, but it is important for clinicians to recognize the indications for referral to a urologist for consideration of invasive therapy. These indications are moderate to severe symptoms, persistent gross hematuria, urinary retention, renal insufficiency due to BPH, recurrent urinary tract infections, and bladder calculi.12
Watchful waiting is a reasonable approach for patients with mild to moderate symptoms.12 These patients are monitored at least yearly or if new symptoms arise. Also, these patients may be advised to practice scheduled voiding (every 3 hours during the day) to avoid excessive evening fluid intake, and to be aware of the potential adverse effects that over-the-counter decongestants can have on voiding.
Most patients presenting initially with BPH are candidates for medical therapy. Moreover, medical therapy has replaced interventional therapy as the most common treatment of BPH.13 The categories of prescription medications currently available for treating BPH are α^sub 1^-adrenergic antagonists (eg, tamsulosin) and 5α-reductase inhibitors (eg, finasteride). These medications act on dynamic and static components of bladder outlet obstruction.13,29
α^sub 1^-Adrenergic antagonists are the initial choice of medical therapy for most men with BPH. Medications from the α^sub 1^-adrenergic antagonist category act on the dynamic component of bladder outlet obstruction by relaxing prostate smooth muscle. A meta-analysis by Djavan and Marberger30 reviewed the randomized controlled trials of the α^sub 1^-adrenergic antagonists used for treatment of BPH. The authors found that, although all these medications are equally efficacious for treating BPH, terazosin and doxazosin have higher adverse effect profiles (namely, orthostatic hypotension) than do other medications from this class. Other common adverse effects of α^sub 1^- adrenergic antagonists include dizziness, headache, nasal congestion, hypotension, edema, palpitations, erectile dysfunction (ED), and fatigue.
Because aging men make up a large proportion of the population, the prevalence and treatment of BPH and ED will increase (indeed, this fact has spawned recent research regarding the relationship between BPH and ED).31 Therefore, it is important to recognize that combining phosphodiesterase type 5 inhibitors (eg, sildenafil) with medications from the α^sub 1^-adrenergic antagonist class can cause profound hypotension. Recommendations regarding combinations of these medications are as follows: (1) sildenafil should not be taken within 4 hours of any α^sub 1^-adrenergic antagonist, (2) vardenafil should not be taken with any α^sub 1^-adrenergic antagonist, and (3) tadalafil should not be taken with any α^sub 1^-adrenergic antagonist except tamsulosin at a 0.4-mg dose.
The second class of medications available for treatment of BPH is the 5α-reductase inhibitors, which act on the static (anatomical) component of bladder outlet obstruction. These medications work by reducing the conversion of testosterone to dihydrotestosterone (DHT) in the prostate, thereby limiting prostate growth. The 2 currently available 5α-reductase inhibitors are finasteride and dutasteride.
Numerous studies reveal the efficacy of, and guide the appropriate prescribing of, finasteride. McConnell et al32 showed that finasteride, compared with placebo, reduces the risks of urinary retention (relative risk, 0.57; P<.001) and surgery (relative risk, 0.55; P<.001), improves urinary flow rates, and decreases prostate volume (P<.001). Results from this study also showed that 6 to 12 months of therapy may be required to see the full effect from the drug. Hence, patients are counseled that they may need to take finasteride for several months before they notice symptom improvement. Abrams et al33 reported that outcomes with finasteride are most favorable in men with large prostate glands (>40 mL). For this reason, finasteride often is used as initial therapy for men with moderate to severe BPH. A randomized placebo- controlled trial by Gormley et al34 showed that finasteride significantly decreased symptom scores and prostate volume and increased maximal urinary flow rates. Moreover, patients taking finasteride experienced significant reductions in serum PSA level. On this basis, experts advocate correction of the assessment of PSA level in patients taking finasteride by multiplying the PSA value by 2.13,35
Finasteride is well tolerated, and serious adverse effects are uncommon. The most frequent adverse effects are related to sexual dysfunction and include decreased libido, ejaculatory dysfunction, and ED. Other adverse effects include gynecomastia and orthostatic hypotension.
Dutasteride, the second medication from the 5α-reductase inhibitor class, inhibits 5α-reductase isoenzyme types 1 and 2,36 whereas finasteride inhibits only 5α-reductase isoenzyme type 2. Likewise, clinical trials in men with BPH showed that dutasteride reduced serum DHT levels by 93%,37 whereas finasteride reduced serum DHT levels by only 70%.38 The safety of dutasteride was shown by a pooled analysis of 3 randomized, blinded placebo- controlled trials. In this analysis,37 at 2-year follow-up, patients taking dutasteride experienced significant reductions in symptom scores, prostate volumes, and risk of surgical intervention. Only 1 clinical trial compared outcomes in patients taking dutasteride vs finasteride.39 The Enlarged Prostate International Comparison Study randomized 1630 patients with BPH to either dutasteride or finasteride.40 Study findings included no significant differences in prostate volume reduction or improvement in urinary flow rates.39 The most common adverse effects, which did not differ significantly between intervention groups, were related to sexual dysfunction.39
Evidence supports combining an α^sub 1^-reductase inhibitor and a 5α-reductase inhibitor when treating BPH; in men with large prostate glands and elevated PSA levels, combination therapy should be considered the first-line approach. The Medical Therapy of Prostatic Symptoms (MTOPS) trial involved 3407 men with BPH who were randomized to placebo, doxazosin, finasteride, or combination therapy.41 Significant findings were a 66% reduction of clinical progression with combination therapy (P<.001), a reduced risk of acute urinary retention or need for invasive therapy with combination therapy (P<.001), and improved symptom scores with invasive therapy (P<.001). However, the most remarkable finding was the low number needed to treat (8.4) to prevent 1 instance of overall clinical progression with combination therapy.
Herbal medicines used to treat BPH include derivatives from African star grass, African plum tree bark, rye grass pollens, stinging nettle, and cactus flower.42 The most commonly used alternative treatment for BPH is saw palmetto (Serenoa repens). Many mechanisms for saw palmetto have been entertained, yet none are proven.43 Saw palmetto is considered safe, and available evidence supports its effectiveness.43-45 In a large European trial by Carraro et al,44 1098 men were randomized to saw palmetto or finasteride. Both treatment arms experienced the same improvement in symptom scores. Furthermore, a meta-analysis by Boyle et al45 showed that compared with placebo, saw palmetto improves peak urinary flow rates and reduces nocturia in men with BPH.
Conclusions: Benign prostatic hyperplasia is common, with clinical evidence for BPH occurring in most men older than 60 years. Although diagnosing BPH can be challenging, obtaining a medical history including an AUA-SS, performing a careful physical examination, and using urinalysis, PSA, and uroflow studies can help exclude other causes of LUTS. Before initiation of medical therapy, indications for referral to a urologist and consideration of invasive therapy should be reviewed. α^sub 1^-Adrenergic antagonists, which act on the dynamic component of bladder outlet obstruction, are the initial choice of medical treatment in most men with BPH. However, in men with large prostate glands (>40 mL), higher PSA levels, and moderate to severe symptoms, treatm\ent with 5α-reductase inhibitors or combination therapy should be considered. Finally, evidence supports the use of saw palmetto for treatment of BPH in men who prefer herbal therapies.
We acknowledge Drs Haitham S. Abu-Lebdeh, Alan K. Duncan, and J. Taylor Hays of the Mayo Clinic Men's Health Center for Urology for their thoughtful comments on the submitted manuscript.