Shaun G.S. Grewal, MD
Gerald L. Andriole, MD, FACS
BASICS
DESCRIPTION
• Benign prostatic hypertrophy (BPH) refers to histologic changes within the prostate gland.
– May not imply the presence of an enlarged prostate or symptoms.
– LUTS are 1 manifestation of BPH.
– Synonym(s): Nodular hyperplasia
• Definitions from the International Continence Society (ICS):
– Benign prostatic hyperplasia is a term used (and reserved for) the typical histologic pattern which defines the disease.
– Benign prostatic obstruction is a form of bladder outlet obstruction (BOO) and may be diagnosed when the cause of outlet obstruction is known to be benign prostatic enlargement, due to histologic benign prostatic hyperplasia.
– Benign prostatic enlargement (BPE) is defined as prostatic enlargement due to histologic benign prostatic hyperplasia. The term “prostatic enlargement” should be used in the absence of prostatic histology.
EPIDEMIOLOGY
Incidence
• 50% of men >40 yr will develop histologic evidence of BPH
– 30–50% of these men will develop bothersome LUTS (1)
Prevalence
• Histologic prevalence of BPH increases with age:
– 10% for men in their 30s
– 20% for men in their 40s
– 50–60% for men in their 60s
– 80–90% for men in their 70s and 80s
• Men with significant prostate enlargement (>50 cc) 3.5 times more likely to have moderate-to-severe LUTS (2)
– BPH is a histologic diagnosis that does not always result in clinical LUTS
RISK FACTORS
• Although family history and advancing age are risk factors for BPH, evidence for comorbidity, environmental, dietary, or lifestyle-related risk factors are generally weak.
• Massachusetts Male Aging Study: Cigarette smoking and increased physical activity protective against BPH, heart disease correlated with development of BPH. Possible association between obesity and prostate volume/LUTS.
Genetics
Some men with younger age of onset and larger glands have a family history of BPH.
PATHOPHYSIOLOGY
• BPH/LUTS begins with abnormal microscopic hyperplasia and macroscopic growth. Causes outflow obstruction and obstructive voiding symptoms (decreased force of stream, intermittent stream, and hesitancy).
• Detrusor response to increased resistance is to generate higher pressures to overcome the outlet resistance. Leads to a variety of cellular and morphologic changes in the bladder. Causes the common storage symptoms of frequency, urgency, and nocturia.
• May lead to bladder decompensation, in which the bladder is no longer able to generate sufficient pressures to empty.
• Primary androgen-dependent growth process involves periurethral and transition zones of the prostate.
ASSOCIATED CONDITIONS
• OAB (overactive bladder defined as urinary frequency, urgency, nocturia, urge incontinence)
• Sexual dysfunction (erectile and/or ejaculatory dysfunction)
GENERAL PREVENTION
• Randomized clinical trials (MTOPS) suggested that the combination of an α-blocker with a 5α-reductase inhibitor (5-ARI) can reduce the lifetime risk of acute urinary retention and may prevent symptomatic disease progression in men with enlarged prostate volume (>25 cc) (3).
• Bladder decompensation may be prevented by treatment of BOO.
DIAGNOSIS
HISTORY
• Focus on identifying the presence of LUTS
– Voiding symptoms (previously called obstructive symptoms): Hesitancy, intermittency, weak stream, abdominal straining to void, postvoid dribbling, incomplete emptying, double voiding)
– Storage symptoms (previously called irritative symptoms): Daytime frequency, nocturia, urgency, urge incontinence, enuresis, dysuria)
• Identify other contributing factors to LUTS
– Medications (ie, diuretics, cold medications)
– Comorbidities (ie, diabetes, multiple sclerosis, Parkinson)
• Previous interventions/therapies
• Family history
• IPSS is a reproducible, validated index designed to determine disease severity and response to therapy:
– Scores of 0–7, 8–19, and 20–35 signify mild, moderate, and severe symptoms, respectively.
– Equivalent to AUASS with the addition of a quality of life (QOL) score
PHYSICAL EXAM
• Evaluation of the abdomen, pelvis, perineum
• Examine external genitalia
• DRE to estimate prostate size and detect any nodularity suggestive of prostate cancer:
– Anal sphincter tone and sensation should be noted
• Focused neurologic exam on the anus and lower extremity motor and sensory function. A more extensive neurologic exam is indicated for patients with possible neurogenic lower urinary tract dysfunction
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis to exclude hematuria or evidence of infection
• PSA:
– May be a proxy for prostate size
PSA of 1.5 ng/dL correlates with prostate volume >30 mL in most men (4)
– Informed discussion of risks/benefits of PSA screening warranted
• Urine cytology: Not considered standard; only if there is a predominance of irritative symptoms, hematuria, and/or risk factors for bladder cancer such as smoking
Imaging
• Not indicated unless there is evidence of upper tract deterioration or a need to further evaluate hematuria
• TRUS may be beneficial in determining accurate size prior to surgical intervention
Diagnostic Procedures/Surgery
• Uroflowmetry is a simple noninvasive urodynamic measurement in which a patient voids into a device that measures the volume/time of urine accumulation:
– Combined with a measurement of PVR (post void residual) volume (see next heading below), it is an excellent screening tool for BOO in men with LUTS.
– Uroflowmetry measures voided volume, voiding time, average flow rate, and maximum flow rate (Qmax), also called the PFR.
– Qmax: The single best measurement obtained by this study to assess voiding dysfunction. While formal definitions vary, in general with a voided volume of >125–150 mL, a Qmax of >15 mL/s is often considered normal, whereas a value of <7 mL/s is suggestive of significant obstruction.
– May need urodynamics to differentiate BOO from hypocontractile bladder (pressure flow study).
Obstruction confirmed with low flow (Qmax <15 mL/s) and high voiding pressure >60 cm water.
• PVR: Although generally used, PVR does not convincingly correlate with the severity of LUTS, the presence of BOO, or treatment outcomes:
• Voiding diary to evaluate for occult polyuria or polydipsia.
• Cystoscopy not essential unless there is concern for malignancy, obstruction due to foreign body, or stricture. May be useful to evaluate for most appropriate surgical or minimally invasive treatments.
Pathologic Findings
• Varying degrees of glandular and stromal nodular hyperplasia (as such, hypertrophy is a misnomer). The glandular component is made up of small and large acini lined by basal and secretory cells. The stromal component is rich in smooth muscles. Nodular growth is a major histologic component of BPH.
• Diffuse stromal infiltration of plasma cells and lymphocytes can be seen, but no infectious agent nor clinical diagnosis of prostatitis is typically present.
DIFFERENTIAL DIAGNOSIS
• Obstructive symptoms: Detrusor sphincter dyssynergia, foreign body, meatal stenosis, neurogenic bladder, pelvic floor dysfunction, prostate cancer, prostatic abscess, prostatitis syndrome, urethral obstruction (stricture, condyloma)
• Irritative/storage symptoms: Bladder cancer, detrusor hyperreflexia/OAB, interstitial cystitis, polyuria/polydipsia, prostatitis syndromes
TREATMENT
GENERAL MEASURES
• Directed at QOL unless evidence of significant damage to urinary tract from obstruction (hydronephrosis, bladder calculi, recurrent infections)
• Guidelines suggest watchful waiting for men with mild symptoms IPSS ≤7 or for more severe symptoms if they are not bothersome to the patient. Simple behavior modification (fluid restriction, decreased alcohol/caffeine) may help
• Medical therapy considered 1st-line by most, but usually requires continuous therapy to maintain benefit
• α-Blocker and 5-ARIs often prescribed together
MEDICATION
First Line
• α-Blockers (reduce muscle tone in prostate/bladder neck):
– Terazosin (start 1 mg/d to max 20 mg)
– Doxazosin (start 1 mg/d to max 8 mg; XL form 2–8 g/d)
– Tamsulosin (start 0.4 mg to max 0.8 mg)
– Alfuzosin (10 mg/d)
– Silodosin (8 mg/d)
Dizziness, orthostatic hypotension, and ejaculatory dysfunction are most common side effects
• 5-ARIs (block intracellular DHT conversion; generally best for larger glands, may take 6–12 mo for improvement):
– Finasteride (5 mg/d)
– Dutasteride (0.5 mg/d)
• α-Blocker (tamsulosin 0.4 mg) combined with 5-ARI (dutasteride 0.5 mg)
Second Line
• Antimuscarinic agents may help with bladder overactivity:
– Various agents including oxybutynin (5 mg TID), tolterodine (2–4 mg/d), solifenacin (5–10 mg/d), others
• Phosphodiesterase-5 inhibitor
– Tadalafil (2.5–5 mg/d)
FDA approved for LUTS secondary to BPH
Contraindicated in patients on nitrates, nonselective α-blockers, and CYP 450 inhibitors
Side effects include back pain, dizziness, headache, and dyspepsia (5)
SURGERY/OTHER PROCEDURES
• Often considered 2nd-line after failure of medical therapy; may be 1st-line in retention or if very large prostate.
• TURP represents gold standard against which all other therapies are compared.
• Open simple prostatectomy usually for glands >100 g:
– Suprapubic prostatectomy: Enucleation of adenoma through bladder; useful with coexisting problems such as very large bladder calculi or to repair diverticulum
– Retropubic simple prostatectomy: Enucleation of adenoma through incision in anterior prostate commissure
• Many minimally invasive alternative surgical procedures: Microwave- and water-induced hyper thermia, transurethral needle ablation, laser vaporization (contact, noncontact, interstitial, diode), laser prostatectomy (holmium, KTP)
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Prostatic stents; best if need TURP but poor surgical risk
• Prostatic urethral lift (UroLift TM) mechanically opens the prostatic urethra with UroLift implants that are placed transurethrally under cystoscopic visualization, thereby separating the encroaching prostatic lobes (6)
Complementary & Alternative Therapies
Phytotherapy (plant extracts) includes saw palmetto, Pygeum africanum; β-sitosterols have limited support in the literature
ONGOING CARE
PROGNOSIS
• Symptoms usually well managed by medications
• Progression of disease, when risk factors identified, can be well managed
COMPLICATIONS
• Generally accepted sequelae of untreated, undertreated, or progressive BPH
• Historically, many men typically had complications of BPH including UTIs, hematuria, bladder calculi, bladder decompensation, incontinence, and upper tract deterioration. With modern awareness and management techniques, this is less common.
• The most commonly used endpoints in medical trials are symptom deterioration, BPH-related surgery, and AUR. AUR continues to be the most widely accepted and most scientific endpoint, although the exact pathophysiologic mechanism is not completely understood.
FOLLOW-UP
Patient Monitoring
• Periodic monitoring depending on severity of symptoms
– Monitor response to therapy with history, AUA SS, PVR, flow rate
– Upper tract imaging and measure of renal function if elevated PVR (>300 cc)
Patient Resources
Urology Care Foundation. www.urologyhealth.org
REFERENCES
1. Roehrborn C. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia. Med Clin North Am. 2011;95:87–100.
2. Bushman W. Etiology, epidemiology and natural history of benign prostatic hyperplasia. Urol Clin North Am. 2009;36:403–415.
3. McConnel JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387–2398.
4. Roehrborn CG, Boyle P, Gould AL. Waldstreicher J Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology. 1999;53(3):581–589.
5. Cantrell MA, Baye J, Vouri SM. Tadalafil: A phosphodiesterase-5 inhibitor for benign prostatic hyperplasia. Pharmacotherapy. 2013;33(6):639–649.
6. McNicholas TA, Woo HH, Chin PT, et al. Minimally invasive prostatic urethral lift: surgical technique and multinational experience. Eur Urol. 2013;64(2):292–299.
ADDITIONAL READING
• AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol. 2003;170:530–547.
• McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185:1793–1803.
See Also (Topic, Algorithm, Media)
• Bladder Outlet Obstruction (BOO)
• Lower Urinary Tract Symptoms (LUTS)
• Prostate, Benign Hyperplasia/Hypertrophy (BPH) Image 
• Prostate, Stents (UroLume and Spanner)
• Reference Tables: AUA Symptom Index/International Prostate Symptom Score (I-PSS)
CODES
ICD9
• 600.00 Hypertrophy (benign) of prostate without urinary obstruction and other lower urinary tract symptom (LUTS)
• 600.01 Hypertrophy (benign) of prostate with urinary obstruction and other lower urinary tract symptoms (LUTS)
• 600.10 Nodular prostate without urinary obstruction
ICD10
• N40.0 Enlarged prostate without lower urinary tract symptoms
• N40.1 Enlarged prostate with lower urinary tract symptoms
• N40.2 Nodular prostate without lower urinary tract symptoms
CLINICAL/SURGICAL PEARLS
• 5-ARIs (such as finasteride and dutasteride) contraindicated if prostate enlargement absent (<25 g).
• Goal of treatment is improving symptoms/QOL.