Benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a non-neoplastic glandular and stromal hyperplasia of the transition zone of the prostate. It is a common disorder affecting ∼ 40% of the male population by the age of 50 years. Although the etiology has not been conclusively established, sex hormones (androgens, estrogens, and androgen-estrogen imbalance) have been implicated as a key factor in the development of prostatic hyperplasia. Patients present with symptoms of bladder irritation (urinary frequency, urgency, urge incontinence), bladder outlet obstruction (urinary hesitancy, straining to urinate, sensation of incomplete voiding), and/or hematuria. Digital rectal examination reveals a smoothly enlarged, non-tender, and firm prostate. Diagnosis can be confirmed on abdominal ultrasound which demonstrates an enlarged prostate and increased post-void residual urine in the bladder. Bladder outlet obstruction can be quantitatively measured on uroflowmetry which shows a decreased maximal urinary flow rate. BPH is graded as mild, moderate and severe based on the frequency and severity of the symptoms. Behavioral modifications (e.g., night-time fluid restriction, urinating in a sitting position) are advised in all patients who are managed conservatively. Patients with mild/moderate BPH respond well to medical management with alpha-blockers (tamsulosin, doxazosin), 5-alpha-reductase inhibitors (finasteride), and parasympatholytics (oxybutynin). Severe BPH, unsuccessful medical therapy, and complications due to BPH are indications for surgery (e.g., transurethral resection of prostate, TURP). Complications of BPH include recurrent urinary tract infections (UTIs), urinary retention, bladder calculi, hydroureteronephrosis, and chronic kidney disease. BPH can recur after TURP in ∼ 15% of men. Prostate cancer can occur in patients with BPH, including in those who have undergone TURP. Normal prostate specific antigen (PSA) screening protocol is followed in these patients.

• Benign prostatic hyperplasia (BPH): benign glandular and stromal hyperplasia of the transitional zone of the prostate
• Benign prostatic syndrome (BPS): lower urinary tract symptoms caused by benign hyperplasia of the transitional zone of the prostate
• Bladder outlet obstruction (BOO): any obstruction to urinary outflow from the bladder which presents with lower urinary tract symptoms and is confirmed on urodynamic testing (see “Lower urinary tract obstruction” for causes of BOO)
• Benign prostatic obstruction (BPO): BOO caused by BPH

Prevalence of BPH increases with age (present in ∼ 50% of men > 50 years and more than 80% of men > 80 years). ^[1]

Epidemiological data refers to the US, unless otherwise specified.

The etiology is not fully understood. The following factors play a role in prostatic hyperplasia and growth:

• Hormonal factors
  • Androgens
    • Dihydrotestosterone (DHT) is a potent prostatic growth factor.
    • Gene amplification of androgen receptors (present in the glandular epithelial cells and stromal cells) → increased androgen receptor sensitivity to androgens → prostatic hyperplasia ^[2]
  • Estrogens: Estrogens (mainly estradiol) are potent stimulators of prostatic hyperplasia. ^[3]
  • Androgen-estrogen imbalance: As men age, testosterone levels decline, but estrogen levels remain the same, which results in a higher estrogen/testosterone ratio.
• Stem cell proliferation and longevity: abnormal proliferation and longer prostatic stem cell life-span ^[4][5]
• Genetic susceptibility: Genes involved in the development of BPH include growth factor genes, androgen-regulator genes, apoptosis genes, and androgen-regulated genes. ^[6]

BPH is not a risk factor for the development of prostate cancer.

• The prostate consists of zones and lobes (see “Prostate gland” for more information).
  • The middle transition zone/the lateral and middle prostatic lobes (periurethral lobes) are involved in development of BPH. ^[3]
  • The outer peripheral zone is involved in development of prostate cancer.
• A combination of hormonal factors, stem cell proliferation and genetic susceptibility → glandular and stromal hyperplasia in the transition zone → formation of smooth, elastic, firm hyperplastic nodule → slit-like prostatic urethral compression → BOO → obstructive symptoms of BPH
• Bladder outlet obstruction leads to:
  • Detrusor overactivity (involuntary detrusor contractions during bladder filling) → irritative symptoms of BPH ^[7]
  • Weakening of the bladder wall → incomplete voiding → urinary stasis → predisposition to urinary tract infections, acute/chronic urinary retention, and formation of bladder stones
  • Increased intracystic pressure while voiding → detrusor muscle hypertrophy → bladder trabeculation and pseudodiverticula formation

• Lower urinary tract symptoms (LUTS): the irritative and obstructive symptoms of BPH, grouped together ^[7]
  • Irritative symptoms of BPH
    • Urinary frequency
    • Urinary urgency and urge incontinence
    • Nocturia
    • Occasionally dysuria
  • Obstructive symptoms of BPH
    • Hesitancy
    • Straining to urinate
    • Poor and/or intermittent stream (not continuous)
    • Prolonged terminal dribbling
    • Sensation of incomplete voiding
• Often gross hematuria ^[8][9]
• Digital rectal examination (DRE) findings: symmetrically enlarged, smooth (no nodules), firm, nontender prostate with rubbery or elastic texture
• International prostate symptom score (IPSS): a scoring system based on the presence and severity of seven BPH symptoms in the past 30 days ^[10]
  • Based on the final scores, BPH is graded as follows:
    • 0–7 points: mild symptoms
    • 8–19 points: moderate symptoms
    • 20–35 points: severe symptoms
  • IPSS is also useful as a prognostic marker of disease progression and response to treatment.

To remember the symptoms of BPH, think “FUNWISE”: Frequency, Urgency, Nocturia, Weak stream /hesitancy, Intermittent stream, Straining to urinate, and Emptying (not emptying completely, terminal dribbling).

• Laboratory studies: mainly used to assess complications and rule out accompanying or differential diagnoses ^[11]
  • Prostate specific antigen levels (PSA)
    • Indicated in men with ≥ 10 year life expectancy to identify co-existent prostate cancer, if present ^[12][13]
    • ↑ Free PSA levels
  • Renal parameters (blood urea nitrogen, creatinine, electrolyte levels): indicated in men with high post-void residual volumes
  • Urinalysis and urine culture: to rule out urinary tract infection and hematuria
• Imaging findings
  • Abdominal ultrasound
    • Increased total prostate volume
    • Elevated post-void residual volume (> 100 ml) ^[14]
    • Bladder wall thickening
    • Hydronephrosis
  • Transrectal ultrasound: indicated only if prostate cancer is suspected (e.g., abnormal DRE, elevated serum PSA)
  • Intravenous pyelogram (IVP) ^[15]
    • Elevation of the bladder floor
    • Fishhook appearance of the distal ureters
  • MRI
    • Allows for the lobar classification and preprocedural assessment of prostatic tissue ^[16]
    • Can be used to differentiate BPH from prostate cancer ^[17]
• Maximal urinary flow rate measurement (uroflowmetry): normal maximal urinary flow rate > 15 mL/sec
  • Maximal flow rates < 15 mL/sec: bladder outlet obstruction
  • Maximal flow rates < 10 mL/sec (due to BPH): indication for surgery
• Core needle biopsy
  • Not routinely performed
  • Findings
    • Differentiated prostatic cells
    • Possible corpora amylacea ^[18]

• Other causes of prostatic enlargement
  • Prostate cancer
  • Prostatitis
  • Prostatic abscess
• Other causes of bladder outlet obstruction (see “Urinary tract obstruction” for more information)

The differential diagnoses listed here are not exhaustive.

Conservative management

• Watchful waiting (behavior modifications): indicated as sole therapy in patients with mildly symptomatic BPH or as supplemental therapy in patients requiring medical therapy
  • Restrict fluid intake before bedtime or before going out.
  • Avoid/reduce caffeine and alcohol intake .
  • Ensure complete bladder .
• Medical therapy (monotherapy/combination of two drugs)
  • Indications
    • Mild BPH
    • Uncomplicated moderate BPH with minimal discomfort due to symptoms
  • Alpha-blockers (first-line)
    • Examples: tamsulosin, doxazosin, terazosin, alfuzosin
    • Mechanism of action: α₁ receptors (α_1A receptors) inhibition of the bladder neck and the prostatic urethra → relaxation of the smooth muscle of the bladder neck and the urethra → decreased resistance to urinary outflow → symptomatic improvement
  • 5-alpha-reductase inhibitors
    • Examples: finasteride, dutasteride
    • Mechanism of action: ↓ conversion of testosterone to DHT → lower intraprostatic DHT levels → decreased prostatic growth and increased prostatic apoptosis and involution → improvement of LUTS
    • Additional indications: androgenetic alopecia in males
    • Adverse effects: sexual dysfunction (erectile dysfunction, decreased libido, ejaculatory dysfunction), gynecomastia
  • Parasympatholytics/anticholinergics
    • Examples: oxybutynin, darifenacin
    • Indications: patients with irritative symptoms without an elevated post-void residual volume
  • Phosphodiesterase type 5 inhibitors
    • Example: tadalafil ^[19]
    • Indications: patients with mild/moderate BPH symptoms and erectile dysfunction
• Combination therapy
  • Indications
    • Severe symptoms of BPH
    • Inadequate response to medical monotherapy
  • Severe BPH symptoms and enlarged prostate: alpha-blockers and 5-alpha-reductase inhibitor ^[20]
  • Irritative symptoms and low post-void residual volumes: alpha-blockers and anticholinergics ^[21]

Surgical intervention ^[22]

• Indications
  • Severe BPH symptoms with/without complications
  • Moderate BPH with complications (see “Complications” below)
• Transurethral resection of the prostate (TURP)
  • Procedure: resection of the hyperplastic prostatic tissue under cystoscopic guidance, using a cautery resectoscope
  • Complications ^[23]
    • Retrograde ejaculation: most common complication (∼ 75% of patients)
    • TUR-syndrome: dilutional hypotonic hyponatremia due to the absorption of the irrigant by the open prostatic blood vessels
    • Urinary incontinence
    • Erectile dysfunction (∼ 10%): may be temporary or permanent
    • Urethral strictures (∼ 10%)
    • Recurrent BPH: ∼ 15% of men need to have a TURP again within 10 years.
• Transurethral incision of the prostate (TUIP): indicated in patients with small prostates with obstructive symptoms or those at high risk for surgical complications ^[24]
• Open/laparoscopic/robotic prostatectomy: the laparotomic/laparoscropic removal of the entire prostate gland or a part of it
  • Indicated in patients with very large prostates (> 75 g)
  • Prostatectomy methods ^[25]
    • Freyer transvesical prostatectomy (enucleation of the prostate through the anterior wall of the bladder )
    • Retropubic prostatectomy
    • Perineal prostatectomy
• Other procedures: Laser ablation, radiofrequency ablation, and microwave thermotherapy are the newest techniques used for prostate tissue resection.

Since the peripheral zone (in which prostate cancer most commonly develops) is left intact in TURP, the risk of developing prostate cancer after TURP is the same as that in the general male population. Normal PSA screening protocol should be followed.

Almost all surgical interventions lead to retrograde ejaculation into the bladder because of anatomical changes.

• Recurrent UTI
• Urinary retention with bladder distension and bladder wall thickening (hypertrophy)
• Bladder calculi
• Hydronephrosis
• Chronic kidney disease

We list the most important complications. The selection is not exhaustive.