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Benign Prostatic Hyperplasia (BPH): Definition, Epidemiology and Etiology

• Benign prostatic hyperplasia: definitions, epidemiology and etiology
• Benign prostatic hyperplasia: signs and symptoms
• Benign prostatic hyperplasia: diagnosis
• Benign prostatic hyperplasia: medical treatment
• Benign prostatic hyperplasia: surgical treatment

Definitions of Benign Prostatic Hyperplasia and Benign Prostatic Syndrome

Pathological Definition

Benign prostatic hyperplasia (BPH) is a common hyperplasia of the periurethral transition zone of the prostate. It involves epithelial and stromal components and may lead to a grossly nodular enlargement of the organ.

Lower Urinary Tract Symptoms (LUTS)

Lower urinary tract symptoms are the collective term for voiding and storage symptoms. They are not specific to benign prostatic syndrome (BPS).

Clinical Definition

LUTS, bladder dysfunction, hematuria, urinary tract infections, urinary retention, or decompensation of the upper urinary tract caused by BPH are termed benign prostatic syndrome (BPS). See the EAU Guidelines on Non-neurogenic Male LUTS and the DGU Guideline.

Epidemiology of Benign Prostatic Hyperplasia and Benign Prostatic Syndrome

Epidemiologic data on BPH and BPS depend strongly on the definition used: histologic findings, prostate volume, uroflowmetry, subjective symptoms, objective findings, or combined criteria.

Pathological Prevalence of BPH

Histologically, the prevalence of BPH increases with age, beginning at approximately 35 years. The prevalence increases by approximately 15% per decade. Histologic BPH is present in nearly all men aged 90 years.

Prostatic Enlargement

Prostate volume increases with age, from approximately 25 ml at 30–35 years to approximately 40–45 ml at 80 years.

Maximum Urinary Flow Rate

Maximum urinary flow decreases with age. In a population-based cohort, median maximum flow decreased from approximately 20 ml/s at 40–44 years to approximately 12 ml/s at 75–79 years; median voided volume decreased simultaneously from approximately 356 ml to 223 ml.

Combined Assessment

Clinically significant BPH is better identified by combining symptoms (IPSS), urinary stream, postvoid residual volume, and prostate volume than by using individual parameters. The risk of developing clinically significant BPS is approximately 10–20% at 50–59 years and approximately 25–35% at 60–79 years.

Mortality

BPS-associated mortality has decreased substantially in Western countries. Causes of death are postrenal kidney failure and urosepsis.

Urinary Retention

The incidence of urinary retention is 50–200 per 100,000. Severe LUTS, large prostate volume, low maximum urinary flow, and advanced age increase the risk.

Risk of Surgery

The incidence of surgical BPS treatment is declining. In 2007, approximately 60,000 surgical procedures for BPH were performed in Germany (75 per 100,000).

Epidemiologic Risk Factors

Age, genetic factors, metabolic comorbidities, obesity, and physical inactivity are relevant risk factors for BPH and BPS.

Medication

Anticholinergics, sympathomimetics, tricyclic antidepressants, antihistamines, opioids, and bronchodilators may worsen LUTS or precipitate urinary retention.

Prostate Cancer

Clinical BPS is associated with an increased incidence of prostate cancer and, in registry studies, with increased prostate cancer mortality (Ørsted et al., 2011). However, BPH is not considered a precancerous lesion. The association is probably explained by age, detection bias, diagnostic selection, comorbidity, and possibly delayed cancer diagnosis. A causal increase in risk has not been established (Kopp et al., 2011).

Etiology of Benign Prostatic Hyperplasia

Hyperplasia

Prostatic hyperplasia increases stromal and epithelial cell components. Molecular data favor reduced apoptosis and altered differentiation, rather than cell proliferation alone, as the cause of increased cell number in BPH. Despite the increased number of glandular cells, the secretory capacity of the prostate decreases with age.

Androgens

Androgens are necessary for the development of BPH; castrated men do not develop BPH. Circulating testosterone is converted to dihydrotestosterone (DHT) by 5-alpha reductase for intraprostatic action. Type 1 5-alpha reductase is found predominantly in extraprostatic tissues, such as the skin and liver, whereas type 2 is found mainly in the prostate. Increased intraprostatic DHT activity contributes to the development of BPH.

Extracellular Matrix

An altered extracellular matrix can influence epithelial–stromal interactions and promote proliferation, similar to embryogenesis. This may occur through binding of growth factors to the extracellular matrix; altered proportions of extracellular-matrix proteins may also promote proliferation.

Growth Factors

Increased expression of growth factors (FGF, KGF, EGF, IGF, and TGF-alpha) or their receptors can promote proliferation and inhibit apoptosis in prostatic gland cells.

Genetic Factors

If surgery for BPH is necessary before 60 years of age, a familial clustering is present in 50% of cases. A monogenic cause or clinically established genetic testing for BPH is not known.

Pathology and Pathophysiology of Benign Prostatic Hyperplasia

Gross Pathology

Enlargement of the periurethral prostate may affect the so-called middle lobe, the lateral lobes, or both. The first changes arise in the periurethral glands around the verumontanum. The rigid prostatic capsule compresses the lumen of the prostatic urethra. Because prostate size does not reliably correlate with the degree of bladder outlet obstruction, further anatomic and functional factors determine the development of symptomatic BPH.

Histopathology

BPH is a true hyperplasia with an increase in cell number. Hyperplastic changes initially lead to a stromal tissue reaction, followed by small nodular fibroadenomatous hyperplasia. The glandular nuclei show no signs of malignancy.

The marked increase in smooth muscle cells in prostatic tissue produces a dynamic, contraction-dependent component of obstruction. Muscle tone is mediated through alpha-1A adrenoceptors. Smooth muscle cells in the prostate and bladder also express phosphodiesterase types 4 and 5. Treatment with alpha-blockers and phosphodiesterase inhibitors relieves BPH symptoms (Laydner et al., 2011).

Impact of Bladder Outlet Obstruction on the Bladder

The initial response to bladder outlet obstruction is detrusor hypertrophy, which permits bladder emptying at higher voiding pressures. Increased collagen deposition and bladder trabeculation follow, reducing compliance. High voiding pressures can cause pseudodiverticula, which increase the functional postvoid residual volume. The pathologic end stage of BPH-related bladder damage is termed a trabeculated bladder.

The intra- and extracellular changes in the bladder predispose to detrusor instability, clinically causing frequency and urgency. Progressive bladder dilation weakens detrusor contraction and causes postvoid residual urine. Eventually, the bladder decompensates and enlarges progressively according to Laplace's law.

Impact of Bladder Outlet Obstruction on the Upper Urinary Tract

Voiding at high pressures, postvoid residual urine, and possibly vesicoureteral reflux can lead to decompensation of the upper urinary tract, with bilateral hydronephrosis and elongated, kinked ureters. This is a late manifestation of BPS and is usually associated with overflow incontinence. Untreated upper urinary tract decompensation leads to uremia and death from kidney failure.

Relief of urinary tract obstruction often causes marked polyuria. Polyuria is caused partly by increased excretion of accumulated osmotically active substances. In addition, continuous perfusion of the renal medulla without urine flow results in loss of the corticomedullary gradient.

Cofactors

BPS symptoms are exacerbated by conditions that cause polyuria, such as heart failure, COPD, or diabetes mellitus, or that weaken detrusor contraction, such as medication or neurologic disorders.

References

Andriole u.a. 2004 ANDRIOLE, G. L. ; ROEHRBORN, C. ; SCHULMAN, C. ; SLAWIN, K. M. ; SOMERVILLE, M. ; RITTMASTER, R. S.: Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia.
In: Urology
64 (2004), Nr. 3, S. 537–41; discussion 542–3

Burnett und Wein 2006 BURNETT, A. L. ; WEIN, A. J.: Benign prostatic hyperplasia in primary care: what you need to know.
In: J Urol
175 (2006), Nr. 3 Pt 2, S. S19–24

Chapple 2004 CHAPPLE, C. R.: Pharmacological therapy of benign prostatic hyperplasia/lower urinary tract symptoms: an overview for the practising clinician.
In: BJU Int
94 (2004), Nr. 5, S. 738–44

DGU Guideline, “S2e Leitlinie Diagnostik und Therapie des Benignen Prostatasyndroms (BPS).,” 2023. [Online]. Available: https://register.awmf.org/assets/guidelines/043-034l_S2e_Diagnostik_Therapie_benignes_Prostatasyndrom_2023-04.pdf

Donovan u.a. 2000 DONOVAN, J. L. ; PETERS, T. J. ; NEAL, D. E. ; BROOKES, S. T. ; GUJRAL, S. ; CHACKO, K. N. ; WRIGHT, M. ; KENNEDY, L. G. ; ABRAMS, P.: A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.
In: J Urol
164 (2000), Nr. 1, S. 65–70

“EAU Guideline: Non-neurogenic Male LUTS,” Available: https://uroweb.org/guidelines/treatment-of-non-neurogenic-male-luts/.

Kopp, R. P.; Freedland, S. J. & Parsons, J. K. Associations of benign prostatic hyperplasia with prostate cancer: the debate continues.
Eur Urol, 2011, 60, 699-700; discussion 701-2.

Ørsted, D. D.; Bojesen, S. E.; Nielsen, S. F. & Nordestgaard, B. G. Association of clinical benign prostate hyperplasia with prostate cancer incidence and mortality revisited: a nationwide cohort study of 3,009,258 men.
Eur Urol, 2011, 60, 691-698.

Parsons, J. Kellogg; Messer, Karen; White, Martha; Barrett-Connor, Elizabeth; Bauer, Douglas C; Marshall, Lynn M; in Men (MrOS) Research Group, Osteoporotic Fractures & the Urologic Diseases in America Project Obesity increases and physical activity decreases lower urinary tract symptom risk in older men: the Osteoporotic Fractures in Men study.
Eur Urol, 2011, 60, 1173-1180.

Reich u.a. 2006 REICH, O. ; GRATZKE, C. ; STIEF, C. G.: Techniques and long-term results of surgical procedures for BPH.
In: Eur Urol
49 (2006), Nr. 6, S. 970–8; discussion 978

Uygur u.a. 1998 UYGUR, M. C. ; GUR, E. ; ARIK, A. I. ; ALTUG, U. ; EROL, D.: Erectile dysfunction following treatments of benign prostatic hyperplasia: a prospective study.
In: Andrologia
30 (1998), Nr. 1, S. 5–10

  Deutsche Version: Benigne Prostatahyperplasie

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