Dr. med. Dirk Manski

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

Review literature: (Burnett und Wein, 2006) (DGU-Guideline: diagnostic work-up, 2009) (DGU-Guideline: treatment, 2009) (EAU-Guideline: Oelke et al, 2010)

Definitions of Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia is a common disease with proliferation of the periurethral zone (transitional zone) of the prostate, which leads to lower urinary tract symptoms (LUTS). Since BPH involves hyperplasia rather than hypertrophy, the often used term benign prostatic hypertrophy should not be used.

Lower Urinary Tract Symptoms (LUTS)

Lower urinary tract symptoms are obstructive symptoms and irritative symptoms (see symptoms of BPH), which are not specific for benign prostatic hyperplasia.

Pathological Definition of Benign Prostatic Hyperplasia (BPH)

BPH is a benign prostatic hyperplasia of the epithelial and stromal components of the prostate, which leads to a nodular enlargement of the organ. Symptoms are not obligatory for the pathological definition of BPH.

Clinical Definition of Benign Prostatic Hyperplasia (BPH)

A sound definition of benign prostatic hyperplasia (BPH) combines the pathologic definition with the presence of symptoms, which are thought to be due to the prostate hyperplasia (e.g. LUTS, hematuria, bladder stones or kidney failure).

Epidemiology of Benign Prostatic Hyperplasia (BPH)

The epidemiological data for BPH are highly dependent on the used definition of BPH: studies have focused on the pathological prostate volume, urine flow, LUTS or combined mentioned parameters.

Prevalence of Prostate Hyperplasia (Pathologic Definition):

The prevalence of benign prostate hyperplasia is age dependent: starting with the age of 35, the prevalence increases each decade by 15%. Nearly 100% of 90 year old men have benign prostate hyperplasia (pathologic definition). The pathologic prevalence does not correlate with the clinical significance.

Increase in Prostate Volume:

The prostate volume of the male population increases with age: 25 ml (30–35 years old) to 45 ml (70 years old). Transition zone volume increases from 15 ml to 25 ml (same age groups).

Decrease of the Maximum Flow Rate:

The maximum flow rate in the male population is age dependent and decreases from 20 ml/s (40–44 years old) to 11 ml/s (75–79 years). At the same time, the micturition volume decreases from 355 ml to 223 ml.

Prevalence of BPH Using Several Parameters:

Clinically significant BPH may be defined using symptoms (IPSS > 7) and maximum flow rate (< 15 ml/s). The prevalence of benign prostate hyperplasia (clinical definition) is age dependent: 14–17% (age 50–59 years), 25–27% (age 60–69 years) and 35–38% (age 70–79 years).

Mortality of Benign Prostatic Hyperplasia (BPH):

In western countries, a significant decrease in mortality has been noted. Causes of death are postrenal kidney failure and urosepsis.

Incidence of Urinary retention:

The incidence of urinary retention is 4.5–18/1000 man-years. Symptoms (LUTS), prostate size and a low maximum flow rate are risk factors for urinary retention.

Incidence of TURP:

The incidence of surgical treatment (TURP or prostatectomy) is decreasing: 15/1000 person-years (1984 to 1990) to 7/1000 person-years (1991 to 1997). Age, residual urine, low maximum urinary flow and prostate size are risk factors for impending TURP or simple prostatectomy.

Epidemiologic Risk Factors for Benign Prostatic Hyperplasia (BPH):

The epidemiology of BPH is fairly constant, some genetic factors or environmental influences may modestly increase the risk for BPH.

Obesity, metabolic syndrome and physical activity:

Obesity increases circulating estrogen in men, which leads to epithelial hyperplasia of the prostate. Obesity is a risk factor for LUTS and increases the risk for surgical treated BPH (RR 2.38). Physical activity decreases the risk for the metabolic syndrome and reduces the prevalence of clinical significant BPH (RR 0.7).

Sexual activity:

Sexual activity is not a risk factor for BPH. On the other hand, BPH and the treatment of BPH may cause erectile dysfunction.


Smoking moderately reduces the risk of clinically significant BPH. The relationship is weak and of limited clinical significance, since the cardiovascular and oncological effects of smoking are well known.

Medication and BPH

Medication like antidepressants, antihistamines or bronchodilators may exacerbate LUTS.

Prostate cancer and benign prostatic hyperplasia:

Clinical significant BPH increases the risk for prostate cancer (RR 2.2–3.3 for incidence) and increases mortality from prostate cancer (RR 2 to 7.4) (├śrsted et al, 2011). The study is controversial (Kopp et al, 2011).

Etiology (Causes) of Benign Prostatic Hyperplasia (BPH)

Prostatic Hyperplasia:

Prostate hyperplasia means increase in number of stromal and epithelial cells. For BPH, molecular data argue for a reduction of apoptosis rather than for a true cell proliferation. Furthermore, there is evidence for a lack of differentiation of the epithelial cells, since in spite of the increased cell number the secretion of the prostate is decreased.

Androgens and BPH:

The presence of androgens is necessary for the development of BPH, castrates do not develop BPH. For the intraprostatic effect, the circulating testosterone is converted to dihydrotestosterone (DHT) through the 5-alpha reductase. Type 1 of the 5-alpha reductase is found mainly in extraprostatic tissues (e.g. skin or liver), type 2 of the 5-alpha reductase is mostly found in the prostate. An increased activity of type 2 5-alpha reductase may cause BPH (Steers, 2001).

Extracellular matrix (ECM) and BPH:

The influence of an altered extracellular matrix on epithelial cells can lead to proliferation, similar to embryogenesis. Mechanisms of the ECM-induced proliferation may be the binding of growth factors to the ECM or altered proportions of extracellular matrix proteins.

Growth Factors and BPH:

The increased expression of growth factors (FGF, KGF, EGF, IGF, TGF-alpha) or their receptors leads to proliferation and inhibition of apoptosis of prostate gland cells.

Genetic Factors of BPH:

If surgical treatment of BPH is due before the age of 60, genetic or familial factors are responsible in 50%. In patients over the age of 60, only 9% have a familial risk. Responsible genes for familial BPH are not known yet.

Pathology and Pathophysiology of Benign Prostatic Hyperplasia

Macroscopic Anatomy of BPH:

The enlargement of the periurethral prostate [fig. prostate zones in BPH] can affect the so-called middle lobe, the lateral lobes or a combination of both. The first changes of BPH take place in the periurethral glands around the verumontanum. Because of the rigid prostatic capsule, the lumen of the prostatic urethra is compressed due to the prostatic hyperplasia. Since the size of the prostate does not correlate with the degree of subvesical obstruction, anatomical and functional variations are in addition responsible for symptomatic BPH.

fig. prostate zones by McNeal in BPH (benign prostatic hyperplasie) Enlargement of the periurethral prostate in BPH (prostate zones classification by McNeal).
Coronal section (top) and sagittal section (bottom): the transition zone (with hatching) surrounds the urethra between colliculus and bladder neck. This zone is pathologically enlarged in BPH. The central zone (without hatching) and peripheral zone (dotted area) are not affected by BPH.

Microscopic Anatomy of BPH:

Benign prostatic hyperplasia is a true hyperplasia with an increase in cell number. The first hyperplastic changes involve the stroma, followed by a small nodular hyperplasia of the glandular tissue. At the cellular level, some hypertrophy (cell enlargement) is also present. The nuclei of the glands show no signs of malignancy. In the further course of the disease, large nodular hyperplasia develops.

The significant increase in the number of smooth muscle cells in the prostate stroma results in a dynamic component of subvesical obstruction, which is caused by smooth muscle contraction. The contraction of smooth muscle cells in the prostate is mediated via alpha-1A-adrenoceptors. In addition, smooth muscle cells of the prostate and bladder express type 4 and type 5 phosphodiesterase isoenzymes. Treatment of erectile dysfunction with inhibitors of phophodiesterases has a beneficial effect on symptomatic BPH.

Impact of Subvesical Obstruction on the Bladder

The initial response of the bladder for subvesical obstruction is hypertrophy of the detrusor muscle; this allows the bladder to empty with higher voiding pressure. After muscular hypertrophy, an increased collagen deposition leads to trabeculation of the bladder and decreased bladder compliance. High voiding pressures lead to the formation of pseudodiverticula that increase the functional residual urine.

The response of the bladder to subvesical obstruction causes detrusor instability resulting in frequency and urgency. The increasing dilatation of the bladder weakens the detrusor muscle and leads to urinary retention. Later on BPH leads to the decompensation of the bladder, resulting in progressive bladder dilatation, chronic urinary retention and urinary (overflow) incontinence.

Impact of Subvesical Obstruction to the Upper Urinary Tract

BPH may lead to the decompensation of the upper urinary tract with hydronephrosis, caused by micturition under high pressures, chronic urinary retention and vesicoureteral reflux. Postrenal kidney failure is a late symptom of BPH and is usually associated with chronic urinary retention with incontinence. The consequences of untreated postrenal kidney failure are uremia and death.

The relief of the urinary tract often leads to massive polyuria. Polyuria is caused by the excretion of accumulated osmotically active substances. Secondly, the continuous perfusion of the renal medulla without urine flow wiped out the corticomedullary osmotic gradient, which is important for concentration of the urine.

Aggravating Factors of BPH:

Symptoms of BPH may be aggravated by conditions that lead to polyuria (heart failure, COPD, diabetes ...) or affect the detrusor muscle (drugs, neurological disorders).

Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


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-Guidelines: diagnostic work-up
Leitlinien der Deutschen Urologen zur Diagnostik des benignen Prostatasyndroms (BPS).
In: Urologe A
48 (2009), S. 1356–60, 1362–4

DGU-Guidelines: treatment
Leitlinien der Deutschen Urologen zur Therapie des benignen Prostatasyndroms (BPS).
In: Urologe A
48 (2009), S. 1503–1516

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.

Oelke, M.; Bachmann, A.; Descazeaud, A. & Emberton, M.
Guidelines on conservative treatment of non-neurogenic male LUTS
www.uroweb.org, 2010.

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