MALE REPRODUCTIVE CANCER AND DISEASE

Benign Prostatic Hyperplasia (BPH)

Ervin Kocjancic, University of Illinois Hospital and Health Science System, Chicago, IL, United States
Valerio Iacovelli, University of Rome Tor Vergata, Rome, Italy
© 2018 Elsevier Inc. All rights reserved.

Introduction

Benign prostatic hyperplasia (BPH), is one of the causes of the lower urinary tract symptoms (LUTS) and a common diagnosis
among the aging male population with increasing prevalence. The understanding of the LUTS as a functional unit, and the multi-
factorial etiology of associated symptoms, means that LUTS now constitute the main focus, rather than the former emphasis on BPH
(European Association of Urology, 2016; Gratzke et al., 2015; McVary et al., 2011). LUTS present with dysfunction of both storage
and emptying phase as well as the post micturition signs. These symptoms are nonspecific in their presentation and multifactorial in
origin. LUTS are a progressive and age related but not sex- or organ-specific. They cause bother and impair quality of life (Agarwal
et al., 2014).
Traditionally, LUTS have been related to bladder outlet obstruction (BOO) as a result of benign prostatic obstruction (BPO),
which is often caused by benign prostatic enlargement (BPE) resulting from the histologic condition benign prostatic hyperplasia
(BPH) (Abrams et al., 2002). Several recent studies have shown, however, that LUTS are not necessarily related to prostatic size.
Major attention is currently oriented to the bladder wall; bladder dysfunctions, such as detrusor underactivity, detrusor overactivity
and other functional abnormalities (van Koeveringe et al., 2014).
As the world population ages, the incidence and prevalence of BPH and LUTS have rapidly increased (Lepor, 2005). Historical
studies have examined nonmodifiable risk factorsdincluding age, genetics and geographydthat have important roles in the
etiology of BPH and BOO (Parsons, 2010). However, several modifiable risk factors present new opportunities for treatment
and prevention (Chughtai et al., 2016).

Epidemiology

Approximately 50% of men > 50 years of age will have pathological evidence of BPH, with this number increasing to > 80% as men
reach their eighth decade of life and older (Berry et al., 1984).
LUTS are strongly associated with aging and progress dynamically: for some individuals LUTS persist and progress over long time
periods, and for others they remit (Société Internationale d’Urologie (SIU), Lower Urinary Tract Symptoms (LUTS), 2013).
Several studies have examined the geographical variations in BPH and LUTS prevalence. Men from Southeast Asia have signif-
icantly smaller prostate volumes than men from western countries. Although differences in geographical prevalence for prostate
disease (including BPH) have been documented, the reasons for such differences are poorly understood. However, these differences
could be due to genetic factors and/or environmental differences (Jin et al., 1999).

Etiology

Many modifiable and nonmodifiable factors can increase the risk of development and progression of BPH and LUTS.

Age
BPH and LUTS increase with age, which has been confirmed by numerous studies (Berry et al., 1984). Prostate volume increases at
a median rate of 0.6 mL per year. Although symptom severity cannot be correlated directly with prostate volume, having a large
prostate volume is a risk factor for the development of LUTS. Thus, the incidence of LUTS also increases with age. That is, larger
prostates are associated with increased risks of urinary retention, increased future need for surgery and clinical progression of
BPH (Société Internationale d’Urologie (SIU), Lower Urinary Tract Symptoms (LUTS), 2013).

Metabolic Syndrome
Many studies have investigated associations between metabolic syndrome and BPH-related LUTS (BPH–LUTS) and results of
several studies support possible roles for the individual components of the syndrome in the development of BPH–LUTS (Vignozzi

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468 Male Reproductive Cancer and Disease j Benign Prostatic Hyperplasia (BPH)

et al., 2016). Metabolic syndrome includes hypertension, dyslipidaemia, glucose intolerance, central obesity and insulin resistance
with compensatory hyperinsulinaemia (De Nunzio et al., 2012).

• Obesity and BPH–LUTS. Obesity, and in particular visceral obesity, is often comorbid with BPH (Parsons, 2010; Vignozzi et al.,
2016). More importantly, the risk of LUTS progression also increased as a function of obesity (BMI
35 kg/m2), visceral
adiposity (waist circumference > 42 in., 106.7 cm). The influence of obesity on prostate overgrowth was observed also in early
adulthood. Overall, these findings support the concept that the treatment of obesity might be important in the prevention and
treatment of LUTS (Vignozzi et al., 2016).
• Glucose intolerance and BPH–LUTS. A possible association between BPH and glucose intolerance or overt T2DM has also been
noted (Hammarsten et al., 1998). In particular, in patients with BPH, a history of T2DM increased the risk of moderate–severe
LUTS twofold (Joseph et al., 2003). Interestingly, individuals with insulin resistance who develop compensatory hyper-
insulinaemia might directly and/or indirectly affect several molecular signaling pathways that promote prostatic growth and
inflammation (Nandeesha et al., 2006).
• Dyslipidaemia and BPH–LUTS. Circulating total cholesterol and HDL cholesterol are positively and negatively associated with
prostate enlargement, respectively (Nandeesha et al., 2006). Furthermore, it has been shown that men with
hypertriglyceridaemia had decreased likelihood of storage LUTS improvement during the follow-up period, and greater
abdominal fat mass was associated with storage LUTS progression. In the same study, lower HDL cholesterol levels, as well as
lower testosterone and higher oestradiol levels, were associated with worsening of voiding LUTS (Martin et al., 2014).
• Hypertension and BPH–LUTS. The role of hypertension is debated. Increased blood pressure seems to be associated with an
increased odds ratio for surgical treatment of BPH (Gann et al., 1995)
Although insulin resistance and visceral obesity are considered to be the main pathophysiological aberrations of metabolic
syndrome, a number of other factors, such as a proinflammatory state and sex steroid imbalance, could also be involved in its path-
ogenesis and clinical manifestation. In particular, chronic low-grade inflammation has been recognized as a central pathogenic
mechanism underlying the development of individual metabolic syndrome components. In addition, in the past decade, clinical
and preclinical evidence has confirmed that chronic inflammation also has a determining role in inducing BPH–LUTS (Fibbi
et al., 2010; Vignozzi et al., 2014). That is, an inflammatory insult is the most plausible candidate bridging the mechanistic gap
between metabolic syndrome and BPH–LUTS (Fibbi et al., 2010; Vignozzi et al., 2014).

Genetics
To date few genetic studies have focused on BPH. A recent study reported that variants in 2q31 and 5p15 are associated with aggres-
sive (defined by multiple criteria) BPH (Qi et al., 2013). Furthermore, twin studies have suggested that heritability is an important
determinant of disease severity in BPH, including the development of LUTS.

Pathogenesis

The pathophysiology of BOO in men with BPH has been attributed to both static (prostatic tissue) and dynamic (smooth muscle)
factors. BPH is a diagnosis based on histological findings of proliferating stromal and epithelial cells within the prostatic transition
zone. The exact etiology of BPH is unclear; however, much epidemiological evidence has led to the hypothesis that a sex steroid
imbalance and an inflammatory process are the key drivers of not only the development but also the progression of BPH (Fibbi
et al., 2010; Vignozzi et al., 2014).
Testicular androgens are required in the prostate for the development of BPH. The enzyme steroid 5a-reductase 2 which is
bound to the nuclear membrane, converts testosterone into dihydrotestosterone (DHT), the principal androgen in the prostate
accounting for 90% of total prostatic androgen. Testosterone and its derivatives interact with the androgen receptor (AR),
which upon binding translocates to the nucleus and binds to the androgen response element (ARE), promoting the expression
of genes encoding various growth factors (including keratinocyte growth factor (KGF), epidermal growth factor (EGF) and
insulin-like growth factors (IGFs). In stromal cells, most of the testosterone is converted to dihydrotestosterone (DHT), which
then acts in an autocrine manner to promote stromal proliferation. DHT can also diffuse into the adjacent epithelial cell to act
in a paracrine manner. DHT produced peripherally in the liver and the skin can also diffuse from the circulation into the
prostate to act in an endocrine manner. BPH probably develops as a result of an imbalance between mechanisms that regulate
cell death and cell proliferation. Growth factors such as KGF, EGF, and IGFs, which are AR target genes, are probably involved,
as is transforming growth factor-b (TGFb), which is negatively regulated by androgens (Chughtai et al., 2016; Roehrborn,
2008).
The metabolic syndrome influences LUTS–BPE development and progression, having direct inflammatory effects within the
prostate (Vignozzi et al., 2014). By acting as antigen-presenting cells or as targets of Toll-like receptor agonists, prostatic stromal
cells can actively contribute to the prostate-specific inflammatory process, resulting in the production of proinflammatory
cytokines and chemokines, which perpetuate chronic inflammation (Vignozzi et al., 2014). Activation of Toll-like receptors and
production of proinflammatory chemokines, such as IL-6 and IL-8, further promote prostate cell hyperplasia through direct prolif-
erative action of IL-8 or through the release of other growth factors, such as FGF-2 (Vignozzi et al., 2014). Activated prostatic cells
 Male Reproductive Cancer and Disease j Benign Prostatic Hyperplasia (BPH) 469

also stimulate CD4 þ lymphocyte proliferation and prompt their differentiation towards a TH1/TH17 phenotype, which shifts an
acute inflammatory response towards a chronic autoimmune inflammatory disease (Vignozzi et al., 2016).

Bladder Structure and Function

The bladder is sensitive to prostatic conditions. BOO caused by BPH has been shown to affect bladder structure and function. The
response of the bladder to obstruction is primarily an adaptive one. Initially, BOO can lead to the development of smooth muscle
hypertrophy in the bladder62,63, which is associated with intracellular and extracellular changes in smooth muscle cells (Levin
et al., 2000). Such changes may lead to detrusor overactivity and deceased compliance, resulting in patients experiencing symptoms
of frequency and urgency as well deterioration in the strength of the urinary stream and incomplete emptying. Trabeculation
(thickening) of the bladder wall is the predominant endoscopic finding in these patients.

Diagnostic Evaluation

As BPH is a common condition affecting a considerable proportion of men, screening and prevention of the disease are not
pertinent.
Several key diagnostic tools and investigations are used to diagnose BPH in men who present with LUTS. The European Asso-
ciation of Urology and the American Urological Association have published guidelines for the investigation of LUTS related to BPH
(European Association of Urology, 2016; Gratzke et al., 2015; McVary et al., 2011).

Medical History
The importance of assessing the patient’s history is well recognized. The aim of obtaining a medical history is to identify potential
causes of LUTS and relevant comorbidities, such as medical (e.g., diabetes mellitus or insipidus, renal disease, heart failure, sleep
apnoea) and neurological diseases. It is useful to review current medication, and assess lifestyle habits, as well as emotional and
psychological factors. Potential erectile and other forms of sexual dysfunction should be investigated (validated symptom question-
naires are helpful).

Symptom Score Questionnaires

Symptom scores are helpful in quantifying LUTS and in identifying which type of symptoms are predominant, yet they are not
disease-, or age-specific. Several questionnaires are available (International Prostate Symptom Score IPSS, International Consulta-
tion on Incontinence Questionnaire ICIQ-MLUTS, Danish Prostate Symptom Score DAN-PSS, AUA Symptom Score), all of which
are sensitive to symptom changes and treatment monitoring.

Frequency Volume Charts and Bladder Diaries

The recording of volume and time of each void by the patient is referred to as a frequency volume chart (FVC). Inclusion of addi-
tional information such as fluid intake, use of pads, activities during recording, or symptom scores is termed a bladder diary
(Abrams et al., 2002). Parameters that can be derived from the FVC and bladder diary include: daytime and night-time voiding
frequency, total voided volume, the fraction of urine production during the night (nocturnal polyuria index), and volume of indi-
vidual voids.

Physical Examination and Digital-Rectal Examination (DRE)

A physical examination should be performed, particularly focusing on the urinary tract. The suprapubic region should be examined
for signs of bladder distension. The penis should be examined for evidence of phimosis, meatal stenosis or abnormal penile lesions.
A neurological examination should also be performed on the lower limbs to rule out a possible underlying neurological condi-
tion that might result in urinary symptoms. A DRE should be performed on all patients with LUTS. A DRE facilitates the estimation
of prostate volume and can also assess the shape and consistency of the prostate and identify the presence of firm or hard areas or
nodules, which can raise suspicions of prostate cancer.

Urinalysis
Urinalysis (dipstick or sediment) is an inexpensive test that must be incorporated in the primary evaluation of any patient present-
ing with LUTS to determine conditions such as urinary tract infection and diabetes mellitus on the basis of abnormal findings
(haematuria, proteinuria, pyuria, glucosuria, ketonuria, positive nitrite test). There is limited evidence, yet general expert consensus
that the benefits outweigh the costs.
470 Male Reproductive Cancer and Disease j Benign Prostatic Hyperplasia (BPH)

Prostate-Specific Antigen (PSA)

The level of PSA has been shown to reflect prostate volume. The higher the PSA level, the greater the likelihood of an enlarged pros-
tatedwith a 69% chance of having a prostate volume of > 40 mL with a PSA level of 4.1–7.0 ng per mL (Bohnen et al., 2007).
However, PSA testing should not be routine; the benefits and risks of testing should be discussed with the patient. In particular,
the test is used in prostate cancer diagnostics, therefore, the possibility of a need for a prostate biopsy and associated risks should
be discussed. The European Association of Urology recommends that PSA testing should only be performed if it can assist in deci-
sion making in patients at risk of BPH progression.

Renal Function Measurement

Renal function may be assessed by measurement of serum creatinine or calculation or determination of the estimated glomerular
filtration rate (eGFR). Hydronephrosis, renal insufficiency, and urinary retention appear with greater prevalence in patients with
symptoms or signs of BPO. In addition, patients with renal insufficiency have a higher risk of developing postoperative complica-
tions compared to those with normal renal function.

Uroflowmetry and Postvoid Residual Urine (PVR)

Urinary flow rate assessment is a basic noninvasive urodynamic test that is widely used to evaluate LUTS. Key parameters are Qmax,
voided volume, and flow pattern. Uroflowmetry parameters should ideally be evaluated when the voided volume is > 150 mL. It is
recommended that at least two flow rates should be obtained. The diagnostic accuracy of uroflowmetry for detecting BOO varies
considerably and is substantially influenced by diagnostic threshold values. A Qmax threshold of 10 mL/s had specificity of 70%,
PPV of 70%, and sensitivity of 47% for BOO; thus, uroflowmetry alone is unsuitable for detection and quantification of BOO.
Low Qmax can arise as a consequence of BOO, detrusor underactivity, or an underfilled bladder. Thus, uroflowmetry is limited
as a diagnostic test because of the inability to discriminate underlying mechanisms in men with low Qmax. Specificity can be
improved by repeated flow-rate testing in individual patients. Uroflowmetry can be used to monitor treatment outcomes and corre-
late symptoms with objective findings.
Postvoid residual urine (PVR) can be measured by transabdominal ultrasonography, a bladder scan, or catheterization. The AUA
states that determination of the PVR volume is optional in the initial diagnostic assessment and during subsequent monitoring as
a safety parameter, whereas the EAU guidelines state that measurement of PVR volume in men with LUTS should be a routine part of
the assessment (European Association of Urology, 2016; Gratzke et al., 2015; McVary et al., 2011).

Imaging
The routine use of upper tract imaging is not recommended for patients with BPH (European Association of Urology, 2016;
Gratzke et al., 2015; McVary et al., 2011); however, it might be helpful in patients who have a urinary tract infection, urolith-
iasis, renal insufficiency and/or haematuria. Patients with LUTS and haematuria should be investigated. The prostate can be
imaged by several modalities including TRUS, CT and MRI (European Association of Urology, 2016). TRUS or transabdominal
ultrasonography are the most easily performed, although TRUS is more accurate for assessing prostate volume. TRUS is also
useful in determining the degree of intravesical prostatic protrusion, which is the distance between the bladder neck and
the tip of the prostate median lobe. The degree of intravesical prostatic protrusion has been shown to correlate with the severity
of BOO on urodynamics. Routine use of urethrocystoscopy is not required for patients with uncomplicated LUTS (which
include those without a history of urinary tract infections, haematuria, bladder stones, predominantly irritative symptoms
or a secondary pathology such as bladder cancer) according to the AUA (McVary et al., 2011). Evaluation of a prostatic middle
lobe in urethrocystocopic findings is necessary to determine the indication for certain interventional treatments (European
Association of Urology, 2016).

Urodynamics and Video-Urodynamics

In male LUTS, the most widespread invasive urodynamic techniques employed are filling cystometry and pressure flow studies
(PFS). The major goal of urodynamics is to explore the functional mechanisms of LUTS and to identify risk factors for adverse
outcomes (for informed/shared decision-making). Although urodynamic pressure–flow investigations are a second line studies,
they might be necessary to measure the relative contribution of the bladder and the prostate to lower urinary tract dysfunction.
Pressure–flow studies are the only method to determine if LUTS are due to BOO or due to an underactive detrusor. The EAU recom-
mends that men < 50 years of age or those > 80 years of age who are being considered for surgery should undergo pressure–flow
studies. If a patient had a previous unsuccessful surgical treatment for BPH, pressure–flow studies should be performed to assess
detrusor function (European Association of Urology, 2016; Gratzke et al., 2015).
Videourodynamics (synchronous x-ray imaging and filling of the bladder with contrast medium for cystometry and PFS) may be
used when there is uncertainty regarding the mechanisms of voiding LUTS. The test provides additional anatomical information.
 Male Reproductive Cancer and Disease j Benign Prostatic Hyperplasia (BPH) 471

Disease Management

Treatment options for men with LUTS start at watchful waiting and progress through medical to surgical interventions.

Conservative Treatment: Watchful Waiting, Behavioral and Dietary Modifications

Many men with LUTS are not troubled enough by their symptoms to need drug treatment or surgical intervention. All men with
LUTS should be formally assessed prior to any allocation of treatment in order to establish symptom severity and to differentiate
between men with uncomplicated (the majority) and complicated LUTS. Watchful waiting includes advice about lifestyle changes
that can help to ameliorate or circumvent symptoms. These changes include advice about volume, type and timing of liquids
consumed, avoidance of caffeine (a diuretic), abstinence of alcohol consumption in the evening and regulation of bowel move-
ments with avoidance of constipation (European Association of Urology, 2016).

Pharmacological Treatment
The aim of medical therapy is to improve symptoms, lower the risk of progression and improve quality of life. Guidelines and algo-
rithms are available to help selection (European Association of Urology, 2016).

• a1-Adrenoceptor antagonists (a1-blockers) (European Association of Urology, 2016). The medical therapies target are adrenergic
receptor subtypes: a1A-adrenoceptor which is the predominate receptor in prostate stromal smooth muscle and bladder neck,
a1B-adrenoceptor and the a1D-adrenoceptor. Blockade adrenoceptors results in smooth muscle relaxation and subsequent
improvement in the passage of urine. a1-blockers are often considered the first line drug treatment of male LUTS because of their
rapid onset of action, good efficacy, and low rate and severity of adverse events (Lepor, 2007). However, a1-blockers do not
prevent occurrence of urinary retention or need for surgery. Ophthalmologists should be informed about a1-blocker use prior to
cataract surgery. Elderly patients treated with nonselective a1-blockers should be informed about the risk of orthostatic
hypotension. Sexually active patients treated with selective a1-blockers should be counseled about the risk of retrograde
ejaculation.
• 5a-reductase inhibitors (European Association of Urology, 2016). Two 5a-reductase inhibitors (5-ARIs) are available for clinical
use: dutasteride and finasteride. Finasteride inhibits only 5a-reductase type 2, whereas dutasteride inhibits 5a-reductase types 1
and 2 with similar potency (dual 5-ARI). 5-ARIs act by inducing apoptosis of prostate epithelial cells leading to prostate size
reduction of about 18%–28% and a decrease in circulating PSA levels of about 50% after 6–12 months of treatment. Treatment
with 5-ARIs should be considered in men with moderate-to-severe LUTS and an enlarged prostate (> 40 mL) and/or elevated
PSA concentration (> 1.4–1.6 ng/mL). 5a-reductase inhibitors can prevent disease progression with regard to acute urinary
retention and the need for surgery. Due to the slow onset of action, they are suitable only for long-term treatment (years). Their
effect on the serum PSA concentration needs to be considered in relation to PCa screening.
• Muscarinic receptor antagonists (antimuscarinics) and Beta-3 agonist (European Association of Urology, 2016). Muscarinic receptors
are involved in the modulation of detrusor contractility; inhibition of these receptors reduces smooth muscle tone and relieves
filling phase symptoms. In the human detrusor M2 and M3 receptors are predominant (M2:M3 ratio 3:1, but the M3 subtype is
functionally more important). Available agents include nonselective antagonists, such as oxybutynin, and selective antagonists,
such as solifenacin and tolterodine (Abrams et al., 2006). Not all antimuscarinics have been tested in elderly men, and long-term
studies on the efficacy of muscarinic receptor antagonists in men of any age with LUTS are not yet available. In addition, only
patients with low PVR volumes at baseline were included in the studies. These drugs should therefore be prescribed with caution,
and regular reevaluation of IPSS and PVR urine is advised. Men should be advised to discontinue medication if worsening
voiding LUTS or urinary stream is noted after initiation of therapy. For patients who have a poor response to anti-muscarinic
drugs or who have previously experienced adverse effects with these drugs, agonism of the b3-adrenoceptor might be an
alternative treatment option (Thiagamoorthy et al., 2016). Beta-3 adrenoceptors are the predominant beta receptors expressed in
the smooth muscle cells of the detrusor and their stimulation is thought to induce detrusor relaxation. Indeed, mirabegron has
recently been made available for men with moderate-to-severe LUTS who mainly have bladder storage symptoms in the United
States and Europe.
• Phosphodiesterase 5 inhibitors (PDE5Is) (European Association of Urology, 2016). Phosphodiesterase type 5 (PDE5) negatively
regulates smooth muscle contraction by hydrolysing cGMP (which is crucial to muscle relaxation via its effects on intracellular
calcium levels). Accordingly, inhibition of PDE5 leads to the relaxation of smooth muscle in the bladder neck, urethra and prostate
(Gacci et al., 2012). To date, only tadalafil 5 mg once daily has been officially licensed for the treatment of male LUTS with or
without ED. The meta-regression suggested that younger men with low body mass index and more severe LUTS benefit the most
from treatment with PDE5Is. There is limited information on reduction of prostate size and no data on disease progression.
• Plant extractsdphytotherapy (European Association of Urology, 2016). Herbal drug preparations are made of roots, seeds,
pollen, bark, or fruits. There are single plant preparations (mono-preparations) and preparations combining two or more plants
in one pill (combination preparations). The most widely used plants are Cucurbita pepo (pumpkin seeds), Hypoxis rooperi
(South African star grass), Pygeum africanum (bark of the African plum tree), Secale cereale (rye pollen), Serenoa repens (syn.
Sabal serrulata; saw palmetto) and Urtica dioica (roots of the stinging nettle). Nowadays, there are not any specific
472 Male Reproductive Cancer and Disease j Benign Prostatic Hyperplasia (BPH)

recommendations on phytotherapy for the treatment of male LUTS due to product heterogeneity, a limited regulatory frame-
work, and methodological limitations of the published trials and meta-analyses.
• Combination therapies (European Association of Urology, 2016). Compared with a1-blockers or 5-ARI monotherapy, combi-
nation therapy results in a greater improvement in LUTS and increase in Qmax, and is superior in prevention of disease
progression. However, combination therapy is also associated with a higher rate of adverse events. Combination therapy should
therefore be prescribed primarily in men who have moderate-to-severe LUTS and are at risk of disease progression (higher
prostate volume, higher PSA concentration, advanced age, higher PVR, lower Qmax, etc.). Combination therapy should only be
used when long-term treatment (more than 12 months) is intended and patients should be informed about this. Discontin-
uation of the a1-blocker after 6 months might be considered in men with moderate LUTS (Roehrborn et al., 2010). Combi-
nation treatment of an a1-blocker with a muscarinic receptor antagonist is helpful in patients with moderate-to-severe LUTS if
relief of storage symptoms has been insufficient with monotherapy with either drug (Filson et al., 2013). However, measuring
PVR is recommended during combination treatment.

Surgical Treatment
Many surgical options are available for men with BPH. Surgical treatment is usually required when patients have experienced recur-
rent or refractory urinary retention, overflow incontinence, recurrent UTIs, bladder stones or diverticula, treatment-resistant macro-
scopic haematuria due to BPH/BPE, or dilatation of the upper urinary tract due to BPO, with or without renal insufficiency (absolute
operation indications, need for surgery).
Additionally, surgery is usually needed when patients have not obtained adequate relief from LUTS or PVR using conservative or
medical treatments (relative operation indications). The choice of surgical technique depends on prostate size, comorbidities of the
patient, ability to have anesthesia, patients’ preferences, willingness to accept surgery-associated specific side-effects, availability of
the surgical armamentarium, and experience of the surgeon with these surgical techniques.

• Transurethral resection of the prostate (TURP) and transurethral incision of the prostate (TUIP) (European Association of Urology,
2016). TURP removes tissue from the transition zone of the gland. TUIP involves incising the bladder outlet without tissue
removal. This technique may replace TURP in selected cases. TURP and TUIP are effective treatments for moderate-to-severe
LUTS secondary to BPO. The choice should be based primarily on prostate volume (< 30 mL and 30–80 mL suitable for
TUIP and TURP, respectively). No studies on the optimal cut-off value exist but the complication rates increase with
prostate size. Bipolar TURP (B-TURP) addresses a major limitation of monopolar TURP (M-TURP) by allowing performance
in normal saline. The choice of B-TURP should be based on equipment availability, surgeon’s experience, and patient’s
preference.
• Open prostatectomy (European Association of Urology, 2016). It is the oldest surgical treatment for moderate-to-severe LUTS
secondary to BPO. Obstructive adenomas are enucleated using the index finger, approaching from within the bladder (Freyer
procedure) or through the anterior prostatic capsule (Millin procedure). It is used for substantially enlarged glands (> 80–
100 mL). Open prostatectomy is the most invasive surgical method but it is an effective and durable procedure for the treat-
ment of LUTS/BPO. In the absence of an endourological armamentarium including a holmium laser or a bipolar system, OP is
the surgical treatment of choice.
• Laser treatments of the prostate (European Association of Urology, 2016). Different types of lasers are available: holmium:yttrium-
aluminium garnet (Ho:YAG) laser, the 532 nm (Greenlight) laser, Diode laser, Thulium:yttrium-aluminium-garnet laser. Laser
operations are surgical procedures that require experience and relevant endoscopic skills. The experience of the surgeon is the
most important factor affecting the results and the overall occurrence of complications. In general, follow-up data showed
efficacy and safety outcomes similar to TURP but long term results are pending.
• Prostatic stents (European Association of Urology, 2016). A prostatic stent requires a functioning detrusor. Permanent stents are
biocompatible, allowing for epithelialisation. Temporary stents do not epithelialise and may be either biostable or biode-
gradable. Temporary stents can provide short-term relief from BPO in patients temporarily unfit for surgery, or after minimally
invasive treatment. Due to common side effects and a high migration rate, prostatic stents have a limited role in the treatment of
moderate-to-severe LUTS. Temporary stents can provide short-term relief from LUTS secondary to BPO in patients temporarily
unfit for surgery or after minimally invasive treatment.
• Prostatic urethral lift (European Association of Urology, 2016). The prostatic urethral lift (PUL) represents a novel minimally
invasive approach under local or general anesthesia. Encroaching lateral lobes are compressed by small permanent suture-based
implants delivered under cystoscopic guidance (UroliftÒ) resulting in an opening of the prostatic urethra that leaves a contin-
uous anterior channel through the prostatic fossa ranging from the bladder neck to the verumontanum. Long-term studies are
needed to evaluate the duration of the effect in comparison to other techniques.

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Further Reading

Loeb, S., Kettermann, A., Carter, H. B., Ferrucci, L., Metter, E. J., & Walsh, P. C. (2009). Prostate volume changes over time: Results from the baltimore longitudinal study of aging.
The Journal of Urology, 182(4), 1458–1462.