Benign follow-up in the overall population to a

Benign Prostatic Hyperplasia (BPH) is defined as the
proliferation of prostatic stromal cells, which results in an enlarged prostate
gland. As a result, the prostatic urethra is compressed, which restricts the
flow of urine from the bladder. This interference in urine flow may cause
uncomfortable symptoms such as frequency, urgency, nocturia, intermittency,
decreased stream and hesitancy. As BPH progresses, complications such as
development of urinary tract infection (UTI) or a bladder stone may occur. In
severe cases patients may develop urinary retention, kidney blockage
(hydronephrosis), or renal failure. 1,2

The exact etiology of BPH is unknown; however, the
similarity between BPH and the embryonic morphogenesis of the prostate has led
to the hypothesis that BPH may result from a “reawakening” in adulthood of
embryonic induction processes.3 The first sign of BPH histologically is the
formation of nodules in the stroma surrounding the urethra. Nodule formation is
then followed by hyperplasia of the epithelial cells of the glands and ducts of
the prostate. Together, this causes compression of the urethra with
progressively worsening obstruction.4  The enlarged gland has been proposed to
contribute to the overall lower urinary tract symptoms (LUTS) complex via at
least two routes: (1) direct bladder outlet obstruction (BOO) from enlarged
tissue (static component) and (2) from increased smooth muscle tone and
resistance within the enlarged gland (dynamic component). Voiding symptoms have
often been attributed to the physical presence of BOO. Detrusor over activity
is thought to be a contributor to the storage symptoms seen in LUTS.3

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The prevalence of LUTs due to BPH increases with
increasing age. Moderate to severe symptoms occur in 40% of man in 60 years and
80% of man by 80 years. Benign
Prostatic Hyperplasia is not a life threatening condition, but has negative
impact on a patient’s quality of life as evidenced in community and clinical
studies.5 Results
from the Olmsted County Study showed a progressive increase in the prevalence
of moderate-to-severe LUTS, rising to nearly 50% by the eighth decade of life.
The presence of moderate-to-severe LUTS was also associated with the
development of acute urinary retention (AUR) as a symptom of BPH progression,
increasing from a prevalence of 6.8 episodes per 1000 patient years of
follow-up in the overall population to a high of 34.7 episodes in men aged 70
and older with moderate to severe LUTS. Another study has estimated that 90% of
men between 45 and 80 years of age suffer some type of LUTS.

 

On a population level,
there are 2 broad categories of risk factors associated with BPH and LUTS:
Non-modifiable (age, geography and genetics) and modifiable (sex steroid
hormones, the metabolic syndrome, obesity, diabetes, physical activity, diet,
and inflammation). The
incidence of histological BPH (diagnosed via biopsy or at autopsy) is similar
across all racial groups studied, but the incidence of clinical BPH (diagnosed
via symptoms, examinations and clinical investigations) is higher among
African-Americans than in Caucasians, which in turn exceeds that in Asian men.
Diet is a potential modifiable risk factor. Asian populations are associated
with soya-rich diets, and this may explain the low incidence of BPH in Asian
men. Soya products are high in phyto-oestrogens (eg, genistein), which have an
inhibitory effect on BPH (and prostate cancer) cells in vitro.

In prostatic secretory
cells, the hormone 5-alpha reductase converts testosterone to DHT, a potent
stimulator of prostate growth that, in addition to being necessary for prostate
development, appears to play a central role in BPH pathogenesis. Multiple
studies have explored associations of endogenous sex steroid hormones – namely
testosterone, DHT and estrogen – with BPH and LUTS. These hormones are either
autocrine factors, which act locally on the same cells that produced them, or
paracrine factors, acting on other nearby cells. Epithelial cell growth and
development, and stromal cell proliferation and stromal extracellular protein
matrix production, are influenced by these autocrine and paracrine pathways.
The theory is that if a growth factor imbalance occurs, this in turn leads to
an imbalance between cell growth and programmed cell death, leading to both
epithelial cell hyperplasia and stromal hyperplasia.

Disruptions in glucose
homeostasis at multiple different levels – from alterations in serum insulin
growth factor (IGF) concentrations to diagnosis of clinical diabetes – are associated
with higher likelihoods of BPH, BPE and LUTS. Higher serum concentrations of
IGF-1 and insulin-like growth factor binding protein 3 have been associated
with increased risk of clinical BPH and BPH surgery. Physician-diagnosed
diabetes, increased serum insulin and elevated fasting plasma glucose have been
associated with increased prostate size and increased risks of prostate
enlargement, clinical BPH, BPH surgery and LUTS in multiple different cohorts
cumulatively incorporating tens of thousands of men. Recent findings from
Olmsted County demonstrate that diabetic men on medical therapy had decreased
odds of moderate/severe LUTS compared with those men not on medications.

A more profound knowledge
of the pathogenesis, the natural history, and risk of the progression enabled
more differentiated therapy of elderly men with BPH. The specific approach used
to treat BPH depends upon a number of factors like age, prostrate size, weight,
prostate-specific antigen level, and severity of symptoms. The options are as
follows:

Watchful waiting

Pharmacological
management

Surgical Treatment

Watchful Waiting

Watchful waiting is a
management strategy in which the patient is monitored by his physician but
currently receives no active intervention for BPH. The level of symptom
distress that individual patients are able to tolerate is highly variable so
watchful waiting may be a patient’s treatment of choice even if he has a high
AUA-SI score.

Watchful waiting (active
surveillance) is the preferred management strategy for patients with mild
symptoms. It is also an appropriate option for men with moderate-to-severe
symptoms who have not yet developed complications of LUTS and BOO (e.g., renal
insufficiency, urinary retention or recurrent infection).

?-Adrenergic blockers are the most commonly used
medical treatment for BPH. ?1-Adrenoreceptors maintain prostate
smooth muscle tone. ?1-Adrenoreceptor antagonists act on prostate
and urethral smooth muscle to reduce the dynamic component (related to
increased prostate smooth muscle tone) of urethral resistance and thus
alleviate voiding symptoms. ?-Adrenergic blockers relieve not only obstructive
but irritative symptoms in patients with BPH, although underlying mechanisms of
the relief of irritative symptoms are still unknown.

Non-selective drugs

Phenoxybenzamine and Thymoxamine

Selective drugs

?1

Short acting: IR Alfuzosin, Indoramin, Prazosin

Long acting: SR Alfuzosin, Doxazosin, Tamsulasin,
Terazosin

Steroidal 5?-reductase is a NADPH-dependent enzyme
that catalyzes the irreversible conversion of 4-en-3-oxo-steroid, that is,
Testosterone (T), the major circulating androgen in male adults, to the corresponding
5?-H-3-oxo-steroid, that is, Dihydrotestosterone (DTH). Two isozymes of
5?-reductase have been cloned, expressed, and characterized on the basis of
differences in chromosomal localization, tissue expression pattern and
biochemical properties. Within the prostate, locally produced DTH acts in a
paracrine fashion to stimulate growth. However, excessive production of DTH is
the cause of major androgen-related disorders such as prostate cancer, acne,
female hirsutism, and BPH. Therefore, inhibitors of androgen action by
5?-reductase is a logical treatment of 5?-reductase activity disorder, that is,
BPH.

Antimuscarinics decrease the contractile response of
the detrusor muscle of ovearactive bladder (OAB) patients. In a patient with
BPH/LUTs and no evidence of BOO, particularly if the predominant symptoms are
those of OAB, it is appropriate to treat them with an antimuscarinic agents.

 

The rationale for using PDE-5 inhibitors for the
treatment of BPH patients originates from the following three observations:
first, the prevalence of LUTs and BPH increases with age.; second, PDE-5
inhibition mediates smooth muscle relaxation in the lower urinary tract; and
third, early clinical evidence demonstrates that PDE-5 inhibitors are
successful in treating LUTS.

Adherence has been linked to perceived efficacy, side
effects, and cost of medical treatment. It is known that patients with worse
LUTS tend to complain less about adverse side effects compared with those with
less severe symptoms. In addition, older patients are more likely to be
adherent. Other risk factors for discontinuation including number of medical
comorbidities, type of treatment, and polypharmacy have also been investigated.
Technical, behavioral, and educational interventions aimed at improving
adherence to medications for chronic diseases have been developed. Less
frequent dosage enhances compliance, and technical adherence interventions are
usually directed at simplifying the medication regimen including use of
extended-release formulations or fixed-dose combination pills. Behavioral
interventions are also used to provide patients with memory aids and reminders.
Educational interventions focus on adequately informing patients about the
disease, its management, and the potential benefits of long-term treatment with
these agents.

 

Surgical
Treatments

Invasive procedures

Minimal Invasive procedures (MIT)

Transurethral electrovapourization (TUVP)

Transurethral microwave thermotherapy (TUMT)

Transurethral needle ablation (TUNA)

Laser ablation

High-intensity focused ultrasound (HIFU)

Transurethral ethanol ablation of the prostate

Water induced thermotherapy

Plasma kinetic tissue management system.