Benign prostatic hyperplasia

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• Benign prostatic hyperplasia (BPH) is the most common benign tumor in men and is responsible for urinary symptoms in the majority of males over the age of 50 years.

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Pathophysiology

• Prostatic hypertrophy is directly related to the ageing process and to hormone activity.

• In the prostate, testosterone is converted by 5α-reductase to dihydrotestosterone (DHT).

• DHT is five times more potent than testosterone and is responsible for stimulating growth factors that influence cell division leading to prostatic hyperplasia and enlargement.

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• The prostate enlarges can compress the urethra and this, together with increased adrenergic tone, can lead to bladder outflow obstruction (BOO) and lower urinary tract symptoms (LUTSs).

• Drugs that can exacerbate symptoms include testosterone, α-adrenergic agonists (eg, decongestants), and those with significant anticholinergic effects (eg, antihistamines, phenothiazines, tricyclic anti-depressants, antispasmodics, and antiparkinsonian agents.

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Clinical presentation

• LUTSs can be divided into symptoms of failure of urine storage (irritative) and those caused by failure to empty the bladder (obstructive or voiding).

Irritative symptoms

• Urinary frequency

• Nocturia

• Urinary urgency

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Obstructive symptoms

• Poor urinary flow

• Hesitancy in initiation of micturition

• Post-micturition dribble

• Sensation of incomplete emptying

• Occasional acute retention of urine requiring emergency treatment

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• BPH may produce complications including chronic kidney disease, hematuria, urinary incontinence, recurrent urinary tract infection, and bladder stones.

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Examination and investigations

• There is a range of investigations and diagnostic tests available for the evaluation of patients with suspected BPH.

• Physical examination

Digital rectal examination (DRE)

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• Urodynamic studies

Urodynamic studies is used to measure of BOO.

These include maximum flow rate and postvoid residual (PVR).

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• Flexible cystoscopy

Flexible cystoscopy provides an endoscopic image of the bladder for the assessment of prostatic obstruction and informs possible management options.

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• Imaging

Prostatic ultrasound scan or TRUS

• laboratory tests

(e.g., urinalysis, blood urea nitrogen, and

prostate-specific antigen [PSA]).

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Treatment

Management options for BPH

include:

• watchful waiting,

• Drug therapy, and

• surgical intervention.

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Watchful waiting • Men with mild or moderate and not significantly

bothersome LUTSs should be offered a trial of watchful waiting education and lifestyle advice to manage their urological symptoms together with a review of their medication, particularly diuretics or other medicines known to affect the urinary system.

• This management strategy does not include any medical or surgical treatment but involves regular active monitoring.

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Advice for the management of lower urinary tract symptoms include

Limit fluid consumption before going out and before going to bed (to reduce urinary frequency and nocturia)

Reduce alcohol and caffeine intake

Schedule toilet visits

Manage constipation

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Review medication (including diuretics and other medicines that can affect the urinary system)

Bladder training (encourage patient to go longer between voiding and increase the volume voided)

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Therapeutic management

The principal treatment options are

• α-adrenoceptor blocking drugs

• 5α-reductase inhibitors

• Combination therapy.

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α-Adrenoceptor blocking drugs

(Prazosin, Terazosin, Indoramin, Doxazosin, Tamsulosin, and Alfuzosin)

• In the prostate, α1-receptors predominate and mediate the contraction of the gland's smooth muscle.

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• Adverse effects of α-Adrenoceptor blocking drugs

include first dose syncope , postural hypotension,

dizziness, fatigue, headache, drowsiness, nasal

congestion and ejaculatory dysfunction.

• Patients should be slowly titrated to

maintenance dose and should take these drugs at

bedtime to minimize orthostatic hypotension and

first-dose syncope with terazosin and doxazosin.

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• Indoramin is hypotensive effect may be increased by diuretics and other anti-hypertensive agents. Alcohol has been reported to increase the bioavailability and sedative effects of indoramin.

• Doxazosin has a long half-life of about 22 h, which allows for once-daily dosing.

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• Tamsulosin has an elimination half-life of about 13 h and is available as a prolonged release formulation that allows once-daily dosing. There is no requirement to titrate the dose upward when initiating treatment.

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• Alfuzosin should not be co- administered with potent inhibitors of cytochrome P450 3A4 such as itraconazole, ketoconazole and ritonavir.

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5α-Reductase inhibitors

DHT is the primary androgen responsible for the development and progression of BPH.

There are two isoenzymes of 5α-reductase: type 1 is found in most 5α-reductase producing tissues such as the liver, skin and hair; type 2 is predominant in genital tissue, including the prostate.

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5α-Reductase inhibitors downregulate prostate growth by blocking the conversion of testosterone to the more potent DHT.

Pregnant women should not handle the tablets or have contact with semen from men receiving 5 α-reductase inhibitors (5 α-Reductase inhibitors are in FDA pregnancy category X ).

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• The two agents currently available in this group are finasteride and dutasteride.

Finasteride

• It is a type 2, 5α-reductase inhibitor that can reduce prostate size by about 30%, improve symptom scores and increase urinary flow.

• Those most likely to benefit are men with a prostate more than 40 gram.

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• Side effects include decreased libido, impotence, reduced ejaculatory volume and, less commonly, gynaecomastia and breast tenderness.

• Serum concentrations of PSA may be reduced by 50% in the first year of treatment with finasteride.

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Dutasteride

• Dutasteride inhibits both type 1 and type 2 isoenzymes of 5α-reductase.

• Dutasteride decreases prostate volume by up to 26% and reduces the risk of progression to serious complications of BPH.

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• LUTSs also improve after 6 months of treatment.

• Dutasteride is well tolerated although side effects which include erectile and ejaculatory dysfunction and breast enlargement occur with similar frequency to finasteride.

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Combination therapy

• Combination therapy (dutasteride and tamsulosin) should be considered for moderate to severe symptoms of BPH and prostate enlargement.

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Surgical treatments

• Surgical interventions are commonly performed in men with LUTSs caused by BPH that have failed to respond to medical treatment.

• Surgery is also indicated in patients who develop complications such as recurrent urinary retention, renal impairment, persistent haematuria, recurrent UTIs or bladder stones.

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Transurethral resection of the prostate

• Transurethral resection of the prostate (TURP) is a common and effective procedure which achieves a high level of improvement in symptoms and flow rate.

• It is the preferred surgical intervention in men with a prostate volume between 30 and 80 mL.

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• Long-term complications of TURP include stress incontinence, urethral and bladder neck strictures and erectile dysfunction.

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Open prostatectomy

• Open prostatectomy involves the surgical removal of an enlarged prostate.

• This procedure is now performed infrequently and restricted to very enlarged prostate glands (larger than 100 mL) .

• Open prostatectomy requires a longer hospital stay than transurethral resection and is associated with a higher incidence of bleeding and other complications.

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Minimally invasive techniques

• Thermotherapy and laser technology are the most commonly used.

• Thermotherapy uses techniques such as electrovaporisation and transurethral microwave heat treatment (TUMT), which heats the prostate to cause vaporisation of the tissue.

• Various types of laser energy can also be used to destroy prostatic tissue mainly by vaporisation.

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