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Benign Prostatic Hyperplasia ( BPH )

Benign prostatic hyperplasia ( BPH ) is a histologic diagnosis that refers the proliferation of smooth muscle and epithelial cell within the prostate transition zone
 ( American Urological Association 2010 ).

The exact etiology is unknown , one of the proposed theories is reawakening on adulthood of embryonic induction processes

The enlarged gland leads to LUTS ( Lower urinary tract symptoms ) by two mechanisms-Direct bladder outlet obstruction
 ( BOO ) from enlarged tissue – this is the static component-Increased smooth muscle tone and resistance within the enlarged gland- this is the dynamic component.

Voiding symptoms are associated due to the physical presence of direct bladder outlet obstruction ( BOO ) – due to BOO compressing the urethra BOO may lead to LUTS , infections , retention , renal failure , hematuria and bladder calculi Detrusor over-activity is thought to be associated with storage symptoms seen in LUTS It is important to note that prostate volume does not linearly correlate with severity of BOO or LUTS

How common ? BPH is a common disease in older men & its prevalence increases with age A paper in 1995 ( Bulletin for decision makers on the effectiveness of health service interventions ) reported 
- prostatic enlargement can be found in majority of men over 60
- changes in prostate suggestive of BPH have been found in up to 70 % of 60-70 yr
 old men
- estimates of clinical prevalence of BPH is between 5-43 % The Urological Diseases in America BPH project reports ( Olmsted County Study ) a progressive increase in prevalence of moderate to severe LUTS , rising to nearly 50 % by the eighth 
decade of life Between 1998 and 2007 the age related prevalence of BPH among hospitalized patients in the USA nearly doubled ( Stroup SP et al 2012 ) GPs in UK will have about 50 patients who are between 60-80 yrs with moderate to 
severe LUTS from BPH ( John Nash 2010 ) BPH has significant economic load – in the year 2000 BPH cost the US health 
system$ 1.1 billion and accounted for over 4.4 million clinic visits , 117,000 emergency visits and 105,000 hospitalisations ( BMJ Best Practice) Autopsy studies have reported a histological prevalence of 8 % , 50 % and 80 % in the 4th , 6th and 9th decades of life. Some evidence to show that BPH is less common in Asian men in comparison to white men.

Risk factors –Etiology of BPH is multifactorial Establishing risk factors for BPH has been controversial possibly because of difference in sampling methods and methods of analysis non modifiable risk factors include age , genetics and geography Recent advances have identified possible modifiable risk factors include
- sex steroid hormones , metabolic syndrome , cardiovascular disease , obesity , diabetes , diet
,physical activity & inflammation Larger prostate volumes are associated with increased risks of BPH and prostate volume increases with age (BLSA study ) Genetics – studies suggest a genetic link to both BPH and LUTS , it thought that an autosomal dominant pattern of inheritance affects men particularly who are less than 60 yrs of age who undergo surgery. These men tend to have a larger prostate volumes and earlier onset of clinical symptoms than men with sporadic BPH DHT ( Dihydrotestosterone ) is the specific androgen which mediates prostate development and growth -an increased risk of BPH with increased serum concentration of DHT and its metabolites has been noted.

Assessment –Nature and duration of symptoms Any previous treatment , interventions Voiding symptoms as hesitancy , intermittency , weak stream , straining , incomplete emptying , post-void dribbling Storage symptoms as urinary frequency , nocturia and urgency Assess for possible co-existing illnesses like CV and renal disease Sexual dysfunction – ask about erectile 
dysfunction ( over whelming evidence to support that ED and LUTS are related ) H/O any previous surgery / trauma Drug history including OTC medications r/o red flags as hematuria , previous genitourinary surgeries , recurrent UTIs ,difficulty emptying the bladder , prostatic nodule or enlargement , PSA elevation , concerns of urinary retention or presence of neurological conditions as spinal cord injury or stroke.

Tools to assess severity- The most widely used tool in epidemiological studies to measure LUTS is the American Urological Association Symptom Index ( AUA-SI ) The International Prostate Scoring System ( I-PSS ) is the internationally validated counterpart of the AUA-SI European Association of Urology and the WHO International Consultation on Urologic Disease recommend the routine use of I-PSS in the clinical evaluation of patients with suspected BPH and BOO Several studies have used the following criteria when studying men to determine prevalence of BPH
- an IPSS score of 8 or more
- peak flow < 15 mL/ s
- prostate volume > 20 cm ( 3 ) A voiding diary could be used if you suspect nocturanl polyuria or excessive fluid intake


Examination –Check BMI Palpate the abdomen for any masses / retention External genitalia for penile causes of urinary obstruction like urethral meatal stenosis or a palpable urethral mass Digital rectal examination -assess the anal spincter tone and estimate prostate size , nodules or a rectal mass ( BPH normally causes smooth enlarged non-tender prostate ) Further examinations for e.g neurological – based on clinical suspicion.

A full biochemical and haematological profile is ordered by most clinicians It is important to check the PSA level and glucose urinalysis

Watchful waiting –For patients with minimally bothersome symptoms watchful waiting may be appropriate. Ensure education ( about disease progression ) , reassurance , ongoing monitoring and behavioural modifications- consider PIL on BPH- find it under links and resources

Alpha blockers –for patients who prefer treatment alpha blockers are an excellent first line therapeutic option alpha blockers cause relaxation of the smooth muscle of bladder neck and smooth component of prostate all 4 commonly used agents (alfuzocin , tamsulocin , terazocin & doxazocin ) are equally effective in improving symptoms most common SEs are dizziness , headache and postural hypotension they do not prevent disease progression

5-alpha reductase inhibitors –considered appropriate and effective for patients with LUTS associated with demonstrable prostatic enlargement or high 
PSA levels ( > 1.6 ng / mL ) they inhibit conversion of testosterone to its active metabolite 5-DHT which is the main stimulator of prostate growth in BPH-this can lead to shrinkage of prostate studies have shown that in addition to improving symptoms that they can alter the natural h/o BPH and reduce the risk of AUR and the need for surgical intervention discuss the common SEs as ED ,decd libido , ejaculatory dysfunction and gynaecomastia

Combination therapy 

alpha 1 blocker + i5ARseffective in patients with moderate to severe LUTS with increased prostate volume or high PSA and reduced maximum urinary flow clinical trials have shown that this significantly improves in symptom score and peak urinary flow compared with either of monotherapy alone can delay symptomatic disease progression decreased risk or urinary retention and / or prostate surgery

Phosphodiesterase inhibitors –FDA approved tadalafil for use in LUTS related to BPH in 2013 Shown to be effective in several studies but the exact mechanism is not known. Possible mechanisms include reduction in smoot muscle tone of the lower UrTr ,endothelial cell proliferation , increased blood flow and oxidation to the prostate and pelvic organs , activity on the prostatic efferent nerves

Beta-3 agonists Mirabegron is the 1st drug liceneced under this class
particularly useful for bladder storage symptoms works by relaxing the detrusor smooth muscle , decreasing affarent signalling from the bladder , improved bladder compliance during filling and improving overall bladder capacity decreases urinary frequency and urinary urgency episodes detrusor contracttion is not affected as it does not interfere with the para-sympathetic system –> minimizes the risk of uriary retention.

Surgery –Despite treatment in some patients disease progression is 
inevitable ( MTOPS and Olmed county study ) Several surgical procedures are available for e.g Monopolar TURP ( gold standard for patients with bothersome ) , Laser prostatectomy , Transurethral incision of the prostate ( TUIP ) , open prostatectomy and minimally invasive procedures as Transurethral microwave 
therapy ( TUMT , transurethral needle ablation TUNA )

BPH complications – worsening of symptoms incomplete emptying detrustor instability more severe bladder outlet obstruction acute urinary retention ( AUR ) recurrent UTI urosepsis chronic kidney disease bladder stones incontinence haematuria


Referral- based on Rosenberg et al
 Canadian Journal of Urology 2014H/O recurrent UTIs or other infections Microscopic or gross haematuria h/o genitouriary surgery PSA out of range ( USC prostate cancer ) Abnormal DRE ( e.g nodules ) If a neurological cause of the symptoms is suspected — LUTS can also happen due to abnormalities in PNS or CNS Urinary retention ( admit via A&E ) Meatal stenosis H/O genitourinary trauma After assessment / tests a diagnosis remains uncertain Patient requests to see a specialist

In UK also take into account the NICE guidelines on LUTS and urological malignancy ( both the topics are available
on A4Medicine ). Both the criteria can help you make a decision on further management and are aimed at finding an underlying serious pathology which requires urological intervention.

BPH natural history-Natural h/o BPH ( that is progression of the disease if left 
untreated over time ) is difficult to study as that would involve subjecting the cohort of these men with symptom scores , TRUS and pressure flow-urodynamic studies. Two important studies have been done which provide an insight into the natural h/o BPH
 Olmsted County Study of Urinary Symptoms and
Health Status ( USA ) Medical Therapy of Prostatic Symptoms ( MTOPS ) this is the largest ever study. It was a long-term

The MTOPS study has shown that the development of AUR is quite common in men with clinical BPH and the we can deduce based on data from the Olmsted study that a 60 yr old man with moderate to severe symptoms has a 13.7 % chance of developing AUR by age of 70.
It is also now known that the risk of AUR is related to both baseline serum PSA level and the prostate volume

PATIENT INFORMATION

American Urological Association on BPH https://www.urologyhealth.org/urologic-conditions/benign-prostatic-hyperplasia-(bph)

Prostate Scotland printable 6 page leaflet https://www.prostatescotland.org.uk/wp-content/uploads/resources/Men-and-thier-PlumbingLarge-Print-1.pdf

Radiology Info Org for patients https://www.radiologyinfo.org/en/info.cfm?pg=bph

A 52 page booklet on enlarged prostate from Prostate Cancer UK https://prostatecanceruk.org/media/41599/enlarged_prostate_booklet.pdf

NHS Inform Scot on Prostate enlargement https://www.nhsinform.scot/illnesses-and-conditions/kidneys-bladder-and-prostate/benign-prostate-enlargement

Benign prostatic hyperplasia https://abuhb.nhs.wales/files/patient-information-leaflets1/bladder-and-kidney-urology/benign-prostatic-hyperplasia-bph-pdf/

BPH information from NHS  https://www.nhs.uk/conditions/prostate-enlargement/

REFERENCES

  1. 2010 Update: Guidelines for the management of benign prostatic hyperplasia cUa gUideline J. Curtis Nickelet al and the Canadian Prostate Health Council and the CUA Guidelines Committee Can Urol Assoc J 2010;4(5):310-316
 https://www.cua.org/themes/web/assets/files/guidelines/en/guidelines_for_the_management_of_benign_prostatic.pdf
  2. Benign prostatic hyperplasia: risk factors and management Dr John Nash* General Practitioner, The Misbourne Surgery, Chalfont St Giles, Buckinghamshire; Hospital Practitioner in Urology, Buckinghamshire Hospitals NHS Trust https://www.gmjournal.co.uk/media/21691/july2010p364.pdf
  3. Treatment of benign prostatic hyperplasia trataMento da hiperplasia prostática Benigna Authorship: Brazilian Society of Urology (SBU) Ricardo Vita Nunes1, João Manzano1, José Carlos Truzzi1, Aguinaldo Nardi1, Antonio Silvinato1, Wanderley Marques Bernardo2 Final draft: August 7, 2016 http://www.scielo.br/pdf/ramb/v63n2/0104-4230-ramb-63-02-0095.pdf
  4. BMJ Best Practice Benign Prostatic Hyperplasia https://bestpractice.bmj.com/topics/en-gb/208/pdf/208/Benign%20prostatic%20hyperplasia.pdf
  5. Benign Prostatic Hyperplasia Treatment for lower urinary tract symptoms in older men Bulletin for decision makers on the effectiveness of health service interventions Nuffield Institute for Health, University of Leeds NHS Centre for Reviews and Dissemination, University of York
  6. European Association of Urology GUIDELINES ON BENIGN PROSTATIC HYPERPLASIA J. de la Rosette, M. Perachino, D. Thomas, S. Madersbacher, F. Desgrandchamps, G. Alivizatos, M.J.A.M. de Wildt https://uroweb.org/wp-content/uploads/EAU-Guidelines-Bening-Prostatic-Hyperplasia-2001.pdf
  7. A practical primary care approach to lower urinary tract symptoms caused by benign prostatic hyperplasia ( BPH-LUTS ) Matt T Rosenberg , MD et al Canadian Journal of Urology ;21 ( Supplement 2 ) ; June 2014 https://www.canjurol.com/html/free-articles/V21I3S1_07F_DrRosenberg.pdf 
  8. Patel ND, Parsons JK. Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet obstruction. Indian J Urol. 2014;30(2):170–176. doi:10.4103/0970-1591.126900 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989819/
  9. Lepor H. Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. Rev Urol. 2004;6 Suppl 9(Suppl 9):S3–S10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472917/
  10. Epidemiology of clinical benign prostatic hyperplasia Author links open overlay panelKok BinLim Asian Journal of Urology Volume 4, Issue 3, July 2017, Pages 148-151 https://www.sciencedirect.com/science/article/pii/S2214388217300553

  11. Benign Prostatic Hyperplasia: Evaluation and Medical Management in Primary Care Effective therapy is available, but underutilized By Raman Unnikrishnan, MD; Nima Almassi, MD; and Khaled Fareed, MD https://consultqd.clevelandclinic.org/benign-prostatic-hyperplasia-evaluation-and-medical-management-in-primary-care/

  12. Primary Care Evaluation and Treatment of Men With Lower Urinary Tract Symptoms Nathan Hale, DO; Kellen Choi, DO; Joshua Lohri, DO The Journal of the American Osteopathic Association, July 2014, Vol. 114, 566-571. doi:https://doi.org/10.7556/jaoa.2014.110

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