Introduction

Benign prostatic hyperplasia (BPH) is a condition which commonly affects men histologically from the age of 40 onwards but symptoms often do not become apparent until later decades.

It involves the proliferation of different prostate layers, with this proliferation tending to be more focussed on the inner prostate. Hyperplasia differs from hypertrophy in that it involves an increase in the number of organ cells rather than the size of the cells.

BPH results in urinary system compression, leading to a range of problems. Men tend to be treated when these problems have a significant impact on their quality of life and this impact outweighs the potential side effects of treatment. Although there is no definitive cure, treatments can be useful in slowing the growth of the prostate.

Epidemiology

  • Incidence: 5000.00 cases per 100,000 person-years
  • Peak incidence: 70+ years
Condition Relative
incidence
Benign prostatic hyperplasia1
Prostate cancer0.03
Urethral stricture0.01
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

The cause of BPH is not well understood. There are however several theories for its aetiology, revolving around reduced cell death, epithelial gland proliferation and increasing dividing potential:

  • Androgens (testosterone and dihydrotestosterone (DHT) play a likely role in the development of BPH
    • BPH does not occur in males who have not gone through puberty due to the lack of these androgens
    • BPH occurs after exposure to these androgens post-puberty
    • Those who undergo castration prior to puberty do not go on to develop BPH

  • Inflammation is also thought to play a role. This can take the form of:
    • Chronic infections such as Escherichia coli
    • Inflammatory cytokines from obesity due to dietary sources such as fats
    • Autoimmune inflammation
    • This is recognised, as serum C-reactive protein levels tend to increase as the severity of LUTS increase

BPH can affect men of different ages:

  • 8% of 31-40 year-olds
  • 40-50% of 51-60 year-olds
  • >80% of 80+ year-olds

Race appears to play some role in the development of BPH:

  • Black men are more likely to need treatment at a younger age compared to White and Asian populations and are more likely to develop moderate to severe LUTS
  • Asian men are the least likely to develop problematic BPH

Genetics also clearly play a role, with apparent familial tendencies. Familial BPH can be discriminated from sporadic BPH due to comparatively larger prostates and an earlier age of LUTS onset. Genetic factors are likely to be a greater determinant of LUTS severity than age or prostate volume.

Pathophysiology

  • There are two prostate growth phases
    • The first phase begins in puberty and involves the prostate doubling in size
    • The second phase occurs from the age of 25 and continues throughout mens' lives
  • BPH tends to occur in the second prostate growth phase
    • This occurs in men from the age of 25
  • As the inner prostate layers propagate, the urethra will be compressed and the bladder wall may thicken
    • These processes result in the LUTS commonly associated with BPH

Clinical features

Patients with BPH may present with a range of lower urinary tract symptoms (LUTS), although the prevalence may be as low as 25-50%. There is often little association with increasing prostate size noticed during examination or imaging and increasing LUTS.

LUTS occur due to bladder outlet obstruction (BOO) caused by BPH. These symptoms are progressive.

LUTS can be separated into voiding and storage symptoms. Voiding LUTS tend to be the most common LUTS in men with BPH, however, storage LUTS tend to be more bothersome to the affected patients.

Voiding LUTS include:

Storage LUTS include:

Patients can experience a range of LUTS, however, nocturia is commonly reported as the most common presentation when men attend to general practice.

The International Prostate Symptom Score (IPSS) can be used to classify the severity of LUTS. This score contains seven questions, with each one being assigned a score between 0 and 5. The score can be interpreted:

  • 0-7 - Mild symptoms
  • 8-19 - Moderate symptoms
  • 20-35 - Severe symptoms

An initial examination may involve a digital rectal examination (DRE). A presentation in line with BPH involves an enlarged, non-tender prostate with loss of the median sulcus. Examinations carried out serially may be useful to track the prostate growth, with a normal prostate being around the same size as a walnut. A painful prostate on DRE may point towards prostatitis whilst an asymmetric, nodular prostate would be more in line with a prostate cancer presentation.

Investigations

The 2015 NICE guidelines recommend the following investigations for men displaying LUTS:

Urinalysis:
  • Urine dipstick to check for blood, glucose, protein, ketones and bacteria
    • These tests are crucial to check for other conditions such as UTIs. Small amounts of haematuria may be present with BPH but larger volumes may point to urinary malignancy

Blood tests:
  • Serum creatinine
    • This may be appropriate if a patient presents with chronic urinary retention, recurrent UTIs or urinary stones. These conditions can cause impaired kidney function, resulting in an increased creatinine measurement
  • PSA test
    • If symptoms suggest BOO, then this test can guide treatments. It can be used to assess prostate volume, which may be helpful before starting a 5α-reductase inhibitor. A PSA measurement before and after starting this medication may be useful in order to effectively screen for prostate cancer in the future. A PSA test can also be used to screen for prostate cancer

Imaging:
  • Bladder ultrasound scan (USS)
    • This investigation can be used in the case of chronic urinary retention. It can assess levels of hydronephrosis and guide further treatment
  • Transrectal USS
    • This scan may be of use when treatment is indicated which requires knowledge of the prostate volume, such as 5α-reductase inhibitor medication or surgical management

Differential diagnosis

BPH may be mistaken for other conditions which also cause LUTS. Examples of these conditions may include:

  • Urological system obstructions (prostate cancer, urethral stricture)
    • Similarities: these conditions lead to a range of voiding LUTS such as incomplete bladder emptying
    • Differences: a DRE would potentially reveal an asymmetric, nodular prostate with prostate cancer and BPH commonly presents with the addition of storage symptoms such as nocturia
  • Urinary tract infections
    • Similarities: cystitis may lead to LUTS such as frequency and urgency
    • Differences: the large, non-tender prostate palpated during a DRE would be more in-line with BPH and would not be present with a UTI
  • Detrusor instability
    • Similarities: this instability may lead to incomplete emptying of the bladder
    • Differences: BPH also involves storage LUTS and also involves an abnormal DRE examination
  • Cardiovascular disease (CVD)
    • Similarities: diuretic use to treat CVD leads to an increase in storage symptoms such as frequency
    • Differences: BPH also commonly presents with voiding LUTS
  • Neurogenic bladder
    • Similarities: diseases such as Parkinson's disease may lead to LUTS such as incontinence because of affected neural connections with the detrusor muscle
    • Differences: an abnormal prostate on DRE is unlikely to be found in Parkinson's disease
  • Diabetes mellitus (DM)
    • Similarities: poorly controlled DM can result in reduced bladder sensation and therefore reduced bladder emptying. Osmotic diuresis caused by DM can increase urinary symptoms such as frequency
    • Differences: an abnormal prostate on DRE is unlikely to be found in DM

Management

In 2015, NICE published guidelines on managing LUTS.

Initially, if patients are experiencing symptoms but their quality of life is unaffected and there is no evidence of complications such as UTIs, they will be encouraged to make lifestyle alterations. These may include:

  • Avoiding fluids right before bed to reduce the likelihood of nocturia
  • Reducing the consumption of diuretic fluids like alcohol and coffee
  • 'Double voiding', which involves emptying one's bladder twice whilst at the toilet

The next stage of management involves medication. This step may be taken if the patient feels that their symptoms are affecting their quality of life or they have developed complications as a result of BOO. There are several drug options available:

  • α-blockers such as tamsulosin to reduce smooth muscle tone to improve urine flow (for mild-moderate IPSS score)
    • These medications act immediately
  • If unfortunate side effects are experienced, patients may choose to switch to a different drug
  • The next option would be a 5α-reductase inhibitor such as finasteride. These drugs reduce the conversion of testosterone to DHT
    • These medications may take 6-12 months before a therapeutic effect is noted
  • For patients with a severe IPSS score, it may be appropriate to begin combined treatment with both an α-blocker and a 5α-reductase inhibitor

A referral to a urologist should be made when patients' symptoms are unable to be kept under control or if they develop complications such as hydronephrosis or urinary retention from BOO which may require invasive therapy. Other indications may include an early-age onset (<45), an abnormal DRE and haematuria.

Surgery (for severe symptoms):
  • Transurethral resection of prostate (TURP) to remove prostate tissue
  • Transurethral incision of prostate (TUIP) to widen the urethra

Common side effects:
  • α-blockers
    • Dizziness, postural hypotension, dry mouth, depression, drowsiness
  • 5α-reductase inhibitors
    • Impotence and reduced interest in sex
  • TURP
    • Impotence

Complications

BPH can result in BOO. This may lead to a range of complications such as:

  • UTIs
    • With chronic obstruction, the bladder may fail to empty urine effectively. This can result in the development of an infection as stagnant urine acts as an effective growth medium for bacteria
  • Urinary stones
    • The inability of the bladder to empty also provides a suitable environment for the development of urinary stones. These may result in further obstruction, severe pain and haematuria
  • Urinary retention
    • This may occur acutely and can be extremely uncomfortable. It can be managed with urethral or suprapubic catheterisation. Alpha-blockers are considered the most effective prophylactic treatment for this condition, but TURP may be resorted to if urinary retention continues to be problematic
  • Acute kidney injury
    • Obstruction may also lead to urine black-flow into the kidneys, leading to swelling and infection transfer from the bladder

Prognosis

  • In the past, chronic BPH at a late stage could lead to processes such as renal failure
  • Due to advances in medical and surgical management, the complications from BPH are now commonly less severe

However, with medical management:
  • Symptoms may still progress, having a large impact on patients' quality of life and leading to the need for surgical management

With surgical management:
  • There is a risk of bleeding after surgery
  • There is the potential for reduced sexual function
    • This may take the form of erectile or ejaculatory dysfunction
  • Trauma to the ureters may lead to the formation of urethral structures from scar tissue
  • Urinary incontinence may occur

  • Therefore, although end-stage processes such as renal failure are unlikely to occur from BPH, continued or potential new symptoms may have a significant impact on patients' quality of life