W13 Benign Prostatic Hyperplasia (MAH/GW)

Question 1

Definition of BPH?

Answer 1

Benign Prostatic Hyperplasia (BPH
➢A non-cancerous enlargement of the prostate gland due to cellular proliferation.
➢Aka benign prostate enlargement

Question 2

The prostate gland anatomy:

Answer 2

• The prostate is a small gland found only in men and trans women.
• Located in the pelvis, under the bladder, between the penis and the rectum– about the size of a
  walnut, surrounds the prostatic urethra.
• Normal growth during puberty and after age 25 due to androgens.
• Gland - role in semen production (thick white prostatic fluid comprises ~30% of ejaculate volume).
• Function in urinary and reproductive systems.
• It can sometimes become swollen or enlarged by conditions such as:
• prostate enlargement
• prostatitis (inflammation of the prostate)
• prostate cancer
• The bladder is a bag of muscle that holds the urine
• Urine exits the bladder via the urethra
• Urethra exits the body through the prostate gland and then the penis
• Prostate is a gland that has a function in male ejaculation and urination – facilitates mechanical switch between urination and ejaculation

Question 3

What are the Prostate zones? (3)

Answer 3

• Peripheral Zone: Largest zone 70% glandular tissue
• Central Zone: 25% glandular tissue,
  ejaculatory ducts that join with the prostatic urethra
• Transitional Zone: 5% glandular tissue, portion of the prostatic urethra

Luminal cells of glandular tissue secrete substances into the prostatic fluid to nourish sperm and ensure survival in the acidic environment of the vagina

Question 4

Ejaculation:

Answer 4

Sperm leaves testes, travels through vas deferens, through the bladder and out through prostatic urethra
PSA from prostatic fluid is produced by luminal cells

The majority of semen is made up of seminal vesicle fluid (∼65%; containing semenolgelins or SEMGs and fibronectin) and prostatic fluid (∼25%; containing pro-kallikrein (Pro-KLK) enzymes and Zn2+ ). Epididymal fluid and testis make up to ∼10% of the semen, while bulbourethral gland (mostly secretes mucinous
proteins) is only 1%.

Question 5

Androgens:

Answer 5

• Sex hormones that give men their ‘male’ characteristics (virilisation).
• The major sex hormone in men is testosterone, which is produced mainly in the testes.
• Dihydrotestosterone produced in prostate (10x more potent)
• Steroids cross PM bind to nuclear receptor to inhibit apoptosis AND stimulate growth and division of luminal and basal cells

Testosterone is converted to Dihydrotestosterone (10x more potent) by 5 a-reductase
more potent as it binds to the androgen receptors for longer and inhibits apoptosis, stimulates growth and dev of vasal and luminar cells
=prostate enlargement

Question 6

Pathophysiology of BPH

Answer 6

Prostate Growth:
➢ Hyperplasia predominantly occurs in the transition zone.
➢ Cause unknown ?linked to hormonal changes as a man gets older.
* Hormonal Mechanisms:
➢ Role of testosterone: Converted to dihydrotestosterone
(DHT) by 5-alpha reductase.
➢ DHT as a key mediator of prostatic growth.
➢ Age-related increase in oestrogen/testosterone ratio may sensitize the prostate to DHT.
* Cellular Mechanisms:
➢ Increased epithelial and stromal cell proliferation.
➢ Decreased apoptosis leads to net tissue enlargement.

1. > 30 yrs testosterone ↓ by 1% a year BUT 5-alpha
   reductase↑ with age
   2.~50% of men will develop BPH by 50 yrs of age
   3.Enlarged prostate with hyperplastic nodules
   which restricts the urethra

Question 7

Pathophysiology of BPH
Effect on Urinary Function? (2)

Answer 7

➢ Prostatic enlargement compresses the urethra, leading to obstruction.
➢ Secondary bladder changes, including detrusor hypertrophy and instability.

Question 8

Signs and symptoms of BPH?
Complications?

Answer 8

Lower Urinary Tract Symptoms (LUTS):
➢ Storage symptoms: Frequency, urgency, nocturia.
➢ Voiding symptoms: Hesitancy, weak stream, incomplete voiding.
Complications:
➢ Urinary retention&raquo_space;> recurrent urinary tract infections (UTIs).
➢ Bladder stones or renal impairment.

Question 9

What steps are in the Diagnosis and Evaluation of BPH?
tests?

Answer 9

• Clinical History: Assessment of LUTS using tools like the International Prostate Symptom Score (IPSS).
• Physical Examination: Digital rectal examination (DRE) to assess prostate size.
• Investigations:
  ➢Urinalysis and prostate-specific antigen (PSA) levels (↑ PSA in BPH).
  ➢Ultrasound or urodynamic studies in select cases.

Question 10

Clinical Management of BPH
Monitor which patients?
Pharmacological Treatment?
Surgical Treatment?
Lifestyle Modifications?

Answer 10

• Monitor: Suitable for mild symptoms or those with minimal impact on quality of life.
• Pharmacological Treatment:
  ➢ 5-alpha reductase inhibitors: E.g., finasteride, reduce prostate size by inhibiting DHT synthesis.
  ➢ Alpha-1 blockers: E.g., tamsulosin, relax smooth muscle in the prostate and bladder neck.
  ➢ Combination therapy: For patients with larger prostates or severe symptoms.
• Surgical Treatment:
  ➢ Transurethral resection of the prostate (TURP): Gold standard for severe cases.
  ➢ Minimally invasive techniques: Laser therapy, prostatic urethral lift.
• Lifestyle Modifications:
  ➢ Reducing fluid intake before bed, avoiding caffeine and alcohol.
  ➢ Timed voiding and bladder training.

Question 11

Lower Urinary Tract Symptoms (LUTS) in men

Answer 11

LUTS = storage, voiding and post-micturition symptoms affecting the lower urinary tract
Will often categorise the symptom(s) into one of the three groups to help define the source of the problem

Voiding: weak/intermittent urinary stream, straining, hesitancy, terminal dribbling and incomplete emptying
Storage: urgency, frequency, urgency incontinence and nocturia
Post-micturition: post-micturition dribbling and sensation of incomplete emptying

Not a severe illness itself – can ↓ QOL and point to serious issue

Question 12

Causes of LUTS?

Answer 12

• Voiding
  Benign prostatic hyperplasia or benign prostatic enlargement (most common)
  Antimuscarinic drugs – e.g. tricyclic antidepressants sedating antihistamines.
  Diabetic autonomic neuropathy
  Urethral stricture and phimosis (foreskin constriction)
  Prostate/bladder cancer
• Storage
  Bladder outlet obstruction (BPH, stricture or bladder stones)
  Neurological conditions – e.g. MS, dementia, Parkinson’s, stroke
  Stress incontinence – physical exertion, alcohol, drugs (e.g. alpha-blockers, antimuscarinics)
• Post-micturition
  Weakness or failure of pelvic floor muscles
  Issues with external urethral sphincter
  Bladder neck obstruction (BPH, tumour, stones)

Question 13

Prevalence and Risk Factors:

Answer 13

LUTS are very common
Most elderly males will have at least one LUTS, usually not too bothersome
30% of men over 65 years experience troublesome LUTS
Prevalence increases with age

Risk factors:
Males of increasing age
Diabetes mellitus
Inflammation
Increased size of prostate gland
Modifiable: diet, physical activity, obesity, smoking

Question 14

Benign Prostatic Hyperplasia
What is it?
What can it lead to?

Answer 14

Enlarged prostate gland
Is not cancer = benign
No link between BPH and prostate cancer risk

Enlarged prostate = increased pressure on bladder and urethra

Leads to:
Difficulty starting to pee
Frequent need to pee
Difficulty fully emptying bladder

Question 15

Complications of BPH?

Answer 15

• Urinary retention
  -Essentially an inability to urinate
• Urinary tract infections
  -Having residual urine in bladder = breeding ground for bacteria
• Bladder stones
  -Can cause illness, irritation, haematuria and full urethra blockage
• Bladder damage
  -Bladder can stretch and weaken over time if not emptied fully = muscle can’t properly force out urine = difficulty urinating
• Kidney damage
  -Increased pressure in bladder from not being able to pee = kidney damage
  -Also risk of UTI traveling up to kidneys = pyelonephritis or urosepsis

Question 16

BPH Diagnosis
Based on..?
Physical assessment?
Tests?

Answer 16

• Based on signs and symptoms
• Physical assessment:
  Key aspect is the digital rectal exam to assess prostate symmetry, size, firmness, surface smoothness, tenderness and midline groove
  -Normal = smooth surface and expected size
  -Prostate cancer = hard gland +/- palpable nodules +/- enlargement
  -BPH = smooth, firm, enlarged gland
• May ask patient to record a urinary frequency volume chart for 3 days
• Urine dipstick – rule out UTI
• U’s and E’s – rule out renal impairment
• Will always need to rule out prostate cancer in these patients
  -Often asymptomatic, but may have LUTS with lower back pain, lethargy, haematuria and/or weight loss
  -Need Prostate-Specific Antigen Testing (PSA) – high levels can mean cancer
  -May need prostate biopsy or imaging to confirm diagnosis

Question 17

BPH Treatment – Lifestyle Advice?

Answer 17

NB will not treat BPH, but may help manage symptoms

• Avoid/reduce bladder irritants – fizzy drinks, alcohol, caffeine and artificial sweeteners
• Stop smoking
• Drink less in the evening to prevent nighttime waking
• Empty the bladder – esp before long journeys or places without easy access to toilet facilities
• Double void – wait a few moments after finishing pee and try to go again (don’t strain or push though)
• Eat more fruit and fibre – constipation can put pressure on the bladder
• Review meds – see if any may cause symptoms and can be changed

Question 19

BPH Pharmacological Treatment?
What are the 4 options?

Answer 19

Option 1: Alpha blockers
Example: Alfuzosin, Doxazocin, Tamsulosin or Terazocin
Usually for men with moderate to severe voiding and storage LUTS

Option 2: 5-alpha reductase inhibitors
Example: Finasteride or Dutasteride
Usually for men with LUTS and an enlarged prostate

Option 3: Try option 1 and 2 together
Work in different ways so can optimise treatment
Can either take 2 separate preparations, or a combination prep (Combodart® capsules contain tamsulosin and dutasteride)

Option 4: Add in an antimuscarinic
Example: oxybutynin, tolterodine or darifenacin
NB will only help with urinary symptoms; won’t manage BPH itself

Question 20

Alpha Blockers
MOA?
Dose?
SE?

Answer 20

Also known as alpha-adrenoreceptor blockers
Works by relaxing muscle around bladder and prostate = makes it easier to pee

-OD dosing
-Side effects of note: postural hypotension (+/- falls), sexual dysfunction
-Take care if co-prescribed other meds affecting BP

Extra notes on tamsulosin:
-Only available as a modified-release prep
-Can be bought OTC (Flomax®) for BPH symptoms in men 45-75 years for up to 6 weeks before clinical assessment by a doctor
-May sometimes see prescribed in hospital for a woman – can be used to help pass kidney stones less than 10mm in size- reduces smooth muscle stimulation to help passage of stone

Question 21

5-alpha Reductase Inhibitors
MOA?
Dose?
SE?

Answer 21

• Dihydrotestosterone (DHT) can cause prostate to grow larger
• Works by inhibiting 5-alpha-reductase = blocks the conversion of testosterone to DHT = less DHT = helps to shrink the prostate = easier to pee
• OD dosing — will likely take several months before benefit seen
  Side effects of note: sexual dysfunction, breast cancer (v rare), depression (rare) and suicidal ideation (rare)
  -NB these are sometimes reported to persist after stopping treatment
  -Patient alert card highlighting psychiatric and sexual side effects is currently in development by MHRA
• Can also decrease PSA levels by 50% - care needed w ?prostate cancer with drug
• Must use effective contraception and women of childbearing potential not to handle crushed/broken tablets or leaking capsules (in semen and absorbed through skin)
  -Can cause birth defects in male foetus – hypospadias affecting genitals where urinary tract appears on underside of penis, not tip.
  -Endorse safe handling advice on drug charts for nursing staff to be aware
• Note on finasteride – can also be used for male pattern baldness
  -DHT suppression encourages hair growth. On private rx only – not available on NHS.

Question 22

What if the drugs don’t work?
3 types of surgery: (for info)
What else can be done?

Answer 22

3 types of surgery:
- Transurethral resection of the prostate (TURP) — most likely to see in practice
- Transurethral vaporisation of the prostate (TUVP)
- Holmium laser enucleation of the prostate (HoLEP)
Prostatectomy absolute last resort in prostates larger than 80g

Catheterisation
- Used if medical management fails and surgery is not appropriate
- Intermittent self-catheterisation preferred
- Long-term indwelling catheter used if cannot self-catheterise or if skin wounds/pressure sores are irritated by urine — comes with risks, esp infection