Benign prostatic hyperplasia
• It is one of the most common benign neoplasm of American men (non-cancerous masses)
• Approximately 80% of older men develop it
• Not all patients are symptomatic – even if they are symptomatic the symptoms may not be
severe enough to start treatment
o Symptomatic
▪ Half require treatment
▪ Half doesn’t require treatment
Disease can be characterized by 3 stages:
1. BPH --- prostate gland itself is enlarging but the enlargement in this gland is not sever enough to
produce treatment (hyperplasia ---- increase in number of cells and size of prostate)
2. Benign prostatic enlargement (BPE) --- the gland itself started to increase in size to an extent
that will lead to symptoms
3. Benign prostatic obstruction (BPO) --- prostate gland will reach very high volume and will apply
very high pressure on the beginning of urethra that will block urine outflow
❖ BPH occurs between ages 63 and 65 years.
❖ Symptomatic disease is uncommon in men younger than 50 years.
Two major functions of the prostate:
1- Secrete fluids (make up a portion of 20-40% of ejaculated volume)
2- Provide the secretion with antibacterial effect.
• At birth prostate weighs 1 gram only
• First growth ---- It will start growing on puberty, it will reach 15-20 grams which is normal adult
size (age will be between 25-30 years old
• Second growth ---- begins at the age of 40 and continues for the rest of his lifetime
o The prostate can quadruple in size or grow even larger (might reach 4 times than normal
individuals e.g. might reach 80 grams or larger)
Prostate gland includes 3 types of tissue:
1- Epithelial tissue
2- Stromal tissue
3- The capsule
Alpha 1 receptor:
• Smooth muscle contraction
• On stromal tissue – will go under very sever contraction
• Do not get involved in growth in anyway
• Responsible for contraction in prostate gland --- constrict urethra --- impair urine outflow –
result in symptoms
1
,Testosterone – principle testicular androgen in males
• If it is there the prostate gland will enlarge
• Not active and needs activation (usually activated in only targeted cells)
• It becomes active by an enzyme called 5 alpha-reductase to give the active form
(dihydrotestosterone DHT) which has a higher affinity and more stable than testosterone
o Dihydrotestosterone is an active metabolite that is responsible for most of the growth
of prostate gland and it has an excellent effect on prostate gland
o Once DHT binds to its receptors --- induce proliferation of prostate tissues --- increase
mass of prostate gland
Androstenedione – principle adrenal androgen
There are 2 types of 5 alpha-reductase:
1- Type 1 is located in sebaceous glands in the frontal scalp, liver, and skin, although a small
amount is in the prostate.
2- Type II enzyme is localized to the prostate, genital tissue, and hair follicles of the scalp. (BPH is
concerned more with this type)
BPH doesn’t develop in:
• Men who are castrated before puberty (testicles were removed before puberty)
• Patients with type 2-- 5 alpha-reductase enzyme deficiency
Castration causes an enlarged prostate to shrink
If an orchiectomized dog of advance age is injected with testosterone --- it will produce BPH
Complications:
• Acute, painfully urinary retention (will lead to acute renal failure)
• Haematuria
• Unstable bladder
• UTI
• Bladder diverticula – when wall of bladder becomes very weak and some out pouching will
develop (will start to extend outside)
• Bladder stones
• Chronic renal failure
Medications that should be avoided:
• Alpha-adrenergic agonists
o Enhance contraction in prostate gland – block urinary outflow
o Used as oral or intranasal decongestants (eg, pseudoephedrine, ephedrine, or
phenylephrine
• Beta- adrenergic agonists
o eg, terbutaline – it is not related to prostate gland but it will enhance the contraction of
the bladder causing the bladder to squeeze the urine out
2
, • any drug with anticholinergic adverse effects
o like antihistamines, phenothiazines, tricyclic antidepressants, or anticholinergic drugs
used as antispasmodics or to treat Parkinson disease
o these drugs will reduce contractility of urinary bladder
o It does the opposite effect of Beta- adrenergic agonists
In general --- most patients with BPH will be presented without any acute distress unless there are some
complications or destructions
Symptoms: (they are in total 7 symptoms – 6 + irritative symptoms)
1- Obstructive symptoms
a. Anticholinergic drugs will aggregate these symptoms
b. Related to the physical pressure that is applied by the gland to the urethra
i. Slow urinary stream
ii. Intermittency (there will be some stopping while peeing)
iii. Hesitancy (there will be some delay before the initiation of peeing)
iv. Straining to urinate (patient will contract abdominal muscle to push the urine out)
v. Incomplete emptying
vi. Dribbling
2- Irritative symptoms
a. Beta-adrenergic drugs will aggregate these symptoms
i. Urgency (patient will suddenly get the urgency to use the bathroom but will not be
able to control it)
ii. Frequency (use the bathroom a lot)
iii. Nocturia (using bathroom during the night a lot)
Depending on the AUA (American urological association) system score:
• Each symptom will be measured on a scale 0-5 (since we have 7 symptoms the maximum is 35)
• The higher the score the more sever the symptoms are
o Mild --- less than 7 (asymptomatic)
o Moderate --- 8-19 (obstructive + irritative)
o Severe – above or equal to 20
▪ In order to classify a patient as severe he has to has all the moderate symptoms
plus one or more complications of BPH
Signs:
• Digital rectal examination test which will reveal an enlarged prostate without nodules or places
of hardening --- thus prostate is soft, symmetric and mobile
• LAB test --- will show elevation in blood urea nitrogen and serum creatinine --- there is an
enzyme (prostatic-specific antigen PSA) will be elevated too
Treatment:
Goals of treatment control:
1- Reduce AUA by at least 3 points (trying to control symptoms in this patient)
3
, 2- Prevent progression of BPH disease by reducing the risk of developing complications
3- Delay needs for surgical intervention
Selection of a single best treatment for a patient must consider:
1- Cost
2- Adverse effects
3- The inability to predict the course of the disease in an individual patient
4- The potential benefit that may occur in a comparatively small number of treated patients
All patients should have a healthy lifestyle, including a low-fat diet, high intake of plenty of fresh fruits
and vegetables, regular physical exercise, and no smoking
Desired outcomes:
1- We want to reduce the lower urinary tract symptoms (LUTS) evident by a reduction in the score
of AUA --- Meaning we want to reduce the severity of the symptoms
2- We want to reduce the complications
3- Reduce the need for surgical intervention
4- Need to be done in a cost-effective way
❖ Mild symptoms --- no medication is given only watching and waiting .. we will see how the disease
will progress and carefully evaluate the patient on constant intervals
❖ Moderate symptoms: (core therapy is alpha-adrenergic antagonists)
1- Small prostate gland (almost normal size) + PSA is low == alpha-adrenergic antagonist
▪ Alpha-adrenergic antagonist will relieve the constriction applied by the prostate
gland and will improve urine outflow and they will produce immediate effect
2- Large prostate and PSA is high == give 5 alpha-reductase inhibitors + alpha-adrenergic
antagonist
▪ The 5 alpha-reductase inhibitors will reduce levels of DHT but it will not produce
immediate effect (might take some time) … they will shrink the size of the prostate
and reduce PSA levels
3- Mainly irritative symptoms (gland is not sever enough, PSA is not high enough but patient is
complaining form irritative symptoms)
▪ We should give combination of alpha-adrenergic antagonist + either anticholinergic
drugs or mirabegron
• The alpha-adrenergic antagonist – will reduce constriction and allow for
more urine outflow
• The anticholinergic or mirabegron – will relax the bladder – once the
bladder is relaxed the irritative symptoms will go away
4- If the patient has erectile dysfunction at the same time
▪ We can use alpha-adrenergic antagonist
▪ Alternatively, we can use phosphodiesterase inhibitors
▪ OR we can use a combination of both
❖ Sever symptoms:
1- Complications of BPH
▪ Either surgery (through endoscope) or complete prostatectomy
4
• It is one of the most common benign neoplasm of American men (non-cancerous masses)
• Approximately 80% of older men develop it
• Not all patients are symptomatic – even if they are symptomatic the symptoms may not be
severe enough to start treatment
o Symptomatic
▪ Half require treatment
▪ Half doesn’t require treatment
Disease can be characterized by 3 stages:
1. BPH --- prostate gland itself is enlarging but the enlargement in this gland is not sever enough to
produce treatment (hyperplasia ---- increase in number of cells and size of prostate)
2. Benign prostatic enlargement (BPE) --- the gland itself started to increase in size to an extent
that will lead to symptoms
3. Benign prostatic obstruction (BPO) --- prostate gland will reach very high volume and will apply
very high pressure on the beginning of urethra that will block urine outflow
❖ BPH occurs between ages 63 and 65 years.
❖ Symptomatic disease is uncommon in men younger than 50 years.
Two major functions of the prostate:
1- Secrete fluids (make up a portion of 20-40% of ejaculated volume)
2- Provide the secretion with antibacterial effect.
• At birth prostate weighs 1 gram only
• First growth ---- It will start growing on puberty, it will reach 15-20 grams which is normal adult
size (age will be between 25-30 years old
• Second growth ---- begins at the age of 40 and continues for the rest of his lifetime
o The prostate can quadruple in size or grow even larger (might reach 4 times than normal
individuals e.g. might reach 80 grams or larger)
Prostate gland includes 3 types of tissue:
1- Epithelial tissue
2- Stromal tissue
3- The capsule
Alpha 1 receptor:
• Smooth muscle contraction
• On stromal tissue – will go under very sever contraction
• Do not get involved in growth in anyway
• Responsible for contraction in prostate gland --- constrict urethra --- impair urine outflow –
result in symptoms
1
,Testosterone – principle testicular androgen in males
• If it is there the prostate gland will enlarge
• Not active and needs activation (usually activated in only targeted cells)
• It becomes active by an enzyme called 5 alpha-reductase to give the active form
(dihydrotestosterone DHT) which has a higher affinity and more stable than testosterone
o Dihydrotestosterone is an active metabolite that is responsible for most of the growth
of prostate gland and it has an excellent effect on prostate gland
o Once DHT binds to its receptors --- induce proliferation of prostate tissues --- increase
mass of prostate gland
Androstenedione – principle adrenal androgen
There are 2 types of 5 alpha-reductase:
1- Type 1 is located in sebaceous glands in the frontal scalp, liver, and skin, although a small
amount is in the prostate.
2- Type II enzyme is localized to the prostate, genital tissue, and hair follicles of the scalp. (BPH is
concerned more with this type)
BPH doesn’t develop in:
• Men who are castrated before puberty (testicles were removed before puberty)
• Patients with type 2-- 5 alpha-reductase enzyme deficiency
Castration causes an enlarged prostate to shrink
If an orchiectomized dog of advance age is injected with testosterone --- it will produce BPH
Complications:
• Acute, painfully urinary retention (will lead to acute renal failure)
• Haematuria
• Unstable bladder
• UTI
• Bladder diverticula – when wall of bladder becomes very weak and some out pouching will
develop (will start to extend outside)
• Bladder stones
• Chronic renal failure
Medications that should be avoided:
• Alpha-adrenergic agonists
o Enhance contraction in prostate gland – block urinary outflow
o Used as oral or intranasal decongestants (eg, pseudoephedrine, ephedrine, or
phenylephrine
• Beta- adrenergic agonists
o eg, terbutaline – it is not related to prostate gland but it will enhance the contraction of
the bladder causing the bladder to squeeze the urine out
2
, • any drug with anticholinergic adverse effects
o like antihistamines, phenothiazines, tricyclic antidepressants, or anticholinergic drugs
used as antispasmodics or to treat Parkinson disease
o these drugs will reduce contractility of urinary bladder
o It does the opposite effect of Beta- adrenergic agonists
In general --- most patients with BPH will be presented without any acute distress unless there are some
complications or destructions
Symptoms: (they are in total 7 symptoms – 6 + irritative symptoms)
1- Obstructive symptoms
a. Anticholinergic drugs will aggregate these symptoms
b. Related to the physical pressure that is applied by the gland to the urethra
i. Slow urinary stream
ii. Intermittency (there will be some stopping while peeing)
iii. Hesitancy (there will be some delay before the initiation of peeing)
iv. Straining to urinate (patient will contract abdominal muscle to push the urine out)
v. Incomplete emptying
vi. Dribbling
2- Irritative symptoms
a. Beta-adrenergic drugs will aggregate these symptoms
i. Urgency (patient will suddenly get the urgency to use the bathroom but will not be
able to control it)
ii. Frequency (use the bathroom a lot)
iii. Nocturia (using bathroom during the night a lot)
Depending on the AUA (American urological association) system score:
• Each symptom will be measured on a scale 0-5 (since we have 7 symptoms the maximum is 35)
• The higher the score the more sever the symptoms are
o Mild --- less than 7 (asymptomatic)
o Moderate --- 8-19 (obstructive + irritative)
o Severe – above or equal to 20
▪ In order to classify a patient as severe he has to has all the moderate symptoms
plus one or more complications of BPH
Signs:
• Digital rectal examination test which will reveal an enlarged prostate without nodules or places
of hardening --- thus prostate is soft, symmetric and mobile
• LAB test --- will show elevation in blood urea nitrogen and serum creatinine --- there is an
enzyme (prostatic-specific antigen PSA) will be elevated too
Treatment:
Goals of treatment control:
1- Reduce AUA by at least 3 points (trying to control symptoms in this patient)
3
, 2- Prevent progression of BPH disease by reducing the risk of developing complications
3- Delay needs for surgical intervention
Selection of a single best treatment for a patient must consider:
1- Cost
2- Adverse effects
3- The inability to predict the course of the disease in an individual patient
4- The potential benefit that may occur in a comparatively small number of treated patients
All patients should have a healthy lifestyle, including a low-fat diet, high intake of plenty of fresh fruits
and vegetables, regular physical exercise, and no smoking
Desired outcomes:
1- We want to reduce the lower urinary tract symptoms (LUTS) evident by a reduction in the score
of AUA --- Meaning we want to reduce the severity of the symptoms
2- We want to reduce the complications
3- Reduce the need for surgical intervention
4- Need to be done in a cost-effective way
❖ Mild symptoms --- no medication is given only watching and waiting .. we will see how the disease
will progress and carefully evaluate the patient on constant intervals
❖ Moderate symptoms: (core therapy is alpha-adrenergic antagonists)
1- Small prostate gland (almost normal size) + PSA is low == alpha-adrenergic antagonist
▪ Alpha-adrenergic antagonist will relieve the constriction applied by the prostate
gland and will improve urine outflow and they will produce immediate effect
2- Large prostate and PSA is high == give 5 alpha-reductase inhibitors + alpha-adrenergic
antagonist
▪ The 5 alpha-reductase inhibitors will reduce levels of DHT but it will not produce
immediate effect (might take some time) … they will shrink the size of the prostate
and reduce PSA levels
3- Mainly irritative symptoms (gland is not sever enough, PSA is not high enough but patient is
complaining form irritative symptoms)
▪ We should give combination of alpha-adrenergic antagonist + either anticholinergic
drugs or mirabegron
• The alpha-adrenergic antagonist – will reduce constriction and allow for
more urine outflow
• The anticholinergic or mirabegron – will relax the bladder – once the
bladder is relaxed the irritative symptoms will go away
4- If the patient has erectile dysfunction at the same time
▪ We can use alpha-adrenergic antagonist
▪ Alternatively, we can use phosphodiesterase inhibitors
▪ OR we can use a combination of both
❖ Sever symptoms:
1- Complications of BPH
▪ Either surgery (through endoscope) or complete prostatectomy
4
