Benign prostatic hyperplasia
Encyclopedia
Benign prostatic hyperplasia (BPH) also known as benign prostatic hypertrophy (technically a misnomer), benign enlargement of the prostate (BEP), and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate
.
Properly, BPH involves hyperplasia
rather than hypertrophy, but the nomenclature is often interchangeable, even amongst urologists
. It involves hyperplasia of prostatic stromal and epithelial
cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethra
l canal to cause partial, or sometimes virtually complete, obstruction of the urethra, which interferes with the normal flow of urine
. It leads to symptoms of urinary hesitancy, frequent urination
, dysuria (painful urination), increased risk of urinary tract infection
s, and urinary retention
. Although prostate specific antigen
levels may be elevated in these patients because of increased organ volume and inflammation
due to urinary tract infections, BPH is not considered to be a premalignant lesion.
Adenoma
tous prostatic growth is believed to begin at approximately age 30 years. An estimated 50% of men have histologic
evidence of BPH by age 50 years and 75% by age 80 years. In 40-50% of these patients, BPH becomes clinically significant.
s are classified as storage or voiding.
Storage symptoms include urinary frequency, urgency (compelling need to void that cannot be deferred), urgency incontinence, and voiding at night (nocturia).
Voiding symptoms include urinary stream, hesitancy (needing to wait for the stream to begin), intermittency (when the stream starts and stops intermittently), straining to void, and dribbling. Pain and dysuria
are usually not present. These storage and voiding symptoms are evaluated using the International Prostate Symptom Score
(IPSS) questionnaire, designed to assess the severity of BPH.
BPH can be a progressive disease
, especially if left untreated. Incomplete voiding results in stasis
of bacteria
in the bladder
residue and an increased risk of urinary tract infection
. Urinary bladder stones are formed from the crystallization
of salts in the residual urine. Urinary retention
, termed acute
or chronic
, is another form of progression. Acute urinary retention is the inability to void, while in chronic urinary retention the residual urinary volume gradually increases, and the bladder distends. Some patients that suffer from chronic urinary retention may eventually progress to renal failure, a condition termed obstructive uropathy
.
, which restores normal pressure in the venous drainage system, effectively reducing the volume of the prostate and clinical manifestation of BPH.
Most experts consider androgen
s (testosterone
and related hormone
s) to play a permissive role. This means that androgens have to be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by the fact that castrated
boys do not develop BPH when they age. On the other hand, administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms. Dihydrotestosterone
(DHT), a metabolite
of testosterone, is a critical mediator of prostatic growth. DHT is synthesized in the prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. This enzyme is localized principally in the stromal cells; hence, those cells are the main site for the synthesis of DHT.
DHT can act in an autocrine fashion on the stromal cells or in paracrine fashion by diffusing into nearby epithelial cells
. In both of these cell types, DHT binds to nuclear androgen receptor
s and signals the transcription
of growth factor
s that are mitogenic to the epithelial and stromal cells. DHT is 10 times more potent than testosterone because it dissociates from the androgen receptor more slowly. The importance of DHT in causing nodular
hyperplasia is supported by clinical observations in which an inhibitor
of 5α-reductase is given to men with this condition. Therapy with 5α-reductase inhibitor markedly reduces the DHT content of the prostate and, in turn, reduces prostate volume and, in many cases, BPH symptoms.
Testosterone promotes prostate cell proliferation, but relatively low levels of serum testosterone are found in patients with BPH. One small study has shown that medical castration lowers the serum and prostate hormone levels unevenly, having less effect on testosterone and dihydrotestosterone levels in the prostate.
While there is some evidence that estrogen may play a role in the etiology of BPH, this effect appears to be mediated mainly through local conversion of estrogen to androgens in the prostate tissue rather than a direct effect of estrogen itself. In canine in vivo studies castration, which significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy of the prostate. Studies looking for a correlation between prostatic hyperplasia and serum estrogen levels in humans have generally shown none.
On a microscopic level, BPH can be seen in the vast majority of men as they age, in particular over the age of 70 years, around the world. However, rates of clinically significant, symptomatic BPH vary dramatically depending on lifestyle. Men that lead a western lifestyle have a much higher incidence of symptomatic BPH than men that lead a traditional or rural lifestyle. This is confirmed by research in China
showing that men in rural areas have very low rates of clinical BPH, while men living in cities adopting a western lifestyle have a skyrocketing incidence of this condition, though it is still below rates seen in the West.
Much work remains to be done to completely clarify the causes of BPH.
Rectal examination
(palpation
of the prostate through the rectum
) may reveal a markedly enlarged prostate, usually affecting the middle lobe.
Often, blood test
s are performed to rule out prostatic malignancy: Elevated prostate specific antigen
(PSA) levels needs further investigations such as reinterpretation of PSA results, in terms of PSA density and PSA free percentage, rectal examination and transrectal ultrasonography
. These combined measures can provide early detection.
Ultrasound
examination of the testicles, prostate, and kidneys is often performed, again to rule out malignancy
and hydronephrosis
.
Screening and diagnostic procedures for BPH are similar to those used for prostate cancer
. Some signs to look for include:
s and 5α-reductase inhibitors
.
Antimuscarinics such as tolterodine
may also be used, especially in combination with alpha blockers. They act by decreasing acetylcholine
effects on the smooth muscle of the bladder
, thus helping control symptoms of an overactive bladder
.
Sildenafil
citrate shows some symptomatic relief, suggesting a possible common etiology with erectile dysfunction
.
from Serenoa repens is one of the most extensively studied. It showed promise in early studies, though later trials of higher methodological quality indicated no difference from placebo. There are no known negative effects of saw palmetto, so if taking the supplement relieves symptoms, there is no harm in taking it. The quality of saw palmetto products varies.
Other herbal medicines that have research support in systematic reviews include beta-sitosterol
from Hypoxis rooperi (African star grass) and pygeum (extracted from the bark of Prunus africana
), while there is less substantial support for the efficacy of pumpkin seed (Cucurbita pepo
) and stinging nettle
(Urtica dioica) root. There is weak evidence that pollen extracts frp, rye grass (Secale cereale) may also correlate with modest symptomatic relief.
(TUMT) and transurethral needle ablation
(TUNA). Both of these procedures rely on delivering enough energy to create sufficient heat to cause cell death (necrosis) in the prostate. The goal of the therapies is to cause enough necrosis so that, when the dead tissue is reabsorbed by the body, the prostate shrinks, relieving the obstruction of the urethra. These procedures are typically performed with local anesthesia, and the patient returns home the same day. Some urologists have studied and published long-term data on the outcomes of these procedures, with data out to five years. The most recent American Urological Association
(AUA) Guidelines for the Treatment of BPH in 2003 lists minimally invasive therapies including TUMT and TUNA as acceptable alternatives for certain patients with BPH.
Transurethral microwave therapy (TUMT) was originally approved by the FDA in 1996, with the first generation system by EDAP Technomed. Since 1996, other companies have received FDA approval for TUMT devices, including Urologix, Dornier, Thermatrix, Celsion, and Prostalund. Multiple clinical studies have been published on TUMT. The general principle underlying all the devices is that a microwave antenna that resides in a urethral catheter is placed in the intraprostatic area of the urethra. The catheter is connected to a control box outside of the patient's body and is energized to emit microwave radiation into the prostate to heat the tissue and cause necrosis. It is a one-time treatment that takes approximately 30 minutes to 1 hour, depending on the system used. It takes approximately 4 to 6 weeks for the damaged tissue to be reabsorbed into the patient's body. Some of the devices incorporate circulating coolant through the treatment area with the intent of preserving the urethra while the microwave energy heats the prostatic tissue surrounding the urethra.
Transurethral needle ablation (TUNA) operates with a different type of energy, radio frequency (RF) energy, but is designed along the same premise as TUMT devices, that the heat the device generates will cause necrosis of the prostatic tissue and shrink the prostate. The TUNA device is inserted into the urethra using a rigid scope much like a cystoscope. The energy is delivered into the prostate using two needles that emerge from the sides of the device, through the urethral wall and into the prostate. The needle-based ablation devices are very effective at heating a localized area to a high enough temperature to cause necrosis. The treatment is typically performed in one session, but may require multiple sticks of the needles depending on the size of the prostate.
. There are also a number of new methods for reducing the size of an enlarged prostate, some of which have not been around long enough to fully establish their safety or side-effects. These include various methods to destroy or remove part of the excess tissue while trying to avoid damaging what remains. Transurethral electrovaporization of the prostate (TVP), laser TURP, visual laser ablation (VLAP), ethanol injection, and others are studied as alternatives.
Newer techniques involving lasers in urology have emerged in the last 5–10 years, starting with the VLAP technique involving the Nd:YAG laser
with contact on the prostatic tissue. A similar technology called Photoselective Vaporization of the Prostate (PVP) with the GreenLight (KTP) laser have emerged very recently. This procedure involves a high-power 80-watt KTP laser with a 550-micrometre laser fiber inserted into the prostate. This fiber has an internal reflection with a 70-degree deflecting angle. It is used to vaporize the tissue to the prostatic capsule. KTP lasers target haemoglobin as the chromophore and typically have a penetration depth of 2.0 mm (four times deeper than holmium).
Another procedure termed Holmium Laser Ablation of the Prostate (HoLAP) has also been gaining acceptance around the world. Like KTP, the delivery device for HoLAP procedures is a 550 um disposable side-firing fiber that directs the beam from a high-power 100-watt laser at a 70-degree angle from the fiber axis. The holmium wavelength is 2,140 nm, which falls within the infrared portion of the spectrum and is invisible to the naked eye. Whereas KTP relies on haemoglobin as a chromophore, water within the target tissue is the chromophore for Holmium lasers. The penetration depth of Holmium lasers is <0.5 mm, avoiding complications associated with tissue necrosis often found with the deeper penetration and lower peak powers of KTP.
HoLEP, Holmium Laser Enucleation of the Prostate, is another Holmium laser procedure reported to carry fewer risks compared with either TURP or open prostatectomy. HoLEP is largely similar to the HoLAP procedure; the main difference is that this procedure is typically performed on larger prostates. Instead of ablating the tissue, the laser cuts a portion of the prostate, which is then cut into smaller pieces and flushed with irrigation fluid. As with the HoLAP procedure, there is little bleeding during or after the procedure.
Both wavelengths, KTP and Holmium, ablate approximately one to two grams of tissue per minute.
Post surgery care often involves placement of a Foley catheter
or a temporary prostatic stent
to permit healing and allow urine to drain from the bladder.
rates increase from 3 cases per 1000 man-years at age 45–49 years, to 38 cases per 1000 man-years by the age of 75–79 years. Whereas the prevalence
rate is 2.7% for men aged 45–49, it increases to 24% by the age of 80 years.
For some men, the symptoms may be severe enough to require treatment.
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
.
Properly, BPH involves hyperplasia
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....
rather than hypertrophy, but the nomenclature is often interchangeable, even amongst urologists
Urology
Urology is the medical and surgical specialty that focuses on the urinary tracts of males and females, and on the reproductive system of males. Medical professionals specializing in the field of urology are called urologists and are trained to diagnose, treat, and manage patients with urological...
. It involves hyperplasia of prostatic stromal and epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
l canal to cause partial, or sometimes virtually complete, obstruction of the urethra, which interferes with the normal flow of urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. It leads to symptoms of urinary hesitancy, frequent urination
Urination
Urination, also known as micturition, voiding, peeing, weeing, pissing, and more rarely, emiction, is the ejection of urine from the urinary bladder through the urethra to the outside of the body. In healthy humans the process of urination is under voluntary control...
, dysuria (painful urination), increased risk of urinary tract infection
Urinary tract infection
A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
s, and urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
. Although prostate specific antigen
Prostate specific antigen
Prostate-specific antigen also known as gamma-seminoprotein or kallikrein-3 is a glycoprotein that in humans is encoded by the KLK3 gene. KLK3 is a member of the kallikrein-related peptidase family that are secreted by the epithelial cells of the prostate gland...
levels may be elevated in these patients because of increased organ volume and inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
due to urinary tract infections, BPH is not considered to be a premalignant lesion.
Adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
tous prostatic growth is believed to begin at approximately age 30 years. An estimated 50% of men have histologic
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
evidence of BPH by age 50 years and 75% by age 80 years. In 40-50% of these patients, BPH becomes clinically significant.
Signs and symptoms
Benign prostatic hyperplasia symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s are classified as storage or voiding.
Storage symptoms include urinary frequency, urgency (compelling need to void that cannot be deferred), urgency incontinence, and voiding at night (nocturia).
Voiding symptoms include urinary stream, hesitancy (needing to wait for the stream to begin), intermittency (when the stream starts and stops intermittently), straining to void, and dribbling. Pain and dysuria
Dysuria
In medicine, specifically urology, dysuria refers to painful urination.Difficult urination is also sometimes described as dysuria.It is one of a constellation of irritative bladder symptoms, which includes urinary frequency and haematuria....
are usually not present. These storage and voiding symptoms are evaluated using the International Prostate Symptom Score
International Prostate Symptom Score
The International Prostate Symptom Score is an 8 question written screening tool used to screen for, rapidly diagnose, track the symptoms of, and suggest management of the symptoms of the disease benign prostatic hyperplasia...
(IPSS) questionnaire, designed to assess the severity of BPH.
BPH can be a progressive disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, especially if left untreated. Incomplete voiding results in stasis
Stasis (medicine)
In medicine, stasis is the state in which the normal flow of a body liquid stops, for example the flow of blood through vessels or of intestinal contents through the digestive tract....
of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
in the bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
residue and an increased risk of urinary tract infection
Urinary tract infection
A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
. Urinary bladder stones are formed from the crystallization
Crystallization
Crystallization is the process of formation of solid crystals precipitating from a solution, melt or more rarely deposited directly from a gas. Crystallization is also a chemical solid–liquid separation technique, in which mass transfer of a solute from the liquid solution to a pure solid...
of salts in the residual urine. Urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
, termed acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....
or chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
, is another form of progression. Acute urinary retention is the inability to void, while in chronic urinary retention the residual urinary volume gradually increases, and the bladder distends. Some patients that suffer from chronic urinary retention may eventually progress to renal failure, a condition termed obstructive uropathy
Obstructive uropathy
Obstructive uropathy is a structural or functional hindrance of normal urine flow, sometimes leading torenal dysfunction .It is a very broad term, and does not imply a location or etiology.-Causes:...
.
Cause
A study published in 2008 in the journal of andrology "Andrologia" reports on a newly discovered venous route by which free (active) testosterone reaches the prostate in extremely high concentrations, promoting the accelerated proliferation of prostate cells, leading to the gland's enlargement. The study (conducted by two Israeli doctors: Dr. Yigal Gat and Dr. Menachem Goren) suggests that BPH is caused by malfunction of the valves in the internal spermatic veins manifesting as varicocele, a phenomenon which has been shown to increase rapidly with age, roughly equal to 10-15% each decade of life. The 6- to 8-fold elevated hydrostatic pressure then leads to retrograde venous drainage, allowing free communication with the prostatic circulation. Having measured a concentration of free testosterone of some 130-fold above serum level in the internal spermatic vein (the testes being the main source and the blood being undiluted in systemic circulation), the authors conclude that the elevated venous pressure causes hypertrophy and exposure to high concentrations of free testosterone causes hyperplasia in the prostate. The study also proposes a treatment method (Gat–Goren Technique) similar to that used in treating varicoceleVaricocele
Varicocele , also known as varicoscele or varicose seal, is an abnormal enlargement of the vein that is in the scrotum draining the testicles. The testicular blood vessels originate in the abdomen and course down through the inguinal canal as part of the spermatic cord on their way to the testis...
, which restores normal pressure in the venous drainage system, effectively reducing the volume of the prostate and clinical manifestation of BPH.
Most experts consider androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
s (testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
and related hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s) to play a permissive role. This means that androgens have to be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by the fact that castrated
Castration
Castration is any action, surgical, chemical, or otherwise, by which a male loses the functions of the testicles or a female loses the functions of the ovaries.-Humans:...
boys do not develop BPH when they age. On the other hand, administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms. Dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(DHT), a metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of testosterone, is a critical mediator of prostatic growth. DHT is synthesized in the prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. This enzyme is localized principally in the stromal cells; hence, those cells are the main site for the synthesis of DHT.
DHT can act in an autocrine fashion on the stromal cells or in paracrine fashion by diffusing into nearby epithelial cells
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
. In both of these cell types, DHT binds to nuclear androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
s and signals the transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s that are mitogenic to the epithelial and stromal cells. DHT is 10 times more potent than testosterone because it dissociates from the androgen receptor more slowly. The importance of DHT in causing nodular
Nodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....
hyperplasia is supported by clinical observations in which an inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of 5α-reductase is given to men with this condition. Therapy with 5α-reductase inhibitor markedly reduces the DHT content of the prostate and, in turn, reduces prostate volume and, in many cases, BPH symptoms.
Testosterone promotes prostate cell proliferation, but relatively low levels of serum testosterone are found in patients with BPH. One small study has shown that medical castration lowers the serum and prostate hormone levels unevenly, having less effect on testosterone and dihydrotestosterone levels in the prostate.
While there is some evidence that estrogen may play a role in the etiology of BPH, this effect appears to be mediated mainly through local conversion of estrogen to androgens in the prostate tissue rather than a direct effect of estrogen itself. In canine in vivo studies castration, which significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy of the prostate. Studies looking for a correlation between prostatic hyperplasia and serum estrogen levels in humans have generally shown none.
On a microscopic level, BPH can be seen in the vast majority of men as they age, in particular over the age of 70 years, around the world. However, rates of clinically significant, symptomatic BPH vary dramatically depending on lifestyle. Men that lead a western lifestyle have a much higher incidence of symptomatic BPH than men that lead a traditional or rural lifestyle. This is confirmed by research in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
showing that men in rural areas have very low rates of clinical BPH, while men living in cities adopting a western lifestyle have a skyrocketing incidence of this condition, though it is still below rates seen in the West.
Much work remains to be done to completely clarify the causes of BPH.
Diagnosis
Rectal examination
A rectal examination or rectal exam is an internal examination of the rectum such as by a physician or other healthcare professional.-Procedure:...
(palpation
Palpation
Palpation is used as part of a physical examination in which an object is felt to determine its size, shape, firmness, or location...
of the prostate through the rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
) may reveal a markedly enlarged prostate, usually affecting the middle lobe.
Often, blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s are performed to rule out prostatic malignancy: Elevated prostate specific antigen
Prostate specific antigen
Prostate-specific antigen also known as gamma-seminoprotein or kallikrein-3 is a glycoprotein that in humans is encoded by the KLK3 gene. KLK3 is a member of the kallikrein-related peptidase family that are secreted by the epithelial cells of the prostate gland...
(PSA) levels needs further investigations such as reinterpretation of PSA results, in terms of PSA density and PSA free percentage, rectal examination and transrectal ultrasonography
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
. These combined measures can provide early detection.
Ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
examination of the testicles, prostate, and kidneys is often performed, again to rule out malignancy
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
and hydronephrosis
Hydronephrosis
Hydronephrosis is distension and dilation of the renal pelvis calyces, usually caused by obstruction of the free flow of urine from the kidney, leading to progressive atrophy of the kidney...
.
Screening and diagnostic procedures for BPH are similar to those used for prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
. Some signs to look for include:
- Weak urinary stream
- Prolonged emptying of the bladder
- Abdominal straining
- Hesitancy
- Irregular need to urinate
- Incomplete bladder emptying
- Post-urination dribble
- Irritation during urination
- Frequent urination
- NocturiaNocturiaNocturia , also called nycturia , is the need to get up in the night to urinate, thus interrupting sleep. Its occurrence is more frequent in pregnant women and in the elderly...
(need to urinate during the night) - Urgency
- IncontinenceUrinary incontinenceUrinary incontinence is any involuntary leakage of urine. It is a common and distressing problem, which may have a profound impact on quality of life. Urinary incontinence almost always results from an underlying treatable medical condition but is under-reported to medical practitioners...
(involuntary leakage of urine) - Bladder pain
- DysuriaDysuriaIn medicine, specifically urology, dysuria refers to painful urination.Difficult urination is also sometimes described as dysuria.It is one of a constellation of irritative bladder symptoms, which includes urinary frequency and haematuria....
(painful urination) - Problems in ejaculationEjaculationEjaculation is the ejecting of semen from the male reproductory tract, and is usually accompanied by orgasm. It is usually the final stage and natural objective of male sexual stimulation, and an essential component of natural conception. In rare cases ejaculation occurs because of prostatic disease...
Lifestyle
Patients should decrease fluid intake before bedtime, moderate the consumption of alcohol and caffeine-containing products, and follow timed voiding schedules.Medications
The two main medications for management of BPH are alpha blockerAlpha blocker
Alpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...
s and 5α-reductase inhibitors
5-alpha-reductase inhibitor
5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...
.
- Alpha blockers (technically α1-adrenergic receptorAdrenergic receptorThe adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
antagonistsReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
) are the most common choice for initial therapy in the USA and Europe. Alpha blockers used for BPH include doxazosinDoxazosinDoxazosin mesylate, a quinazoline compound sold by Pfizer under the brand names Cardura and Carduran, is an α1a-selective alpha blocker used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia ....
, terazosinTerazosinTerazosin is a selective alpha 1 antagonist used for treatment of symptoms of an enlarged prostate...
, alfuzosinAlfuzosinAlfuzosin is an α1 receptor antagonist used to treat benign prostatic hyperplasia . It works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate....
, tamsulosinTamsulosinTamsulosin is an α1a-selective alpha blocker used in the symptomatic treatment of benign prostatic hyperplasia . Tamsulosin was developed by Yamanouchi Pharmaceuticals and is marketed by various companies under licence, including Boehringer-Ingelheim and CSL...
, and silodosinSilodosinSilodosin is a medication for the symptomatic treatment of benign prostatic hyperplasia...
. All five are equally effective but have slightly different side effect profiles. The older drugs phenoxybenzaminePhenoxybenzaminePhenoxybenzamine is a non-selective, irreversible alpha antagonist.-Uses:It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma...
and prazosinPrazosinPrazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
are not recommended. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotensionOrthostatic hypotensionOrthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
, ejaculationEjaculationEjaculation is the ejecting of semen from the male reproductory tract, and is usually accompanied by orgasm. It is usually the final stage and natural objective of male sexual stimulation, and an essential component of natural conception. In rare cases ejaculation occurs because of prostatic disease...
changes, nasal congestion, and weakness.
- The 5α-reductase inhibitors5-alpha-reductase inhibitor5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...
finasterideFinasterideFinasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
and dutasterideDutasterideDutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
are another treatment option. These medications inhibit 5a-reductase, which in turn inhibits production of DHTDihydrotestosteroneDihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, a reduction of BPH progression to acute urinary retention and surgery has been noted in patients with larger prostates. Side effects include decreased libidoLibidoLibido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
and ejaculatory or erectile dysfunction.
Antimuscarinics such as tolterodine
Tolterodine
Tolterodine is an antimuscarinic drug that is used to treat urinary incontinence.It is marketed by Pfizer in Canada and the United States by its brand name Detrol. In Egypt it is also found under the trade names Tolterodine by Sabaa and Incont L.A...
may also be used, especially in combination with alpha blockers. They act by decreasing acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
effects on the smooth muscle of the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
, thus helping control symptoms of an overactive bladder
Overactive bladder
Overactive bladder is a urological condition defined by a set of symptoms: urgency, with or without urge incontinence, usually with frequency and nocturia. Frequency is usually defined as urinating more than 8 times a day. The International Continence Society is responsible for this definition...
.
Sildenafil
Sildenafil
Sildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
citrate shows some symptomatic relief, suggesting a possible common etiology with erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
.
Herbal remedies
People often seek herbal remedies for BPH. Several are approved in European countries, but none in the USA. Saw palmetto extractSaw palmetto extract
Saw palmetto extract is an extract of the fruit of Serenoa repens. It is rich in fatty acids and phytosterols. It has been used in traditional, eclectic, and alternative medicine for a variety of indications, most notably benign prostatic hyperplasia....
from Serenoa repens is one of the most extensively studied. It showed promise in early studies, though later trials of higher methodological quality indicated no difference from placebo. There are no known negative effects of saw palmetto, so if taking the supplement relieves symptoms, there is no harm in taking it. The quality of saw palmetto products varies.
Other herbal medicines that have research support in systematic reviews include beta-sitosterol
Beta-sitosterol
β-Sitosterol is one of several phytosterols with chemical structures similar to that of cholesterol. Sitosterols are white, waxy powders with a characteristic odor...
from Hypoxis rooperi (African star grass) and pygeum (extracted from the bark of Prunus africana
Prunus africana
Prunus africana, or Red Stinkwood , is an evergreen tree native to the montane regions of Sub-Saharan Africa and the Islands of Madagascar, Sao Tome, Fernando Po and Grande Comore at about 900–3400 m. of altitude. The mature tree is 10–25 m. high, open-branched and often pendulous in forest,...
), while there is less substantial support for the efficacy of pumpkin seed (Cucurbita pepo
Cucurbita pepo
The species Cucurbita pepo is a cultivated plant of the genus Cucurbita. It includes varieties of squash, gourd, and pumpkin.*Acorn squash*Delicata squash*Dodi marrow, grown in South Asia*Gem squash*Heart of gold squash*Pattypan squash...
) and stinging nettle
Stinging nettle
Stinging nettle or common nettle, Urtica dioica, is a herbaceous perennial flowering plant, native to Europe, Asia, northern Africa, and North America, and is the best-known member of the nettle genus Urtica...
(Urtica dioica) root. There is weak evidence that pollen extracts frp, rye grass (Secale cereale) may also correlate with modest symptomatic relief.
Minimally invasive therapies
Medication is often prescribed as the first treatment option, there are many patients who do not achieve success with this line of treatment. Those patients may not achieve sustained improvement in symptoms or they may stop taking the medication because of side-effects. There are options for treatment in a urologist's office before proceeding to surgery. The two most common types of office-based therapies are transurethral microwave thermotherapyTransurethral microwave thermotherapy
Transurethral microwave thermotherapy is one of a number of effective and safe procedures used in the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia . TUMT provides a one-time efficacious treatment of LUTS due to BPH...
(TUMT) and transurethral needle ablation
Transurethral needle ablation of the prostate
Transurethral needle ablation is a technique that uses low energy radio frequency energy delivered through two needles to ablate excess prostate tissue. It can be done with a local anesthetic on an outpatient basis...
(TUNA). Both of these procedures rely on delivering enough energy to create sufficient heat to cause cell death (necrosis) in the prostate. The goal of the therapies is to cause enough necrosis so that, when the dead tissue is reabsorbed by the body, the prostate shrinks, relieving the obstruction of the urethra. These procedures are typically performed with local anesthesia, and the patient returns home the same day. Some urologists have studied and published long-term data on the outcomes of these procedures, with data out to five years. The most recent American Urological Association
American Urological Association
The American Urological Association is a professional association in the United States for urology professionals.-Awards:*Hugh Hampton Young Award. Presented annually to an individual for outstanding contributions to the study of genitourinary tract disease. This award is sponsored by Karl Storz...
(AUA) Guidelines for the Treatment of BPH in 2003 lists minimally invasive therapies including TUMT and TUNA as acceptable alternatives for certain patients with BPH.
Transurethral microwave therapy (TUMT) was originally approved by the FDA in 1996, with the first generation system by EDAP Technomed. Since 1996, other companies have received FDA approval for TUMT devices, including Urologix, Dornier, Thermatrix, Celsion, and Prostalund. Multiple clinical studies have been published on TUMT. The general principle underlying all the devices is that a microwave antenna that resides in a urethral catheter is placed in the intraprostatic area of the urethra. The catheter is connected to a control box outside of the patient's body and is energized to emit microwave radiation into the prostate to heat the tissue and cause necrosis. It is a one-time treatment that takes approximately 30 minutes to 1 hour, depending on the system used. It takes approximately 4 to 6 weeks for the damaged tissue to be reabsorbed into the patient's body. Some of the devices incorporate circulating coolant through the treatment area with the intent of preserving the urethra while the microwave energy heats the prostatic tissue surrounding the urethra.
Transurethral needle ablation (TUNA) operates with a different type of energy, radio frequency (RF) energy, but is designed along the same premise as TUMT devices, that the heat the device generates will cause necrosis of the prostatic tissue and shrink the prostate. The TUNA device is inserted into the urethra using a rigid scope much like a cystoscope. The energy is delivered into the prostate using two needles that emerge from the sides of the device, through the urethral wall and into the prostate. The needle-based ablation devices are very effective at heating a localized area to a high enough temperature to cause necrosis. The treatment is typically performed in one session, but may require multiple sticks of the needles depending on the size of the prostate.
Surgery
If medical treatment fails, and the patient elects not to try office-based therapies or the physician determines the patient is a better candidate for transurethral resection of prostate (TURP), surgery may need to be performed. In general, TURP is still considered the gold standard of prostate interventions for patients that require a procedure. This involves removing (part of) the prostate through the urethraUrethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
. There are also a number of new methods for reducing the size of an enlarged prostate, some of which have not been around long enough to fully establish their safety or side-effects. These include various methods to destroy or remove part of the excess tissue while trying to avoid damaging what remains. Transurethral electrovaporization of the prostate (TVP), laser TURP, visual laser ablation (VLAP), ethanol injection, and others are studied as alternatives.
Newer techniques involving lasers in urology have emerged in the last 5–10 years, starting with the VLAP technique involving the Nd:YAG laser
Nd:YAG laser
Nd:YAG is a crystal that is used as a lasing medium for solid-state lasers. The dopant, triply ionized neodymium, typically replaces yttrium in the crystal structure of the yttrium aluminium garnet , since they are of similar size...
with contact on the prostatic tissue. A similar technology called Photoselective Vaporization of the Prostate (PVP) with the GreenLight (KTP) laser have emerged very recently. This procedure involves a high-power 80-watt KTP laser with a 550-micrometre laser fiber inserted into the prostate. This fiber has an internal reflection with a 70-degree deflecting angle. It is used to vaporize the tissue to the prostatic capsule. KTP lasers target haemoglobin as the chromophore and typically have a penetration depth of 2.0 mm (four times deeper than holmium).
Another procedure termed Holmium Laser Ablation of the Prostate (HoLAP) has also been gaining acceptance around the world. Like KTP, the delivery device for HoLAP procedures is a 550 um disposable side-firing fiber that directs the beam from a high-power 100-watt laser at a 70-degree angle from the fiber axis. The holmium wavelength is 2,140 nm, which falls within the infrared portion of the spectrum and is invisible to the naked eye. Whereas KTP relies on haemoglobin as a chromophore, water within the target tissue is the chromophore for Holmium lasers. The penetration depth of Holmium lasers is <0.5 mm, avoiding complications associated with tissue necrosis often found with the deeper penetration and lower peak powers of KTP.
HoLEP, Holmium Laser Enucleation of the Prostate, is another Holmium laser procedure reported to carry fewer risks compared with either TURP or open prostatectomy. HoLEP is largely similar to the HoLAP procedure; the main difference is that this procedure is typically performed on larger prostates. Instead of ablating the tissue, the laser cuts a portion of the prostate, which is then cut into smaller pieces and flushed with irrigation fluid. As with the HoLAP procedure, there is little bleeding during or after the procedure.
Both wavelengths, KTP and Holmium, ablate approximately one to two grams of tissue per minute.
Post surgery care often involves placement of a Foley catheter
Foley catheter
A Foley catheter is a flexible tube that is often passed through the urethra and into the bladder. The tube has two separated channels, or lumens, running down its length. One lumen is open at both ends, and allows urine to drain out into a collection bag...
or a temporary prostatic stent
Prostatic stent
A prostatic stent is a stent used to keep open the male urethra and allow the passing of urine in cases of prostatic obstruction and lower urinary tract symptoms . Prostatic obstruction is a common condition with a variety of etiologies...
to permit healing and allow urine to drain from the bladder.
Epidemiology
The prostate gets larger in most men as they get older, and, overall, 45% of men over the age of 46 can expect to suffer from the symptoms of BPH if they survive 30 years. IncidenceIncidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
rates increase from 3 cases per 1000 man-years at age 45–49 years, to 38 cases per 1000 man-years by the age of 75–79 years. Whereas the prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
rate is 2.7% for men aged 45–49, it increases to 24% by the age of 80 years.
For some men, the symptoms may be severe enough to require treatment.
See also
- ProstateProstateThe prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
- Prostate cancerProstate cancerProstate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
- Prostate specific antigenProstate specific antigenProstate-specific antigen also known as gamma-seminoprotein or kallikrein-3 is a glycoprotein that in humans is encoded by the KLK3 gene. KLK3 is a member of the kallikrein-related peptidase family that are secreted by the epithelial cells of the prostate gland...
- ProstatectomyProstatectomyA prostatectomy is the surgical removal of all or part of the prostate gland. Abnormalities of the prostate, such as a tumour, or if the gland itself becomes enlarged for any reason, can restrict the normal flow of urine along the urethra....
- Urinary retentionUrinary retentionUrinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
- Uvula of urinary bladderUvula of urinary bladderThe mucous membrane immediately behind the internal urethral orifice presents a slight elevation, the uvula of urinary bladder, caused by the middle lobe of the prostate....