Benign prostatic hyperplasia

Source: Wikipedia, the free encyclopedia.

Benign prostatic hyperplasia
Other namesBenign enlargement of the prostate (BEP, BPE), adenofibromyomatous hyperplasia, benign prostatic hypertrophy,
5α-reductase inhibitors such as finasteride[1]
Frequency105 million affected globally (2015)[3]

Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the

chronic kidney problems.[2]

The cause is unclear.[1] Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction.[1] Medications like pseudoephedrine, anticholinergics, and calcium channel blockers may worsen symptoms.[2] The underlying mechanism involves the prostate pressing on the urethra and thereby making it difficult to pass urine out of the bladder.[1] Diagnosis is typically based on symptoms and examination after ruling out other possible causes.[2]

Treatment options include lifestyle changes, medications, a number of procedures, and surgery.

stinging nettle (Urtica dioica) root.[7]

About 105 million men are affected globally.

prostate specific antigen levels may be elevated in males with BPH, the condition does not increase the risk of prostate cancer.[10]

Signs and symptoms

BPH is the most common cause of

urinary hesitancy (a delay between trying to urinate and the flow actually beginning), intermittency (not continuous),[13] involuntary interruption of voiding, weak urinary stream, straining to void, a sensation of incomplete emptying, and uncontrollable leaking after the end of urination.[14][15][16] These symptoms may be accompanied by bladder pain or pain while urinating, called dysuria.[17]

Bladder outlet obstruction (BOO) can be caused by BPH.[18] Symptoms are abdominal pain, a continuous feeling of a full bladder, frequent urination, acute urinary retention (inability to urinate), pain during urination (dysuria), problems starting urination (urinary hesitancy), slow urine flow, starting and stopping (urinary intermittency), and nocturia.[19]

BPH can be a progressive disease, especially if left untreated. Incomplete voiding results in residual urine or urinary stasis, which can lead to an increased risk of urinary tract infection.[20]

Causes

Hormones

Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. This means that androgens must be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by evidence suggesting that castrated boys do not develop BPH when they age. In an unusual study of 26 eunuchs from the palace of the Qing dynasty still living in Beijing in 1960, the prostate could not be felt in 81% of the studied eunuchs.[21] The average time since castration was 54 years (range, 41–65 years). On the other hand, some studies suggest that administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms, so the role of testosterone in prostate cancer and BPH is still unclear. Further randomized controlled trials with more participants are needed to quantify any risk of giving exogenous testosterone.[22]

transcription of growth factors that are mitogenic to the epithelial and stromal cells. DHT is ten 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 such as finasteride is given to men with this condition. Therapy with a 5α-reductase inhibitor markedly reduces the DHT content of the prostate and, in turn, reduces prostate volume and BPH symptoms.[23][24]

Testosterone promotes prostate cell proliferation,[25] but relatively low levels of serum testosterone are found in patients with BPH.[26][27] 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.[28]

Besides testosterone and DHT, other androgens are also known to play a crucial role in BPH development. C
21 11-oxygenated steroids (pregnanes) have been identified are precursors to 11-oxygenated androgens which are also potent agonists for the androgen receptor.

11-ketodihydrotestosterone, an 11-oxo form of DHT with the same potency. These precursors have also been detected in tissue biopsy samples from patients with BPH, as well as in their serum levels.[30][31][32] Besides that, androgens biosythnesized via a backdoor pathway can contribute to the development of BPH.[30]

While there is some evidence that estrogen may play a role in the cause of BPH, this effect appears to be mediated mainly through local conversion of androgens to estrogen in the prostate tissue rather than a direct effect of estrogen itself.[33] In canine in vivo studies castration, which significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy of the prostate.[34] Studies looking for a correlation between prostatic hyperplasia and serum estrogen levels in humans have generally shown none.[27][35]

In 2008, Gat et al. published evidence that BPH is caused by failure in the spermatic venous drainage system resulting in increased hydrostatic pressure and local testosterone levels elevated more than 100 fold above serum levels.[36] If confirmed, this mechanism explains why serum androgen levels do not seem to correlate with BPH and why giving exogenous testosterone would not make much difference.

Diet

Studies indicate that dietary patterns may affect development of BPH, but further research is needed to clarify any important relationship.[37] Studies from China suggest that greater protein intake may be a factor in development of BPH. Men older than 60 in rural areas had very low rates of clinical BPH, while men living in cities and consuming more animal protein had a higher incidence.[38][39] On the other hand, a study in Japanese-American men in Hawaii found a strong negative association with alcohol intake, but a weak positive association with beef intake.[40] In a large prospective cohort study in the US (the Health Professionals Follow-up Study), investigators reported modest associations between BPH (men with strong symptoms of BPH or surgically confirmed BPH) and total energy and protein, but not fat intake.[41] There is also epidemiological evidence linking BPH with metabolic syndrome (concurrent obesity, impaired glucose metabolism and diabetes, high triglyceride levels, high levels of low-density cholesterol, and hypertension).[42]

Degeneration

Benign prostatic hyperplasia is an age-related disease. Misrepair-accumulation aging theory[43] suggests that development of benign prostatic hyperplasia is a consequence of fibrosis and weakening of the muscular tissue in the prostate.[44] The muscular tissue is important in the functionality of the prostate, and provides the force for excreting the fluid produced by prostatic glands. However, repeated contractions and dilations of myofibers will unavoidably cause injuries and broken myofibers. Myofibers have a low potential for regeneration; therefore, collagen fibers need to be used to replace the broken myofibers. Such misrepairs make the muscular tissue weak in functioning, and the fluid secreted by glands cannot be excreted completely. Then, the accumulation of fluid in glands increases the resistance of muscular tissue during the movements of contractions and dilations, and more and more myofibers will be broken and replaced by collagen fibers.[45]

Pathophysiology

Benign prostate hyperplasia

As men age, the enzymes

5-alpha reductase increase in activity. These enzymes are responsible for converting androgen hormones into estrogen and dihydrotestosterone
, respectively. This metabolism of androgen hormones leads to a decrease in testosterone but increased levels of DHT and estrogen.

Both the glandular epithelial cells and the stromal cells (including muscular fibers) undergo hyperplasia in BPH.[2] Most sources agree that of the two tissues, stromal hyperplasia predominates, but the exact ratio of the two is unclear.[46]: 694 

Anatomically the median and lateral lobes are usually enlarged, due to their highly glandular composition. The anterior lobe has little in the way of glandular tissue and is seldom enlarged. (Carcinoma of the prostate typically occurs in the posterior lobe – hence the ability to discern an irregular outline per rectal examination). The earliest microscopic signs of BPH usually begin between the age of 30 and 50 years old in the PUG, which is posterior to the proximal urethra.[46]: 694  In BPH, the majority of growth occurs in the transition zone (TZ) of the prostate.[46]: 694  In addition to these two classic areas, the peripheral zone (PZ) is also involved to a lesser extent.[46]: 695  Prostatic cancer typically occurs in the PZ. However, BPH nodules, usually from the TZ are often biopsied anyway to rule out cancer in the TZ.[46]: 695  BPH can be a progressive growth that in rare instances leads to exceptional enlargement.[47] In some males, the prostate enlargement exceeds 200 to 500 grams.[47] This condition has been defined as giant prostatic hyperplasia (GPH).[47]

Diagnosis

The clinical diagnosis of BPH is based on a history of LUTS (lower urinary tract symptoms), a digital rectal exam, and exclusion of other causes of similar signs and symptoms. The degree of LUTS does not necessarily correspond to the size of the prostate. An enlarged prostate gland on rectal examination that is symmetric and smooth supports a diagnosis of BPH.[2] However, if the prostate gland feels asymmetrical, firm, or nodular, this raises concern for prostate cancer.[2]

Validated questionnaires such as the American Urological Association Symptom Index (AUA-SI), the International Prostate Symptom Score (I-PSS), and more recently the UWIN score (urgency, weak stream, incomplete emptying, and nocturia) are useful aids to making the diagnosis of BPH and quantifying the severity of symptoms.[2][48][49]

Laboratory investigations

ultrasonography may be helpful in determining whether a PSA increase is due to BPH or prostate cancer.[2]

Imaging and other investigations

Uroflowmetry is done to measure the rate of urine flow and total volume of urine voided when the subject is urinating.[50]

Abdominal ultrasound examination of the prostate and kidneys is often performed to rule out hydronephrosis and hydroureter. Incidentally, cysts, tumours, and stones may be found on ultrasound. Post-void residual volume of more than 100 ml may indicate significant obstruction.[51] Prostate size of 30 cc or more indicates enlargement of the prostate.[52]

Prostatic calcification can be detected through transrectal ultrasound (TRUS). Calcification is due to solidification of prostatic secretions or calcified corpora amylacea (hyaline masses on the prostate gland). Calcification is also found in a variety of other conditions such as prostatitis, chronic pelvic pain syndrome, and prostate cancer.[53][54] For those with elevated levels of PSA, TRUS guided biopsy is performed to take a sample of the prostate for investigation.[55] Although MRI is more accurate than TRUS in determining prostate volume, TRUS is less expensive and almost as accurate as MRI. Therefore, TRUS is still preferred to measure prostate volume.[56]

Differential diagnosis

Medical conditions

The differential diagnosis for LUTS is broad and includes various medical conditions, neurologic disorders, and other diseases of the bladder, urethra, and prostate such as

alcohol-induced nerve damage.[2] Individuals affected by heart failure often experience nighttime awakenings to urinate due to redistribution of fluid accumulated in swollen legs.[2]

Medications

Certain medications can increase urination difficulties by increasing bladder outlet resistance due to increased

chlorthalidone) can cause or worsen urinary frequency and nighttime awakenings to urinate.[2]

Management

When treating and managing benign prostatic hyperplasia, the aim is to prevent complications related to the disease and improve or relieve symptoms.[57] Approaches used include lifestyle modifications, medications, catheterisation and surgery.

Lifestyle

Lifestyle alterations to address the symptoms of BPH include physical activity,[58] decreasing fluid intake before bedtime, moderating the consumption of alcohol and caffeine-containing products and following a timed voiding schedule.

Patients can also attempt to avoid products and medications with anticholinergic properties that may exacerbate urinary retention symptoms of BPH, including antihistamines, decongestants, opioids, and tricyclic antidepressants; however, changes in medications should be done with input from a medical professional.[59]

Physical activity

Physical activity has been recommended as a treatment for urinary tract symptoms. A 2019 Cochrane review of six studies involving 652 men assessing the effects of physical activity alone, physical activity as a part of a self-management program, among others. However, the quality of evidence was very low and therefore it remains uncertain whether physical activity is helpful in men experiencing urinary symptoms caused by benign prostatic hyperplasia.[60]

Voiding position

Voiding position when urinating may influence urodynamic parameters (urinary flow rate, voiding time, and post-void residual volume).[61] A meta-analysis found no differences between the standing and sitting positions for healthy males, but that, for elderly males with lower urinary tract symptoms, voiding in the sitting position-- [62]

  • decreased the post void residual volume;
  • increased the maximum urinary flow, comparable with pharmacological intervention; and
  • decreased the voiding time.

This

bladder stones
.

Medications

The two main medication classes for BPH management are

5α-reductase inhibitors.[63]

Alpha blockers

Selective α1-blockers are the most common choice for initial therapy.[64][65][66] They include alfuzosin,[67][68] doxazosin,[69] silodosin, tamsulosin, terazosin, and naftopidil.[57] They have a small to moderate benefit at improving symptoms.[70][57][71] Selective alpha-1 blockers are similar in effectiveness but have slightly different side effect profiles.[70][57][71] 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 hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction,[72] headaches, nasal congestion, and weakness. For men with LUTS due to an enlarged prostate, the effects of naftopidil, tamsulosin and silodosin on urinary symptoms and quality of life may be similar.[57] Naftopidil and tamsulosin may have similar levels of unwanted sexual side effects but fewer unwanted side effects than silodosin.[57]

Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH.[73] Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong.

5α-reductase inhibitors

The 5α-reductase inhibitors

teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets.[82]

Phosphodiesterase inhibitors (PDE)

A 2018 Cochrane review of studies on men over 60 with moderate to severe

5-alpha reductase inhibitors
.

Several phosphodiesterase-5 inhibitors are also effective, but may require multiple doses daily to maintain adequate urine flow.[84][85] Tadalafil, a phosphodiesterase-5 inhibitor, was considered then rejected by NICE in the UK for the treatment of symptoms associated with BPH.[86] In 2011, the U.S. Food and Drug Administration approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia, and for the treatment of BPH and erectile dysfunction (ED), when the conditions occur simultaneously.[87]

Others

Antimuscarinics such as tolterodine may also be used, especially in combination with alpha blockers.[88] They act by decreasing acetylcholine effects on the smooth muscle of the bladder, thus helping control symptoms of an overactive bladder.[89]

Self-catheterization

Intermittent urinary catheterization is used to relieve the bladder in people with urinary retention. Self-catheterization is an option in BPH when it is difficult or impossible to completely empty the bladder.[90] Urinary tract infection is the most common complication of intermittent catheterization.[91] Several techniques and types of catheter are available, including sterile (single-use) and clean (multiple use) catheters, but, based on current information, none is superior to others in reducing the incidence of urinary tract infection.[92]

Surgery

Main article: Surgery for benign prostatic hyperplasia
Transurethral resection of the prostate (TURP)

If medical treatment is not effective, surgery may be performed. Surgical techniques used include the following:

Other less invasive surgical approaches (requiring spinal anesthesia) include:

Minimally invasive procedures

Some less invasive procedures are available according to patients' preferences and co-morbidities. These are performed as

outpatient procedures with local anesthesia
.

Alternative medicine

While

herbal remedies are commonly used, a 2016 review found the herbs studied to be no better than placebos.[99] Particularly, several reviews found that saw palmetto extract, while one of the most commonly used, is no better than a placebo both in symptom relief and in decreasing prostate size.[100][101][102]

Epidemiology

Disability-adjusted life year for benign prostatic hyperplasia per 100,000 inhabitants in 2004[103]
  no data
  less than 20
  20–28
  28–36
  36–44
  44–52
  52–60
  60–68
  68–76
  76–84
  84–92
  92–100
  more than 100

Globally, benign prostatic hyperplasia affects about 210 million males as of 2010 (6% of the population).[104]

The prostate gets larger in most men as they get older. For a symptom-free man of 46 years, the risk of developing BPH over the next 30 years is 45%. Incidence 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. While the prevalence rate is 2.7% for men aged 45–49, it increases to 24% by the age of 80 years.[105]

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