Benign prostatic hyperplasia

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Overview
Benign prostatic hyperplasia (BPH) also known as Nodular hyperplasia, Benign prostatic hypertrophy or Benign enlargement of the prostate (BEP) refers to the increase in size of the prostate in middle-aged and elderly men. To be accurate, the process is one of hyperplasia rather than hypertrophy, but the nomenclature is often interchangeable, even amongst urologists. It is characterized by 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 urethral canal to cause partial, or sometimes virtually complete, obstruction of the urethra which interferes the normal flow of urine. It leads to symptoms of urinary hesitancy, frequent urination, increased risk of urinary tract infections 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.

Symptoms
Benign prostatic hyperplasia symptoms are classified as obstructive or irritative. Obstructive symptoms include hesitancy, intermittency, incomplete voiding, weak urinary stream, and straining.

Irritative symptoms include frequency of urination, which is called nocturia when occurring at night time, and urgency (compelling need to void that can not be deferred). These obstructive and irritative 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 infections. Urinary bladder stones, are formed from the crystallisation 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 who suffer from chronic urinary retention may eventually progress to renal failure, a condition termed obstructive uropathy.

Etiology
Androgens (testosterone and related hormones) are considered to play a permissive role in BPH by most experts. 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, unlike intact men. Additionally, 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, these 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 receptors and signals the transcription of growth factors 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.

There is growing evidence that estrogens play a role in the etiology of BPH. This is based on the fact that BPH occurs when men generally have elevated estrogen levels and relatively reduced free testosterone levels, and when prostate tissue becomes more sensitive to estrogens and less responsive to DHT. Cells taken from the prostates of men who have BPH have been shown to grow in response to high estradiol levels with low androgens present. Estrogens may render cells more susceptible to the action of DHT.

On a microscopic level, BPH can be seen in the vast majority of men as they age, particularly over the age of 70 years, around the world. However, rates of clinically significant, symptomatic BPH vary dramatically depending on lifestyle. Men who lead a western lifestyle have a much higher incidence of symptomatic BPH than men who 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.

Diagnosis
Rectal examination (palpation of the prostate through the rectum) may reveal a markedly enlarged prostate.

Often, blood tests 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 cancer detection.

Ultrasound examination of the testicles, prostate and kidneys is often performed, again to rule out malignancy and hydronephrosis.

Epidemiology
More than half of the men in the United States between the ages of 60 and 70 and as many as 90% between the ages of 70 and 90 have symptoms of BPH. For some men, the symptoms may be severe enough to require treatment.

Lifestyle
Patients should decrease fluid intake before bedtime, moderate the consumption of alcohol and caffeine-containing products, and follow timed voiding schedules.

Medications
Alpha blockers (α1-adrenergic receptor antagonists) provide symptomatic relief of BPH symptoms. Available drugs include doxazosin, terazosin, alfuzosin and tamsulosin. Older drugs, phenoxybenzamine and prazosin are not recommended for treatment of BPH. Alpha-blockers relax smooth muscle in the prostate and the bladder neck, and decrease the degree of blockage of urine flow. Alpha-blockers may cause ejaculation back into the bladder (retrograde ejaculation).

The 5α-reductase inhibitors (finasteride and dutasteride) are another treatment option. 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.

There is also extensive evidence of the efficacy of Serenoa repens (saw palmetto) fruit extracts in alleviating mild-to-moderate BPH symptoms; a systematic review of evidence found comparable efficacy to finasteride. Other herbal medicines that have solid 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 Cucurbita pepo (pumpkin) seed and Urtica dioica (stinging nettle) root. At least one double-blind trial has also supported the efficacy of rye flower pollen.

Sildenafil shows some symptomatic relief, suggesting a possible common etiology with erectile dysfunction.

Surgery
If medical treatment fails, transurethral resection of prostate (TURP) surgery may need to be performed. This involves removing (part of) the prostate through the urethra. 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's left. Transurethral electrovaporization of the prostate (TVP), laser TURP, visual laser ablation (VLAP), TransUrethral Microwave ThermoTherapy (TUMT), TransUrethral Needle Ablation (TUNA), 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 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 powered 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 have typically have a penetration depth of 2.0mm (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 550um disposable side-firing fiber that directs the beam from a high powered 100 Watt laser at a 70degree from the fiber axis. The holmium wavelength is 2,140nm, which falls within the infrared portion of the spectrum and is invisible to the naked eye. Where KTP relies on haemoglobin as a chromophore, water within the target tissue is the chromophore for Holmium lasers. The pentration depth of Holmium lasers is <0.5mm avoiding complications associated with tissue necrosis often found with the deeper penetration and lower peak powers of KTP.

Both wavelengths, KTP and Holmium, ablate approximately one to two grams of tissue per minute.

Related chapters

 * Prostate
 * Prostate cancer
 * Prostate specific antigen
 * Prostatectomy
 * Urinary retention
 * Uvula of urinary bladder