Benign prostate hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) also known as 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. In BPH, the prostate grows larger and presses against the urethra and bladder, interfering with the normal flow of urine. It leads to symptoms of urinary hesitancy, frequent urination, increased risk of urinary tract infections and urinary retention. There is little correlation between BPH symptoms and the presence of prostate cancer.

Symptoms
Urinary symptoms of hesitancy, sensation of incomplete voiding and frequently passing small amounts of urine are all suggestive of BPH in middle-aged and elderly men. Due to the incomplete voiding, there is stasis of bacteria in the bladder residue and an increased risk of urinary tract infections.

A small proportion presents with urinary retention, in which inadequate amounts of urine are passed and the bladder distends greatly. Untreated, this leads to a decrease in renal function and hydronephrosis (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.

DHT is localized principally in the stromal cells. Once synthesized, 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. 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.

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. It is dependent on the skills of the doctor.

Often, blood tests are performed to rule out prostatic malignancy: elevated prostate specific antigen (PSA) levels suggest prostate cancer. It has to be borne in mind that rectal examination can increase PSA levels in patients without malignancy.

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.

Treatment
Alpha blockers (&alpha;1-adrenergic receptor antagonists) (such as doxazosin, prazosin and tamsulosin) and certain antiandrogens such as the 5&alpha;-reductase inhibitors (finasteride and dutasteride) are used, often together, in suppressing the symptoms.

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. (Wilt et al., 2002) Other herbal medicines that have solid research support in systematic reviews include beta-sitosterol from Hypoxis rooperi (African star grass) and Prunus africanum (pygeum) bark, while there is less substantial support for the efficacy of Cucurbita pepo (pumpkin) seed and Urtica dioica (stinging nettle) root. (Wilt et al., 2000) At least one double-blind trial has also supported the efficacy of rye flower pollen. (Buck, et al., 1990)

Sildenafil shows some symptomatic relief, suggesting a possible common etiology with erectile disfunction. (Brown 2005)

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 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 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.