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.

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.

 

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