Benign Prostatic Hyperplasia
Also Known As: Benign Prostatic Hyperplasia, BPH, benign prostatic hypertrophy, Adenofibromyomatous hyperplasia
Benign prostatic hyperplasia (BPH), benign enlargement of the prostate (BEP), adenofibromyomatous hyperplasia and incorrectly referred to benign prostatic hypertrophy, is an increase in size of the prostate. BPH involves hyperplasia (an increase in the number of cells) rather than hypertrophy (a growth in the size of individual cells), but the two terms are often used interchangeably, 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 urethral 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 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 does not lead to cancer or increase the risk of cancer. Adenomatous 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 men, BPH becomes clinically significant.
Benign prostatic hyperplasia symptoms 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. This can result in bladder hypotonia. Some patients that suffer from chronic urinary retention may eventually progress to renal failure, a condition termed obstructive uropathy.
Most experts consider androgens (testosterone and related hormones) 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 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 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, 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 androgens to estrogen 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.