Benign prostatic hyperplasia
Benign prostatic hyperplasia, also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.
The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. Medications like pseudoephedrine, anticholinergics, and calcium channel blockers may worsen symptoms. The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. Diagnosis is typically based on symptoms and examination after ruling out other possible causes.
Treatment options include lifestyle changes, medications, a number of procedures, and surgery. In those with mild symptoms, weight loss, decreasing caffeine intake, and exercise are recommended, although the quality of the evidence for exercise is low. In those with more significant symptoms, medications may include alpha blockers such as terazosin or 5α-reductase inhibitors such as finasteride. Surgical removal of part of the prostate may be carried out in those who do not improve with other measures. Some studies have suggested that certain plant extracts may help mitigate symptoms of BPH. Examples include saw palmetto, stinging nettle root, beta-sitosterol from African star grass, and pygeum. However, meta-analyses have called these conclusions into question, highlighting methodological problems showing no difference from a placebo, and lack of support from larger scale trials.
, about 94 million men aged 40 years and older are affected globally. BPH typically begins after the age of 40. The prevalence of clinically diagnosed BPH peaks at 24% in men aged 75–79 years. Based on autopsy studies, half of males aged 50 and over are affected, and this figure climbs to 80% after the age of 80. Although prostate specific antigen levels may be elevated in males with BPH, the condition does not increase the risk of prostate cancer.
Signs and symptoms
BPH is the most common cause of lower urinary tract symptoms, which are divided into storage, voiding, and symptoms which occur after urination. Storage symptoms include the need to urinate frequently, waking at night to urinate, urgency, involuntary urination, including involuntary urination at night, or urge incontinence. Voiding symptoms include urinary hesitancy, intermittency, involuntary interruption of voiding, weak urinary stream, straining to void, a sensation of incomplete emptying, and uncontrollable leaking after the end of urination. These symptoms may be accompanied by bladder pain or pain while urinating, called dysuria.Bladder outlet obstruction can be caused by BPH. Symptoms are abdominal pain, a continuous feeling of a full bladder, frequent urination, acute urinary retention, pain during urination, problems starting urination, slow urine flow, starting and stopping, and nocturia.
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.
Causes
Hormones
Most experts consider androgens 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 a 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. The average time since castration was 54 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.Dihydrotestosterone, 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. 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 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.
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 DHT levels in the prostate.
Besides testosterone and DHT, other androgens are also known to play a crucial role in BPH development. 11-oxygenated steroids have been identified are precursors to 11-oxygenated androgens which are also potent agonists for the androgen receptor. Specifically, steroids like 11β-hydroxyprogesterone and 11-ketoprogesterone can be converted to 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. Besides that, androgens biosynthesized via a backdoor pathway can contribute to the development of BPH.
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. 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.
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. 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 the development of BPH, but further research is needed to clarify any important relationship. Studies from China suggest that greater protein intake may be a factor in the 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. 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. In a large prospective cohort study in the US, investigators reported modest associations between BPH and total energy and protein, but not fat intake. There is also epidemiological evidence linking BPH with metabolic syndrome.Degeneration
Benign prostatic hyperplasia is an age-related disease. Misrepair-accumulation aging theory suggests that the development of benign prostatic hyperplasia is a consequence of fibrosis and weakening of the muscular tissue in the prostate. 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.Pathophysiology
As men age, the enzymes aromatase and 5-alpha reductase increase in activity. These enzymes are responsible for converting androgen hormones into estrogen and DHT, 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 undergo hyperplasia in BPH. Most sources agree that of the two tissues, stromal hyperplasia predominates, but the exact ratio of the two is unclear.
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.. 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. In BPH, the majority of growth occurs in the transition zone of the prostate. In addition to these two classic areas, the peripheral zone is also involved to a lesser extent. 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. BPH can be a progressive growth that in rare instances leads to exceptional enlargement. In some males, the prostate enlargement exceeds 200 to 500 grams. This condition has been defined as giant prostatic hyperplasia.