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PubMed2004

[Dutasteride: main results in the treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a progressive disease characterized by an increase in prostatic volume. The resulting urinary irritative and/or obstructive symptoms, when present, often reduce the patient's quality of life. Prostatic dihydrotestosterone, the androgen produced following transformation of testosterone by the enzyme 5-alpha-reductase, is responsible for these changes. Among various products used for drug therapy, 5-alpha-reductase inhibitors play a specific role in the long-term management of BPH. Between the two currently available products, dutasteride is the only dual 5-alpha-reductase inhibitor (types 1 and 2). The efficacy of dutasteride was tested in several scientific studies and the cumulative results of three controlled, double-blind pivotal studies, showed at 2-year a clear improvement in all parameters modified during this disorder. A significant decrease in the severity and frequency of the urinary symptoms, in prostate volume, the risk of urine retention, the necessity to resort to surgery and an increase in peak urinary flow were observed with dutasteride. These results were confirmed in the 4-year-open label extension of these pivot studies both for tolerability of the product and the maintenance of its efficacy over time.

Azasteroids↗
PubMed1993

A case of giant prostatic hyperplasia.

Giant prostatic hyperplasia (GPH) is an uncommon pathologic entity with only 10 reported cases of prostate glands exceeding 500 g. We report the uncomplicated removal of a 526-g prostatic adenoma by simple retropubic prostatectomy.

Aged↗
PubMed2006

Drug Insight: 5alpha-reductase inhibitors for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common problem among older men, which is characterized by an enlarged prostate, lower urinary tract symptoms, and decreased flow of urine. It is a progressive disease that can lead to complications such as acute urinary retention (AUR) or a need for BPH-related surgery in some men. Dihydrotestosterone is the primary androgen involved in both normal and abnormal prostate growth and 5alpha-reductase inhibitors (5ARIs) inhibit the conversion of testosterone to dihydrotestosterone. There are two 5ARIs licensed for the treatment of BPH; dutasteride, which inhibits both type 1 and type 2 isoenzymes of 5alpha reductase, and finasteride, which inhibits the type 2 isoenzyme. Both 5ARIs have been shown to decrease prostate volume, improve urinary flow and lower urinary tract symptoms and reduce the risk of AUR and BPH-related surgery. The prevention of disease progression, by treating the underlying cause, and the alleviation of symptoms are important aims of BPH therapy. 5ARIs are the only currently available medical therapy that can reduce the risk of AUR and BPH-related surgery while providing long-term symptom control. This provides a mandate for their use in men with enlarged prostates (volume >or=30 ml), who are at increased risk of disease progression.

5-alpha Reductase Inhibitors↗
PubMed2004

Activation of caspases-3, -6, and -9 during finasteride treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) results from an increase in both epithelial and stromal compartments of the human prostate. Although inhibitors of 5alpha-reductase such as finasteride have been shown to reduce the size of BPH tissues by inducing apoptosis, their mechanisms of action still remain unknown. The present study supports that such a process triggered by finasteride is caspase dependent with a possible involvement of two effector caspases (caspase-3 and 6) and two initiator caspases (caspase-8 and 9). Indeed, by using tissues from patients affected by BPH and treated by finasteride (5 mg/d) for 2-3, 6-8, or 27-32 d, we observed that the 5alpha-reductase inhibitor induced apoptosis in epithelial cells (evaluated through cell number positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) as early as 2-3 d of treatment, with a maximal activity (250-fold increase, P < 0.0001) at 6-8 d of treatment. However, after 27-32 d of treatment, the number of apoptotic cells was reduced and was close to control. Caspases-3, -6, -8, and -9 were immunolocalized to (basal and secretory) epithelial cells and to a lesser extent to stromal cells. Activated caspase-3 immunoexpression was restricted to epithelial secretory cells, and its immunostaining intensity appeared to be higher in BPH tissues from patients treated for 2-3 or 6-8 d. Consistently, in Western blotting analyses, activated caspases-3 and -6 were detected as early as 2-3 d of treatment in BPH tissues, and their levels were increased after 6-8 d of treatment. In real time quantitative PCR experiments, caspase-3 and -6 mRNA levels were found to be unchanged after finasteride treatment. Activated caspase-8 was not detected in the different conditions tested, whereas activated caspase-9 protein levels were maximally enhanced after 2-3 d of finasteride treatment. In conclusion, we report here that finasteride treatment of BPH tissues induced a caspase-dependent apoptotic process restricted to epithelial cells by activating effector caspases-3 and -6 and exhibited a transient action because the apoptotic process was no longer observed after 27-32 d of treatment.

Aged↗
PubMed1997

A nationwide survey of practicing urologists: current management of benign prostatic hyperplasia and clinically localized prostate cancer.

PURPOSE: Our aim was to define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. MATERIALS AND METHODS: In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%. RESULTS: Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH. Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry. Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably. CONCLUSIONS: These data provide a picture of current practice regarding the management of BPH and prostate cancer.

Data Collection↗
PubMed1993

Development of a rapidly computable descriptor of prostate tissue temperature during transurethral conductive heat therapy for benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is a condition in older men in which the mass of tissue in the prostate gland gradually increases over the course of many years, ultimately leading to urinary outflow obstruction. Current treatment of this condition is to surgically remove the obstructing tissue. One novel alternative therapy being studied is transurethral thermocoagulation of excessive prostatic mass. In this approach, a heat-emitting catheter is placed in the prostatic urethra, and the intraprostatic segment of the catheter is heated to temperatures above 60 degrees C for one hour. Two-dimensional cylindrical-co-ordinate computer simulations of this treatment modality were run to model resultant temperature distributions within the prostate gland and surrounding tissues. The simulations revealed that resultant tissue temperature changes were related directly to the power delivered to the catheter and inversely to the rate of blood perfusion. Further analysis of the temperature profiles produced a rapidly computable predictor of tissue temperature in the radial dimension. Using the predictor, a 'kill radius' around the prostatic urethra can be easily computed on-line, during treatment, from clinically available data, catheter power and catheter temperature. The computed kill radius may serve as a useful predictor of the extent of thermal devitalization of unwanted obstructing tissue and the long-term success of the treatment in relieving urinary outflow obstruction without surgery.

Computer Simulation↗
PubMed2006

Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level.

BACKGROUND: The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (> or =60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately.

Age Factors↗
PubMed2006

Trends in the development of new drugs for treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common condition in aging men that is characterized by nonmalignant enlargement of the prostate gland, and is frequently accompanied by urinary obstruction, and lower urinary tract symptoms (LUST). Currently pharmacotherapy of BPH is based on two classes of drugs: alpha(1)-adrenoceptor (alpha(1)-AR) antagonists and 5alpha-reductase inhibitors. It has been shown that alpha(1)-AR antagonists reduce symptom scores and increase peak urinary flow rates in BPH. Of particular importance for BPH therapy are uroselective alpha(1)-AR antagonists for which the hypotensive related side-effect caused by alpha(1)-AR blockade is reduced. 5alpha-Reductase inhibitors reduce prostate volume and symptom scores, while increasing peak urinary flow rates. This review describes new alpha(1)-AR antagonists and 5alpha-reductase inhibitors in the treatment of BPH. The new alpha(1)-AR antagonists represent various structures such as quinazolines, phenylethylamines, piperidines, and arylpiperazines. 5alpha-Reductase inhibitors are classified into two groups: steroidal and non-steroidal. The newer non-steroidal inhibitors include derivatives of benzo[c]quinolizinones, benzo[f]quinolonones, piperidones and carboxylic acids. Besides the development of new compounds belonging to the above mentioned groups, new agents for BPH treatment are sought among combined 5alpha-reductase/alpha(1)-AR inhibitors, endothelins, androgen receptors antagonists, growth factors, estrogens and phosphodiesterase isoenzymes as well as several phytomedicines, used for prevention and treatment of prostate disorders. These new agents can be used for the design of future targets and development of new drugs in the treatment of BPH. The discovery of a number of active leads may also ultimately help in developing new safe and effective drugs.

5-alpha Reductase Inhibitors↗
PubMed2001

Interleukin-8 is a paracrine inducer of fibroblast growth factor 2, a stromal and epithelial growth factor in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, leading to obstruction of urine outflow. Fibroblast growth factor (FGF) 2, a potent growth factor for prostatic stromal and epithelial cells, is increased twofold in BPH and its concentration is correlated with stromal proliferation in this condition. Immunohistochemistry of normal and hyperplastic prostate revealed that FGF2-expressing stromal cells were present in higher numbers near the epithelial acini, implying that epithelial cells may express a factor that induces FGF2 expression by stromal cells. Conditioned medium from primary cultures of prostatic epithelial cells was capable of inducing increased expression of FGF2 by primary stromal cultures. Blocking experiments with neutralizing anti-interleukin (IL)-8 antibodies and pretreatment with lipopolysaccharide, which down-regulates the IL-8 receptor, show that this inducing activity is because of the presence of IL-8 in the epithelial-conditioned medium. Analysis of normal prostatic peripheral zone and BPH tissue by enzyme-linked immunosorbent assay reveals that IL-8 is present at increased levels in hyperplastic prostate. Therefore IL-8 produced by prostatic epithelial cells can induce FGF2, a potent stromal and epithelial growth factor, and in this manner promote the abnormal proliferation of the prostatic transition zone that is critical in the pathogenesis of BPH.

Cells, Cultured↗
PubMed2000

Interleukin-1alpha is a paracrine inducer of FGF7, a key epithelial growth factor in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, leading to obstruction of urine outflow. FGF7, a potent growth factor for prostatic epithelial cells, is increased by threefold in BPH and is correlated with increased epithelial proliferation in this condition. Immunohistochemistry of normal and hyperplastic prostate revealed that FGF7-expressing fibroblastic cells were present in higher numbers near the epithelial acini, implying that epithelial cells may express a factor that induces FGF7 expression by stromal cells. Conditioned medium (CM) from primary cultures of prostatic epithelial cells was capable of inducing a two- to sixfold increase in the expression of FGF7 by primary stromal cultures. Blocking experiments with neutralizing anti-interleukin-1alpha (Il-1alpha) antibodies and IL-1Ra, an Il-1alpha receptor antagonist, show that this inducing activity was due to the presence of Il-1alpha in the epithelial CM. Analysis of normal prostatic peripheral zone and BPH tissue by enzyme-linked immunoabsorption assay reveal that Il-1alpha is present at increased levels in hyperplastic prostate and that levels of Il-1alpha correlate strongly with tissue FGF7 concentration in BPH. Therefore Il-1alpha is produced by prostatic epithelial cells and can induce FGF7, a potent epithelial growth factor, which can in turn lead to further epithelial growth and increased Il-1alpha secretion, thus establishing a double paracrine loop that is functionally equivalent to an autocrine growth loop. This double paracrine loop may play a key role in the abnormal proliferation of the transition zone, which is critical to the pathogenesis of BPH.

Cells, Cultured↗
PubMed1995

Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a pathologic disorder that develops in response to the action of dihydrotestosterone on the aging prostate and to changes in stromal and epithelial cells in this exocrine gland. The current therapies for this disorder are chosen after other causes for irritative and obstructive symptoms have been excluded and the status of the urinary tract has been assessed. This evaluation includes a detailed medical history, a thorough genitourinary and neurological examination, assessment of serum prostate specific antigen and creatinine levels, as well as a urinalysis. A urodynamic evaluation consisting of a combined pressure-flow study is required if the diagnosis of obstruction is to be made. Patients with minimal symptoms and normal test results require no therapy. Mild to moderate symptoms can be controlled, at least temporarily, with alpha-adrenergic blockers such as terazosin or doxazosin. A subset of BPH patients with obstructive symptoms respond to the 5 alpha-reductase inhibitor finasteride. Early results with minimally invasive treatments such as laser prostatectomies, hyperthermia, and ultrasonic and radiofrequency ablation appear encouraging for those with moderate symptoms of prostatism. Severe symptoms, urinary retention, gross hematuria, recurrent urinary tract infections, bladder calculi, and hydronephrosis or renal insufficiency warrant transurethral incision, resection, vaporization, or open prostatectomy (for very large neoplasms). Although the morbidities of these latter surgical therapies are not insignificant, these treatments offer the best and most durable results for relief of obstruction and amelioration of symptoms.

Adrenergic alpha-Antagonists↗
PubMed1994

Insulin-like growth factor axis abnormalities in prostatic stromal cells from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. To assess whether patients with BPH have alterations in their prostatic IGF axis, we measured the expression (by Northern blotting) and the production (by Western ligand blotting and RIA) of insulin-like growth factor-II (IGF-II) and IGF-binding proteins (IGFBPs) in prostatic epithelial and stromal cell strains grown from normal (n = 7), hyperplastic (n = 7), and malignant (n = 5) surgical specimens. Levels of IGF-II messenger ribonucleic acid (mRNA; normalized for actin expression) were 10-fold higher in BPH stromal cell strains compared to those in normal stromal cell strains (P < 0.0001). Western ligand blotting of conditioned medium (CM) from normal stromal cells demonstrated the presence of IGFBP-2, -3, and -4. In the CM of BPH stromal cells, IGFBP-2 levels were dramatically reduced to less than 20% of normal (P < 0.001). Additionally, IGFBP-5, which was not observed in significant amounts in normal stromal cell-CM, was found in large quantities in BPH stromal cell-CM. Northern blot analysis of mRNA from normal and BPH stromal cells demonstrated a 5-fold decrease in IGFBP-2 mRNA (P < 0.001) and a 4-fold increase in IGFBP-5 mRNA (P < 0.01) in BPH compared to normal cells. In prostate stromal cells from cancer specimens, no abnormalities were found. No abnormalities were observed in the IGF axis parameters evaluated in prostate epithelial cells from BPH or cancer strains. We conclude that prostatic stromal cell strains isolated from patients with BPH hyperexpress the mRNA for IGF-II and IGFBP-5 while expressing reduced amounts of IGFBP-2 mRNA. IGFBP, but not IGF-II, peptide levels in CM correspond to the mRNA differences. This is the first documentation of altered gene and protein expression in this common disease. We speculate that these abnormalities in the IGF axis may be important in the pathogenesis of BPH.

Blotting, Northern↗
PubMedDate not supplied

Infrared microspectroscopic detection of epithelial and stromal growth in the human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. It describes an overgrowth of the epithelial and fibromuscular tissues in the human prostate, in which both epithelium and stroma continue to proliferate at different rates. There is lack of suitable techniques for direct evaluation of the biophysical structure of molecular constituents and the proliferative changes in the structure of both compartments at the microscopic level. Reflectance Fourier transform infrared (FT-IR) microspectroscopy was used to pathologically image and examine the structural changes in the proliferation of epithelial and stromal tissues of human BPH. Two successive thin tissue slices were obtained by cutting the tissue with a microtome: one unstained slice was used for FT-IR spectroscopic analysis and the other stained slice was used for position referencing. The result indicates that the amide I maximum for BPH epithelial tissue was near 1,638 cm(-1) and showed its protein secondary structure by a combination of unordered and beta-sheet structures. However, an intense absorption band of amide I was at 1,630 cm(-1) for stromal BPH tissue due to the predominant beta-sheet structure. The higher peak intensity of several IR bands at 1,337, 1,281, 1,238, 1,206, 1,055, and 1,034 cm(-1), assigned to the C-O stretching mode of collagen, was observed in BPH stromal tissue. This suggests that the obvious collagen will be more enriched in the stroma of BPH tissue.

Aged↗
PubMed2006

[Advances in the studies of morphological histology and imaging of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a familiar usually involves senile males. In recent 50 years, the incidence of BPH in China has been increasing. The morphological histology of hyperplastic prostate showed the volume enlarged and weight increase, and the hyperplastic part was mainly located in transitional zone. Researchers at home and abroad studied the tissue characteristics of hyperplastic prostate by routine and special staining coupled with computer-assisted quantitative image analysis system, and found that the proliferation was mainly occurred in interstitial tissue of prostate. The imaging examination is an important assistant method to diagnose BPH. Especially, Transrectal ultrasound and magnetic resonance imaging can displayed hyperplastic prostate more clearly.

Humans↗
PubMedDate not supplied

Morphologic basis of MR imaging of benign prostatic hyperplasia.

Fifteen prostates were obtained from patients autopsied at The Johns Hopkins Hospital and imaged fresh in vitro by high resolution magnetic resonance (MR) imaging with a surface coil. Following scanning, the specimens were fixed and sectioned in the same plane as the MR images. The prostate sections, corresponding to the MR images, were examined grossly and histologically for prostate pathology. Tissue characteristics were quantified by morphometric techniques and correlated with MR image intensity. Five prostates were normal and showed two distinct anatomic zones, a central periurethral zone and a peripheral zone. These two zones corresponded to two zones identified on MR of the five normal prostates. In contrast, both the MR images and the pathologic and morphometric studies of nine of the 10 prostates with benign prostatic hyperplasia (BPH) showed three distinct zones: a central region of BPH, a surrounding fibrous capsule, and a peripheral zone. This study suggests that there is a morphologic basis for MR intensity in the prostate.

Adult↗
PubMed2004

[Progress in the studies of alpha1-receptor blocker for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a common senile disease, and its main clinical manifestation is lower urinary tract symptom (LUTS), which has long been afflicting old male patients. Previous study showed that alpha1-receptor in the prostate was involved in the development of LUTS. At present, alpha1-receptor blocker is generally accepted as a choice drug for treating BPH and relieving LUTS. The article reviews the tissue distribution of alpha1-receptor and clinical application of alpha1-receptor blocker.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

Evaluation and medical management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is common among aging men. Untreated BPH may lead to complications including urinary tract infection, acute urinary retention, and obstructive nephropathy. Diagnosing BPH can be challenging because lower urinary tract symptoms are found in conditions other than BPH, and prostate size correlates poorly with symptoms of obstruction. Nonetheless, a careful medical history and physical examination, along with prudent use of diagnostic tests, can yield an accurate diagnosis. We review the evaluation of men with suspected BPH and indications for referral to a urologist for invasive therapy. We also review supporting evidence and treatment considerations for saw palmetto and the 2 major classes of prescription medications, alpha1-adrenergic antagonists and 5alpha-reductase inhibitors.

Adrenergic alpha-Antagonists↗
PubMed2001

Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common histologic condition among older men, which conveys its morbidity through lower urinary tract symptoms and complications, such as acute urinary retention, obstructive uropathy, and urinary tract infections. The mechanisms linking the histologic process and lower urinary tract symptoms remain uncertain; prostatic enlargement and bladder outlet obstruction are involved. However, measurements of prostate size and the severity of bladder outlet obstruction correlate poorly with the severity of lower urinary tract symptoms. The severity of lower urinary tract symptoms associated with BPH can be measured reliably, from the patient's perspective, with a number of validated questionnaires, including the International Prostate Symptom Score, the Danish Prostate Symptom Score, and the International Continence Society (ICS)male questionnaire. In the clinical setting, these questionnaires can be used (1) to assess the severity of symptoms in men with lower urinary tract symptoms that may be attributable to BPH, based on their age and clinical characteristics; and (2) to follow changes in symptoms over time and with treatment. None of these questionnaires can accurately determine whether a symptomatic patient has underlying bladder outlet obstruction. Additional questionnaires are available to measure the impact of lower urinary tract symptoms on men's lives, as well as associated phenomena, such as continence and sexual function, which may be affected by BPH and its treatments. Men with a severe burden of lower urinary tract symptoms often have measurable decrements in overall health-related quality of life, which can be ameliorated by treatment.

Aged↗