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Results for “benign prostatic hyperplasia”

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PubMed1997

Resistance to apoptosis and up regulation of Bcl-2 in benign prostatic hyperplasia after androgen deprivation.

PURPOSE: Benign prostatic hyperplasia (BPH) is related to advancing age and the presence of androgens and occurs in virtually all older men. BPH causes morbidity, most often by urinary obstruction, in a substantial fraction of men over sixty. Both finasteride and androgen ablation induce partial diminution in BPH that occurs over weeks to months. This is in contrast to the often rapid involution seen in both normal prostatic epithelium and prostatic carcinoma in response to androgen withdrawal. This study was performed to analyze the response of prostatic cells, and in particular BPH, to acute androgen ablation. MATERIALS AND METHODS: We subjected a cohort of 26 men to androgen ablation with goserelin, a gonadotrophin releasing hormone agonist, for 3-4 weeks prior to radical prostatectomy for prostate cancer. Preablation biopsy specimens and prostatectomy specimens were immunohistochemically stained for apoptotic cells and for expression of apoptosis regulatory proteins Bcl-2, Bax, Bcl-x, and Bak. RESULTS: Normal prostatic epithelial cells and prostate cancer responded to hormone deprivation by undergoing apoptosis, but in 19/26 specimens prostatic hyperplasia had a total absence of apoptosis. In all 26 specimens, benign prostatic hyperplasia demonstrated increased expression of the Bcl-2 protein, but no change in the expression of Bax, Bcl-x, and Bak. In contrast, adjacent normal and malignant prostatic epithelium showed positive staining for apoptosis and did not alter Bcl-2 expression in response to androgen ablation. CONCLUSIONS: BPH demonstrated increased staining for Bcl-2 after androgen deprivation that may render hyperplastic epithelium relatively resistant to apoptosis induced acutely by androgen withdrawal.

Apoptosis↗

PubMed2004

Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue.

BACKGROUND: Benign prostatic hyperplasia (BPH) development requires testicular androgens and aging. The principle prostatic androgen is dihydrotestosterone (DHT). Testosterone is converted to DHT by the enzyme 5 alpha-reductase. Two distinct 5 alpha-reductase enzymes, types 1 and 2, have been identified. While some studies have suggested that type 2 isoenzyme predominates in the prostate, studies on the prostatic localization of the two isoenzymes are controversial. The purpose of this study was to determine the quantitative expressions of 5 alpha-reductase types 1 and 2 in BPH tissues. METHODS: We examined the localizations of types 1 and 2 isoenzymes in BPH tissues using immunohistochemical staining and a real-time quantitative RT-PCR assay using the TaqMan system. We measured the enzyme activities of types 1 and 2 at pH values of 7.5 and 5.0, respectively. RESULTS: Our immunohistochemical study showed that type 1 isoenzyme was expressed predominantly in epithelial cells, whereas type 2 isoenzyme was expressed in both stromal and epithelial cells. The real-time RT-PCR assay demonstrated that the copy numbers of type 1 isoenzyme mRNA were significantly higher than those of type 2 isoenzyme mRNA. There were significant associations between enzyme activity at pH 7.5 and type 1 isoenzyme mRNA expression, and between the activity at pH 5.0 and type 2 mRNA expressions. CONCLUSIONS: We demonstrated that 5 alpha-reductase type 1 had a specific enzyme activity in the prostate, which supports the hypothesis that the type 1 isoenzyme may play a significant role in maintaining prostate enlargement along with the type 2 isoenzyme.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1989

Diagnostic assessment of benign prostatic hyperplasia.

Clinical evaluations of benign prostatic hyperplasia (BPH) are based upon careful history taking, uroflowmetry, palpation of the prostate, and diagnosis of urinary infection or possible damage to the kidneys caused by outflow obstruction. Symptom assessment includes scoring by the patient of the four obstructive and five irritative symptoms of prostatic obstruction: a simple questionnaire is used. The scoring system should be reviewed with the urinary flow measurements as part of the workup. The various forms of ultrasound used for diagnosis, although invaluable, may not be assessed out of context, and the combination of digital palpation and endoscopy generally provide most information leading to a decision for operation. When available, perrectal ultrasound scanning should be used to investigate palpable abnormalities and to identify unexpected prostatic cancer.

Humans↗

PubMed1993

Atamestane: an aromatase inhibitor for the treatment of benign prostatic hyperplasia. A short review.

Benign prostatic hyperplasia (BPH) is the most common neoplastic growth in men and is the most frequent cause of urinary flow obstruction at the bladder neck. In addition to the clear evidence in favor of the androgen dependency of BPH, the involvement of the stroma, stromal-epithelial interaction and the role of estrogens have gained much interest in connection with the pathogenesis of this disease. For this reason, specific aromatase inhibitors such as atamestane (1-methyl-1,4-androstadiene-3,17-dione) have recently attracted attention due to their potential use in the treatment of BPH. The pharmacological action of atamestane as a new competitive and irreversible inhibitor of estrogen biosynthesis has been evaluated in mice, rats, rabbits, dogs, monkeys and in man. In all species tested so far, atamestane lacks other intrinsic hormonal or antihormonal activities and shows no inhibition of other cytochrome-P450 dependent enzymes of adrenal steroidogenesis. However, it inhibits the estrogen-related negative feed-back. The extent and consequence of the induced counter-regulation of the pituitary-hypothalamic axis show major sex- and species-specific differences. In BPH animal models, atamestane is highly effective in inhibiting estrogen-induced hyperplastic changes in the fibromuscular stroma of the prostate in androstenedione-treated dogs and monkeys. In male volunteers and BPH patients, atamestane induces an expected dose-dependent reduction of serum estrogen concentrations with slight increases in androgen level. In conclusion, all available results indicate that atamestane is a selective (no inhibition of adrenal function), pure (= specific--no endocrine side-effects) and highly effective steroidal aromatase inhibitor with excellent safety profile. Based on our preliminary results aromatase inhibitors seem to be promising compounds for the treatment of BPH.

Androgens↗

PubMed2005

[GnRH antagonists and benign prostatic hyperplasia].

Early treatment of benign prostatic hyperplasia (BPH) helps to decrease the need for surgery and thus places the medical treatment at the forefront which implies, optimising its efficacy and tolerance. Alpha-blockers and 5-alpha-reductase inhibitors are the two main classes of currently used drugs. The role in the growth of glandular, muscular and fibroblastic tissues of the prostate of androgens, testosterone and especially intraprostatic dihydrotestosterone was properly established. These physiopathological data prompted to evaluate the efficacy of inhibition of the hypothalamic-pituitary-gonadal axis, by means of LH-RH analogues. The agonists lead to a biological castration associated with a significant improvement of BPH symptoms. Unfortunately clinical relapse is systematic when treatment is discontinued. The antagonists, particulary cetrorelix, improve BPH symptoms, with a persistant benefit after treatment, discontinuation, although the effect on the prostate volume reduction is transitory. It can be suggested that beside the well known hormonal action, there is a direct apoptic effect cells as well as inhibition of the intratissue growth factors. The LH-RH antagonists could thus become an alternative to the current drugs by offering a relatively short treatment with a prolonged benefit.

Apoptosis↗

PubMed1996

Prostates and profits: the social construction of benign prostatic hyperplasia in American men.

Benign prostatic hyperplasia (BPH) is clinically diagnosed in approximately three-fourths of American men, a prevalence two to three times higher than that currently reported in Scotland and Japan. Prostatectomy is the most common operation performed on American men over 65. A critical medical anthropological analysis reveals that American urologists rely on prostatectomy to maintain their practices, and the growth of urology as a specialty is significantly related to the 50% increase in the rate of surgery since 1965. Marketing campaigns and studies funded by pharmaceutical companies promote the perception of urinary difficulties as problematic, encourage men to medicalize their symptoms, and create demand for drug therapy and urologist treatment. The social construction of BPH as a progressive age-related disorder and the profit orientation of American medicine account for the elevated prevalence of BPH.

Age Factors↗

PubMed1997

Cell kinetic in epithelium and stroma of benign prostatic hyperplasia.

The induction of benign prostatic hyperplasia (BPH) from normal prostate is obviously associated with a distinct increase in epithelial and stromal proliferation. We have shown previously that the further increase of BPH volume in aging men is not associated with a further increase in proliferation. We studied whether an imbalance between programmed cell death (apoptosis) and cell proliferation may explain continuing growth in aging men. In prostates of 17 men with BPH removed by open prostatectomy proliferating cells were localized immunohistochemically with the Ki-67 antibody. Apoptotic cells were detected with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. Proliferation and apoptotic index was calculated with a computer assisted image analysis system. Mean proliferation index +/- standard deviation in epithelium (0.142 +/- 0.097) and stroma (0.121 +/- 0.082) was nearly identical. Mean apoptotic index in epithelium (0.172 +/- 0.156) was negligibly higher than the corresponding proliferation index. In stroma, however, no apoptotic cells were detectable. Proliferation index and apoptotic index in epithelium and proliferation index in stroma showed no correlation to patient age or prostate volume. In the epithelium of BPH, obviously the cell kinetic is balanced. On the other hand, our results indicate stromal growth due to cell proliferation in the absence of cell death. This may explain the continuous increase of BPH volume in aging men.

Adult↗

PubMed1998

Role of the transition zone for elevating serum prostate-specific antigen in benign prostatic hyperplasia.

BACKGROUND: Patients with benign prostatic hyperplasia (BPH) have a wide range of concentrations of PSA. However, it is not known what factors influence the concentration of serum PSA other than the prostate volume. BPH is composed of an enlarged transition zone (TZ) and other zones (nonTZ). The TZ is thought to play a more important role than the nonTZ in determining the concentration of serum PSA in BPH patients. METHODS: We investigated the individual glandular zone volume, the amount of PSA produced by each zone and the PSA density in each zone in 23 patients with histologically-confirmed BPH. The PSA density in the TZ was calculated by dividing the difference between the serum PSA before and after surgical resection by the specimen weight. We examined the influence of these parameters on the concentration of serum PSA in BPH patients. RESULTS: The serum PSA concentration correlated with the amount of PSA produced by the TZ (r=0.90, P< 0.0 1), but not the nonTZ (r=0.25, P=0.29). The concentration of serum PSA also showed a significant correlation with the TZ volume (r=0.67, P< 0.01) and the PSA density in the TZ (r=0.51, P< 0.05), but not with the PSA density in the nonTZ (r=-0.06, P=0.81). Also, age was inversely correlated with the PSA density in the TZ (r=-0.69, P< 0.01). CONCLUSION: The hypertrophic prostate cell volume (TZ volume) and activity (PSA density in the TZ) significantly correlated with the concentration of serum PSA in BPH patients, and the TZ cell activity decreased inversely with age in these BPH patients.

Age Factors↗

PubMed2006

The natural history of benign prostatic hyperplasia.

The progression of benign prostatic hyperplasia (BPH) can be defined as a deterioration of clinical variables such as lower urinary tract symptoms (LUTS), health-related quality of life and peak flow rate, increased prostate size, or unfavourable outcomes such as acute urinary retention (AUR) and BPH-related surgery. The natural history of BPH is best analysed from longitudinal studies of community-dwelling men. In the Olmsted county study, which followed for 12 years a randomly selected cohort of 2115 men aged 40-79 years, there was an average increase in the International Prostate Symptom Score (IPSS) of 0.18 points per year, ranging from 0.05 for men in their fifties to 0.44 for those in their seventies. There was also a decrease in peak flow rate of 2% per year and a median prostate growth of 1.9% per year. The cumulative incidence of AUR was low (2.7% over 4 years). Information can also be collected from the placebo arms of controlled studies of men with symptomatic BPH, although the strict trial inclusion criteria and indeed the taking of a placebo itself introduce biases which limit the analysis of the natural history of the disease in this way, and its applicability to the general population. Hence, in the Medical Therapy of Prostatic Symptoms study, there is clear evidence that symptom deterioration, defined by a worsening of the IPSS of > or = 4 points, was by far the most prevalent progression event (79.5%), with a cumulative incidence of 14% over a mean follow-up of 4.5 years. As in the longitudinal community-based studies, AUR was rather uncommon (14.8% of overall progression events) with a cumulative incidence of 2%. BPH-related surgery, which was a secondary criterion in the study, was required in 5% of men. Similar conclusions can be drawn from a 2-year placebo-controlled study (ALTESS) assessing the impact of alfuzosin 10 mg once daily on LUTS/BPH progression in 1522 men with symptomatic BPH at high risk of developing AUR. Symptom deterioration was clearly the main progression event, with a cumulative incidence of 16.8%, compared to BPH-related surgery (6.5%) and AUR (2.2%). Thus, there is evidence from longitudinal studies, and to a lesser extent from the placebo arms of large controlled studies, that BPH is a progressive disease. Symptom worsening is by far the most frequently occurring progression event. Identifying those patients at risk of BPH progression is crucial to optimize their management.

Adrenergic alpha-Antagonists↗

PubMed1995

Correlation of transrectal ultrasonographic findings of the prostate with the occurrence of detrusor instability in patients with benign prostatic hyperplasia.

Forty patients with benign prostatic hyperplasia were evaluated with urodynamics and transrectal ultrasonography. Seventeen patients were found to have detrusor instability while the remaining 23 did not. No significant differences were noted during ultrasonography in the estimated prostatic volume, the presumed circle area ratio and the incidence of finding prostatic calcification between these two groups. However, the incidence of detecting intravesical protrusion of the prostate is significantly higher in patients with instability than in patients with stable bladder (53 vs. 13%, p < 0.01). It is therefore postulated that intravesical protrusion may increase afferent impulses from the prostate and alter the stability status of the urinary bladder.

Aged↗

PubMed1991

Pathogenesis of benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia (BPH) remains largely unresolved. Three major theories have evolved over the years, each emphasizing a possible causative mechanism. The first theory, the dihydrotestosterone hypothesis, is based on the failure of BPH to develop in men castrated prior to puberty. The second, the embryonic reawakening theory, assumes a reawakening of the embryonic induction potential of prostatic stroma. The third, or stem cell theory, postulates the development of BPH through an increase in the number of stem cells or through an abnormal increase in clonal expansion of amplifying or transit cells. These mechanisms may act in concert.

Androgens↗

PubMed1991

Symptomatology and diagnosis of benign prostatic hyperplasia.

The symptoms of benign prostatic hyperplasia are well known. Diagnosis rests on digital palpation of the enlarged prostate. Objective parameters are laboratory tests, imaging techniques, endoscopy, and urodynamic investigations. Laboratory tests include urinalysis and serum creatinine measurement. Markers are not reliable and the determination of acid phosphatase and prostate-specific antigen is not recommended routinely for patients with prostatism. Imaging techniques are usually restricted to a complete echographic investigation of the entire urinary tract. Endoscopic manipulations are seldom necessary. Uroflow measurements are customarily performed, but the need for a complete urodynamic investigation is still open to debate.

Humans↗

PubMed1991

Steroid hormones and the pathogenesis of benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia (BPH) is still poorly understood: there is, however, general acceptance that the condition is not premalignant and that it has an etiology distinct from that of cancer. Interest now focuses on the biochemistry of the target prostate cells and the propensity of the gland for uncontrolled growth. Dihydrotestosterone (DHT) is the active intracellular androgen formed from testosterone by 5 alpha-reductase. DHT concentrations appear a little higher in BPH tissue than in normal tissue, and there is no doubt that DHT-receptor complex modulates gene expression. Current studies suggest that DHT is essential but not sufficient for proliferation, and that other regulatory factors, including peptide growth factors, are prerequisite. The growth responsiveness of prostate tissue to androgens may be dependent on the balance between epithelial and stromal tissues, with biologic processes in the epithelium indirectly controlled by androgen-dependent mediators of stromal origin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1994

Review of current treatment of benign prostatic hyperplasia.

The treatment of benign prostatic hyperplasia is changing, with many new modalities being tested: Some are already used routinely, others are still investigational. Surgery, however, is still the principal treatment, producing an 85-90% improvement in symptoms and urodynamics. Stents are being used more frequently, particularly in patients with a high operative risk. Balloon dilation can be performed in small glands; however, the durability of results remains in doubt. Thermotherapy has been found to produce histologic changes in the prostate and may change the urodynamics as well. Finally, drug treatment, which is currently limited to a-blocking agents and 5 a-reductase inhibitors, has proven to be effective symptomatically, with small, but significant changes in urodynamics.

Humans↗

PubMed2003

Development of quantitative detection assays for CYR61 as a new marker for benign prostatic hyperplasia.

Among urological diseases, benign prostatic hyperplasia (BPH) exhibits a high morbidity rate, afflicting approximately 50% of men older than age 50 years. Despite intense research efforts over the past decades, the etiology and mechanisms of BPH progression are only poorly understood. Employing oligonucleotide microarrays, the authors analyzed the gene expression profiles in normal and BPH prostate samples and found that CYR61, an immediate early gene, is markedly overexpressed in BPH. To quantify cellular CYR61 mRNA expression directly, the authors developed an assay using branched-chain DNA (bDNA) technology. A human prostatic epithelial cell line, BRF-55T, derived from a BPH patient, was treated with fetal bovine serum to stimulate gene expression, and then the induction profile of the CYR61 mRNA in these serum-stimulated cells was quantitated using both bDNA and quantitative reverse transcriptase-PCR (RT-PCR). The results obtained with the 2 detection systems were found to be very similar. The bDNA assay was also found to be sensitive and highly reproducible. To the authors' knowledge, this is the first time that identifying CYR61 as a novel marker for BPH and its quantitation has been reported. These detection methods not only may be useful for diagnostic purposes but may also be used to identify suppressors of CYR61 expression for BPH therapy employing high-throughput screening assays.

Animals↗

PubMed1993

Annual costs of benign prostatic hyperplasia in New Zealand.

Benign prostatic hyperplasia (BPH) has been regarded as part of the normal aging process in men and little attention has been focused on the cost of the disease in New Zealand. The purpose of this study was to estimate the direct and indirect costs of treating BPH in both the public and the private sectors in New Zealand. The costs of treatment were estimated from public and private hospital data on admissions for BPH, obtained from the New Zealand Department of Health, medical insurance reimbursement schedules, hospital ward costs at one centre, and urology and general practitioner consultation fees. The length of time spent off work, as a measure of indirect costs, during urological investigations or treatment was estimated from interviews with urologists. The annual 1991 total direct medical costs of treated BPH as primary diagnosis in New Zealand were estimated at $NZ16 million (the average of the end-month mid-point exchange rate for the first quarter of 1992 was $US0.5457 per $NZ1), and the costs of lost production plus loss of leisure time by patients was estimated at $NZ4 million (1992 dollars). Patients with a principal diagnosis of BPH stayed on average 8.9 days in a public hospital and 4.6 days in a private hospital. Based on the above costs, if the average length of stay of public hospital patients could be reduced to that of private hospital patients, then hospital ward costs for BPH could fall by 37% and the total direct medical costs by 21%. The most commonly performed surgical operation for BPH was transurethral prostatectomy (TURP). For operations performed in a public hospital, patients stayed on average 8.5 days, while patients whose operations were performed in private hospitals stayed 4.3 days. The mean age of these public hospital patients was 71 years compared with 67 years for those in private hospitals. A complication rate of 2.02% was recorded for TURP in public hospitals but audits (conducted by the researchers) in both public and private settings indicated that the complication rate was substantially under-recorded.

Aged↗

PubMed1997

Prostatic stents for benign prostatic hyperplasia.

Treatment options for benign prostatic hyperplasia (BPH) have developed rapidly over the past several years. These options include surgical intervention, medical therapy, and minimally invasive modalities such as prostatic stents. Prostatectomy remains the treatment of choice for symptoms that are the result of bladder outflow obstruction, with success rates of 85-90%. Medical therapy with selective alpha-1 antagonists, 5 alpha-reductase inhibitors, LHRH antagonists, antiandrogens, and aromatase inhibitors have increased in popularity and are mainly used to treat patients with mild to moderate prostatic obstruction. Prostatic urethral stents have recently emerged as an alternative treatment for BPH throughout Europe and Asia, but few investigators have used prostatic stents in the United States because of strict regulatory forces and a debate concerning the indications for these devices. The possibility of providing a treatment option for BPH to patients who are frail and elderly, as well as to patients with multiple medical problems, has prompted enthusiasm toward prostatic stents in the urologic community. The focus of this review will be an up-to-date discussion of the types of prostatic stent available, including a review of recent clinical trials involving the use of each available stent.

Equipment Design↗

PubMed2002

Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia.

PURPOSE: For treating benign prostatic hyperplasia (BPH) 5 or 10 mg. terazosin hydrochloride daily has been routinely used in North America and Europe. We investigated the urodynamic effects of 2 mg. terazosin daily on Japanese patients with symptomatic BPH using pressure flow study. MATERIALS AND METHODS: A total of 20 Japanese patients 50 years old or older with symptomatic BPH underwent symptomatic and urodynamic evaluations, including pressure flow study, before and after terazosin treatment. Patients were given 1 mg. terazosin once daily for the first 7 days and they continued to receive 1 mg. terazosin twice daily for the following 3 weeks. RESULTS: At 4 weeks after terazosin treatment the International Prostate Symptom Score, quality of life index and maximum and average flow rates were significantly improved. Pressure flow study demonstrated decreased detrusor pressure at maximum flow, and minimum detrusor pressure during voiding and urethral resistance factor after terazosin treatment. Of the 20 patients 13 (65%) showed improvement in the linear passive urethral resistance relation. There was no significant difference in the maximum W. factor before and after terazosin treatment. CONCLUSIONS: Terazosin treatment, even 2 mg. daily, urodynamically relieved bladder outlet obstruction in Japanese patients with symptomatic BPH without any changes in detrusor contractility.

Adrenergic alpha-Antagonists↗