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PubMed1993

Medical management of benign prostatic hyperplasia: a canine model comparing the in vivo efficacy of alpha-1 adrenergic antagonists in the prostate.

Medical management of benign prostatic hyperplasia (BPH) is an alternative to surgical treatment of this disease. A major target for pharmacologic therapy is the alpha-1 adrenergic receptor, since activation of this receptor by endogenous catecholamines is thought to contribute to outlet obstruction. In the present study, we compared the potency of various alpha-1 adrenergic antagonists against epinephrine-induced contraction of the canine prostate. The drugs tested were dibenzyline, prazosin, terazosin and YM617. The rank order of potency, comparing inhibitory constants (Ki's), was found to be YM617 >> prazosin > terazosin > dibenzyline. This study is the first to compare all of these drugs directly in the prostate in vivo. The rank order of potency of the drugs is similar to the rank order of potency at other alpha-1 receptors. These results demonstrate that 1) our model is useful in confirming activity of drugs at the alpha-1 receptor and 2) the prostate alpha-1 receptor is similar to other alpha-1 receptors. Whether activity at the alpha-1 adrenergic receptor is a sufficient determinant of clinical efficacy of these drugs remains to be determined.

Adrenergic alpha-Antagonists↗
PubMed1993

[Recent advances and trends in the therapies for benign prostatic hyperplasia].

A number of new treatment modalities for benign prostatic hyperplasia (BPH) have been introduced in these days: for example, laser ablation, alpha-adrenergic blocker, antiandrogens, hyperthermia, stenting and balloon dilation. The author basically mentioned the personal experiences in some of these modalities, and gave a general review on their effectiveness and safety. Also pointed out were a variety of problems, important but sometimes ignored, in the evaluation of treatments for BPH, including severity grading of BPH, response criteria of effectiveness, method for proper selection of treatment.

Adrenergic alpha-Antagonists↗
PubMed2001

Benign prostatic hyperplasia. Patient evaluation and relief of obstructive symptoms.

Benign prostatic hyperplasia (BPH) is a common and highly manageable disorder that affects most men at some point after age 50. Although classic BPH symptoms mimic those of other genitourinary conditions, several straightforward tools are available to aid accurate diagnosis. For patients in whom the condition is identified early in its progression, prudent management includes periodic assessment of disease progression, pharmacotherapy, and phytotherapy. Some patients presenting with BPH may require or request surgical intervention and several minimally invasive procedures are available, although outcomes and complication rates vary for each.

Adrenergic alpha-Antagonists↗
PubMed1998

Evaluation of histological structure and its effect on the distribution of alpha1-adrenoceptors in human benign prostatic hyperplasia.

OBJECTIVE: To evaluate the histological structure of benign prostatic hyperplasia (BPH) and its relationship with the density of alpha1-adrenoceptors in smooth muscle. MATERIALS AND METHODS: Specimens from hyperplastic tissues obtained from 14 patients with BPH were evaluated for the density of alpha1-adrenoceptors in smooth muscle using autoradiography, Mallory-Azan staining and computer-assisted image analyses. The binding of [3H] tamsulosin (a selective alpha1-blocker) and the ratio of smooth muscle area was calculated, and the density of alpha1-adrenoceptors per area of smooth muscle determined by dividing the degree of binding by the ratio of smooth muscle to total area. RESULTS: There was a significant difference between the ratio of smooth muscle area in the hyperplastic acinar nodule and the surrounding stroma (P < 0.01). The density of alpha1-adrenoceptor per smooth muscle area was significantly higher in the hyperplastic acinar nodule than in the surrounding stroma (P < 0.05). There was no correlation between prostatic weight and the ratio of smooth muscle area or the density of alpha1-adrenoceptors in each region. CONCLUSION: The distribution of alpha1-adrenoceptors on smooth muscle differed with histological structure; both the histological conformation and the difference in the distribution of alpha1-adrenoceptors could affect urethral obstruction in BPH.

Autoradiography↗
PubMedDate not supplied

Pharmacological treatment of benign prostatic hyperplasia.

Although surgery remains the standard treatment for benign prostatic hyperplasia there has been a rise in the number of available drugs for this condition. The current drug therapies appear to be useful for symptomatic short-term treatment, particularly for those patients unfit or unwilling to undergo surgical intervention. Further evaluation of the long-term effects of these treatments and their role in early disease is required, but drug therapy is likely to play a more important part in the management of this condition in the future.

5-alpha Reductase Inhibitors↗
PubMed2004

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI.

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4 +/- 0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k(ep) and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k(ep) decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.

Animals↗
PubMed2006

Dutasteride: a dual 5-alpha reductase inhibitor for the treatment of symptomatic benign prostatic hyperplasia.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, drug interactions, and dosing recommendations of dutasteride, a 5-alpha reductase inhibitor for benign prostatic hyperplasia (BPH). DATA SOURCES: A MEDLINE search (1966-February 2006) was conducted to extract human research data in the English language on dutasteride. Search terms included benign prostatic hyperplasia, dutasteride, and finasteride. The reference lists of articles identified through this search process, the manufacturer's Web site, and dutasteride prescribing information were also examined. STUDY SELECTION AND DATA EXTRACTION: All published studies and clinical data from the manufacturer were included, with emphasis placed on randomized, controlled trials. DATA SYNTHESIS: Dutasteride is approved for the treatment of symptomatic BPH in men with an enlarged prostate to improve urinary symptoms, reduce the risk of acute urinary retention, and reduce the need for BPH-related surgical interventions. Compared with placebo, dutasteride has been shown to significantly improve BPH symptoms, reduce the incidence of acute urinary retention and BPH-related surgery, and improve BPH-related quality of life. Few published data exist comparing dutasteride with finasteride. The most common adverse effects of dutasteride include ear, nose, and throat infection; malaise; headache; dizziness; and musculoskeletal pain. CONCLUSIONS: Clinical trials, sponsored primarily by the manufacturer, have shown dutasteride to be an effective treatment of BPH compared with placebo and to likely possess efficacy similar to that of finasteride. Further studies are needed to gain a more clear understanding of any clinically significant differences between dutasteride and finasteride.

Azasteroids↗
PubMed1984

Testicular androgen and estrogen secretion and benign prostatic hyperplasia in the beagle.

The natural history of benign prostatic hyperplasia (BPH) in the dog is characterized by a slow progression through two phases. The early phase of the disease process is characterized by glandular hyperplasia and occurs as early as 2.5 yr of age. The late phase of the disease is characterized by cystic hyperplasia and occurs after 4 yr. The results of the present study are the first to compare Leydig cell structure and steroidogenic function in dogs with BPH with those in age-matched controls. It was discovered that glandular BPH can occur in young dogs (2.5 yr) in which Leydig cell mass and ultrastructure and maximally stimulated androgen secretion are indistinguishable from those in age-matched controls. These results support the concept that the early phase of BPH (glandular hyperplasia) is not related temporally to some defect in the Leydig cell. In contrast, the late phase of BPH (cystic hyperplasia) in beagles 6 yr of age is associated with diminished smooth endoplasmic reticulum in the Leydig cell and with diminished production of androgens by perfused testes in vitro. During the course of these studies, we discovered that the testes of young beagles with BPH, but not age-matched controls or old beagles with BPH, secrete an unidentified molecule (putative estrogen). This molecule was characterized partially in that it is extractable from testicular venous effluent with diethyl ether, elutes in a discrete fraction in several different high performance liquid chromatographic systems, reacts with an antibody that recognizes 17 beta-estradiol, estrone, and estriol, and competes with 17 beta-[3H]estradiol for the rat uterine estrogen receptor. Based on the elution volume from high performance liquid chromatography, the unknown molecule (putative estrogen) is not estriol, estradiol, or estrone.

Androgens↗
PubMed1995

Interstitial laser therapy outcomes in benign prostatic hyperplasia.

Two hundred thirty-nine patients with benign prostatic hyperplasia (BPH) were treated using interstitial laser coagulation (ILC or LITT; laser-induced interstitial thermotherapy), and the long-term results were determined. In this minimally invasive procedure, special laser light guides were inserted into the adenoma tissue in order to achieve primary large-volume coagulation necrosis and secondary shrinking, leaving the urethra intact. The AUA Symptom Scores improved markedly, from an average of 25 pretreatment to an average of 6 at 1 year. Peak urine flow rates improved commensurably, from 8 mL/sec pretreatment to 18 mL/sec at 1 year. Postoperative irritative symptoms occurred occasionally, affecting only 12% of patients. Significant complications were rare, with 4% of patients suffering strictures and 7% retrograde ejaculation. No patients suffered impotence or incontinence. Only 9.6% of patients required retreatment for BPH during 12 months of follow-up. Twelve patients were treated with subsequent transurethral laser incision of the bladder neck in order to shorten the time required for improvement of voiding function.

Aged↗
PubMed1997

Genetic variations in human benign prostatic hyperplasia detected by restriction landmark genomic scanning.

Alterations in the genomic DNAs of benign prostatic hyperplasias were examined using restriction landmark genomic scanning. This methodology allows the visual comparison of a large number of loci as spots within a gel that has been electrophoresed in 2 dimensions. Within each of the 16 hyperplasias examined, we found 2 to 10 spots with altered intensities, as compared to equivalent spots from normal prostate, but could detect few common spot profiles for any hyperplasia samples. These data conflict with data from previous studies and suggest that there may be no consistent genetic changes in the pathogenesis of some forms of human benign prostatic hyperplasia.

Aged↗
PubMed1991

[Transrectal hyperthermia for benign prostatic hyperplasia].

Transrectal hyperthermia was performed on 30 patients with benign prostatic hyperplasia twice a week for a total of ten times with the temperature of the prostatic tissue set at 43.0 degrees C. In our in vitro experiment using an agar phantom, the highest temperature was observed at approx. 1.5 cm from the point where the 915-MHz microwave was generated. Our histopathological study of the prostatic tissue, resected at open surgery after three days of hyperthermia, indicated that the effect of hyperthermia first occurred in the interstitial tissues, and then extended to the epithelial cells. Subjective symptoms and objective findings were evaluated. In almost all cases, improvement was observed in subjective symptoms after completion of the treatment. The residual urine volume improved significantly. Also, significant improvement was observed in our urodynamics study. In 16 out of 30 cases (53%), both subjective symptoms and objective findings were still improved after six months.

Aged↗
PubMed1997

[Qualitative grading of detrusor contractility in benign prostatic hyperplasia patients].

To grade qualitatively detrusor contractility in benign prostatic hyperplasia (BPH), we studied 120 BPH patients aged from 58 to 89 years. The pressure-flow studies were performed. The passive urethral resistance relation (PURR) and Schäfer diagram were used to analyse the results. The detrusor contractility was divided into 4 classes: very weak (VW), weak (W), normal (N), and strong (ST). The types of pressure-flow were high pressure--low flow (HP-LF), high pressure--high flow (HP-HF), low pressure--low flow (LP-LF) and low pressure--high flow (LP-HF) type. The results showed that the incidence of VW, W, N and ST class was 12.5%, 26.7%, 47.5% and 13.3% respectively; the incidence of HP-LF, HP-HF and LP-LF type was 55%, 1.7% and 43.3% respectively. The weak detrusor strength could become powerful by the surgery treatment of bladder outflow obstruction (BOO) and the function training of detrusor. The detrusor strength class of a BPH patient was improved from W before surgery to N after surgery in our studies. The principles of the fluid dynamics and urodynamic and the clinical application of the qualitative grading of detrusor contractility were discussed.

Aged↗
PubMed1993

Follow-up of a cohort of men with untreated benign prostatic hyperplasia.

A cohort of 266 men with untreated benign prostatic hyperplasia (BPH) identified in a community-based survey were followed for a period of 1 year. Although the overall prevalence of urinary symptoms increased during the year, substantial within-subject variation in urinary symptomatology occurred, with up to a quarter of men reporting urgency and dribbling to have improved whilst one third of men reported other urinary symptoms to have deteriorated. Levels of bothersomeness caused by urinary symptoms did not show much change during the period of follow-up. An overall increase of 19% in urinary peak flow which was also consistent across all age groups was present at 1 year compared with baseline, even after adjusting for increased urinary void volume. A slow progression in the extent to which interference with selected activities of daily living by urinary dysfunction occurred. This was greater in men of working age (40-64 years), compared with men of retirement age (65-79 years). A longer period of observation is required in order to determine the extent to which a consistent pattern of urinary symptomatology exists in untreated BPH, as well as whether interference with daily living activities continues to progress over time.

Activities of Daily Living↗
PubMed1996

5 alpha-reductase expression by prostate cancer cell lines and benign prostatic hyperplasia in vitro.

5 alpha-reductase (5 alpha R) activity in two human prostate cancer cell lines was compared to that in benign prostatic hyperplasia (BPH) tissue and COS cells transfected with and expressing the human genes for 5 alpha-reductase type 1 (5 alpha R1) and type 2 (5 alpha R2). Comparisons were based on pH profiles and sensitivities to selective inhibitors of 5 alpha-reductase In the cancer lines, activity was greatest over the pH range 7-8, compared to a sharp peak of activity between pH 5-5.5 in BPH tissue and COS cells expressing 5 alpha R2. Finasteride and SKF105,657 were potent inhibitors of 5 alpha-reductase activity in BPH tissue and COS cells expressing 5 alpha R2, but weak inhibitors in the cancer lines and in COS cells expressing 5 alpha R1. In contrast, UK117,026 was a more potent inhibitor of 5 alpha-reductase activity in the prostate cancer cell lines and in COS cells expressing 5 alpha R1. These data indicate that human prostate cancer cell lines express 5 alpha-reductase activity similar to that in COS cells transfected with 5 alpha R1, but different from that in BPH tissue. This may be a consequence of in vitro culture. Alternatively, it may reflect a change occurring as a result of neoplastic transformation in which case it will be important to select appropriate inhibitors in the clinic.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis.

BACKGROUND: Despite the high prevalence of benign prostatic hyperplasia (BPH) in the aging male, little is known regarding the etiology of this disease. A better understanding of the molecular etiology of BPH would be facilitated by a comprehensive analysis of gene expression patterns that are characteristic of benign growth in the prostate gland. Since genes differentially expressed between BPH and normal prostate tissues are likely to reflect underlying pathogenic mechanisms involved in the development of BPH, we performed comparative gene expression analysis using cDNA microarray technology to identify candidate genes associated with BPH. METHODS: Total RNA was extracted from a set of 9 BPH specimens from men with extensive hyperplasia and a set of 12 histologically normal prostate tissues excised from radical prostatectomy specimens. Each of these 21 RNA samples was labeled with Cy3 in a reverse transcription reaction and cohybridized with a Cy5 labeled common reference sample to a cDNA microarray containing 6,500 human genes. Normalized fluorescent intensity ratios from each hybridization experiment were extracted to represent the relative mRNA abundance for each gene in each sample. Weighted gene and random permutation analyses were performed to generate a subset of genes with statistically significant differences in expression between BPH and normal prostate tissues. Semi-quantitative PCR analysis was performed to validate differential expression. RESULTS: A subset of 76 genes involved in a wide range of cellular functions was identified to be differentially expressed between BPH and normal prostate tissues. Semi-quantitative PCR was performed on 10 genes and 8 were validated. Genes consistently upregulated in BPH when compared to normal prostate tissues included: a restricted set of growth factors and their binding proteins (e.g. IGF-1 and -2, TGF-beta3, BMP5, latent TGF-beta binding protein 1 and -2); hydrolases, proteases, and protease inhibitors (e.g. neuropathy target esterase, MMP2, alpha-2-macroglobulin); stress response enzymes (e.g. COX2, GSTM5); and extracellular matrix molecules (e.g. laminin alpha 4 and beta 1, chondroitin sulfate proteoglycan 2, lumican). Genes consistently expressing less mRNA in BPH than in normal prostate tissues were less commonly observed and included the transcription factor KLF4, thrombospondin 4, nitric oxide synthase 2A, transglutaminase 3, and gastrin releasing peptide. CONCLUSIONS: We identified a diverse set of genes that are potentially related to benign prostatic hyperplasia, including genes both previously implicated in BPH pathogenesis as well as others not previously linked to this disease. Further targeted validation and investigations of these genes at the DNA, mRNA, and protein levels are warranted to determine the clinical relevance and possible therapeutic utility of these genes.

Adult↗
PubMed1993

Transurethral radio frequency thermotherapy for symptomatic benign prostatic hyperplasia.

A total of 90 patients with symptomatic benign prostatic hyperplasia (BPH) were treated with transurethral radio frequency thermotherapy. The treatment consisted of one 180-min session at 48 degrees C. All patients were evaluated before treatment and 80 (10 with urinary retention) were reevaluated at 3 months for follow-up. The analysis of the results of this group of patients is the subject of this presentation. Results were defined according to the variation in three parameters: nocturia, symptomatic score (Madsen) and urinary peak flow. Improvement (defined as a change of 50% or more in any of the three measured parameters) was found in 78% of the patients. Improvement in all of the above-mentioned parameters was found in 34.08% of the patients. In 29.82% of the patients improvement was found in two parameters and 14.02% of the patients improvement was found in one parameter and none in 21.30%. The percent variations in each parameter before and after treatment were: nocturia and symptom score decreased by 33.33% and 50%, respectively, and urinary peak flow increased by 33.65%. Age was the most important predictive factor. Of the patients under 65 years of age, 85% showed very good and good results. In comparison, only 42% of the patients over 65 years showed similar results. Immediate complications were 4 cases of acute urinary retention (5.71%) and 4 cases of urinary infection (5.71%). Transurethral radio frequency thermotherapy, having a low toxicity and complication rate, has comparable results to other nonsurgical treatment modalities. It is a viable alternative treatment for symptomatic BPH.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Comparative effects of alfuzosin versus Serenoa repens in the treatment of symptomatic benign prostatic hyperplasia.

OBJECTIVES: Sixty-three patients suffering from benign prostatic hyperplasia (BPH) entered a double-blind, comparative, parallel-groups study lasting 3 weeks, carried out to compare the efficacy and safety of alfuzosin 2.5 mg tid (n = 32) vs serenoa repens 160 mg bid (n = 31) in BPH. METHODS: Efficacy was assessed both on clinical symptoms (Boyarsky's scale, visual analogue scale, clinical global impression), urinary flow rates (uroflowmetry) and residual urinary volume (transabdominal ultrasound). Events and reported signs were recorded throughout the entire study. RESULTS: Statistically significant and clinically relevant differences were found between the two treatments in favour of alfuzosin for Boyarsky's total score (decrease from 9.6 +/- 3.0 to 5.9 +/- 3.0, 38.8% for alfuzosin and from 9.3 +/- 2.5 to 6.8 +/- 2.8, 26.9% for serenoa repens) and obstructive score (decrease from 4.9 +/- 2.1 to 3.0 +/- 1.9, 37.8% for alfuzosin; from 4.4 +/- 1.7 to 3.4 +/- 1.8, 23.1% for Serenoa repens; p = 0.01 for both). Clinically relevant differences were found between the two treatments for visual analogue scale and overall clinical impression at the end of the study. Furthermore, the increase in quality of micturition was better with alfuzosin. The proportion of responders (increase on day 21 in peak flow rate of at least 25% relative to the baseline values) was in favour of alfuzosin (71.8% and 48.4% for alfuzosin and Serenoa repens, respectively; p = 0.057). Both treatments were well tolerated. No patient treated with alfuzosin complained of any adverse event at any time during the study. One patient in the Serenoa group complained of mild pruritus which cleared spontaneously. Systolic, diastolic blood pressure and heart rate did not show any clinically relevant change during treatment with alfuzosin. CONCLUSIONS: The findings confirm the efficacy and safety of alfuzosin in symptomatic BPH and indicate the superiority of alfuzosin over Serenoa repens in the treatment of urinary signs and symptoms of BPH.

Adrenergic alpha-Antagonists↗
PubMed1996

Correlation between the International Prostatic Symptom Score and a pressure-flow study in the evaluation of symptomatic benign prostatic hyperplasia.

PURPOSE: We examined the relationship between the International Prostatic Symptom Score (I-PSS) and the occurrence of bladder outlet obstruction caused by benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: The American Urological Association developed a questionnaire to quantify the severity of symptoms resulting from BPH. A further question relating the impact of BPH to the quality of life was subsequently added. This questionnaire has been adopted by the World Health Organization and is known as the I-PSS. There are 4 questions related to obstructive symptoms and 3 related to irritative symptoms. Scores of 0 to 7, 8 to 19 and 20 to 35 represent mild, moderate and severe symptoms, respectively. During an 18-month interval the I-PSS questionnaire was administered to 258 patients 50 to 81 years old (mean age 63 years) with BPH. A pressure-flow study was used to determine the presence of bladder outlet obstruction in 227 patients. Based on the scores, the patients were divided into 31 with mild, 116 with moderate and 111 with severe obstruction. The pressure-flow study was not conducted on patients with a mild symptom score. RESULTS: Of the patients with a severe symptom score 92 (82.9%) had bladder outlet obstruction, compared to 62 (53.4%) with a moderate symptom score. Statistical analysis (Pearson chi-square test) showed that there was a significant positive correlation between the symptoms and the presence of bladder outlet obstruction. Thus, when the I-PSS was greater than 28, the probability of bladder outlet obstruction was more than 0.91. Stratification of the results according to the obstructive (0 to 20) and irritative (0 to 15) symptoms of the I-PSS yielded a significant positive correlation between obstructive symptoms and the presence of bladder outlet obstruction. Thus, when the obstructive symptom score was greater than 15, the probability of bladder outlet obstruction was greater than 0.91. CONCLUSIONS: When the total I-PSS is greater than 28 or the obstructive symptom score is greater than 15, a pressure-flow study must be avoided.

Case-Control Studies↗