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PubMed1996

Selective alpha 1-adrenoceptor antagonists in benign prostatic hyperplasia: rationale and clinical experience.

Symptomatic benign prostatic hyperplasia (BPH) is a common condition in older men and has a significant impact on their daily lives. Transurethral resection of the prostate is currently the most effective remedy for BPH but is not suitable for all patients. There is now clear evidence for the efficacy of alpha-adrenoceptor antagonists, particularly selective alpha 1-adrenoceptor antagonists, in the treatment of BPH. Inhibition of alpha-adrenoceptors significantly increases urinary flow and improves symptoms in BPH. alpha 1-Adrenoceptor antagonists have a place in the management of BPH patients with mild to moderate disease, who are bothered by their symptoms, or for those awaiting or wishing to delay surgery. Treatment with selective alpha 1-adrenoceptor antagonists is generally better tolerated than nonselective-alpha-blockers. alpha 1-Selective adrenoceptor antagonists with a long half-life such as terazosin, doxazosin and tamsulosin, as a modified release formulation, permit once-daily dosing. Tamsulosin is the first subtype-specific (cloned alpha 1c/functional alpha 1A) adrenoceptor antagonist in clinical practice. Initial reports suggest that it gives no clinically relevant lowering of blood pressure and that its (vasodilatory) side effect profile is minimal. The scientific rationale behind the therapeutic use of alpha-adrenergic blockade as treatment for BPH and the trials data relating to the various agents which are available for clinical use are reviewed in the context of the contemporary literature.

Adrenergic alpha-Antagonists↗
PubMed1998

A risk-benefit assessment of treatment with finasteride in benign prostatic hyperplasia.

As an androgen target organ, the prostate gland has the almost unique characteristic of being less sensitive to testosterone than to its metabolite 5 alpha-dihydrotestosterone (5 alpha-DHT). The conversion of testosterone to 5 alpha-DHT is induced by the enzyme 5 alpha-reductase. By blocking the activity of 5 alpha-reductase, the androgenic stimulation of the prostate gland can be significantly reduced. The first drug with such capacity to be introduced on the market was finasteride. Following the administration of this drug to men, serum 5 alpha-DHT levels were reduced by approximately 80%. Large phase III trials have demonstrated the efficacy of finasteride in treating benign prostatic hyperplasia (BPH). While in some patients the drug was poorly effective, other patients showed significant improvements. The mean reduction in size of the prostate gland was 20 to 25% after 6 months of therapy, and this effect was maintained as long as the patient was on the drug, at least up to the end of a 6-year follow-up period. Prostatic symptom scores were improved by a mean of 30%, while urinary flow was only improved by a mean of 1.5 ml/sec (15%). In a recent double-blind, placebo-controlled study comparing the alpha-blocker terazosin with finasteride, significant improvement was demonstrated for the alpha-blocker, while finasteride produced little improvement overall and was not significantly more effective than placebo in treating moderately symptomatic BPH. However, a subanalysis of this study showed that while finasteride was poorly effective in patients with small prostate glands, a significant improvement was apparent in those with glands larger than 40 ml. There is some evidence that early intervention with finasteride can reduce the number of surgical procedures that are required, at least over a 2-year period. Finasteride is very well tolerated. However, since 5 alpha-DHT potentiates erectile capacity, a 3 to 4% incidence of impotence has been reported, as well as a decreased ejaculatory volume. Gynaecomastia has been noted in a few patients (0.4%). In conclusion, finasteride appears to be a very well tolerated drug to treat outflow obstruction in patients with moderately symptomatic BPH caused by large prostate glands.

Enzyme Inhibitors↗
PubMed1998

Transurethral needle ablation of the prostate: an alternative minimally invasive therapeutic concept in the treatment of benign prostate hyperplasia.

Alternative minimally invasive methods treating benign prostate hyperplasia (BPH) have become more and more important. Transurethral needle ablation (TUNATM) has been demonstrated to be effective in both canine and the human prostate. The goal of our study was to prove the safety, feasibility and tolerance of this new procedure. In this prospective nonrandomized study, 33 patients underwent TUNATM-treatment. One, 3 and 6 months postoperatively, follow-up examinations were carried out assessing urodynamic parameters such as urinary flow rates, residual urine levels, and IPSS-scores. During the last visit additional cystomanometry and urethrocystoscopy were done. Six months postoperatively IPSS-score and residual urine volumes were decreased by 50% (range: 1-72%) and 75% (range: 12-97%). Improvement in maximum flow rate was 63% (range: 5-125%). No serious postoperative complications occurred. After a short 'learning period' most of the treatments where performed as an out-patient-procedure so the patients could leave the hospital without the need for indwelling catheters. The TUNATM appears to be a minimally invasive and safe out-patient procedure for the treatment of selected cases of BPH.

Aged↗
PubMed1993

Prostatic UroLume Wallstent for benign prostatic hyperplasia patients at poor operative risk: clinical, uroflowmetric and ultrasonographic patterns.

The prostatic UroLume Wallstent was positioned in 30 poor operative risk patients with bladder outlet obstruction due to benign prostatic hyperplasia. Preoperatively, 12 patients (40%) could still void spontaneously (group 1), while 18 (60%) had an indwelling catheter (group 2). Preoperative and postoperative assessment included scoring of subjective symptoms, physical examination, uroflowmetry with maximum flow nomogram, transrectal ultrasonography of the prostate, determination of residual urine volume and cystourethroscopy. All but 1 patient could void spontaneously after insertion of the stent. In group 1 preoperative and 1-year followup mean (plus or minus standard error) peak flow rates were 8.0 +/- 0.7 ml. per second and 15.8 +/- 1.8 ml. per second, respectively (p < 0.01), the mean residual urine volumes were 127 +/- 27 ml. and 38 +/- 11 ml. (p < 0.05), respectively, and the mean maximum flow nomograms (plus or minus standard deviation) were -2.6 +/- 0.1 and -1.4 +/- 0.4, respectively. In group 2 the 1-year followup mean peak flow rate, residual urine volume and maximum flow nomogram were 13.2 +/- 0.8 ml. per second (standard error), 32 +/- 14 ml. (standard error) and -1.5 +/- 0.1 (standard deviation), respectively. According to the maximum flow nomogram values all patients were nonobstructed postoperatively. At 1 year the stent was completely covered by prostatic epithelium in 90% of the patients, while in the remainder it was still partially visible at urethroscopy. Transrectal ultrasonography had an essential role in patient followup by accurately assessing the position of the stent. Placement of this prostatic stent is safe and effective for selected benign prostatic hyperplasia patients who cannot undergo surgical treatment due to poor operative risk.

Aged↗
PubMed1997

Latin American study on patient acceptance of the International Prostate Symptom Score (IPSS) in the evaluation of symptomatic benign prostatic hyperplasia.

OBJECTIVES: To determine the acceptance of the self-administered International Prostate Symptom Score (IPSS) by people of differing educational levels in two different countries. METHODS: The questionnaire adopted by the World Health Organization and known as the IPSS attempts to measure the severity of lower urinary tract symptoms in men with benign prostatic hyperplasia. An international study was performed in Brazil and Argentina and included 768 patients. The IPSS was self-administered and used to evaluate and quantify the clinical symptoms resulting from benign prostatic hyperplasia. The patients were asked not to answer any questions that they did not clearly understand or about which they were unsure of the information they should give. The patients were assessed into two subgroups according to their level of education. The Brazilian group consisted of 458 men in which subgroup 1 was composed of 244 (53%) men who had an elementary school education, whereas subgroup 2 consisted of 214 (47%) men who had a higher education level, including a university degree. The Argentinian group consisted of 310 patients, 158 (51%) of whom had an elementary school education, whereas the remaining 152 (49%) had received higher education, including a university degree. RESULTS: A total of 77 men (16.8%), 35 (45.5%) from subgroup 1 and 42 (54.5%) from subgroup 2, failed to complete the questionnaire. The difference between the two subgroups was not significant. A total of 189 questions were not answered. There was no significant difference among the three questions most frequently unanswered by each subgroup. A total of 40 (12.9%) men filled out the questionnaire incompletely, 31 (77.5%) in the lower-education subgroup and 9 (22.5%) in the higher-education subgroup. An incomplete questionnaire was more frequent among the patients with lower education (P < 0.01). CONCLUSIONS: In spite of the cultural variations, there was no significant difference in the number of patients unable to answer the questionnaire in the two countries.

Aged↗
PubMed1996

Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate.

1. We have previously shown that among alpha 1-adrenoceptor antagonists used or investigated for the treatment of benign prostatic hyperplasia, tamsulosin discriminates alpha 1-adrenoceptor subtypes in rat tissues whereas alfuzosin and naftopidil do not. We now expand these studies to additional drugs (doxazosin, terazosin) being used and/or investigated for this purpose, and have evaluated all of these drugs at cloned subtypes and in human prostate. 2. Competition binding studies were performed with [3H]-prazosin in membrane samples from rat spleen, kidney and cerebral cortex and human prostate and with cloned alpha 1-adrenoceptors expressed in COS cells. Doxazosin and terazosin did not discriminate alpha 1-adrenoceptor subtypes in rat kidney and cerebral cortex. In contrast, the subtypes present in the tissues were well discriminated by the alpha 1A-adrenoceptor-selective reference drug WB 4101. 3. Alfuzosin, doxazosin, naftopidil and terazosin did not discriminate cloned alpha 1-adrenoceptor subtypes transiently expressed in COS cells whereas tamsulosin and WB 4101 did. 4. In human prostate, alfuzosin, doxazosin, naftopidil and terazosin did not discriminate the alpha 1-adrenoceptor subtypes present in this tissue whereas tamsulosin and the alpha 1A-adrenoceptor-selective reference drugs WB 4101, phentolamine and 5-methylurapidil did. Based on data with the alpha 1A-adrenoceptor-selective drugs, human prostate contains alpha 1A- and alpha 1B-adrenoceptors in an approximate 70:30% ratio. 5. We conclude that tamsulosin, in common with WB 4101, but in contrast to alfuzosin, doxazosin, naftopidil, and terazosin is selective for alpha 1A-adrenoceptors which appear to dominate in the human prostate; the therapeutic relevance of this selectivity remains to be assessed in clinical studies.

Adrenergic alpha-Antagonists↗
PubMed1990

[Clinical evaluation of isometric detrusor pressure in patients with benign prostatic hyperplasia].

The subjects chosen for this investigation were 88 patients with benign prostatic hyperplasia who proved not to have neurogenic bladder and 6 male volunteers without lower urinary tract disorders. In addition to the conventional preoperative urodynamic studies, isometric detrusor pressure was measured by the technique with balloon occlusion at the bladder neck. Although all 88 patients had undergone either transurethral resection of the prostate or subcapsular prostatectomy and routine postoperative examinations revealed sufficient canal formation in the prostatic urethra, in 23 patients (26.1%) a significant amount of residual urine was still observed and/or maximum urinary flow rate was considerably low. A retrospective analysis of the data from this study suggested that maximum isometric detrusor pressure is a useful parameter for the prediction whether or not micturition is improved after the removal of organic lower urinary tract obstruction, especially in cases with low detrusor pressure during urination. Furthermore, measurement of the maximum isometric detrusor pressure might be helpful in making the diagnosis of the clinical stage of benign prostatic hyperplasia, since several different stages could be defined by the value of maximum detrusor pressure during urination and maximum isometric detrusor pressure.

Adult↗
PubMed1997

Transurethral balloon laser thermotherapy for urinary retention in patients with benign prostatic hyperplasia who are at high surgical risk.

BACKGROUND: Twelve patients with benign prostatic hyperplasia and urinary retention, who were considered to be poor candidates for prostatectomy, were treated by transurethral balloon laser thermotherapy (TUBAL-T). The mean patient age was 78.9 years (range, 66 to 93 years) and the mean duration of bladder catheterization was 11 weeks (range, 2 to 48 weeks). METHODS: Irradiation into the prostatic tissue was done through 360 degrees with a neodymium: yttrium aluminum garnet (Nd:YAG) laser balloon placed in the prostatic urethra, with pain relief provided by using local topical anesthesia. The total laser dose was from 45,000 to 123,376 J, with an average of 73,089 J. The irradiation time was from 40 to 54 minutes, with an average of 45.2 minutes. RESULTS: Spontaneous voiding became possible in all patients at a mean of 2.8 days (range, 1 to 7 days) after irradiation. The mean catheter-free period was 20.5 months (range, 6 to 34 months), with the longest being 34 months. The international prostatic symptom scores, quality-of-life scores, and peak uroflow rates showed substantial improvement after laser thermotherapy. To date, long-term resumption of spontaneous voiding was successfully achieved in 9 of 12 cases (75%). CONCLUSION: TUBAL-T is safe and effective alternative for treatment of urinary retention in patients with benign prostatic hyperplasia who are considered to be at high surgical risk.

Aged↗
PubMed2006

Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia.

Alpha1-receptor blockers have become first-line therapy for the medical management of lower urinary tract symptoms associated with benign prostatic hyperplasia. However, adverse effects such as cardiovascular intolerance can limit their use. This article focuses on alfuzosin, a clinically uroselective, alpha1-adrenergic antagonist that is available as a novel once-daily formulation that does not require dose titration. Alfuzosin is less vasoactive than other non-subtype selective alpha1-receptor blockers. In addition to effects on lower urinary tract symptoms, it is also used as an adjunct to urethral catheterisation in patients with acute urinary retention related to benign prostatic hyperplasia, and can improve sexual function and health-related quality of life in benign prostatic hyperplasia sufferers.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Symptoms and quality of life versus age, prostate volume, and urodynamic parameters in 565 strictly selected men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVES: To investigate the associations of symptoms and quality of life with age, prostate volume, and urodynamic parameters in a large group of strictly selected men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS: The 565 consecutive men met all the criteria of the International Consensus Committee on benign prostatic hyperplasia and voided more than 150 mL during uroflowmetry. The residual volumes and prostate sizes were estimated. The International Prostate Symptom Score (IPSS) and quality-of-life score were collected and urodynamic evaluations performed. RESULTS: The prostate volume and obstruction grade were not, but low detrusor contractility and low bladder capacity were, significantly associated with symptoms. Except for nocturia, older men presented with lower voiding scores on the IPSS. The presence of a residual urine volume hardly influenced patients' symptoms and quality of life. Men with an unstable bladder scored higher on frequency, urgency, and nocturia on the IPSS, but the symptom index and quality-of-life score were not affected by the presence of an unstable bladder. Because of the high variability and subjective interpretation of symptoms and because urodynamic parameters may have opposite implications than symptoms and vice versa, associations were still weak. CONCLUSIONS: Except for nocturia, older men had lower voiding scores on the IPSS. Prostate volume and obstruction grade were not, but low detrusor contractility and low capacities were, associated with the symptom index. The presence of an unstable bladder and/or residual volume was hardly associated with the symptom index or quality-of-life score. Although we used a large group of strictly selected men, the associations were still weak.

Age Factors↗
PubMed1999

A randomized double-blind study assessing 4 versus 8 mg. doxazosin for benign prostatic hyperplasia.

PURPOSE: We compare the efficacy of 4 versus 8 mg. doxazosin for benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 82 patients with benign prostatic hyperplasia successfully treated with 4 mg. doxazosin were randomized in a double-blind fashion to take 4 or 8 mg. Patients were evaluated with American Urological Association (AUA) symptom score, Boyarsky score, uroflowmetry and side effect profile before, and 1 and 3 months following randomization. RESULTS: Of the patients 42 and 40 were randomized to receive 4 and 8 mg. doxazosin, respectively. Both groups were similar with respect to patient age, baseline Boyarsky and AUA symptom scores, and baseline maximum urinary flow rate. At 3 months mean improvement from baseline plus or minus standard deviation in Boyarsky score was 0.6 +/- 6.5 and 4.9 +/- 6.6 in the 4 and 8 mg. groups (p <0.05), respectively, mean improvement in AUA symptom score was 1.6 +/- 5.3 and 5.3 +/- 8.0 (p <0.05), and mean maximum flow rate difference was -0.6 +/- 6.4 and +1.4 +/- 7.9 (p >0.05). Of the patients 7 and 8 in the 4 and 8 mg. groups dropped out of the study, and there were no statistical differences in side effects between dosages. CONCLUSIONS: A dose of 8 mg. doxazosin was more efficacious than 4 mg. and the side effects associated with both dosages appeared to be similar. The 8 mg. dose should be tried in patients who have not achieved an adequate therapeutic response to 4 mg. and are tolerating the medication. Consideration should be given to increasing the dosage to 8 mg. in patients who are clinically improved at lower dosages.

Adrenergic alpha-Antagonists↗
PubMed1979

Role of the pituitary gland in experimental hormonal induction and prevention of benign prostatic hyperplasia in the dog.

The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.

Androstane-3,17-diol↗
PubMed1996

Sabal serrulata extract (Strogen forte) in the treatment of symptomatic benign prostatic hyperplasia.

The effectivity of Sabal serrulata extract in the treatment of symptomatic prostatic hyperplasia was scrutinized in 38 patients. In the course of the 12-month treatment followed up by examinations, the subjective complaints abated in almost 3/4 of the cases. Adverse effects were not encountered. According to uroflowmetry, the average peak flow rate increased from 10.36 ml/s to 14.44 ml/s (p < 0.0001), while the average middle stream increased from 6.02 ml/s to 7.45 ml/s (p < 0.001). Urinary retention decreased or disappeared in more than 9/10 of the cases. The average amount of the residue decreased by 47 ml (p < 0.001). The average volume of the prostate was reduced by 10.6% (p < 0.02). On the basis of the favourable results, Sabal serrulata extract is recommended in the treatment of prostatic hyperplasia producing symptoms of mild and moderate severity.

Aged↗
PubMed1988

Benign prostatic hyperplasia. Universal problem among aging men.

Benign prostatic hyperplasia (BPH) is a nonmalignant, age-related condition that affects most men who enjoy a long life. The diagnosis of BPH is generally straightforward and easily established. At the present time, transurethral resection of the prostate is considered the best mode of therapy for symptomatic BPH requiring active intervention. However, since people are likely to avoid surgery when provided a reasonable alternative, it is likely that pharmacologic treatments will be tried with increasing frequency.

Adult↗
PubMed1995

Autoantibodies to prostate specific antigen in patients with benign prostatic hyperplasia.

PURPOSE: We tested for a possible autoimmune process in benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Titers of IgG antibodies to prostate specific antigen (PSA) were measured in the sera of 85 BPH patients, 20 controls and 17 chronic prostatitis patients by enzyme-linked immunosorbent assay. RESULTS: The mean anti-PSA titers in the BPH group were significantly higher than in the controls and prostatitis group (p < 0.0005). Accordingly, 59% of BPH patients could be defined as responders to PSA compared to none among the controls (p < 0.0005). CONCLUSIONS: Circulating autoantibodies to PSA were shown to exist in the sera of BPH patients. This observation suggests that autoimmune processes may have a role in BPH.

Adult↗
PubMed2005

Resistance index in benign prostatic hyperplasia using power Doppler imaging and clinical outcomes after transurethral vaporization of the prostate.

BACKGROUND: Using power Doppler ultrasonography (PDUS), we investigate the change of resistance index (RI) before and after transurethral vaporization of the prostate (TUVP) in benign prostatic hyperplasia (BPH) patients. METHODS: In all, 49 patients underwent transrectal PDUS before receiving TUVP, three were excluded because of cancer and three could not be followed up. The remaining 43 were enrolled in the present study. Patients were assessed before and 1, 3 and 6 months after surgery, giving a mean duration of follow-up of 9.1 months. International prostate symptom scores (IPSS), quality of life (QOL) scores, postvoiding residual urine volumes (PVR) and maximum urinary flow rates (Qmax) were evaluated and total prostatic volume (TPV) and RI were measured using PDUS. RESULTS: Resistance index ranged from 0.64 to 0.91. The postoperative parameters except for RI, such as TPV, PVR, IPSS and QOL scores improved significantly at the follow-up assessment after surgery. The elevated RI decreased significantly 1, 3 and 6 months after the treatment. Resistance index significantly decreased after TUVP and IPSS and other urodymamics parameters improved. CONCLUSIONS: The present study suggested that RI could evaluate the severity of BPH and the degree of intraprostatic pressure or bladder outlet obstruction.

Aged↗
PubMed1989

Binding of soybean agglutinin lectin to prostatic hyperplasia and adenocarcinoma.

The binding of soybean agglutinin (SBA) lectin to routinely processed surgical pathology material from cases of prostatic hyperplasia, atypical hyperplasia, and adenocarcinoma was studied using an immunoperoxidase technique. Positive staining was obtained in eight of eight cases of nodular hyperplasia, eight of eight cases of atypical hyperplasia, and ten of 11 cases of adenocarcinoma. This report indicates that this lectin is not useful in distinguishing prostatic hyperplasia from adenocarcinoma.

Adenocarcinoma↗
PubMed2006

A randomised, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia in Brazil.

Brazilian patients with benign prostatic hyperplasia were randomised in a 12-week, double-blind, double-dummy study to receive doxazosin gastrointestinal therapeutic system (GITS) 4 mg q.i.d. (n = 82) or tamsulosin 0.4 q.i.d. (n = 83). Primary endpoints were the absolute and percentage change from baseline in symptoms measured by International Prostate Symptom Score (IPSS). Secondary endpoints included IPSS, quality-of-life (QOL) question from the IPSS, and questions 6 and 7 of the Sexual Function Abbreviated Questionnaire (SFAQ) at weeks 4 and 12. Doxazosin GITS and tamsulosin improved IPSS with no significant differences between groups at week 12. During weeks 4-8, tamsulosin-treated patients demonstrated a slower improvement (p < 0.001) in IPSS than doxazosin GITS-treated patients. The proportion of satisfied patients was observed earlier with doxazosin GITS (p = 0.006) vs. tamsulosin. At week 12, the proportion of patients with little or no difficulty at ejaculation (Q6 of SFAQ) was higher in the doxazosin GITS group (p = 0.019). Both treatments were well tolerated.

Adrenergic alpha-Antagonists↗