Alpha 1-antichymotrypsin production in PSA-producing cells is common in prostate cancer but rare in benign prostatic hyperplasia.
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Humans↗
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Diagnosis and treatment of benign prostatic hyperplasia.
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Humans↗
A study of benign prostatic hyperplasia--a challenge to British urology.
A community study to determine the prevalence and natural history of benign prostatic hyperplasia (BPH) in a typical Scottish community has been undertaken in men from 40 to 79 years of age. From 2497 eligible men, 1627 (65%) agreed to take part and after screening by symptom score and urinary flow rate 561 were offered a full investigation including transrectal ultrasonography; 492 (87.7%) attended and 415 were found to have BPH, which was defined as a prostate > or = 20 g. Following urological consultation, 3 groups of patients with BPH were recognised: those requiring no therapy (39.5%), those in whom therapy options were considered (50.5%) and those where operation was advised (10%). Seventeen patients with prostatic carcinoma were found, 4 of whom were treated by radical prostatectomy. A total of 67 operations for BPH resulted from the study in patients not previously referred to our urological unit, the majority of whom had not consulted their GP for symptoms of prostatism. This represents a serious challenge to British urology.
Adult↗
Apoptotic and proliferative index after Alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia.
INTRODUCTION: The induction of apoptosis has emerged as a potential target for optimization of the medical management of benign prostatic hyperplasia (BPH), recently. The influence of alpha1-adrenoceptor antagonist (alpha1-ARA), 5-alpha reductase inhibitor and their combination on prostatic cell apoptotic and proliferative indices of benign hyperplastic prostate gland were investigated. MATERIALS AND METHODS: A total of 49 male patients with BPH (mean age: 66.5 years) treated with alpha1-ARA and/or finasteride were retrospectively evaluated. Patients treated with alpha1-ARA (doxazosin n = 12 and terazosin n = 10), finasteride (n = 9) and combination of finasteride and alpha1-ARA (n = 9) were enrolled in the study. Primary antibodies were Ki-67 and proliferating cell nuclear antigen for the evaluation of proliferation in prostate stromal and epithelial cells. In situ apoptotic DNA fragmentation was evaluated using TUNEL assay. RESULTS: All treatment groups had no significant changes in the rate of prostate stromal and epithelial cell proliferation. Epithelial apoptotic index (AI) was not statistically significant for finasteride vs. alpha1- ARA, alpha1-ARA vs. finasteride + alpha1-ARA and finasteride + alpha1-ARA vs. finasteride groups. While alpha1-ARA was more effective than finasteride on stromal apoptosis, alpha1-ARA-induced stromal apoptosis was not significantly different from alpha1-ARA plus finasteirde treatment. CONCLUSION: Not only androgen variabilities but also alterations in sympathetic neurotransmission with age could have important implications for pathophysiological prostate growth. The combination of finasteride and alpha1-ARA is not superior to alpha1-ARA therapy with their similar epithelial and stromal apoptotic effects with unaffected cell proliferation.
Adrenergic alpha-Antagonists↗
High-intensity focused ultrasound in the treatment of benign prostatic hyperplasia.
OBJECTIVE: To assess the role of high-intensity focused ultrasound (HIFU) in the treatment of symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Thirteen patients (mean age 65 years, range 58-74) were treated with HIFU as part of a phase-2 clinical trial and evaluated prospectively using the International Prostate Symptom Score, uroflowmetry, and transrectal and transabdominal ultrasonography to determine prostate size and post-void residual urine volume, respectively. The results and the patients' satisfaction were assessed at regular intervals for 2 years. RESULTS: The new procedure was learned quickly and was easy to perform. Symptom scores decreased from a mean of 23 before treatment to 5 after 12 months and 7 after 2 years. There was an initial improvement in flow rates but they then declined. The size of the prostate and the post-void residual volume were both decreased after treatment. CONCLUSIONS: The treatment is safe, easy to implement and was effective in substantially reducing symptom scores in these few patients. However, we would not encourage its use as an alternative to other well established treatment modalities until it has been assessed fully in a randomized trial.
Aged↗
Lower urinary tract symptoms/benign prostatic hyperplasia: minimizing morbidity caused by treatment.
The beneficial effects of treatment for lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH), or LUTS/BPH, have to be balanced against the morbidity associated with treatment. Invasive surgery, such as transurethral resection of the prostate, has been associated with irreversible complications (eg, impotence and retrograde ejaculation). Alpha(1)-adrenoceptor antagonists provide effective and fast relief of LUTS/BPH. In contrast to finasteride, they are not associated with sexual dysfunction (eg, decreased libido or impotence). Alpha(1)-adrenoceptor antagonists induce adverse events associated with interference with blood pressure regulation. The alpha(1A)/alpha(1D)-adrenoceptor antagonist tamsulosin has the lowest potential to interfere with blood pressure regulation and induce related adverse events. In addition, tamsulosin seems to be as well tolerated as phytotherapy, except for a higher incidence of abnormal ejaculation. Abnormal ejaculation occurs in 4% to 11% of patients receiving a alpha(1)-adrenoceptor antagonist, which is, however, well tolerated; <1% of patients discontinue because of this adverse event. In placebo-controlled trials, abnormal ejaculation has been predominantly reported for tamsulosin, but in most direct comparative studies, the incidence was comparable to that of other alpha(1)-adrenoceptor antagonists. Men with LUTS/BPH have an increased risk of impaired sexual function. However, alpha(1)-adrenoceptor antagonists, such as tamsulosin, may slightly improve sexual dysfunction together with LUTS problems. Combination therapy of an alpha(1)-adrenoceptor antagonist and finasteride has a similar adverse-event profile as each monotherapy, except for an increased risk of abnormal ejaculation. The discontinuation rate because of adverse events does not seem to be higher than with monotherapy. Medical therapies, and particularly alpha(1)-adrenoceptor antagonists such as tamsulosin, can be considered a first-line treatment option for LUTS/BPH because they provide effective relief of bothersome LUTS with excellent tolerability.
5-alpha Reductase Inhibitors↗
Could inflammation be a key component in the progression of benign prostatic hyperplasia?
PURPOSE OF REVIEW: This review covers recent developments in the role of chronic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). RECENT FINDINGS: A paper on the subanalysis of the Medical Therapy of Prostate Symptoms study highlighted the role of chronic inflammation in the progression of BPH as determined by the pathological tissue obtained in the 4.5-year study. It shows patients with inflammation had significantly larger prostates, higher serum prostate specific antigen and a greater risk of urinary retention. This follows several other in-situ studies which demonstrated that elevated expression of pro-inflammatory cytokines in BPH. IL-6, IL-8 and IL-17 may perpetuate chronic immune response in BPH and induce fibromuscular growth by an autocrine or paracrine loop or via induction of COX-2 expression. Immune reaction may be activated via Toll-like receptor signalling and mediated by macrophages and T cells. Conversely, anti-inflammatory factors such as macrophage inhibitory cytokine-1 decreased in symptomatic BPH tissues. Animal models provided evidence for the presence of unique T-cell subsets which may suppress autoimmunity in healthy Sprague-Dawley rats resistant to chronic nonbacterial prostatitis. SUMMARY: The pathogenesis of BPH is still unresolved, although chronic inflammation may play a significant role in disease progression. Further research is required to determine the putative (auto)antigen, the influence of infiltrating inflammatory cells on the stromal/epithelial cell crosstalk and a new classification of BPH quantifying local and systemic inflammatory/immune reactions in relation to clinical relevance. New treatments for BPH investigating these specific inflammatory pathways may arise as we learn more about the way they work.
Animals↗
Manual versus computer methods for diagnosing obstruction from pressure-flow tracings in patients with benign prostatic hyperplasia.
PURPOSE: We compared manual versus computer analysis of pressure-flow tracings for diagnosing bladder outlet obstruction in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 105 patients with a clinical diagnosis of prostate enlargement and lower urinary tract symptoms was included in the study irrespective of free flow rates. Pressure-flow studies were performed in duplicate and tracings were evaluated by 2 independent investigators blinded to patients status. Manual reading of urodynamic printouts and fully computerized analysis using CLIM software were done. All urodynamic parameters relevant to the diagnosis of outlet obstruction were compared using the Abrams-Griffiths and Schäfer nomograms. Group specific urethral resistance factors were also compared. RESULTS: There was good correlation between manual and computer derived values of maximum flow (r = 0.9874, p < or = 0.0001), detrusor pressure at maximum flow (r = 0.9943, p < or = 0.0001), minimum detrusor pressure during voiding (r = 0.8816, p < or = 0.0001) and group specific urethral resistance factor (r = 0.9917, p < or = 0.0001). The diagnosis of outlet obstruction according to the group specific urethral resistance factor, and the Abrams-Griffiths and Schäfer nomograms was highly consistent using the manual and computerized approaches. CONCLUSIONS: Manual analysis of pressure-flow tracings generated by urodynamic equipment and digital data obtained by CLIM software appeared to be highly consistent and equally reliable for diagnosing and grading outlet obstruction.
Aged↗
Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia.
Permixon, the lipidosterolic extract of Serenoa repens, is widely used for the treatment of symptoms associated with benign prostatic hyperplasia (BPH). This open study assessed the efficacy and tolerability of Permixon 160 mg twice daily administered for 2 years. One hundred fifty-five men with clinically diagnosed BPH and complaints of prostatic symptoms were enrolled in the study. At 6, 12, 18, and 24 months, the International Prostate Symptom Score (I-PSS), quality of life, and sexual function score were recorded, and urodynamics and biologic values were measured. Adverse events were recorded every 3 months. I-PSS and quality of life improved significantly from baseline at each evaluation time point. At the end of the study and at each evaluation, maximum urinary flow also improved significantly. Prostate size decreased. Sexual function remained stable during the first year of treatment and significantly improved (P = .001) during the second year. Prostate-specific antigen was not affected, and no changes in plasma hormone levels were observed. Nine patients reported 10 adverse events, none related to treatment. Improvements in efficacy parameters began at 6 months and were maintained up to 24 months. These data demonstrate the long-term efficacy and tolerability of Permixon and support its use as a first-line medical therapy for uncomplicated symptomatic BPH.
Aged↗
Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in relation to the patient's risk profile for progression.
Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is a slowly progressing disease, with some patients progressing more rapidly than others. In 80% of patients who progress this is caused by the worsening of symptoms. The physician can predict the risk of progression from the patient's clinical profile; increased symptom severity, a poor maximum urinary flow rate (Qmax), and a high postvoid residual urine volume (PVR), are major risk factors for overall clinical progression of LUTS/BPH. A large baseline prostate volume and a high serum prostate-specific antigen (PSA) level are the predominant risk factors for developing acute urinary retention. After predicting risk, the most appropriate treatment should be established by balancing the benefits of treatment against the possible risks and bother resulting from adverse events. From the Medical Therapy Of Prostatic Symptoms study it can be concluded that monotherapy with an alpha1-adrenoceptor (AR) antagonist is an appropriate treatment for many patients with LUTS/BPH. However, for those at high risk of progression (those with a large prostate volume and high PSA level), it appears more appropriate to add a 5alpha-reductase inhibitor to the alpha1-AR antagonist to obtain maximum relief of symptoms, and ideally to halt the progression of the disease. This was confirmed by the RAND Appropriateness Method study, in which 12 urologists determined the most appropriate treatment for patients with LUTS/BPH based on their clinical profile, combination of clinical variables and/or risk factors. This study also indicates that patients at very high risk of progression, with severe obstruction (poor Qmax and high PVR), are potential candidates for immediate surgery.
5-alpha Reductase Inhibitors↗
Transurethral needle ablation of the prostate for treatment of benign prostatic hyperplasia: early clinical experience.
OBJECTIVES: Many attempts have been made to develop a method for treatment of benign prostatic hyperplasia (BPH) that is minimally invasive, efficacious, and low-cost. Transurethral needle ablation (TUNA) is a new, fast outpatient anesthesia-free procedure, using interstitial low-level radio frequency energy to produce a temperature above 100 degrees C. We describe our early clinical experience with TUNA as an outpatient procedure. METHODS: This technique was used in 20 patients with symptomatic BPH. All men were evaluated prior to treatment with flow rates, residual urine, International Prostate Symptom Score (IPSS), and quality of life. Follow-up occurred at 3 and 6 months after treatment, analyzing the same parameters. RESULTS: Tolerance using topical anesthetic and intravenous diazepam was excellent. Peak flow rate increased from a mean 9.5 +/- 3.3 mL/s to 14.7 +/- 6.3 mL/s (P < 0.05) at 3 months (19 patients) and to 15.0 +/- 4.9 mL/s (P < 0.05) at 6-month follow-up (12 patients). IPSS and quality of life improved from an average of 21.9 +/- 5.0 and 4.4 +/- 0.7 (P < 0.005) to 10.2 +/- 4.8 and 2.4 +/- 1.2 (P < 0.005), respectively, at 3-month follow-up. No significant complications were encountered. Retention was observed in 25% of the cases after the TUNA treatment. CONCLUSIONS: This initial study demonstrates the safety and effectiveness of TUNA. TUNA is a promising, anesthesia-free alternative treatment for men with symptomatic BPH. Long-term follow-up and randomized comparative studies with transurethral resection of the prostate (TURP) are planned to establish the place of this new alternative treatment of BPH in the urologist's armamentarium.
Aged↗
[Potential sexual consequences associated with benign prostatic hyperplasia and its treatments].
In this article, an updated review of the potential consequences of treatment of benign prostatic hyperplasia (BPH) on sexual function is proposed in the light of recent data. Differences exist between the different therapeutic options available for the treatment of lower urinary tract symptoms (LUTS) when we want to analyze the impact on sexuality. Surgical procedures including minimally invasive techniques are associated with ejaculation and also erection disorders. Drug treatments also have repercussions on sexuality though there are significant differences between the various classes of these drugs. In daily practice, the relation between the prostate and sexuality must be assessed during any medical examination for one of these diseases and before any decision on treatment.
Humans↗
[Pharmacological properties of naftopidil, a drug for treatment of the bladder outlet obstruction for patients with benign prostatic hyperplasia].
Naftopidil, a phenylpiperazine derivative, is a novel alpha 1-adrenoceptor antagonist and is new drug for the bladder outlet obstruction in patients with benign prostatic hyperplasia (BPH). Naftopidil competitively inhibited specific [3H]prazosin binding in prostatic membranes of humans, and its Ki value was 11.6 nM. Using cloned human alpha 1-adrenoceptor subtypes (alpha 1a, alpha 1b and alpha 1d), naftopidil was selective for the alpha 1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha 1a- and alpha 1b-adrenoceptor subtypes, respectively. In anesthetized dogs, naftopidil selectively inhibited the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure. The selectivity of naftopidil for prostatic pressure was more potent than those of tamsulosin and prazosin. In conscious rabbits, the effect of naftopidil on the blood pressure reactions following the tilting was less potent than those of tamsulosin and prazosin. In clinical studies, naftopidil has been demonstrated to be effective in the treatment of bladder outlet obstruction in patients with BPH. In Japan, naftopidil has been already approved for clinical use as a drug for BPH.
Adrenergic alpha-Antagonists↗
Nonsurgical treatment of prostatic hyperplasia.
BACKGROUND: Epidemiologic studies in castrates strongly support the key role of the testis in the pathogenesis of benign prostatic hyperplasia (BPH). Since the testis secretes both androgen and estrogen, both of these hormones have been implicated in BPH. Many data support the important role of dihydrotestosterone (DHT) in BPH. It is now possible to quantify prostate size and function with reliable new techniques and to utilize androgen withdrawal studies to test the validity of the DHT theory. METHODS: A variety of androgen-blocking drugs have been demonstrated to decrease prostate size by approximately 30% by either blocking secretion of circulating testosterone and adrenal androgen, inhibiting 5 alpha-reductase to prevent DHT formation, or blocking DHT binding to androgen receptors. RESULTS: Accompanying these changes in size have been significant improvement in clinical symptoms of prostatism in approximately 50% of patients when double-blind, large multicenter studies were conducted with one of these drugs. Although these results suggest a very important role for androgen, particularly dihydrotestosterone, in the pathogenesis of BPH, other abnormalities besides those of androgen metabolism may coexist since significant numbers of patients do not show a total reversal of disease. There is strong indirect evidence for a possible role for estrogen in the pathogenesis of BPH and studies are under way to test the effects of estrogen withdrawal on prostate size and symptoms. Similarly, dynamic aspects of prostatic obstruction, which are under alpha adrenergic regulation, may also be a component of this disease and amenable to therapy with alpha-adrenergic blockers. CONCLUSIONS: Therefore it would seem that BPH may be multifactorial and require combined therapy. Androgen would certainly appear to be necessary, but perhaps not sufficient, for the pathogenesis of this disorder.
5-alpha Reductase Inhibitors↗
Sex steroids and epidermal growth factor in benign prostatic hyperplasia (BPH).
Androgens provide the primary signal for the onset of DNA synthesis and cell division in normal prostate and benign prostatic hyperplasia (BPH). It is possible, however, that androgen mitogenic activity is in part indirect and mediated by peptide growth factors. In LNCaP cell lines, R1881 added to DCC-FCS medium increases DNA, epidermal growth factor (EGF) and EGF receptor (EGFR) levels: the antiandrogen hydroxy-flutamide prevents the increase of the growth factor and increases its receptor. In BPH tissue removed by transvesical prostatectomy, DHT, testosterone, 3 alpha-androstanediol and nuclear androgen receptors (AR) show a positive linear correlation with EGF: treatment with flutamide decreases significantly the EGF production. Androgens, therefore, represent important modulatory factors of prostatic EGF release. Moreover, androgens and EGF downregulate EGFR, which is probably internalized into the cell and degraded by lisosomes: in fact, a negative linear correlation between EGF, nuclear AR and the high- and low-affinity binding of EGFR is observed. These findings support the hypothesis that the growth-promoting effects of androgens in the prostate are in part mediated by peptide growth factors. The inhibitory effect of antiandrogens on prostatic cell proliferation may be the result of the decreased androgenic support and decreased EGF release and expression.
Aged↗
The international terazosin trial: a multicentre study of the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. The ITT Group.
OBJECTIVE: To evaluate the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia (BPH). METHODS: Thirty-three sites in 13 countries enrolled men with BPH who had an International Prostate Symptom Score (IPSS) > or = 12 [corrected]. After a 2-week, no-treatment lead-in period and a 26-week, single-blind treatment period, patients responding to terazosin were randomly assigned to receive either terazosin or placebo for a 24-week, double-blind withdrawal period. RESULTS: Of the initial 427 patients enrolled, 378 were evaluable, 273 of whom completed the single-blind period, of which 186 patients were randomized. During the single-blind treatment period, IPSS, quality-of-life score (QOL), peak flow rate (PFR), and nocturia score (NOC) improved significantly (p < or = 0.05). During the double-blind withdrawal period, IPSS, QOL, PFR, and NOC deteriorated significantly in the placebo group compared with the terazosin group. The most common adverse event resulting in premature termination from the study was dizziness. There were no clinically important mean reductions in diastolic blood pressure (DBP) for patients normotensive at baseline. Terazosin significantly reduced mean DBP in hypertensive patients during the single-blind period and maintained the reduction during the double-blind period. CONCLUSION: Treatment with terazosin has a beneficial effect on BPH, continuing for at least 12 months, and can be safely considered for medium- to long-term use in those who benefit.
Adrenergic alpha-Antagonists↗
Aggressive angiomyxoma of the prostate mimicking benign prostatic hyperplasia.
Aggressive angiomyxoma (AAM) is a locally invasive soft tissue tumor with a high risk of local recurrence but without metastatic spread. The mesenchymal tumor is relatively site-specific and has a peak incidence in females in their 2nd or 4th decade. Only few cases in males have been reported in the literature. We describe what we think is the first case of an aggressive angiomyxoma arising in the prostate presenting with classical symptoms of benign prostatic hyperplasia.
Biomarkers, Tumor↗
A meta-analysis of trials of transurethral needle ablation for treating symptomatic benign prostatic hyperplasia.
OBJECTIVES: To investigate the short- and long-term effectiveness of transurethral needle ablation (TUNA) of the prostate for clinical benign prostatic hyperplasia (BPH), using a meta-analysis of all clinical studies involving TUNA. METHODS: Data were extracted from two randomized trials, two non-randomized observational protocols and 10 single-arm studies conducted on TUNA, according to a determined protocol. The meta-analysis was based on the change in the mean score at the end of study from that at baseline. The estimation of the effects from the meta-analysis used a multilevel model including random effects for the studies. RESULTS: In all studies the patients recruited had severe lower urinary tract symptoms and a mean International Prostate Symptom Score (IPSS) of > 20 before treatment. The effect of TUNA was to halve the mean IPSS at 1 year after treatment and, although there was a slight tendency for the IPSS to increase in all arms from year 1 to year 5, this decrease by half was maintained at 5 years. The maximum urinary flow rate (Q(max)) also increased by approximately 70% from baseline to 1 year and in virtually all studies the mean Q(max) approached or exceeded 15 mL/s. Although there was a tendency for Q(max) to decline slightly over time, the mean Q(max) 5 years after treatment was > 50% over baseline. CONCLUSIONS: This meta-analysis shows that TUNA is an effective and minimally invasive treatment for men with clinical BPH, even when the symptoms are severe. There is a significant improvement in symptoms and flow rate after 1 year which persists for at least 5 years. TUNA therapy would appear to be an alternative to surgery and an attractive option for men who do not wish to undergo long-term medical therapy, are poor candidates for surgery or are concerned about the side-effects of TURP.
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