[Benign prostatic hyperplasia -- transurethral holmium-laser enucleation even in large prostate].
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Holmium↗
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Randomized double-blind study comparing the effectiveness of balloon dilation of the prostate and cystoscopy for the treatment of symptomatic benign prostatic hyperplasia.
We attempted to determine the effectiveness of balloon dilation of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). A total of 33 men with symptomatic BPH signed informed consent to participate in a randomized, double-blind study comparing balloon dilation of the prostate and cystoscopy. Balloon dilation of the prostate and cystoscopy were performed with the patient under intravenous sedation after intraurethral instillation of viscous lidocaine and infiltration of the autonomic neural innervation of the prostate with 1% lidocaine. Efficacy was based upon improvement in Boyarsky symptom scores, increases in peak urinary flow rates and patient global assessment of symptomatic improvement. Efficacy was assessed at 1 and 3 months after treatment. A study nurse blinded to the randomization scheme administered the symptom score questionnaires and supervised the uroflowmetry studies. The study was randomized, since the mean baseline prostate sizes, peak urine flow rates, obstructive and irritative symptoms scores, post-void residual volumes and patient ages were similar in the 2 groups. The patient perceptions of treatment rendered were similar for the 2 treatment groups, confirming that the study was double-blind. The patients undergoing cystoscopy and balloon dilation of the prostate experienced a statistically significant improvement in the mean total symptom scores at 1 and 3 months. The mean total symptom scores after balloon dilation of the prostate and cystoscopy at 1 and 3 months were not significantly different. The mean peak urinary flow rates 1 and 3 months after balloon dilation of the prostate and cystoscopy were not significantly different from the baseline mean peak urinary flow rates. We demonstrate that balloon dilation of the prostate and cystoscopy are equally effective for the treatment of BPH. Since cystoscopy is considered a diagnostic modality, our study suggests that the efficacy previously observed after balloon dilation of the prostate is primarily placebo-related. The study does not support the indication of balloon dilation of the prostate for the treatment of symptomatic BPH.
Aged↗
Changing approaches in the treatment of benign prostatic hyperplasia.
A large number of new options for the management of benign prostatic hyperplasia (BPH) have become available, including several classes of drugs that are under investigation. Various principles of management include hyperthermia, balloon dilatation, the introduction of spirals to keep the prostate open, and exploitation of the endocrine dependence of BPH through androgen withdrawal, using 5 alpha-reductase and aromatase inhibition. The efficacy of these alternative forms of treatment will become better defined during the next few years. Whatever the result, it is likely that the indication for surgery will decrease. Therapy must also take into account the sexual activity and expectations of the patient, an area that until recently has been largely neglected.
5-alpha Reductase Inhibitors↗
Safety assessment of terazosin in the treatment of patients with symptomatic benign prostatic hyperplasia: a combined analysis.
OBJECTIVES: This study reviews and assesses the safety of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: Six placebo-controlled trials (including two unpublished series) involving 996 patients provide the database for this evaluation. Six hundred thirty-six patients received terazosin from 1 to 20 mg daily for a total of 229 patient-years of exposure to terazosin. The most common final dose of terazosin was 10 mg once daily. RESULTS: Side effects were generally mild or moderate in severity and resolved following cessation of therapy. Side effects resulted in premature withdrawal in 9% of terazosin-treated patients and 7% of placebo-treated patients (difference not significant). Dizziness (2.0%) and headache (1.1%) were the most common symptoms leading to premature withdrawal from the studies. Although postural symptoms and dizziness were slightly more common in those terazosin-treated patients 65 or more years old compared with patients less than 65 years old, this difference was not statistically significant. Only 4 of the 636 patients (0.6%) had syncopal episodes; 2 of these occurred at initiation of terazosin therapy or at dose escalation. Minimal reductions in blood pressure were observed in normotensive patients and patients with hypertension controlled by concomitant medication, whereas patients with untreated hypertension had substantial decreases in both systolic and diastolic blood pressures. Statistically significant increases in high density lipoprotein to cholesterol ratio and reductions in total cholesterol, low density lipoprotein, and triglycerides were also seen. CONCLUSIONS: This combined analysis suggests that terazosin can be safely administered to both normotensive and hypertensive patients with symptomatic BPH.
Adrenergic alpha-Antagonists↗
Transurethral prostate vaporization using an oval electrode in 82 cases of benign prostatic hyperplasia.
OBJECTIVE: To present our initial experience in transurethral vaporization of the prostate (TVP) using an oval electrode for the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 82 patients underwent TVP procedures with the oval electrode. The newly designed oval-shaped electrode can work with a High Frequency Electrosurgery Unit. Prostate gland tissue was vaporized through an Fr 24 percutaneous nephroscope transurethrally. The operation procedure was similar to transurethral resection of the prostate (TURP) or transurethral laser prostatectomy (TULP). Power setting ranged from 240 W to 320 W. Local vaporization temperature reached 120 degrees C. RESULTS: Urination was recovered in all 82 patients after TVP. Mean post-treatment International Prostate Symptom Score (I-PSS) reduced from 27.10 to 5.05; mean bladder residual urine volume dropped from 147.71 ml to 33.2 ml; and mean urine flow rate (MFR) increased from 4.45 ml/s to 14.57 ml/s (P < 0.01). The initial results of short-term follow-up were excellent. CONCLUSIONS: TVP with the oval electrode is easy to perform and causes less hemorrhage and few complications. It especially benefits elderly and/or critically-ill patients. We believe that TVP with our oval electrode is feasible with low risk.
Aged↗
Serum triiodothyronine is increased in men with prostate cancer and benign prostatic hyperplasia.
UNLABELLED: Triiodothyronine is the active thyroid hormone produced by de-iodination of the precursor thyroxine that is necessary for the growth of prostate cancer cells in vitro. For this reason we assessed serum triiodothyronine levels in men with localized prostate cancer, benign prostatic hyperplasia (BPH) and controls in the same age group. MATERIALS AND METHODS: We studied 161 men referred for treatment of localized prostate cancer, 20 with BPH and 27 controls. Serum triiodothyronine was determined by fluorometric immunoassay and a commercially available instrument. RESULTS: Men with BPH had the highest triiodothyronine levels, followed by those with prostate cancer. Controls had the lowest triiodothyronine. There was significant triiodothyronine variation among the 3 groups (1-way ANOVA p = 0.001). In men with BPH serum triiodothyronine was significantly different from that in men with prostate cancer (Tukey's multiple range test p = 0.013). Men with prostate cancer had serum triiodothyronine that was significantly different than in controls (p = 0.048), as did those with BPH (p <0.001). Because serum triiodothyronine normally decreases with age, we performed multivariate analysis of variance controlling for age. There was a significant decrease in serum triiodothyronine with age (p = 0.020). There was also significant triiodothyronine variation among the 3 subject groups independent of age (p <0.001). CONCLUSIONS: Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem but it is impossible to identify such tumors with certainty. With more and better biomarkers many older men with prostate cancer may be spared the rigors of radiation therapy and/or surgery as well as complications. Triiodothyronine may be such a biomarker. Also, new prostate cancer and BPH therapies may be directed toward inhibiting the mitogenic effects of triiodothyronine.
Biomarkers↗
Relationship between the shape of passive urethral resistance relation and prostatic histology in patients with benign prostatic hyperplasia.
We assessed the relationship between the type of passive urethral resistance relation (PURR) and prostatic histology in 28 patients with benign prostatic hyperplasia (BPH), who underwent transurethral resection of the prostate. PURR was classified into three types according to pressure-flow plots, and resected specimens were analyzed by quantitative morphometry. Patient age, prostatic volume and the area densities of each histological component did not show significant differences among the three groups. However, there was a trend to correlation between prostates with a high glandular component and urethral compliance. Further studies of larger populations are needed to validate this assumption.
Aged↗
Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial.
OBJECTIVES: To assess the efficacy and safety, and determine the optimal dosage, of a once-daily (OD) formulation of the clinically uroselective alpha(1)-blocker, alfuzosin, in patients with lower urinary tract symptoms and symptomatic benign prostatic hyperplasia. METHODS: Five hundred thirty-six patients were randomized to receive alfuzosin (10 mg OD or 15 mg OD), without initial dose titration, or placebo in a 3-month double-blind trial conducted in North America. The primary efficacy criteria were improvement in symptoms (International Prostate Symptom Score) and peak urinary flow rate. RESULTS: Alfuzosin was significantly more effective than placebo in improving the symptoms and peak urinary flow rate from the first follow-up visit (day 28). The mean change in the International Prostate Symptom Score from baseline at endpoint was -3.6 and -3.4 with alfuzosin 10 mg and 15 mg, respectively, compared with -1.6 with placebo (alfuzosin 10 mg versus placebo, P = 0.001; alfuzosin 15 mg versus placebo, P = 0.004). The median increase in the peak urinary flow rate was +1.1 mL/s and +1.0 mL/s with alfuzosin 10 mg and 15 mg, respectively, compared with 0.0 mL/s with placebo (P = 0.0006 versus placebo for both dose groups). The patients' quality of life also significantly improved with both alfuzosin doses. Overall, alfuzosin at both doses was well tolerated. The incidence of orthostatic hypotension as determined by systematic blood pressure measurements with both doses of alfuzosin was similar to placebo. No clinically relevant ejaculation disorders were observed with alfuzosin. CONCLUSIONS: Alfuzosin 10 mg OD, administered without dose titration, provides effective relief from the symptoms of benign prostatic hyperplasia with no additional benefit from a 15-mg dose. It is well tolerated from a cardiovascular viewpoint and is not associated with abnormal ejaculation.
Adrenergic alpha-Antagonists↗
The cost of feedback microwave thermotherapy compared with transurethral resection of the prostate for treating benign prostatic hyperplasia.
OBJECTIVE: To compare the efficacy of a new microwave thermotherapy for treating benign prostatic hyperplasia (BPH), the ProstaLund Feedback Treatment (PLFT, ProstaLund Operations AB, Lund, Sweden) and transurethral resection of the prostate (TURP) in a clinical trial to their effectiveness in clinical practice over 1 year, to estimate their cost over 1 year, and to evaluate the cost of re-interventions over a longer period (2-3 years). PATIENTS AND METHODS: In a large randomized international 1-year clinical trial PLFT was as effective as TURP in improving symptoms of BPH and urinary flow. Because PLFT is an outpatient procedure it was less costly than TURP. However, the cost-effectiveness of the new procedure depends on its long-term effectiveness in clinical practice. All 146 patients in the randomized clinical trial were included in the present analysis. The outcome was based on the International Prostate Symptom Score (IPSS) and the bother score, and costs were estimated from treatment-related adverse events and hospitalization. To validate the estimates based on the clinical trial 1-year data on effectiveness and complete resource use in clinical practice were collected in a retrospective observational study from hospital charts and patient questionnaires of 88 patients who had undergone either TURP or PLFT. To assess the number of re-interventions after TURP after the first year information was obtained from hospital and surgical procedure data in the Swedish inpatient registry. The 3-year data for a total of 52,010 patients who had an index hospitalization for TURP between 1990 and 1995 were available for the analysis. The estimate of long-term consequences of PLFT was based on complication and re-intervention data for 87 patients who had undergone PLFT between 1997 and 1999. RESULTS: The mean 1-year costs in the clinical trial were estimated at [symbol: see text] 1763 for PLFT and [symbol: see text] 3209 for TURP. When all treatment-related resource use in clinical practice for 88 patients was included the costs were estimated at [symbol: see text] 1924 and [symbol: see text] 3264 for PLFT and TURP, respectively. The IPSS and bother scores were not significantly different between the groups in both datasets. Using the registry data the cost of TURP including re-interventions (TURP and bladder neck incisions) was estimated at [symbol: see text] 3159 over 2 years and [symbol: see text] 3185 over 3 years; the respective costs for PLFT were [symbol: see text] 2121 and at [symbol: see text] 2151. CONCLUSIONS: In the 1-year clinical trial PLFT was as effective but less costly than TURP, but long-term data are still lacking. However, the preliminary analysis over 3 years indicates that the average cost of the procedure remains lower than the total cost of TURP for the same period.
Aged↗
Asymptomatic inflammation and/or infection in benign prostatic hyperplasia.
OBJECTIVE: To determine the extent, pattern and clinical significance of asymptomatic histological inflammation and latent infection (National Institute of Health Category IV prostatitis) in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study included 80 patients (from a cohort of 100 consecutive potentially eligible subjects) with a diagnosis of BPH, but no history or symptoms of prostatitis. Histological sections were obtained from specimens collected prospectively at transurethral resection of the prostate (TURP), immunostained for leukocyte common antigen and scanned using a computerized image-analysis system. Foci of inflammation were categorized as glandular, periglandular, stromal or peri-urethral, and the inflammatory cell density graded from 1 to 3. Relationships and correlations were calculated between the volume, degree and type of inflammation, presence and type of bacteria (culture of deep prostatic biopsies), the use of catheters and prostate specific antigen (PSA) levels. RESULTS: Inflammation was identified in all patients but the mean tissue surface area involved was only 1.1% of the total specimen, with periglandular inflammation being the predominant pattern (0.5%). Of the prostate specimens, 44% showed bacterial growth (in 67% of the catheterized patients and 28% of those uncatheterized; 42% of patients were catheterized before TURP). There was no significant difference between any combination of inflammation pattern, volume or grade of inflammation in those catheterized or not (P=0.15) or culture-positive (pathogenic or not) and culture-negative cases (P=0.06). Neither total PSA or PSA density was significantly correlated (P>0.05) with the amount, degree or distribution of inflammation. CONCLUSION: Prostatic inflammation is an extremely common histological finding in patients with symptoms of BPH who have no symptoms of prostatitis. There was no correlation between the degree and pattern of inflammation, catheterization, presence of bacteria, serum PSA or PSA density. The clinical significance of asymptomatic Category IV chronic prostatitis associated with BPH has yet to be determined.
Bacterial Infections↗
Estimated costs of treatment of benign prostate hyperplasia in Brazil.
INTRODUCTION: The treatment of benign prostate hyperplasia (BPH) presents 2 options: medical or surgical, and there are doubts about what is the best treatment since 80% of patients who undergo surgery become asymptomatic and 10 to 40% of those under medical regimen undergo surgery within a 5 years period. It is difficult to assess the actual costs of treating BPH in Brazil due to several factors, among them regional particularities and the scarcity of current statistical data. PATIENTS AND METHODS: Recently, in the Ribeirao Preto area, Sao Paulo, Brazil, the IPSS (International Prostatic Symptoms Score) and quality of life were verified in 934 volunteers. It was determined the percentage of individuals with ages ranging from 40 to 79 years with moderate symptoms (score 8-19) and with severe symptoms (score 20-35), values for which are indicated medical and surgical treatment, respectively, according to the Brazilian Society of Urology consensus on BPH. Data on Brazilian population in that age range were obtained from the Brazilian Institute of Geography and Statistics referent to the year of 2000. It was determined the number of patients, according to the criteria above, subjected to either one of the treatments mentioned. Surgical costs of prostate transurethral resection were researched according to Unified Health System - SUS tables (173 US dollars) and of Brazilian Medical Society - AMB with a mean cost in 3 hospitals of 933 US dollars. Drug costs were calculated by the annual mean price (355 US dollars) of 4 alpha-blockers (tamsulosin, alfuzosin, doxazosin and terazosin). RESULTS: The estimated population for medical treatment was 5,397,321 individuals, with a cost corresponding to 1,916,489,055.00 US dollars. The estimated population for surgical treatment was 2,040,299 men, what would represent a cost of 353,291,204.00 US dollars based on the SUS table and of 1,904,279,066.00 US dollars based on AMB with hospital expenses included. CONCLUSION: All theses facts induce us to predict that the treatment of BPH in a not-so-far future can become a public health problem for Brazilian society, since the current estimate would be, approximately, costs around 2.26 - 3.83 billion dollars, added by the yearly increase in the risk population (24.99%) for the group under medical treatment and over the non-operated amount of the surgical group.
Journal Article↗
The endothelial nitric oxide synthase Glu-298-Asp polymorphism and its mRNA expression in the peripheral blood of patients with prostate cancer and benign prostatic hyperplasia.
BACKGROUND: The endothelial nitric oxide synthase (ecNOS) has an important role in vascular development and in the carcinogenesis process of prostate cancer (PCa). The nitric oxide (NO) production may promote cancer progression by providing a selective growth advantage to tumor cells, by angiogenic stimulus and by direct DNA damage. METHODS: The present study aimed at evaluating the ecNOS Glu-298-Asp polymorphism by the PCR-RFLP technique, associating genotypes with gene expression levels and the tumor biomarker, Prostate Cancer Antigen (DD3), through semi-quantitative RT-PCR. Pre-surgical peripheral blood samples from 160 patients were analyzed: 84 PCa, 11 prostate intraepithelial neoplasia (PIN) and 65 benign prostatic hyperplasia (BPH). RESULTS: The GG and GT Glu-298-Asp genotypes were associated with positive DD3 expression in the peripheral blood, presenting a 3.32-fold higher risk of PCa occurrence. There was no association between genotypes and ecNOS mRNA expression levels; however, the presence of the G allele is closely related to the hematogenous dissemination event of tumoral cells, as evidenced by the DD3 positivity. The higher G allele frequency among pT3 and pT4 staged PCa patients suggests that this would be associated with advanced phenotypes of the disease and may also be contributing to higher NO levels, causing cancer progression. CONCLUSIONS: The G allele may have a secondary influence on the prostate cancer predisposition, but an essential role on the event of tumor cells hematogenous dissemination, probably due to the angiogenic stimulus.
Antigens, Neoplasm↗
Leptin in relation to prostate cancer and benign prostatic hyperplasia.
The aim of our study was to determine whether leptin, a hormone implicated in both energy-balance and reproductive function, is involved in the etiology of prostate cancer or benign prostatic hyperplasia (BPH). We compared the serum leptin levels of 43 cases of incident prostate cancer, 41 patients with BPH, and 48 healthy controls, all recruited in Athens, Greece. Multiple logistic regression modeling was used, with adjustment for age, height, body mass index, education, estradiol, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin and insulin like growth factor 1. Odds ratios per 4 ng/ml increment of leptin were 0.70 [95% confidence interval (CI) (0.32,1.55)] for prostate cancer and 1.06 [95% CI (0.67,1.67)] for BPH. After adjustment for body mass index, serum leptin levels were not significantly correlated with levels of any of the other hormones under study. Leptin levels are unlikely to affect the risk of either prostate cancer or BPH substantially.
Aged↗
The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia.
This study was designed to investigate the relationship of serum prostate-specific antigen to prostatic size and hormonal stimulation. Seven patients with benign prostatic hyperplasia were treated for six months with nafarelin acetate and then followed for an additional six months. Nafarelin acetate is a potent luteinizing-hormone-releasing hormone agonist which causes reversible testosterone deprivation resulting in involution of the prostate. During therapy and follow up, serum prostate-specific antigen correlated with: 1) serum testosterone (p less than 0.001); 2) quantity of prostatic epithelium (p less than 0.001); and 3) prostatic size (p less than 0.05). Before therapy, serum prostate-specific antigen (mean +/- SD) was 0.43 +/- 0.2 ng./ml. per gram of epithelium. This did not change significantly after six months of androgen deprivation (0.48 +/- 0.36), although the ratios of prostate-specific antigen to testosterone and to prostatic size each changed significantly. Despite testosterone levels in the castrate range at six months, five of seven patients had serum prostate-specific antigen concentrations above the female range and three of seven patients had prostatic biopsies containing columnar epithelium which stained positively for prostate-specific antigen. These results demonstrate that serum prostate-specific antigen is related to prostatic size, prostatic epithelial weight, and testosterone stimulation. However, prostatic size is not a good predictor of serum prostate-specific antigen because there is tremendous variation in the relative amount of epithelium in a prostate; in this study the ratio of prostatic size to epithelial weight varied threefold. Furthermore, although testosterone determines prostatic size and amount of prostatic epithelium, it may not totally control prostate-specific antigen production.
Aged↗
Transurethral visual laser ablation of the prostate for benign prostatic hyperplasia using a KTP/YAG laser.
BACKGROUND: Transurethral visual laser ablation of the prostate (VLAP) has been established as an alternative method for the treatment of benign prostatic hyperplasia (BPH). However, most VLAP procedures utilize only a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Since a potassium-titenyl-phosphate (KTP) laser offers limited tissue penetration, KTP can be safely utilized to excise part of the obstructing prostatic tissue. This study assessed the interaction between KTP vaporization and YAG coagulative ablation to determine the safety and efficacy of VLAP utilizing a combined KTP/YAG treatment. METHODS: Forty patients with bladder outlet obstruction secondary to BPH were treated with VLAP using a KTP/YAG laser. The laser light was delivered by an angle delivery device. RESULTS: Most cases demonstrated a significant improvement in routine subjective and objective parameters (AUA symptom score, peak flow rate, average flow rate, and amount of residual urine). No significant complications relating to this procedure were reported, however, 4 patients experienced postoperative acute urinary retention. CONCLUSION: KTP/YAG laser ablation of the prostate is safe and effective for the treatment of BPH.
Aged↗
Are neuroendocrine cells responsible for the development of benign prostatic hyperplasia?
OBJECTIVES: To examine the possible relationship between the distribution of neuroendocrine (NE) cells and the development of benign prostatic hyperplasia (BPH) in the human prostate, we performed an NE cells-distribution analysis and made morphological observations of acinous structures in different-aged prostates. METHODS: Forty-three human prostates obtained from surgical and autopsy cases aged from 2 months to 86 years were examined immunohistochemically using Chromogranin A and analyzed with special reference to the development of BPH. RESULTS: NE cells were distributed predominantly in the verumontanum and main prostatic ducts and were fewer in number in the terminal acini. As BPH development progressed, the NE cells were greatly diminished in number or completely lost from most adenoma nodules. CONCLUSIONS: The NE cells of the prostate may be distributed and transported from the periurethral region near the verumontanum to the terminal acini during the development of the acinar structures. The distribution pattern is relatively consistent among prostates of all ages. However, NE cells do not appear in acquired tissue within BPH nodules as the nodules develop. Thus, the distribution of NE cells does not seem to be related to the development of BPH.
Adolescent↗
Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia.
OBJECTIVE: To present a comprehensive experience with intraprostatic botulinum toxin-type A (BoNT-A) injection in men with symptomatic benign prostatic hyperplasia (BPH) and to assess the efficacy on lower urinary tract symptoms (LUTS) and quality of life (QoL). PATIENTS AND METHODS: In all, 41 men (mean age 69.1 years, sd 7.1 ) with an International Prostate Symptom Score of > or = 8, peak flow rate of < 12 mL/s, and who were refractory to medical treatment were injected with BoNT-A (Botox, Allergan, Inc., CA, USA) at 100 U (21 men, for prostate volume < 30 mL) or 200 U (20, for prostate volume > 30 mL) into the prostate transperineally under transrectal ultrasonography guidance. Study exclusion criteria were confirmed or suspected malignancy, previous pelvic surgery or trauma and previous invasive treatment for BPH. The clinical effects were evaluated at baseline and at 1, 3 and 6 months after treatment. RESULTS: There were no significant local or systemic side-effects in any men. LUTS and QoL indices improved by > 30% in 31 of the 41 men (76%), and four of five men with urinary retention for > 1 month could void spontaneously at 1 week to 1 month after the BoNT-A injection. In 12 of 41 men (29%) there was no change in prostate volume, yet seven of these men still had a > 30% improvement in maximum flow rate, LUTS and QoL. The efficacy was sustained at 12 months. CONCLUSION: BoNT-A injected into the prostate is safe and effective for men with symptomatic BPH. The mechanisms of relief of symptoms might not depend totally on the volume shrinkage; the inhibitory effect on the smooth muscle tone and aberrant sensory function might also be important.
Aged↗
Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.
PURPOSE: Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. MATERIALS AND METHODS: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity. RESULTS: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. CONCLUSIONS: These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.
Adrenergic alpha-Antagonists↗