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PubMedDate not supplied

Effect of doxazosin on the symptoms of benign prostatic hyperplasia: results from three double-blind placebo-controlled studies.

The urinary symptoms characteristic of benign prostatic hyperplasia (BPH) can have a considerable impact on patients' quality of life. Symptom score assessment is now used in BPH, although a number of different instruments are available. Controlled clinical trials with selective alpha 1 adrenoceptor antagonists such as doxazosin, prazosin and terazosin have shown these agents to be effective in the treatment of BPH. The effects of doxazosin on the severity and bothersomeness of BPH symptoms were determined in three multicentre, double-blind, placebo-controlled clinical studies, involving a total of 609 normotensive and hypertensive patients. Doxazosin was initiated at a dosage of 0.5 or 1 mg once daily, with a final dose range of up to 12 mg once daily. The duration of active treatment was 12 to 14 weeks. Significant improvements were seen in symptom severity and bothersomeness with doxazosin compared with placebo, in both patient populations. The onset of symptomatic improvement was rapid, occurring within two weeks of treatment initiation, and efficacy was sustained throughout the treatment period. A long-term, open label extension of these studies has demonstrated sustained efficacy during 48 months of follow-up. Since symptom relief is the primary goal of therapy in BPH, and since doxazosin's effects are rapid in onset and sustained in duration, it appears that doxazosin is an effective agent for the treatment of symptomatic BPH in both normotensive and hypertensive men.

Adrenergic alpha-Antagonists↗
PubMed2006

Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive bladder symptoms in patients with benign prostatic hyperplasia.

AIM: We evaluated the efficacy of an alpha1a/d blocker, naftopidil, on storage symptoms in patients with benign prostatic hyperplasia (BPH), using frequency/volume charts (FVC). METHODS: A total of 81 patients with BPH (52-91 years, mean age 69.0 years) were studied. The inclusion criteria were: (i) one or more episode(s) of urinary urgency/day; (ii) a score of eight or more points on the International Prostate Symptom Score (I-PSS); and (iii) three or more points in any of the scores for three items (frequency, nocturia, and urgency) of the I-PSS. The patients received 50-75 mg/day of naftopidil for 6 weeks. All the patients were examined for 2-day FVC before and after the administration of naftopidil. I-PSS, quality of life index, and uroflowmetry were also evaluated. RESULTS: Total I-PSS decreased from 19.1 to 10.5 points (P < 0.0001), with significant improvement of both storage and voiding symptom scores (P < 0.0001, both). The score for urgency decreased from 3.1 to 1.4 (P < 0.0001). Daytime and night-time frequency decreased from 9.3 to 8.0 (P < 0.0001) and from 2.7 to 2.0 (P = 0.0009), respectively. Mean volume/void increased from 174.0 to 188.6 mL (P = 0.0453). Nocturia decreased from 3.2 to 2.3 (P < 0.0001) in 40 patients who suffered from nocturia two times or more. Notably, significant improvement of nocturia was observed in the patients both with and without nocturnal polyuria (P = 0.0006 and 0.0135, respectively). CONCLUSION: The alpha1a/d blocker naftopidil improves not only voiding symptoms but also storage symptoms, and is effective for nocturia in patients with BPH regardless of the existence of nocturnal polyuria.

Adrenergic alpha-Antagonists↗
PubMed1996

Tamsulosin. A review of its pharmacological properties and therapeutic potential in the management of symptomatic benign prostatic hyperplasia.

Tamsulosin is the first subtype-selective (alpha IA) alpha 1 adrenoceptor antagonist with specificity for prostatic alpha 1 adrenoceptors (alpha 1A adrenoceptors are thought to be involved in prostatic smooth muscle contraction) to become available for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). With tamsulosin, the incidence of adverse events commonly associated with alpha 1 adrenoceptor antagonism is similar to that with placebo (except for ejaculation disorders) and alfuzosin. The incidence of other adverse events is similar with tamsulosin and placebo. Furthermore, blood pressure and heart rate are not significantly affected by tamsulosin in patients with symptomatic BPH. In contrast, blood pressure is significantly reduced by alfuzosin compared with tamsulosin. Tamsulosin is available as a controlled release formulation suitable for once daily administration; dose titration is not required. The overall efficacy of this agent administered at a dosage of 0.1 to 0.4 mg/day in Japan, 0.4 mg/day in Europe and 0.4 to 0.8 mg/day in the US to patients with symptomatic BPH is greater than that of placebo was similar to that of alfuzosin or prazosin in the 2 available studies. Efficacy was primarily assessed by changes in maximum and average urinary flow rates, residual urinary volume and total symptom scores. Improvements in these parameters in short term trials (< or = 13 weeks) appear to be maintained in the longer term (< or = 60 weeks). Quality-of-life effects also appear to be similar with tamsulosin and alfuzosin. In conclusion, the pharmacodynamic properties of this agent appear to translate into tolerability and administration advantages over other alpha 1 adrenoceptor antagonists. If future investigations confirm its promising efficacy and tolerability, tamsulosin will be ideally placed as a valuable therapeutic option for patients with symptomatic BPH and in patients awaiting surgery or in those unable to undergo surgery.

Adrenergic alpha-Agonists↗
PubMed2006

Food groups and risk of benign prostatic hyperplasia.

OBJECTIVES: To evaluate the role of a wide range of foods on the risk of benign prostatic hyperplasia (BPH), we conducted a case-control study in Italy between 1991 and 2002. Although BPH is an extremely common condition, particularly among older men, its risk factors, including dietary ones, remain largely undefined. METHODS: Included in the study were 1369 patients younger than 75 years old surgically treated for BPH and 1451 controls younger than 75 years of age who had been admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcoholic beverages, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major potential confounding factors. RESULTS: A significant trend of increasing risk with more frequent consumption was found for cereals (OR 1.55 for the greatest versus lowest quintile), bread (OR 1.69), eggs (OR 1.43), and poultry (OR 1.39). Inverse associations were observed for soups (OR 0.74), pulses (OR 0.74), cooked vegetables (OR 0.66), and citrus fruit (OR 0.82). No association was observed for milk and yogurt products, coffee and tea, pasta and rice, fish, cheese, row vegetables, potatoes, fruit, or desserts. CONCLUSIONS: The results of this study suggest a role for dietary habits on the risk of BPH. In particular, a diet rich in cereals and some types of meat and poor in vegetables and pulses may have an unfavorable effect in this Italian population.

Aged↗
PubMed2000

[National trend of management of benign prostatic hyperplasia in Japan during 1990s: analysis of national health statistics].

To review the contemporary management of benign prostatic hyperplasia (BPH) in Japan during 1990s, we analyzed several nationwide health statistics by the Ministry of Health and Welfare of Japan. The cross-sectional surveys revealed that the estimated total number of patients receiving treatment increased from 202,000 in 1987, to 335,000 and 590,000, respectively, in 1995 and 1998. Approximately 73-80% of patients were men aged 65 years or over and 94-98% 55 years or older. Urologists treated two thirds of the BPH patients. The incidence of prostatectomies remained relatively stable at 50,000/year (3.0-3.8 prostatectomies/1,000 men aged 55 or over). The average hospital stay in 1996 was 24.7 days. The total cost of BPH therapy nearly doubled between 1988 and 1998. The ratio of outpatient to inpatient costs ranged from 1.5 to 2.2 and 60% of the outpatient cost was spent for medical therapy. The total value of the market for medical therapy increased from 30-40 billion yen in 1989 to more than 80 billion yen in 1998. The application of alpha-blockers increased from 243,000 men (70% of all patients) in 1995 to 452,000 (77%) in 1998, whereas the number of patients taking antiandrogens, plant extracts and antispasmodic agents/Ca antagonists (for pollakisuria), respectively, remained relatively stable at 60,000-70,000, 180,000 and 300,000. Because Japan is a rapidly aging society and men aged 55 or older are expected to increase from 15 million in 1995 to 21 million in 2010, cost-effective treatment guidelines for the Japanese BPH patients are needed.

Aged↗
PubMed2002

Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia.

OBJECTIVES: To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II. METHODS: A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments. RESULTS: At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated. CONCLUSIONS: Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.

5-alpha Reductase Inhibitors↗
PubMed2000

Race, ethnicity and benign prostatic hyperplasia in the health professionals follow-up study.

PURPOSE: We examined whether the prevalence of benign prostatic hyperplasia (BPH) varies by racial or ethnic origin in a large cohort of American male health professionals. MATERIALS AND METHODS: Included in our study were 1,508 men who underwent surgery for BPH between 1986 and 1994, and 1,837 with high moderate to severe lower urinary tract symptoms assessed by the American Urological Association symptom index in 1992 or 1994. "Noncases" comprised 23,246 asymptomatic participants. Self-reported major ancestry was black in 201 men, Asian in 413, other origin in 604 and white in 25,373. White heritage was further classified as southern European in 6,408 men, Scandinavian in 2,951 and other white in 16,014. The relative risk of BPH and 95% confidence intervals (CI) adjusted for age, body mass index, alcohol consumption, smoking and physical activity were calculated by logistic regression. RESULTS: Black men were not at increased risk for BPH (relative risk 0.85, 95% CI 0.55 to 1.31) compared with white men. Asian men were less likely to have undergone BPH surgery (relative risk 0.41, 95% CI 0.21 to 0.82), although the relative risk for symptoms was similar to that of white men. White men whose major ancestry was southern European were at modestly higher risk for BPH surgery (relative risk 1.28, 95% CI 1.12 to 1.46) and symptoms (relative risk 1.34, 95% CI 1.20 to 1.50), whereas men of Scandinavian heritage were at slightly decreased risk for symptoms than those of other white heritages. CONCLUSIONS: Racial and ethnic variation is evident in the incidence of BPH surgery and symptom severity. Whether this observed variation reflects underlying biological phenomena rather than differences in symptom tolerance requires further exploration.

Adult↗
PubMed2005

Intake of selected micronutrients and the risk of surgically treated benign prostatic hyperplasia: a case-control study from Italy.

OBJECTIVE: To analyze the relationship between surgically treated benign prostatic hyperplasia (BPH) and intake of selected micronutrients. METHODS: A multicentric case-control study was conducted in Italy between 1991 and 2002. Cases were 1369 men with histologically confirmed, surgically treated BPH and controls were 1451 men younger than 75 yr, frequency matched by quinquennium of age and study center, admitted to the hospital for acute nonneoplastic diseases. Information was collected by trained interviewers using a structured validated food-frequency questionnaire. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional multiple logistic regression models. RESULTS: The risk of BPH significantly decreased with increasing intake of carotene (OR=0.80 for an increment equal to the difference between the 80th and 20th percentile of intake), alpha-carotene (OR=0.83), beta-carotene (OR=0.82), and cis beta-carotene (OR=0.82) and tended to decrease with the intake of vitamin C (OR=0.89) and iron (OR=0.79). The OR tended to increase with the intake of sodium (OR=1.30) and zinc (OR=1.10). No systematic heterogeneity was observed across strata of age, education, and body mass index. No meaningful associations emerged for other antioxidants, such as folic acid, lycopene, lutein/zeaxanthin, vitamin E, vitamin D, nor for retinol. CONCLUSIONS: Our results suggest a protective effect of carotene on the risk of BPH. The risk tended to decrease also with the intake of vitamin C and iron and tended to increase with the intake of sodium and zinc. Results also indicate that other antioxidants, including folic acid, lycopene, lutein/zeaxanthin, and vitamins D and E, and retinol were not related to the risk for this disease.

Adult↗
PubMed1996

Is one single prostate biopsy helpful for choosing a medical treatment of benign prostatic hyperplasia? A quantitative computerized morphometric study.

OBJECTIVES: Individual differences in proportion of stroma, epithelium, and luminal space components prostatic hyperplasia (BPH) may explain the differences in clinical outcome of the patients treated with alpha-reductase inhibitors or alpha-blocking agents and other alternative treatments. Knowledge of the individual proportions of these elements may orient the clinician toward different therapeutic approaches. To determine whether a single prostate biopsy is representative of the whole adenoma, using quantitative morphometry, we have compared the percentage of smooth muscle cells and glandular cells in one prostate needle biopsy and in the corresponding prostate adenoma removed by open surgery. METHODS: Quantification was made using a computerized image analysis system and immunohistochemical staining (actin antiactin for the smooth muscle cells and anti-prostate-specific antigen (PSA) for the epithelial cells) in 14 patients who underwent retropubic prostatectomy. RESULTS: Mean percentage of smooth muscle fibers, glandular epithelium, and glandular lumina in the prostate biopsy were, respectively, 34% (range, 20% to 42%, SD 5.9), 29% (range, 13% to 42%, SD 7.2), and 20% (range, 13% to 30%, SD 4.8). In the corresponding prostate adenoma, they were, respectively, 38% (range, 28% to 45%, SD 4.7), 32% (range, 25% to 40%, SD 4.5), and 19% (range, 13% to 34%, SD 6.1). The mean percentages of epithelial or glandular cells in the prostate biopsy and the corresponding adenoma were not statistically different (P > 0.05), whereas those for the smooth muscle cell percentage were different (P = 0.02). However, a statistically significant correlation between the whole adenoma and the needle biopsy sample was found in the percentage of smooth muscle cells (P = 0.028). Analyzing the morphometric data in conjunction with the serum PSA level and the volume of the adenoma, we found a statistically significant positive correlation between the volume of the adenoma and the ratio (percentage of epithelial cells/serum PSA level) (P = 0.009, r = 0.67). CONCLUSIONS: Major differences are found in the primary tissue composition of different hyperplastic prostates. Computerized histologic quantification of the different components of BPH in the entire adenoma and a needle biopsy demonstrate that a single prostate biopsy is representative of the entire prostate adenoma. Morphometric data from a single biopsy of the prostate adenoma in combination with the serum PSA level and the volume of the prostate adenoma could therefore help to orient medical treatment of BPH by patient selection based on the knowledge of the distribution of the various components of BPH.

Actins↗
PubMed2004

Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor.

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

Androgen Antagonists↗
PubMed2001

Changing therapeutic regimens in benign prostatic hyperplasia. Clinical and economic considerations.

About one-quarter of men aged 50 years and older experience voiding problems due to benign prostatic hyperplasia (BPH). Until about 10 years ago, surgery (particularly transurethral resection of the prostate) was the only effective treatment for symptomatic BPH. Over the last decade, several new treatments have been introduced. These include different types of medication (alpha-blockers and finasteride), thermotherapy, laser prostatectomy, needle ablation and vaporisation methods. The diffusion of these less invasive treatment modalities has resulted not only in a decrease in the age-adjusted surgery rates, but also in an increase of the total number of men treated for BPH. A large number of studies on clinical benefits and risks reveal that the conventional types of surgery remain the most effective treatments, whereas new interventional therapies require a shorter hospital stay and result in fewer short term complications. The efficacy of medication is lower than that of interventional treatments. Adverse effects include dizziness and orthostatic hypotension (alpha-blockers) and decreased sexual function (finasteride), but are generally mild. There is some evidence that medication and minimally invasive treatments may preclude eventual surgical treatment, but the precise effect is difficult to estimate because of differences in the study populations and the relatively short study periods. As a result of the dynamic nature of BPH treatment and the lack of long term data, the cost effects of the introduction of the various new treatments are also difficult to assess. Given the aging of the population and the growing percentage of patients with BPH for whom any type of treatment can be considered, a considerable increase of total costs can be expected. Long term prospective studies are necessary to gain insight into the most cost-effective treatment for different patient groups.

Costs and Cost Analysis↗
PubMed1995

Interstitial laser coagulation for benign prostatic hyperplasia: preliminary clinical results.

We report our early experience in the clinical application of interstitial laser coagulation of the prostate (ILCP) in the treatment of benign prostatic hyperplasia (BPH). Neodymium: YAG laser energy is transmitted via a specially designed interstitial thermotherapy light-guide. The light guides were inserted transurethrally into each lobe of the prostate by direct puncture, under direct visualization. The prostatic urethra is preserved during the procedure. From December 1993 to March 1994, 37 patients with symptomatic BPH were treated with ILCP. Treatment outcome was evaluated by the International Prostatic Symptom Score (I-PSS), flow rate, postvoided residual urine volume and quality of life score. Significant improvement in I-PSS and peak flow rate was observed at 3 months: I-PSS decreased from a mean of 19.3 to 10.4, and the peak flow rate increased from a mean of 7.2 to 9.4 ml/sec (p < 0.0001). The mean postvoided residual urine volume significantly decreased from 91 to 47 ml (p < 0.01). Two days after ILCP the serum prostate-specific antigen had increased by 860%, evidence of the significant tissue damage produced by laser irradiation. The quality of life score significantly decreased from a mean of 4.8 to 2.1 (p < 0.0001). No serious side-effects were observed. The early clinical results suggest that ILCP is safe and effective as a treatment of BPH and is less invasive than some other methods.

Aged↗
PubMed1991

Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia.

The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population.

Dose-Response Relationship, Drug↗
PubMed2001

Randomized study of transurethral resection of the prostate and combined transurethral resection and vaporization of the prostate as a therapeutic alternative in men with benign prostatic hyperplasia.

BACKGROUND AND PURPOSE: In recent years, various minimally invasive alternatives to transurethral resection have become available for treatment of benign prostatic hyperplasia (BPH). Transurethral electrovaporization has become popular, with reported improvements in subjective and objectives measures, but a high rate of postoperative irritative symptoms and lack of tissue for histologic examination are the two most commonly reported disadvantages of this procedure. To decrease the postoperative irritative symptoms while minimizing intraoperative and postoperative bleeding and also to obtain tissue samples, we have combined the techniques of vaporization, which was termed "vapor-cut." The aim of this randomized study was to compare the efficacy and safety of vapor-cut with those of the gold standard, transurethral resection. PATIENTS AND METHODS: A series of 100 consecutive men (mean age 63.5 +/- 3.4 years) with moderate to severe symptoms of prostatism were randomized to receive transurethral resection of the prostate (TURP) or vapor-cut since November 1997. Adverse events during the procedure, including serial changes in both serum hematocrit and sodium and postoperative irritative symptoms, were recorded after removal of the urethral catheter. Preoperative and postoperative symptom scores and maximum flow rates (Qmax) were obtained from all patients. The volume of the prostate was measured preoperatively and postoperatively using transrectal ultrasonography. The mean follow-up of the patients was 6.7 months (range 6-10 months). RESULTS: The mean operative times for the vapor-cut group and the TURP group were 48.2 minutes and 42.7 minutes, respectively (P > 0.05). In the TURP group and the vapor-cut group, the International Prostate Symptom Score (I-PSS) decreased from 21.6 to 5.0 (P < 0.01) and from 19.4 to 4.0 (P < 0.01), respectively, at 6 months. The Qmax increased from 9.2 +/- 2.6 mL/sec to 24.6 +/- 3.4 mL/sec (P < 0.01) in the TURP group and from 7.9 +/- 2.1 mL/sec to 26.7 +/- 3.7 mL/sec (P < 0.01) in the vapor-cut group. The mean reductions in the weight of the prostate were 49.8% in the TURP group (P < 0.05) and 53.6% in the vapor-cut group (P < 0.05). Both catheterization time and hospital stay were significantly shorter for the vapor-cut group (P < 0.05). The decreases in the mean serum sodium concentration were statistically insignificant in both groups. However, the decrease in the mean hematocrit was statistically significant in the TURP group but not in the vapor-cut group. No patient in either group had the transurethral resection syndrome or required blood transfusion. After removal of the urethral catheter, irritative voiding symptoms, usually associated with frequency, were greater in those patients treated with TURP than in those having vapor-cut. None of the patients demonstrated sphincteric incontinence, bladder neck contracture, or urethral stricture. CONCLUSION: From our preliminary experience, vapor-cut seems to give results comparable to those of TURP. Because there is almost no bleeding during vapor-cut, the procedure is performed under excellent visibility, which permits more rapid and effective resection.

Aged↗
PubMed2000

alpha(1)-Adrenoceptor selectivity and the treatment of benign prostatic hyperplasia and lower urinary tract symptoms.

The storage (irritative) and voiding (obstructive) symptoms associated with benign prostatic hyperplasia are generally attributed to prostate enlargement and increased prostatic smooth muscle tone mediated by the prevailing alpha(1)-adrenoceptors in the bladder neck and prostate. This results in obstruction and subsequent secondary changes to the bladder. However, there is growing evidence that many of these symptoms may be due to changes in extraprostatic alpha(1)-adrenoceptors, possibly alpha(1D)-adrenoceptors. Findings from the VA cooperative trial challenge the current theory that the common side effects associated with these agents are due to vascular action of alpha(1)-adrenoceptor blockers. Prostate Cancer and Prostatic Diseases (2000) 3, 76-83

Journal Article↗
PubMed1998

[Clinical efficacy and reduction effect on prostatic volume of chlormadinone acetate combined with tamsulosin hydrochloride in benign prostatic hyperplasia patients insufficiently treated with tamsulosin hydrochloride only].

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.

Adrenergic alpha-Antagonists↗
PubMed1993

Finasteride. A review of its potential in the treatment of benign prostatic hyperplasia.

Finasteride is a novel therapeutic agent that selectively inhibits the enzyme 5 alpha-reductase, thereby reducing prostatic dihydrotestosterone (DHT) levels and prostate size. In men with symptomatic benign prostatic hyperplasia (BPH), these effects have been associated with improvements in peak urinary flow rate and urological symptoms; withdrawal from therapy, however, results in regrowth of the adenoma and long term therapy is therefore necessary. Although the magnitude of clinical improvement seen with finasteride has been perceived to be modest [especially when compared with that associated with transurethral resection of the prostate (TURP)], it has been maintained in the medium term (up to 2 years) and thus may represent significant reversal of disease progression. Such beneficial effects, however, may not become apparent until completion of at least 6 months of therapy. Furthermore, since clinical studies have been unable to proactively identify a responsive subgroup, a trial period of 6 or possibly 12 months is necessary to assess patient responsiveness. Despite these potential shortcomings, the benefits of therapy appear to outweigh the risks. Indeed, finasteride is well tolerated; most adverse events have been related to sexual dysfunction (decreased libido, ejaculation disorders and impotence) and occurred in only a small proportion (about 2 to 3%) of patients. Moreover, although there has been concern that finasteride might mask the detection of prostate cancer through its decremental effects on serum prostate specific antigen (PSA) levels, careful monitoring in clinical trials appears to have avoided this problem. Thorough pretreatment assessment and periodic follow-up examinations for malignancy are therefore required in clinical practice. The role of finasteride in the treatment of patients with BPH is still emerging and will no doubt gain in clarity with further planned investigations. TURP (or other invasive procedures such as the insertion of prostatic stents in patients unsuitable for resection), continues to be the mainstay of therapy for those patients with severe symptomatic BPH. However, available data support a first line role for finasteride in the treatment of patients with uncomplicated symptomatic BPH. Within this setting, finasteride appears to offer a needed additional treatment option for those patients in whom surgery is not indicated, and may be of special benefit to the considerable proportion of patients who opt not to undergo prostatectomy.

Animals↗