Pharmacologic therapy for prostatism

Although the general approach to management of a sufficient degree of benign prostatic hyperplasia in the past was surgical intervention (transurethral resection of the prostate), the current availability of effective pharmacologic therapy has changed the initial management strategy. At present, two types of drugs are available for treatment of prostatism: (1) selective alpha-adrenergic blocking agents (terazosin, doxazosin, and tamsulosin) and (2) an inhibitor of the 5 alpha-reductase enzyme (finasteride). Pharmacologic blockade of the alpha(1)-adrenoceptors is thought to result in relaxation of the smooth muscle in the prostate and bladder neck, which reduces urethral resistance, improves voiding function, and minimizes the symptoms of prostatism. These effects may be noted by the patient within several weeks after initiation of treatment. The mechanism of action of finasteride is a blocking of the conversion of testosterone to dihydrotestosterone and an associated volume shrinkage of the prostate. On the average, a 25% reduction in prostate volume can be achieved, but a period of 12 months or longer of finasteride therapy is needed for maximal shrinkage and maximal decrease in symptoms of prostatism. The expanding population of middle-aged and elderly men with prostatism of moderate severity will undoubtedly prompt the development of additional pharmacologic options for treatment of prostatism and benign prostatic hyperplasia.     

Medical management of benign prostatic hyperplasia: a review

Benign prostatic hyperplasia (BPH) is a common disease affecting elderly men with 70% of men over 70 years showing microscopic evidence of hyperplasia. Transurethral resection of the prostate is the gold standard treatment. Medical management of BPH has involved the use of plant extracts, amino acids, kampo and animal organ preparations in various countries with unsatisfactory results. The use of alpha adrenergic antagonists dates back twenty years representing a major breakthrough in the treatment by relaxation of the dynamic contraction of smooth muscle component of prostatic obstruction. The evolution of alpha antagonist therapy resulted in clinical trials with selective antagonists such as prazosin, alfuzosin, indoramin, terazosin and doxazosin all of which achieve similar effective relief of obstructive symptoms as phenoxybenzamine, but with fewer side effects related to postural hypotension. 5-alpha reductase inhibitors, finasteride and episteride, recently synthesised act on the static component of obstruction caused by the enlarging prostate. They inhibit conversion of testosterone to the potent intracellular androgen dihydrotestosterone (DHT) resulting in the reduction of prostate volume and improvement of obstructive symptoms. Clinical trials with finasteride for three years indicate that 63% of patients had a reduction of greater than 20% in prostatic volume and 42% had a decrease of greater than 30% with a mean increase peak flow rate of 2.4 mls/s equivalent, to 20 years reversal of disease progression.     

Factors related to delayed treatment and posttreatment symptom severity in Taiwanese patients with benign prostatic hyperplasia

We evaluated the sociodemographic and clinical factors of delayed treatment and posttreatment symptom severity in outpatients with benign prostatic hyperplasia (BPH). The study included 146 BPH patients treated at the National Taiwan University Hospital in early 1997. All patients were treated with alpha-adrenergic antagonists or finasteride for at least 2 weeks. A questionnaire based on Andersen's Health Behavior Model was used to assess various sociodemographic features, while the pre- and posttreatment symptoms severity was rated according to the International Prostate Symptom Score (IPSS). Multiple logistic regression was used to assess the associations of these factors with delayed treatment and posttreatment symptom severity. Subjects who had recently quit smoking or were blue-collar workers tended to delay treatment, while those who chose a medical center as the care provider for chronic diseases tended to be less likely to delay treatment. However, none of these associations were statistically significant. No enabling factors (income, insurance) or need factors (symptom scores) evaluated were associated with delayed treatment. Predisposing factors associated with higher posttreatment symptom severity were delayed treatment (over 12 months) (adjusted odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.16-6.16), quitting smoking (adjusted OR: 4.47, 95% CI: 1.34-14.94), and having never smoked (adjusted OR: 3.73, 95% CI: 1.15-12.11). Subjects with severe pretreatment symptoms were far more likely than subjects with mild pretreatment symptoms to have severe symptoms after treatment (adjusted OR: 52.69, 95% CI: 54.46-621.90). Our findings, though based on a limited number of subjects, suggest sociodemographic factors rather than objective clinical attributes (prostate specific antigen level, prostate volume, and urodynamic results) are associated with delayed treatment in Taiwanese men with BPH. Both pretreatment symptom severity and sociodemographic factors are related to posttreatment symptom severity.     

Dependency scoring in a critical care area: a direct nursing assessment method

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.     

Pharmacokinetic interaction between finasteride and terazosin, but not finasteride and doxazosin

The alpha 1-adrenoceptor antagonists doxazosin and terazosin and the 5 alpha-reductase inhibitor finasteride are used in the treatment of benign prostatic hyperplasia. The aim of this study was to assess the potential pharmacokinetic interaction of doxazosin or terazosin when coadministered with finasteride. This was a randomized, placebo-controlled, multi-center study. Ninety healthy men were assigned to one of six treatment groups: doxazosin; doxazosin plus finasteride; terazosin; terazosin plus finasteride; placebo; and placebo plus finasteride. Plasma concentrations, maximum plasma concentration (Cmax), time to maximum concentration (tmax), and area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) of doxazosin, terazosin, and finasteride were determined. Ratios of Cmax and AUC for doxazosin and terazosin were not significantly altered by coadministration with finasteride. The Cmax and AUC0-24 of finasteride were not significantly altered by coadministration with doxazosin. However, Cmax and AUC0-24 of finasteride were significantly higher after coadministration with terazosin. There is no statistically significant pharmacokinetic interaction between finasteride and doxazosin; however, there is a statistically significant interaction between finasteride and terazosin, which affects the pharmacokinetics of finasteride but not those of terazosin. The clinical significance of this interaction remains to be determined.     

Restricted occurrence of an unusual ganglioside GD1 alpha in rat brain and its possible involvement in dendritic growth of cerebellar Purkinje neurons

The type and magnitude of urinary symptoms, the behavioral adjustments necessitated by such symptoms, and the degree of patient satisfaction with treatment and current health were evaluated in 102 men with symptomatic benign prostatic hyperplasia (BPH) who had been receiving finasteride for 9 to 12 months. We also evaluated these variables in a group of 109 men who had undergone transurethral resection of the prostate (TURP) for symptomatic BPH 9 to 12 months before the study. A validated, patient-directed telephone questionnaire was used to solicit information. Men with BPH who continued to receive finasteride therapy for at least 9 months experienced considerable symptomatic relief during the first year of therapy, and reported a high degree of satisfaction with their urinary condition. Urinary symptoms either resolved or occurred only rarely in the majority of men treated with finasteride. Most of the BPH patients taking finasteride (78%) indicated that urinary symptoms did not restrict their participation in normal activities. Fifty-four percent of finasteride patients rated their current health as excellent or very good, and 87% indicated that their current condition represented an improvement over their pretreatment state. Responses in the men treated with TURP reinforced previous observations about the effectiveness of this treatment in men with symptomatic BPH. Thus in the appropriate patient group, finasteride represents an effective management option for symptomatic BPH.     

Digital image ratio: a new radiographic method for quantifying changes in alveolar bone. Part II: Clinical application

BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.     

Evaluation of patients with bladder outlet obstruction and mild international prostate symptom score followed up by watchful waiting

OBJECTIVES: To examine the variability of bladder outlet obstruction and mild lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH) followed up by watchful waiting. METHODS: The International Prostate Symptom Score (IPSS) has four questions related to voiding symptoms and three related to filling symptoms. Scores of 0 to 7, 8 to 19, and 20 to 35 represent mild, moderate, and severe symptoms, respectively. Over a period of 36 months the IPSS questionnaire was administered to 479 patients 50 to 81 years old (mean age 63) with BPH. A pressure-flow study was used to determine the presence of bladder outlet obstruction. On the basis of their scores, the patients were classified into 50 with mild, 227 with moderate, and 202 with severe symptoms. In the present study only patients with a mild score were analyzed. RESULTS: Of 50 patients with mild symptoms, 16 (32%) had bladder outlet obstruction. After a period of 9 to 22 months (mean 17) of watchful waiting, these 16 patients were reviewed. Twelve (75%) of the 16 had bladder outlet obstruction reconfirmed by pressure-flow studies, and 3 (18.8%) of 16 had increased symptoms (moderate symptomatic) and underwent treatment (1 began pharmacologic treatment, and 2 chose transurethral resection). A total of 4 (25%) of 16 patients still had mild voiding disturbances and refused the second urodynamic evaluation. The remaining 34 patients with no obstruction had annual routine follow-up and had persistent mild symptom scores and normal uroflowmetric results. These patients did not undergo another pressure-flow evaluation. CONCLUSIONS: A pressure-flow study is routinely avoided in patients with a mild IPSS. From symptoms alone it was not possible to diagnose bladder outlet obstruction in these patients. Pressure-flow studies and symptom profiles measure different aspects of the clinical condition. After a mean follow-up of 17 months of watchful waiting, 13 (81.2%) of 1 6 patients were clinically stable. Because the need for therapy is dictated by quality of life, it is difficult to propose treatment for patients with minimal symptoms, even in the presence of bladder outlet obstruction.     

Positioning of positively charged residues in the V3 loop correlates with HIV type 1 syncytium-inducing phenotype

The effects of urinary symptoms on health-related quality of life (HRQL) are important in therapeutic decision making. Few have evaluated the treatment effects on HRQL in men with benign prostatic hyperplasia (BPH), even though increased urinary symptoms are associated with greater worry, bother, and interference with living activities. We report on patient assessments of such disease-specific measures as well as general HRQL measures from two placebo-controlled clinical trials of finasteride in the treatment of symptomatic BPH. Patients treated with finasteride appeared to have greater improvement than placebo-treated patients in disease-specific measures and in patient global assessment. The treated group appeared to have a greater mean increase in sexual domain scores. As expected, general measures (health rating, life satisfaction, ladder of life) changed little. Thus, treatment with finasteride appears to reduce bother, worry, and activity interference due to symptoms but in a small percentage of men may lead to slightly reduced sexual function.     

Efficacy and safety of luteinizing hormone-releasing hormone antagonist cetrorelix in the treatment of symptomatic benign prostatic hyperplasia

As the life expectancy for men increases, more cases of benign prostatic hyperplasia (BPH) will be expected. Symptomatic BPH causes morbidity and can lower the quality of life. We investigated whether short term administration of the LH-releasing hormone antagonist cetrorelix could provide an improved treatment for men with BPH. Thirteen patients with moderate to severe symptomatic BPH were treated with cetrorelix (5 mg, s.c., twice daily for 2 days followed by 1 mg/day, s.c., for 2 months). Patients were evaluated at baseline, during treatment, and up to 18 months after therapy. We determined the effects of cetrorelix on the International Prostate Symptom Score (IPSS), Quality of Life score, sexual function, prostate size, uroflowmetry, and hormonal levels. Treatment with cetrorelix produced a decline of 52.9% (P < 0.0001) in IPSS, a 46% improvement in the Quality of Life score (P < 0.001), a rapid reduction of 27% (P < 0.006) in prostatic volume, and an increase in peak urinary flow rates by 2.86 mL/s. Serum testosterone fell to castrate levels on day 2, but was inhibited only by 64-74% during maintenance therapy, and after cessation of treatment returned to normal. During long term follow-up, most patients continued to show a progressive improvement in urinary symptoms (decline in IPSS from 67% to 72% at weeks 20 and 85, respectively) and an enhancement of sexual function, and prostatic volume remained normal. Our study demonstrates that in patients with symptomatic BPH, treatment with cetrorelix is safe and produces long term improvement.     

Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group

OBJECTIVES: To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH). METHODS: Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention). RESULTS: Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo. CONCLUSIONS: Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.     

Transurethral microwave thermotherapy: what role should it play versus medical management in the treatment of benign prostatic hyperplasia?

Both transurethral microwave thermotherapy (TUMT) and medical management by alpha-blockade or 5-alpha-reductase inhibition are increasingly being considered as alternatives to surgery for treatment of patients with benign prostatic hyperplasia (BPH). We review current evidence supporting the effectiveness and safety of TUMT and medical management. Factors for consideration in appropriately selecting patients for TUMT versus medical management are suggested. Available data indicate that TUMT confers greater long-term benefits than medical management as judged by symptom score and peak urinary flow rate improvements. TUMT-associated morbidity is comparatively low. Alpha-blockade affords more rapid relief than TUMT for patients with BPH; however, other strategies such as the use of temporary intraurethral endoprostheses during the acute post-TUMT recovery period may diminish or abolish the differences in time-course of symptom and flow rate improvement between TUMT and alpha-blockade. 5-Alpha-reductase inhibition with finasteride offers a favorable side-effect profile, although the magnitude of symptom and flow rate improvements is modest, and maximal effects of finasteride do not become manifest until after several months of treatment. As TUMT continues to evolve, increasing attention is being accorded the delivery of high thermal doses and precise targeting of the thermal energy delivered. The development of alpha-blockers with a more favorable side-effect profile continues to be a major focus of investigation. The potential clinical utility of combination therapy with TUMT and alpha-blockade is currently under investigation.     

Treatment of benign prostatic hyperplasia with alpha 1-adrenoreceptor antagonists

The International Consensus Committee recommends alpha-adrenoceptor antagonists for medical therapy benign prostatic hyperplasia (BPH). This review evaluates 52 randomized, placebo-controlled, double-blind studies, including 10399 patients and, moreover, 40 clinical studies including 33600 patients undergoing treatment with alpha-adrenoceptor antagonists because of BPH. The therapeutic efficacy of all alpha-adrenoceptor antagonists is more or less the same. There is an average improvement of symptom scores of about 35% and a mean increase in maximum flow rate of between 1.8 and 2.5 ml/s. Studies investigating long-term efficacy and quality of life tend to show a long-term benefit. The introduction of selective alpha 1-adrenoceptor antagonists led to a significant reduction of side effects. These side effects are primarily caused by the vasodilatatory qualities of alpha-blockers. The development of so-called uroselective alpha 1A-adrenoceptor antagonists in the treatment of BPH possibly leads to further reduction of side effects related to vasodilatation. Medical therapy by alpha 1-adrenoceptor antagonists seems to be superior to phytotherapy or treatment with 5 alpha-reductase inhibitors, as shown in a few studies. So far, it is not clear whether there is any advantage of combination therapy. The application of alpha 1-adrenoceptor antagonists is indicated in all cases of symptomatic BPH, excluding patients who need TUR-P (e.g., middle lobe) or prostatectomy. If patients are either willing or eligible to have surgical treatment, therapy by alpha 1-adrenoceptor antagonists is a rational choice. Comparative clinical trials have to be conducted to provide additional information and to clarify which alpha-blocker may be recommended as the first choice. Until then, those alpha 1-adrenoceptor antagonists should be used for which safety and efficacy are well documented and which can be prescribed at reasonable costs.     

Genetic alterations in the development of mammary and prostate cancer in the C3(1)/Tag transgenic mouse model

PURPOSE: Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels. MATERIALS AND METHODS: In a randomized, placebo controlled, double-blind trial 40 men with histologically confirmed BPH (age range 52 to 78 years) were treated with either 5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months. Prostate volume was assessed by transrectal ultrasound. Serum levels of free and total PSA were measured from archived serum samples stored at -70C at baseline and for as long as 9 months of treatment. RESULTS: In the finasteride group mean total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6 months of treatment (50% decrease, p <0.01). In the placebo group, with similar baseline levels, no significant change was observed. PSA density declined significantly in finasteride treated men (p <0.01) but not in men receiving placebo. The mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo. CONCLUSIONS: Total PSA serum levels decreased by an average of 50% during finasteride therapy but percent free PSA did not change significantly. This information is potentially useful in the interpretation of PSA data used for early detection of prostate cancer in men receiving finasteride. However, further studies are required to demonstrate the use of percent free PSA to detect the development of cancer.     

An evaluation of the use made of cosmetic and functional prostheses by unilateral upper limb amputees

PURPOSE: To review the available data on the treatment of chronic stable angina and formulate a rational approach to the use of pharmacologic therapy, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass graft surgery (CABG). DATA SOURCES: A MEDLINE search of English-language literature published between 1976 and 1996 and the bibliographies of relevant articles. STUDY SELECTION: Primary research articles, meta-analyses, and meeting abstracts related to the management of chronic stable angina with an emphasis on comparisons of medical therapy, PTCA, and CABG. DATA EXTRACTION: Three trials comparing medical therapy with PTCA, seven trials comparing medical therapy with CABG, and nine trials comparing PTCA with CABG. DATA SYNTHESIS: Low-risk patients with single-vessel coronary artery disease and normal left ventricular function had greater alleviation of symptoms with PTCA than with medical treatment; mortality rates and rates of myocardial infarction were unchanged. In high-risk patients (risk was defined by severity of ischemia, number of diseased vessels, and presence of left ventricular dysfunction), improvement of survival was greater with CABG than with medical therapy. In moderate-risk patients with multivessel coronary artery disease (most had two-vessel disease and normal left ventricular function), PTCA and CABG produced equivalent mortality rates and rates of myocardial infarction. CONCLUSIONS: In low-risk patients, a strategy of initial medical therapy is reasonable. In moderate-risk patients, PTCA and CABG produce similar mortality rates and rates of myocardial infarction but PTCA-treated patients require more revascularization procedures. In high-risk patients, CABG is usually preferred.     

The effect of 5-alpha-reductase inhibitors on benign prostatic hyperplasia

The prevalence of BPH is high in elderly men with more than 60% of patients over the age of 60 experiencing some form of prostatism. Balancing the superior benefit of TUR/P are the small but significant risks and complications of surgery and the high cost of the procedure. The WHO guidelines recommend finasteride or alpha-blockers as treatment options for men with bothersome symptoms. Finasteride therapy reduces the volume of the hyperplastic prostate gland by more than 20%, improves the urinary flow rate and the symptoms associated with bladder outlet obstruction. Although statistically significant, results obtained with finasteride are just slightly better than placebo and TUR/P still offers the greatest improvement of symptoms. Finasteride is well tolerated and adverse events are rare. However, it decreases serum PSA (prostate specific antigen) by 50%, suggesting careful monitoring and exclusion of prostate cancer before initiation and during therapy. Current research is focusing on developing new 5-alpha-reductase inhibitors (type I and II) using polyunsaturated fatty acids and nonsteroidal inhibitors. Given the multifactorial nature of BPH, further clinical trials combining 5-alpha-reductors inhibitors and 5-alpha-receptor blockers are still needed.     

The treatment of benign prostatic hyperplasia with alpha blockers in men over the age of 80 years

OBJECTIVE: To determine the safety and efficacy of alpha blockade with doxazosin and terazosin in men over the age of 80 years with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Thirty-six men (mean age 83.6 years, SD 5.6, range 80-96) received either doxazosin 4 mg (11 men) or 8 mg (10 men), or terazosin 5 mg (five men) or 10 mg (10 men), once daily at night. Twenty-eight men (78%) were on other anti-hypertensive medication; the type and dosage were not changed during the study. Efficacy and safety were assessed using measurements of peak urinary flow rate, symptom scores and the incidence of adverse events. RESULTS: Of the 36 men, 33 (92%) remained on study medication at 6 months; the remaining three (8%) discontinued because of asthenia. After 3 months of treatment, the peak urinary flow rate increased significantly (P < 0.008) for both doxazosin (+3.7 mL/s) and terazosin (+3.2 mL/s). The American Urological Association symptom score improved significantly (P < 0.01) with both alpha blocker after 3 months of treatment and efficacy was maintained at 6 months. There were small, non-significant decreases in blood pressure in patients receiving doxazosin or terazosin, but no differences between patients who were normotensive at baseline and those whose blood pressure was controlled by other anti-hypertensive drugs. CONCLUSION: These results suggest that alpha blockade with either doxazosin or terazosin is well tolerated and effective in older men with symptomatic BPH. Furthermore, patients on concomitant anti-hypertensive medication need no alteration of their therapeutic regimen before the initiation of alpha blockade for BPH.     

Serial prostate-specific antigen measurements in men with clinically benign prostatic hyperplasia during a 12-month placebo-controlled study with terazosin. HYCAT Investigator Group. Hytrin Community Assessment Trial

OBJECTIVES: To prospectively analyze whether the treatment of men with clinically benign prostatic hyperplasia (BPH) with alpha blocking agents affects the serum prostate-specific antigen (PSA) levels, and to determine the magnitude of such effect. METHODS: Serial PSA measurements were performed using the Abbott IMx assay over 1 year in 134 men over the age of 55 years participating in the Hytrin Community Assessment Trial (HYCAT). HYCAT is a 1-year, randomized, placebo-controlled, double-blinded study of the alpha1-adrenergic antagonist terazosin. All men had lower urinary tract symptoms and a clinical diagnosis of BPH with an American Urological Association (AUA) symptom index of 13 points or more, an AUA bother score of 8 points or more, and a peak urinary flow rate of less than 15 mL/s. PSA was measured at baseline and at 8, 26, 39, and 52 (end of study) weeks. RESULTS: Baseline serum PSA levels weakly correlated with patients' age at study entry, and modestly with residual urine (positive correlation) and peak flow rate (negative correlation), although none of the levels were statistically significant. Changes of serum PSA during the course of the study did not correlate with either one of the symptom severity or bother assessment tools, residual urine, or peak flow rate. Mean PSA increased from a baseline of 2.5+/-0.22 ng/mL (mean+/-SE) by 0.5+/-0.11 ng/mL in the placebo-, and from 2.7+/-0.23 ng/mL by 0.3+/-0.11 ng/mL in the terazosin-treated patients (P = 0.36 by ANOVA). There were no differences in the changes in serum PSA when patients were stratified by decade of life according to the age-specific PSA reference ranges, or by the final dose of terazosin (2, 5, or 10 mg daily). CONCLUSIONS: The treatment of men with lower urinary tract symptoms and clinical BPH with the alpha1-adrenergic antagonist terazosin does not affect serum PSA concentration, and thus does not confound longitudinal monitoring of serum PSA levels in patients at risk for prostate carcinoma.     

Prostate tissue composition and response to finasteride in men with symptomatic benign prostatic hyperplasia

PURPOSE: We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial. MATERIALS AND METHODS: Men with symptomatic BPH (52 to 78 years old) were randomly assigned to 6 months of treatment with finasteride (26) or placebo (15). Outcome measures were clinical (urinary symptom score and flow rate), chemical (serum prostate specific antigen and dihydrotestosterone levels), volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and zonal prostate volumes) and histological (morphometry of prostate sextant biopsies, separated into inner and outer gland segments, to measure the percent epithelium, stroma and glandular lumen). RESULTS: In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates (not significant) with significant decreases (p < 0.01) in prostate specific antigen (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on stroma or lumina. We also found a linear correlation between pretreatment inner gland epithelial content and prostate volume decrease induced by the drug (tau = 0.58, p = 0.01). CONCLUSIONS: Finasteride treatment results in a major suppression of prostate epithelium, which is most pronounced in the inner gland. Moreover, a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gland. These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH.     

Tamsulosin and chlormadinone for the treatment of benign prostatic hyperplasia. The Kobe University YM617 Study Group

The recent introduction of selective alpha-adrenoceptor blockers adds a further therapeutic option for the treatment of benign prostatic hyperplasia (BPH). Tamsulosin, a selective alpha 1-blocker, has proved effective in relieving irritative and obstructive symptoms caused by BPH. To investigate whether the combination of tamsulosin with the anti-androgenic drug chlormadinone is of further therapeutic benefit, 80 patients randomly received tamsulosin 0.2 mg daily, chlormadinone 50 mg daily or a combination of tamsulosin 0.2 mg and chlormadinone 50 mg daily for 16 weeks. Greater improvement in subjective symptoms of BPH was obtained with either tamsulosin alone or in combination with chlormadinone than with chlormadinone alone. However, the greatest improvement in objective uroflowmetric data was obtained with chlormadinone in combination with tamsulosin. Thus, the combination of tamsulosin with chlormadinone appears to be more beneficial than either of these agents used as monotherapy. Further investigation is required to fully evaluate the therapeutic effects of this combination. After the trial period one-third of the chlormadinone and tamsulosin/chlormadinone-treated patients needed no further treatment due to the satisfactory relief of symptoms. At 12 months follow-up, however, one-fourth of the patients had undergone transurethral resection of the prostate (TUR-P) regardless of medication. This suggests a limitation of the medical treatment of BPH.