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.     

Frictional work in double-sided tablet compression

OBJECTIVE: To critique the US Department of Health and Human Services Public Health Service, Agency for Health Care Policy and Research, Clinical Practice Guideline on Benign Prostatic Hyperplasia: Diagnosis and Treatment; and to provide an update on management and treatment of benign prostatic hyperplasia (BPH) since the Guideline was published. DATA SOURCES: A review of the published medical literature in MEDLINE from 1994 to April 1996, limited in focus to drug treatment of BPH, English language, and human subjects, was performed. STUDY SELECTION: Controlled clinical studies of drug treatment for symptomatic BPH that used objective parameters (e.g., urinary flow rate, prostatic volume, voiding symptom scores) were evaluated. A single reviewer assessed each study. DATA EXTRACTION: Study methods, inclusion and exclusion criteria, and treatment outcomes were assessed for all studies. Independent extraction was performed by a single observer. DATA SYNTHESIS: Management of BPH is directed at ameliorating voiding symptoms. For moderate or severe BPH, medical or surgical therapy should be offered to the majority of patients. Medical therapy options include alpha-adrenergic antagonists and finasteride. The former offer the advantage of a more prompt onset of action (within weeks) when compared with finasteride. Finasteride produces a lower response rate and smaller improvement in voiding symptoms. Combination therapy of terazosin and finasteride has not been proven to be more effective than terazosin monotherapy. CONCLUSIONS: When medical therapy is indicated for moderate or severe BPH, alpha-adrenergic antagonists exhibit a faster onset of action and produce greater improvement of voiding symptoms than does finasteride.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Laser prostatectomy: initial experience and urodynamic follow-up

OBJECTIVES: An evolving technology for the treatment of bladder outlet obstruction due to benign prostatic hyperplasia (BPH) is the use of the side-firing neodymium: yttrium-aluminum-garnet (Nd:YAG) laser to achieve prostatic tissue ablation. The purpose of this study was to determine the short-term efficacy of this procedure in both an objective and subjective manner. METHODS: We examined this technique by carefully evaluating our first 25 men undergoing the procedure. Each patient was subjected to careful symptom score analysis using the American Urological Association symptom index and multichannel urodynamics, including pressure-flow studies both preoperatively and at 3 months postoperatively. RESULTS: At the 3-month follow-up, symptom scores improved from a preoperative mean of 11.4 to 7.2 and the mean maximum flow rate improved from 6.1 to 14.5 cc/s. These are both significant at P < 0.001. Statistically similar improvement was seen in detrusor pressure at opening and at maximum flow. Eighty percent of the men studied had at least a 50% reduction in symptom score and a 50% improvement in flow rate. CONCLUSIONS: We conclude that laser prostatectomy is a promising minimally invasive treatment for bladder outlet obstruction secondary to BPH and deserves further evaluation at longer terms of follow-up.     

A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 Study Group

PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND METHODS: Patients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period. RESULTS: When efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point. CONCLUSIONS: Tamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.     

A comparison of transurethral resection of the prostate and medical treatment for the patient with moderate symptoms of benign prostatic hyperplasia

Transurethral resection of the prostate is the most common surgical treatment for benign prostatic hyperplasia. We conducted a prospective randomized clinical trial to compare this surgery with medical treatment in men with moderate symptoms of benign prostatic hyperplasia. Of 98 men over the age of 54 years who were screened between June 1993 and June 1995, 53 were studied (25 in the surgery group and 28 in the medication group). Patients' symptoms and the degree to which they were bothered by urinary difficulties were measured with standardized questionnaires and medical evaluations. The men randomly assigned to the surgery group underwent surgery within 2 weeks after the assignment. Surgery was not associated with an impotence or urinary incontinence. The follow-up period was 1 year. Surgery was significantly associated with improvement in residual urinary volume and peak flow rate; and also in the scores for urinary difficulties, sexual performance and interference with activities of daily living (P < 0.001 for all comparisons). We concluded that for patients with moderate symptoms of benign prostatic hyperplasia, surgery is more effective than medication in improving genitourinary symptoms and enhancing the quality of life. Thus, medication as treatment should be reserved for patients who are less bothered by urinary difficulty or who wish to delay surgery.     

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.     

The natural history of patients with benign prostatic hyperplasia as diagnosed by North American urologists

PURPOSE: We defined outcomes for men with a clinical diagnosis of benign prostatic hyperplasia. MATERIALS AND METHODS: We followed for 4 years 500 candidates for elective prostatectomy treated nonoperatively in 5 North American urology practices. RESULTS: There were 371 survivors with complete data at 4 years. Of 60 men with mild, 245 with moderate and 66 with severe baseline symptoms 10, 24 and 39%, respectively, had undergone surgery; 27, 31 and 27%, respectively, were on pharmacological therapy, and 63, 45 and 33%, respectively, were off active treatment at 4 years. Mild or moderate symptoms were noted at 4 years in 83, 59 and 23% of the patients, respectively, while 17, 41 and 77%, respectively, had severe symptoms or had undergone surgery. CONCLUSIONS: Outcomes for men with a clinical diagnosis of benign prostatic hyperplasia depend on initial symptom severity. However, the course of symptoms also varies among patients even with the same initial symptom severity.     

Monoclonal antibody FC-5.01, directed against CD63 antigen, is internalized into cytoplasmic vesicles in the IIB-BR-G human breast cancer cell line

PURPOSE: Benign prostatic hyperplasia is common among men who may be candidates for prostate cancer screening using prostate-specific antigen (PSA) testing. Patterns of PSA testing among men with evidence of benign prostatic hyperplasia have not been studied. METHODS: We examined the prevalence and correlates of a self-reported history of PSA testing. In 1994, 33,028 US health professionals without prostate cancer aged 47 to 85 years provided information on prior PSA testing, lower urinary tract symptoms characteristic of benign prostatic hyperplasia, history of prostatectomy, and prostate cancer risk factors. In 1995, a subset of 7,070 men provided additional information on diagnosis and treatment of benign prostatic hyperplasia. RESULTS: From 39% of men in their 50s to 53% of men in their 80s reported PSA testing in the prior year (P <0.0001 for trend with age). Men were more likely to report PSA testing if they had lower urinary tract symptoms characteristic of benign prostatic hyperplasia (age-adjusted odds ratio for severe symptoms 2.2, 95% confidence interval 1.8 to 2.6), a prior history of prostatectomy (age-adjusted odds ratio 1.1, 95% confidence interval 1.02 to 1.2), or a physician diagnosis of benign prostatic hyperplasia (odds ratio 1.9, 95% confidence interval 1.7 to 2.2; adjusted for age, signs or symptoms of benign prostatic hyperplasia, and prostate cancer risk factors). CONCLUSIONS: These US health professionals reported preferential use of PSA testing among men least likely to benefit from early cancer detection (older men) and among men most likely to have a false-positive PSA result (men with benign prostatic hyperplasia). Physician and patient education are needed to promote more rational and selective use of this screening test.     

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.     

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.     

A nationwide survey of practicing urologists: current management of benign prostatic hyperplasia and clinically localized prostate cancer

PURPOSE: Our aim was to define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. MATERIALS AND METHODS: In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%. RESULTS: Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH. Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry. Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably. CONCLUSIONS: These data provide a picture of current practice regarding the management of BPH and prostate cancer.     

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.     

Finasteride: a review of its use in male pattern hair loss

The 5alpha-reductase inhibitor finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT), the androgen responsible for male pattern hair loss (androgenetic alopecia) in genetically predisposed men. Results of phase III clinical studies in 1879 men have shown that oral finasteride 1 mg/day promotes hair growth and prevents further hair loss in a significant proportion of men with male pattern hair loss. Evidence suggests that the improvement in hair count reported after 1 year is maintained during 2 years' treatment. In men with vertex hair loss, global photographs showed improvement in hair growth in 48% of finasteride recipients at 1 year and in 66% at 2 years compared with 7% of placebo recipients at each time point. Furthermore, hair counts in these men showed that 83% of finasteride versus 28% of placebo recipients had no further hair loss compared with baseline after 2 years. The clinical efficacy of oral finasteride has not yet been compared with that of topical minoxidil, the only other drug used clinically in patients with male pattern hair loss. Therapeutic dosages of finasteride are generally well tolerated. In phase III studies, 7.7% of patients receiving finasteride 1 mg/day compared with 7.0% of those receiving placebo reported treatment-related adverse events. The overall incidence of sexual function disorders, comprising decreased libido, ejaculation disorder and erectile dysfunction, was significantly greater in finasteride than placebo recipients (3.8 vs 2.1%). All sexual adverse events were reversed on discontinuation of therapy and many resolved in patients who continued therapy. No other drug-related events were reported with an incidence > or =1% in patients receiving finasteride. Most events were of mild to moderate severity. Oral finasteride is contraindicated in pregnant women because of the risk of hypospadias in male fetuses. CONCLUSIONS: Oral finasteride promotes scalp hair growth and prevents further hair loss in a significant proportion of men with male pattern hair loss. With its generally good tolerability profile, finasteride is a new approach to the management of this condition, for which treatment options are few. Its role relative to topical minoxidil has yet to be determined.