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.     

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.     

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.     

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.     

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.     

Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer

OBJECTIVE: To analyse the efficacy, correlations and adverse-event profile of placebo therapy from the initial placebo run-in period to beyond 2 years of treatment. PATIENTS AND METHODS: The effects of placebo therapy on prostate size, maximum urinary flow rate (Qmax) and symptoms were analysed, and adverse drug experiences documented, for a period of 25 months in 303 patients randomized to the placebo arm of a controlled trial evaluating finasteride in the treatment of BPH (the Canadian PROSPECT study). RESULTS: For all variables, the values during follow-up were significantly different from baseline (P < or = 0.001). Transrectal ultrasonography confirmed a progressive increase in prostate volume over 25 months (+8.4%) but Qmax improved for the first 5 months (to 1.4 mL/s over baseline) and remained 1.0 mL/s more than baseline at 25 months. The total symptom score improved by -2.9 points in the first 2 months on placebo and was ultimately 2.3 points below baseline at 25 months. The extent of the placebo response for symptoms (r=0.08, P=.180) and Qmax (r=0.04, P=0.550) was independent of age, but the response correlated with the initial severity of symptoms (r= -0.394, P < or = 0.001) and initial Qmax (r= -0.134, P=0.023). Patients with a prostate of < or = 40 mL had a clinically more important placebo response than those with larger prostates. In all, 246 patients (81.2%) reported adverse events thought to be secondary to placebo therapy. The most common complaint was urogenital (40.3%), specifically impotence (6.3%) and decreased libido (6.3%); 13.2% of patients discontinued placebo therapy because of significant adverse reactions. CONCLUSIONS: Placebo therapy rapidly produces a significant improvement in Qmax and symptoms of BPH but also causes clinically important adverse effects. The beneficial effect fades but remains after 2 years.     

Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate

OBJECTIVES: Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide. METHODS: Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values. RESULTS: The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). CONCLUSIONS: Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed.     

Cholestasis assessment by activity of antioxidant enzymes and composition of plasma lipoproteins in patients with liver diseases]

23 patients with benign prostatic hyperplasia (BPH) aged 60-82 years underwent transurethral resection (TUR) of the prostate in different periods after thermal treatment which had appeared uneffective or brought complications. In the performance of the endoscopic techniques we found macroscopic changes of the prostatic parts of the urethra and bladder cervix characteristic for certain thermal impact (energy, power, site of exposure). Intraoperative bleeding of prostatic tissue was also different depending primarily on the time which had passed after the thermal treatment. Minimal bleeding occurred at least 3 months after the thermotherapy. Thus, thermal treatment of the prostate can be used in combined treatment of BPH for reducing intra- and postoperative hemorrhage due to subsequent TUR. Among the methods of thermal therapy, transurethral microwave thermotherapy is preferable as minimally invasive and deeply penetrating into the depth of the prostatic gland with maximal effect. TUR of the prostate should be performed not earlier than 3 months after thermotherapy which is indicated only for patients at high risk of intraoperative hemorrhage because of unaffected circulation. Therefore, it is desirable to include transrectal dopplerography of the prostate to urological examination of BPH patients.     

G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension

OBJECTIVES: To evaluate the response of testicular androgen ablation in patients with advanced prostate cancer with a biochemical recurrence after finasteride or combined finasteride and flutamide therapy. METHODS: Eighteen hormone na?ve men with advanced prostate cancer (10 with detectable prostate-specific antigen [PSA] levels after radical prostatectomy, 4 with rising PSA levels after definitive radiation therapy, and 4 with Stage D2 disease) were treated with finasteride (5 mg/day) alone or in combination with flutamide (250 mg three times a day). All men experienced an initial reduction in serum PSA, but later had treatment failure with two consecutive rising PSA measurements. All men were then treated with testicular androgen ablation (bilateral orchiectomy in 15 and luteinizing hormone-releasing hormone analogue in 3). RESULTS: Overall, serum PSA declined by more than 80% in 15 (83%) of 18 and to undetectable levels in 14 (78%) of 18. With a median+/-semi-interquartile range follow-up of 22+/-14.5 months from the initiation of hormone therapy, 12 (67%) of 18 currently have undetectable PSA levels. Two men having rising serum PSA levels above 100 ng/mL and 1 man has died from complications of metastatic prostate cancer. CONCLUSIONS: Testicular androgen ablation effectively lowers serum PSA levels in most men with advanced prostate cancer who have experienced a biochemical recurrence despite initial response and subsequent relapse on finasteride or combined finasteride and flutamide therapy.     

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.     

Evidence for atrophy and apoptosis in the prostates of men given finasteride

Finasteride, a 5 alpha-reductase inhibitor, decreases prostate size and improves symptoms in men with benign prostatic hyperplasia. However, little is known about prostate histopathology in men taking finasteride. To determine the mechanism by which finasteride reduces prostate size, tissue was collected at the time of prostatectomy from men taking either no medication (n = 10) or 5 mg finasteride daily for 6-18 days (n = 6; group 1), 23-73 days (n = 5; group 2), or 3 months to 4 yr (n = 5; group 3). To assess whether finasteride causes epithelial atrophy, morphometric measurement of epithelial cell and duct width was used. The mean epithelial cell width in control prostates (mean +/- SEM, 21 +/- 0.7 microns) decreased with duration of treatment to 19 +/- 1 microns in group 1, 15 +/- 2 microns in group 2, and 8 +/- 0.3 microns in group 3. Mean duct width decreased from 135 +/- 6 microns in the control prostates to 128 +/- 10 microns in group 1, 103 +/- 3 microns in group 2, and 63 +/- 6 microns in group 3. To assess whether prostate cell death was occurring, sections were in situ end labeled for DNA breaks and immunostained for tissue transglutaminase (tTG), a marker of apoptosis (programmed cell death). The percentage of epithelial cells staining for DNA breaks was 0.4 +/- 0.2 in control prostates, 2.8 +/- 0.9 in group 1, 1.7 +/- 0.5 in group 2, and 0.7 +/- 0.3 microns in group 3. Anti-tTG staining of epithelial cells was graded on a scale of 0-4. In control prostates, 3 +/- 1% of the ducts were grade 3 or 4 (> 50% of epithelial cells staining). In finasteride-treated prostates, 2 +/- 2% of the prostates in group 1, 13 +/- 4% of the prostates in group 2, and 0.5 +/- 0.5% of the prostates in group 3 were grade 3-4. These results indicate that a progressive decrease in epithelial cell size and function occurs during the first several months in the prostates of men treated with finasteride. The staining for DNA breaks and the tTG staining also indicate that an increased rate of apoptosis is occurring transiently in these prostates. We conclude that finasteride causes prostate involution through a combination of atrophy and cell death.     

Prevalence of benign prostatic hyperplasia in Spanish men 40 years old or older

PURPOSE: We estimate the prevalence of benign prostatic hyperplasia (BPH) according to symptoms as well as prostate obstruction determined by uroflowmetry and prostate size. MATERIALS AND METHODS: A cross-sectional study was performed at the autonomous community of Andalusia in 1,106 men 40 years old or older. The International Prostate Symptom Score (I-PSS) questionnaire was used to establish symptoms, abdominal and transrectal ultrasonography was done to measure prostate size and uroflowmetry was performed to measure urinary flow obstruction. RESULTS: The prevalence of moderate or severe symptoms was 24.94% and it increased with age. Of the 1,106 subjects 4.19% had severe prostatism, while 12.45% had poor quality of life (I-PSS greater than 3). Average prostate size was greater than 30 gm. in men 60 years old or older. Maximum urine flow was less than 10 and 15 ml. per second in 25.97 and 55.67% of the men, respectively. The prevalence of BPH, defined as I-PSS greater than 7, maximum flow less than 15 ml. per second and prostate size greater than 30 gm., was 11.77% (range 0.75 to 30 at ages 40 to 49 and greater than 70 years, respectively). CONCLUSIONS: The prevalence of BPH increases with age. Moderate prostatism is perceived as resulting in poor quality of life by young subjects and good quality of life by some older subjects. In some men there were symptoms and obstruction but no prostate enlargement. This percentage persists with age after 50 years, when the prevalence of BPH starts to increase.     

The influence of prostate volume on the ratio of free to total prostate specific antigen in serum of patients with prostate carcinoma and benign prostate hyperplasia

BACKGROUND: Determining the ratio of free to total prostate specific antigen (f-PSA to t-PSA, calculated as the percentage of f-PSA [f-PSA%]) in serum allow for a clearer distinction between patients with prostate carcinoma (PCa) and patients with benign prostate hyperplasia (BPH) than determining the level of t-PSA alone. To find influencing factors on f-PSA%, the authors investigated prostate volume, TNM classification, and tumor stage. METHODS: The authors measured f-PSA and t-PSA in 36 men with untreated PCa (tumor classification: T1, 2, 3pNO, MO), 44 patients with BPH, and 54 healthy controls. Prostate volume was determined by transrectal ultrasound. RESULTS: The median values of t-PSA and f-PSA% were 7.8 micrograms/L and 10.5% in PCa patients, 4.3 micrograms/L and 20.8% in patients with BPH, and 1.4 micrograms/L and 23.6% in the control group. Patients with PCa had a significantly lower proportion of f-PSA than BPH patients and healthy men. There was no correlation of f-PSA% to TNM stage or tumor grade. In PCa patients a significant positive correlation (correlation coefficient [r] = 0.51, P < 0.001) was found between f-PSA% and prostate volume, whereas there was no significant correlation in BPH patients (r = -0.27, P > 0.05). There was a significant difference in f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm3 (9.0% vs. 21.6%, P < 0.01) but not between patients in these 2 groups with prostate volumes exceeding 40 cm3 (15.1% vs. 18.2%, P = 0.11). CONCLUSIONS: Determining the ratio of f-PSA to t-PSA to discriminate between PCa and BPH patients yields significant results only in men with a prostate volume of less than 40 cm3.     

The current approach to the management of benign hypertrophy of the prostate

Epidemiology. The incidence of benign prostatic hyperplasia (BPH) has increased in proportion to the life expectancy and has become the third leading cause of health expenditure in industrialized countries. Eighty per cent of men are treated for benign prostatic hyperplasia during their lifetime. In Europe, the mean age of diagnosis is 65 years. The clinical symptoms are assessed by the IPSS score (International Prostate Symptom Score) and by the maximum flow rate, where frank dysuria is defined as a flow rate of less than 10 ml/sec. Physiology. The prostate contains equal proportions of glandular epithelial structures and fibromuscular connective tissue stroma. The glandular prostate is innervated by cholinergic nerves, while the smooth muscle of the stroma and the urethra are innervated by adrenergic nerves. BPH arises in the transitional zone (fairly glandular). Androgen deprivation (castration, antiandrogens, progestogens, 5-alpha-reductase inhibitors) induces a 30% reduction of the prostatic volume (especially epithelial). BPH could be due to reactivation of the embryonic potential of the stroma. Certain growth factors appear to be involved in BPH. Inflammatory and immunological phenomena may also be involved. Evaluation. Plan of clinical interview, clinical examination and laboratory and radiological data. A 40-year-old man has one chance in 30 of being operated for benign prostatic hyperplasia if he lives to the age of 80. Medical treatments have been developed since 1980 which inhibit the course of BPH and minimize some of the clinical symptoms: plant extracts, alpha-blockers, 5-alpha-reductase inhibitors. Conventional surgical treatments, open prostatectomy and endoscopic resection, have been completed by laser therapy, thermotherapy and cryotherapy.     

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.     

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.     

Increased incidence of depressive symptoms in men with erectile dysfunction

OBJECTIVES: To investigate the hypothesis that men with erectile dysfunction (ED) have a higher incidence of depressive symptoms compared with age-matched control subjects. We also hypothesized that depressive symptoms impact on the level of libido and on the success of treatment of ED. METHODS: One hundred twenty men with ED or benign prostatic hyperplasia (BPH) were divided into three groups. Group 1 had ED only, group 2 had BPH only, and group 3 had both ED and BPH. Patients were screened for depressive symptoms using the Primary Care Evaluation of Mental Disorders and the Beck Depression Inventory. They were also surveyed for comorbidity, marital status, severity of ED, level of libido, prior ED treatment choice (if any), success of treatment, and others. RESULTS: One hundred patients completed the questionnaires. Depressive symptoms were reported by 26 (54%) of 48 men with ED alone, 10 (56%) of 18 men with ED and BPH, and 7 (21 %) of 34 men with BPH alone. Patients with ED were 2.6 times more likely to report depressive symptoms than men with BPH alone (P < 0.005). Patients with depressive symptoms reported lower libido than other patients (P < 0.0001). Severity of comorbidities did not differ among the three groups. A total of 33 patients with ED had prior treatment for ED using penile injections or vacuum devices. All 15 (100%) patients with ED only continued treatment and were satisfied with its outcome, whereas only 7 (38.9%) of 18 patients with ED and depressive symptoms continued treatment (P < 0.00021). CONCLUSIONS: ED is associated with high incidence of depressive symptoms, regardless of age, marital status, or comorbidities. Patients with ED have a decreased libido compared with control subjects. In addition, patients with depressive symptoms have a lower libido than patients without depressive symptoms. Patients with ED and depressive symptoms are more likely to discontinue treatment for ED than other patients with ED. These data emphasize the importance of a multidisciplinary approach to the treatment of erectile dysfunction.     

Is the ratio of transition zone to total prostate volume higher in African-American men than in their Caucasian or Hispanic counterparts?

OBJECTIVE: To determine if the transition zone index (TZI, the ratio between transition zone volume, TZV, and total prostate volume, as estimated by transrectal ultrasonography, TRUS) differs among African-American (AA), Hispanic and Caucasian men. PATIENTS AND METHODS: The study group consisted of 104 age-matched men (36 AA, 34 Hispanic and 34 Caucasian) with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). A control group of 55 age-matched men, equally distributed among the three ethnic groups, but with no BPH (based on a digital rectal examination) were also evaluated. All men completed the International Prostate Symptom Score (IPSS) and a measurement of peak urinary flow rate (Qmax), prostate volume and TZV (by TRUS) and the TZI calculated. RESULTS: In the control group, the mean prostate volume was 20.9, 18.2 and 19.8 mL, the TZV 6.9, 4.9, and 5.4 mL and the TZI 0.33, 0.27 and 0.25 for AA, Hispanic and Caucasian men, respectively. The TZI was significantly higher in AA than in either Hispanic or Caucasian men (P < 0.03). Although there were no differences in prostate volume among the three ethnic groups with BPH, the mean (SD) TZV and TZI were significantly higher in AA men than in either their Hispanic or Caucasian counterparts, at 15.8 (7.6) mL and 0.43, 12.7 (8.1) mL and 0.37, and 13.8 (6.7) mL and 0.37, respectively. For all groups, age correlated with the IPSS (r = 0.22, P < 0.04); the mean (SD) IPSS was 14.3 (5.7), 10.2 (2.9) and 10.6 (4.9) for AA, Hispanic and Caucasian men, respectively. There was no correlation between the IPSS and either prostate volume or TZV, but there was a strong correlation with the TZI (r = 0.29, P < 0.01), regardless of race. CONCLUSIONS: These results suggest that AA men have a greater TZV and a higher TZI than their Caucasian or Hispanic counterparts, regardless of the presence of lower urinary tract symptoms. Studies are underway to determine if these differences are clinically significant and correlate with either subjective and/or objective parameters of BPH.