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Serum steroids in relation to benign prostatic hyperplasia.

In order to investigate the endocrine etiology of benign prostatic hyperplasia (BPH), we conducted a case-control study in Athens, Greece using 52 patients with histologically confirmed BPH and 52 healthy controls matched according to age and town of residence. Blood samples were collected from all participants and analyzed blindly in Boston, Mass. regarding testosterone (T), dihydrotestosterone, estradiol (E2), sex hormone-binding globulin, and dehydroepiandrosterone sulfate (DHEAS). Results from logistic regression models, adjusting for age, height, body mass index, years of schooling, and mutually among the measured hormones, indicate that DHEAS is significantly positively associated with the risk of BPH [odds ratio = 3.10 per standard deviation (60 micrograms/dl), 95% confidence interval (1.28,7.50)]. T and E2 were not significantly related to the risk of BPH.

Aged↗

[Sexual readaptation after the surgical treatment of benign prostatic hyperplasia].

Sexual function was studied in 818 patients with benign prostatic hyperplasia (BPH) before and after surgical treatment of this disease. Before surgery, sexual activity was absent in 276 examinees. After surgery 4.3% of them retained erection, 95.7% remained impotent. 542 patients before operations were sexually active. Surgical treatment of BPH (transurethral resection, transvesical adenomectomy) creates grounds for deterioration of sexual function and risk of erection loss. Thus, 77 operated patients had no erection, 176 had weak libido, 159--insufficient erection, 244 retrograde ejaculation, 188 painful orgasm. Transurethral resection led to a complete loss of copulative function in 5.3% of patients, transvesical adenomectomy--in 9.9%. Sexual readaptation after transurethral resection and transvesical adenomectomy has been improved due to a special complex developed by the authors. This complex consists of 14 therapeutic and prophylactic procedures.

Adaptation, Physiological↗

Divergent effects of interferons on the growth of human benign prostatic hyperplasia cells in primary culture.

Epithelial cells from human benign prostatic hyperplasia tissues were grown in primary cultures for up to 21 days and the effects of interferons on the growth of the cells were investigated. Interferon-alpha (Wellferon) showed growth inhibition both in the presence and in the absence of 3 x 10(-10)M testosterone propionate (TP) whereas interferon-gamma stimulated growth in a dose dependent manner under similar conditions. Interferon-beta had little effect on growth at the dose levels used in the study. The growth inhibition by interferon-alpha can be induced after stimulation of growth is achieved either with TP or with interferon-gamma. Implications of these findings for clinical use of these lymphokines is discussed.

Cell Division↗

Nonsurgical treatment evaluation in benign prostatic hyperplasia patients.

The development of new methods for treating benign prostatic hyperplasia (BPH) requires the choice of reliable criteria in order to assess their efficiency. It is, first of all, necessary to choose clinical as well as urodynamic criteria. Clinical criteria must be quantified and then gathered in scores, so that they can be compared. These changes, essential to the statistician, alter the true meaning of symptoms. The value of urodynamic parameters to 'measure' obstruction differs widely: the pressure/flow relationship as well as micturitional bladder pressure are probably the most reliable. Statistical data processing for both qualitative and quantitative variables, is still likely to alter the true meaning of these variables. This article takes a critical approach to all these problems, and also focuses on the real aim of the BPH treatment, which above all is to restore comfortable functional balance but not necessarily urodynamic performance.

Clinical Protocols↗

A comparison of transrectal hyperthermia, transurethral thermotherapy, urolume wallstent, and prostatic spiral for benign prostatic hyperplasia patients at poor operative risk.

Transrectal hyperthermia, transurethral thermotherapy, prostatic stent, and prostatic spiral were used to treat 120 poor operative risk patients with symptomatic benign prostatic hyperplasia. The preoperative subjective and objective conditions of the four groups (each of 30 patients) were comparable. None of the patients had an indwelling catheter, but according to flow nomograms, all were obstructed. The greatest increase in peak flow rate was observed after stent placement, while the greatest decrease of residual urine volume was seen after the insertion of the stent and transrectal hyperthermia. According to maximum flow nomograms, only the placement of the stent resolved bladder outlet obstruction. The greatest improvement in subjective symptoms was the result of stent insertion, but the heating procedures also caused a significant reduction of symptom scores. The spiral produced satisfactory results only in the short term.

Aged↗

1997 American Urological Association Gallup survey: Changes in diagnosis and management of prostate cancer and benign prostatic hyperplasia, and other practice trends from 1994 to 1997.

PURPOSE: The American Urological Association first commissioned the Gallup Organization to conduct a study to assess urologist practice patterns in 1992. We present the results of the 1997 survey, the sixth consecutive Gallup survey performed for the Association. MATERIALS AND METHODS: A random sample of 502 American urologists who had completed urological residency and practiced at least 20 hours weekly in 1996 was interviewed by telephone in February and March 1997. RESULTS: Emerging trends showed significant changes since 1994 in how urologists diagnosed and treated prostate cancer. The survey revealed a significant change in the tests routinely ordered to stage newly diagnosed prostate cancer and for diagnostic evaluation of patients with benign prostatic hyperplasia. CONCLUSIONS: Urologists are becoming more cost conscious and effective in ordering pretreatment testing. Urologists are becoming more oriented toward medical treatment for the management of benign prostatic hyperplasia, and less laser surgery is being performed.

Adult↗

Conservative non-instrumental treatment of benign prostatic hyperplasia.

This paper critically reviews the clinical effects in benign prostatic hyperplasia (BPH) patients that can be achieved with the presently available medical treatment options. The classes of drugs that are reviewed include: 5-alpha-reductase inhibitors, alpha-blockers, cholesterol-lowering agents and phytotherapeutic drugs. Only double-blind placebo-controlled studies with a duration of at least 3 months that have reported symptomatic changes and changes in flow rate in a quantitative fashion have been included. Studies that exclusively included selected groups of patients such as hypertensives or non-hypertensives have been excluded. The results of the clinical trials that are reviewed in this paper often show improvements in symptom score and maximum flow rate in the patients taking the active drug. These improvements are often statistically significantly better than the improvements seen in the placebo groups. However, taking into account that the symptomatic and the flow rate improvements achieved are below the level of perception in most of these trials, there seems to be no convincing evidence that medical treatment of BPH with the presently available drugs is also clinically more effective than placebo.

5-alpha Reductase Inhibitors↗

Effects of terazosin in the treatment of benign prostatic hyperplasia. A pilot study.

Several reports in the literature suggest that alpha-receptor blockade may have therapeutic value in treating the symptoms of patients with benign prostatic hyperplasia (BPH). Terazosin (Heitrin, Hytrin) is a long acting, highly selective alpha 1-adrenergic blocking agent structurally similar to prazosin. The present study, which also can be regarded as a pilot study, was undertaken as part of a multicenter study to evaluate the safety and efficacy of terazosin in the treatment of patients with BPH. This article presents the results with terazosin in the first 15 patients who completed a dose-ranging, non-comparative single-blind study. These preliminary results confirm that terazosin significantly improved peak as well as mean urine flow rates and significantly reduced residual volume and significantly improved obstructive symptoms in patients with benign prostatic hyperplasia (p less than 0.001). The results of this study support the conclusion that terazosin is beneficial for treatment of symptoms in patients with BPH.

Adrenergic alpha-Antagonists↗

Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia.

The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate. In the placebo group the mean concentration of prostatic dihydrotestosterone was 10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7 +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride, prostatic dihydrotestosterone declined to 15% or less of control levels, and the testosterone concentration increased in a reciprocal fashion. Compared to the placebo group, there was no significant difference in the mean prostatic dihydrotestosterone level achieved in any of the finasteride-treated groups. However, prostatic dihydrotestosterone levels were lower in the groups receiving higher doses of the drug. In two additional patients, finasteride treatment for 2 days also caused a decrease in prostatic dihydrotestosterone levels. No significant adverse experiences occurred during the study. We conclude that finasteride causes profound decrease in prostatic dihydrotestosterone.

5-alpha Reductase Inhibitors↗

[The efficacy of alfuzosin (dalfaz) in patients with benign prostatic hyperplasia].

A daily dose of alfusosine (an uroselective blocker alpha-l-adrenoreceptors produced as dalfas by Synthelabo Group, France) was given for 12 weeks to 124 patients with benign prostatic hyperplasia. The patients were examined before the treatment and on the treatment week 4, 8 and 12. The response (improved quality of life, higher rate of urine flow, smaller amount of residual urine in the bladder) was achieved in 120 (96%) patients. Alfusosine effect was more pronounced in patients with severe defects of urination. The drug was well tolerated, side effects observed in 7(5.6%) patients were mild and did not require treatment discontinuation. Alfusosine is indicated in benign prostatic hyperplasia with moderate infravesical obstruction, significantly disturbed urination caused by hypertonicity of bladder cervix smooth muscles, posterior urethra and prostate.

Adrenergic alpha-Antagonists↗

Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: sexual function.

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), and sexual dysfunction, are common, highly bothersome conditions in older men, and the prevalence of both disorders increases with age. Sexual dysfunction manifests mainly as erectile dysfunction (ED), ejaculatory disorders, or decreased libido/hypoactive sexual desire (HSD). Whereas both reduced rigidity and reduced ejaculate volume are highly prevalent in ageing men, reduced rigidity and pain on ejaculation are considered to be most bothersome. Sexual dysfunction is much more prevalent in patients with LUTS/BPH than in men with no LUTS/BPH, even after controlling for confounding variables such as age or comorbidities. Hence LUTS/BPH is considered an independent risk factor for sexual dysfunction. Whether this is because of a common underlying pathology, or whether the considerable bother associated with LUTS/BPH leads to reduced sexual functioning, remains to be elucidated. Despite a decline in the frequency of sexual intercourse, as well as in overall sexual functioning, most ageing men report regular sexual activity and consider their sex life as an important dimension of their quality of life (QoL). However, most patients with LUTS/BPH experience a negative effect of their LUTS on their sex life. Hence, treatment of LUTS/BPH should aim to at least maintain or, if possible, improve sexual function. Current medical treatment of LUTS/BPH consists of monotherapy with alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors (RIs) or a combination of these. Whereas 5alpha-RIs increase the risk of ED, ejaculatory disorders and HSD, alpha1-AR antagonists can induce ejaculatory disorders, but do not provoke HSD or ED. Combined therapy carries the cumulative risk for sexual dysfunction associated with either type of drug. As already indicated, ED is generally perceived as more bothersome than ejaculatory disorders. In addition, alpha1-AR antagonists slightly improve overall sexual function, possibly by increasing blood flow in the penis through alpha1-AR blockade and/or to an increased overall QoL from the relief of LUTS. It can be concluded that alpha1-AR antagonists constitute a first-line therapy for LUTS/BPH because they combine good treatment efficacy with very few adverse effects on sexual function.

5-alpha Reductase Inhibitors↗

An evaluation of the economic costs and patient-related consequences of treatments for benign prostatic hyperplasia.

OBJECTIVE: To compare the costs and effectiveness of treatments for benign prostatic hyperplasia (BPH), including watchful waiting, pharmaceuticals (alpha-blockers, 5-alpha-reductase inhibitors, combined therapy), transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP). PATIENTS AND METHODS: This study used a Markov model over a 20-year period and the societal perspective to evaluate the costs of treatment alternatives for BPH. Markov states include urinary symptom improvement, symptom improvement with adverse effects, or no urinary symptom improvement. For the analysis, patients could remain on their initial treatment, change to a different treatment, have treatment failure that required TURP, or die (all-cause mortality). We used published data for outcomes, including systematic reviews when possible. Costs were estimated using a managed-care claims database and Medicare fee schedules. Costs and effectiveness outcomes were discounted at 3%/year where appropriate. Men (aged > or = 45 years) with moderate-to-severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age. Outcomes include costs, disease progression, surgery, hospitalization, and catheterization time. RESULTS: What is the 'best' treatment depends on the value that an individual and society place on costs and consequences. alpha-Blockers are less expensive than the alternatives, and are effective at relieving patient-reported symptoms. Unfortunately, they have little effect on clinical outcomes and have the highest BPH progression rate. Other treatments have lower disease progression and better clinical outcomes, but are more expensive and entail more invasive treatments, and/or more uncertainty. CONCLUSIONS: Treatment decisions are made using a variety of information, including the cost and consequences of treatment. The best treatment depends on the patient's preference and the outcome considered most important. alpha-Blockers are very effective at treating urinary symptoms but do not improve clinical outcomes, including disease progression, relative to other treatments. TURP remains the 'gold standard' for surgical procedures. The desire to avoid TURP or the 2 weeks of catheterization associated with TUMT might affect a patient's treatment decision when symptoms are severe. Therefore, more information about patient preferences and risk aversion is needed to inform treatment decision-making for BPH.

5-alpha Reductase Inhibitors↗

Differential expression of acidic and basic fibroblast growth factors in benign prostatic hyperplasia identified by immunohistochemistry.

OBJECTIVE: To detect the expression and to determine the relative cellular locations of the two peptide growth factors, acidic fibroblast growth factor (a-FGF) and basic (b)-FGF in tissues from human benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A series of 50 sequential and unselected cases of human BPH tissues, obtained after transurethral prostatectomy, was examined. Adjacent sections of formalin-fixed and paraffin wax-embedded tissues were stained immunohistochemically for expression of a-FGF and b-FGF using well-characterized and commercially available antibodies. The stained tissue sections were assessed for the cellular distribution of immunohistochemical products and analysed according to the relative intensity of staining as well as the spatial relationships of positively stained cells. RESULTS: Acidic-FGF was weakly expressed with a pancytoplasmic distribution within luminal glandular epithelial cells in regions of prostatic intra-epithelial neoplasia (both PIN I and II) but not by non-dysplastic normal or hyperplastic tissues. No expression of a-FGF was detected in basal epithelial cells or in the stromal compartment of any tissue examined. In contrast, b-FGF was strongly expressed within the cytoplasm of all basal epithelial cells, but not by luminal epithelial cells, in morphologically normal regions of all cases examined. Basal expression of b-FGF was diminished, or absent, in regions of mild epithelial dysplasia, particularly those strongly expressing a-FGF. Extensive nuclear and cytoplasmic expression of b-FGF occurred predominantly in smooth muscle-type stromal cells but not in all types of stromal cells. CONCLUSIONS: This study confirmed both a differential and a reciprocal expression of a- and b-FGF in non-dysplastic prostatic hyperplasia and in mildly dysplastic regions of prostatic tissues. While only small amounts of a-FGF were expressed in BPH, exclusively in the luminal epithelial compartment, its consistent appearance in PIN I and II suggests that it might contribute to the early stages of PIN. Conversely, b-FGF may be an important mediator of stromal-epithelial interaction during the pathogenesis of BPH. These results provide new information about the relative expression of these growth factors, particularly in the architectural relationships between different cell-types within normal and non-malignant prostatic tissues.

Epithelium↗

International Continence Society "Benign Prostatic Hyperplasia" Study: background, aims, and methodology.

The International Continence Society Benign Prostatic Hyperplasia Study (ICS-BPH) was devised in response to the perceived underutilization of urodynamics in the diagnosis of benign prostatic obstruction (BPO), together with the apparent reliance on symptoms alone when selecting patients for invasive therapies, despite evidence that lower urinary tract symptoms (LUTS) had poor diagnostic specificity for BPO. The ICS-BPH Study is an international multicenter study employing a wide-ranging patient-completed questionnaire, with questions on symptoms, bothersomeness, quality of life, and sexual function. In addition, each patient underwent multiple urine flow studies and standardized urodynamic investigations (phase I). Phase II was an observational assessment of outcome following a range of treatments: conservative, medical, and surgical. Phase III included data from randomized controlled trials involving a wide range of therapies. One thousand, two hundred and seventy-one patients (mean age, 66 years) were included in phase I from 12 countries: 18% of patients were unobstructed, 22% mildly obstructed, and 60% obstructed on pressure flow studies; 83% of patients performed at least two flow studies. The ICS-BPH Study will allow definitive statements to be made concerning the diagnostic potential of a wide range of LUTS, and will define the place of urine flow studies, describe patients who will need pressure flow studies prior to invasive treatment, and identify those likely to experience an adverse outcome. Although an aim of the study is to produce a diagnostic symptom score, there is considerable doubt as to whether this can be achieved where aging and a variety of lower urinary tract dysfunctions often coexist.

Aged↗

The long-term risk of development of prostate cancer in patients with benign prostatic hyperplasia: correlation with stage A1 disease.

Although historical data generally attest to a relatively benign course for stage A1 prostate cancer, at least some recent studies suggest that with prolonged followup patients have a significant risk of disease progression. This study was done with the hypothesis that such disease progression is a function of patient age and close, prolonged followup, and not the mere presence of stage A1 disease. A total of 304 patients who underwent transurethral resection of the prostate for histologically confirmed benign prostatic hyperplasia was reviewed, with a minimum followup of 8 years. Of 269 patients with full followup data 187 (70%) are alive without prostate cancer and 61 (23%) died without development of the disease. A total of 21 patients (7.8%) had clinically apparent prostate cancer at a mean of 7.0 years following transurethral resection, of whom 3 (14%) died of prostate cancer and 1 died of other causes. These data suggest that the risk of progression and death from prostate cancer may not be significantly greater in patients with stage A1 disease than in those reported to have benign disease at transurethral prostatectomy.

Actuarial Analysis↗

Interstitial laser therapy for benign prostatic hyperplasia in the anticoagulated patient.

PURPOSE: Interstitial laser therapy (ILT) was performed without discontinuing warfarin anticoagulation therapy in eight patients (mean international normalized ratio 2.8 +/- 0.8) with benign prostatic hyperplasia. Three patients were in urinary retention and had failed voiding trials. Five had severe symptoms (mean American Urological Association symptom score 22 +/- 7) and had failed medical therapy. MATERIALS AND METHODS: Interstitial laser therapy was performed using the Indigo model 830e LaserOptic Treatment System with the patient under local anesthesia. Mean operative time was 25 minutes and mean total laser energy was 6,785 J. RESULTS: After surgery, spontaneous voiding was achieved by 7 of the 8 patients at 1 week and by all 8 patients at 3 weeks. At 3-month follow-up, mean American Urological Association symptom score was 13 +/- 5, and mean peak urinary flow rate had increased to 12.2 +/- 3.2 mL/s from 8.8 mL/s (excluding retention) before surgery. Interstitial diode laser therapy appears to be a safe and effective technique for treatment of benign prostatic hyperplasia in the fully anticoagulated patient.

Aged↗

Norepinephrine contents of human prostatic hyperplasia: differences between pathological subtypes.

Tissue norepinephrine content in benign prostatic hyperplasia (BPH) was evaluated to detect possible histological differences in BPH subtypes and to investigate the correlation between norepinephrine levels and age, prostatic weight and clinical symptom score, respectively. Specimens were obtained from 28 patients who underwent transurethral resection of the prostate. Pathologically, 18 out of 28 specimens were classified as fibromyoadenomatous hyperplasia and the remaining 10 as fibromuscular type. Norepinephrine content in the fibromyoadenomatous type was 133.1 +/- 23.1 ng/g, whereas it was 340.3 +/- 60.5 ng/g in the fibromuscular type. Norepinephrine level in the former group was significantly lower than that in the latter group (p < 0.001). In both groups, there was no correlation between norepinephrine content, age and clinical symptom score, while the norepinephrine content had a reverse correlation with prostatic weight only in the former group (p < 0.05). In conclusion, norepinephrine levels were dependent upon histological differences, especially upon the amount of smooth muscle elements, in the evaluated specimen. Severity of prostatism and patients' age showed no correlation with tissue norepinephrine content.

Aged↗

Three-month treatment with a long-acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5 alpha-reductase activity and androgen receptor content.

The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3 alpha-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 0.01 for DHT and P less than 0.05 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (0.10 greater than P greater than 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 +/- 1.79 (SD) ng/mL (16.5 +/- 6.2 nmol/L) to 0.27 +/- 0.42 ng/mL (0.9 +/- 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter. We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗