Treatment Of BPH Research Articles

Pilot study with combined alfuzosin + finasteride in BPH treatment

Today there are many types of therapies (medical and surgical) in BPH treatment. The Authors suggest dividing BPH into two components: a dynamic phase and a static phase. On the basis of this, they used an association of finasteride and alfuzosin in short and long-term therapy. Provided the rationale is correct, the results in terms of improved flow and symptomatology score suggest that this is an optimal solution.

Identification of a prostate inhibitory substance in a pollen extract

Recently, much attention has focused on the treatment of BPH with the pollen extract, Cernilton. The present investigation was designed to identify the active component in this agent which might be responsible for the symptomatic relief of BPH as previously reported. Sequential purification of the active component present in the pollen extract was carried out by a combination of dialysis, gel filtration, and reverse phase chromatography. To monitor the biological activity of each of the purified fractions, a biological assay employing the human prostate cancer cell line DU145 was undertaken. While we have identified a number of constituent components in the pollen extract, only one fraction designated V-7 (FV-7) maintained a strong inhibitory effect on the growth of DU145 cells. The inhibition was time- and dose-dependent, and the concentrations of FV-7 required to reduce the cell numbers by 50% (IC50) after 2 days of exposure was 5 micrograms/ml. FV-7 was also inhibitory towards the primary culture of prostate stroma and epithelial cells, with the stroma/fibroblast showing greater sensitivity towards the HPLC-purified component. However, it should be noted that this inhibitory activity measured in the primary culture cells was only achieved at higher concentrations of FV-7. Preliminary characterization of the active ingredient identified FV-7 as DIBOA which is a cyclic hydroxamic acid. FV-7 and DIBOA induce similar inhibitory effects on the growth of DU145 cells.

Turapy-Transurethral Ablation Prostatectomy by High Temperature Radiofrequency-Preliminary Results of A Multicenter Study.

Thermal treatment of BPH has been introduced several years ago as an alternative treatment modality for patients suffering from symptomatic BPH. The initial temperatures ranged from 44.5 to 48 degrees C. With these temperatures, about 60-70% of the patients showed significant improvement of their subjective, mainly irritative symptoms with only mild changes in their obstructive parameters. In order to improve the therapeutic effects, increase in energy delivered allowing higher temperatures in the order to 70-100 degrees C was investigated regarding the feasibility, tolerance, pathological lesions and clinical effectiveness. A new radiofrequency technique, TURAPY--TransURethral Ablation Prostatectomy, an outpatient ablative BPH treatment has been introduced recently. The treatment is applied transurethrally with a helicoidal antenna without any cooling system. Temperature delivery in the order of medium 75 degrees C was applied during a medium time of 45 minutes. An ongoing multicenter study included 38 patients. 15 patients were operated by retropubic prostatectomy after 6-30 days, for a histopathology study and 23 eligible patients were entered in a clinical study and analyzed to determine the efficacy of the TURAPY treatment. The tolerance was excellent and although patients experienced initial heating sensation at the onset of treatment, as the temperature rose to 40-50 degrees C (as with previous modalities of thermotherapy), they did not experience further pain and the procedure was never stopped. Urinary retention was observed in about 80% of the patients, due to the extensive tissular destruction. These patients had suprapubic catheter inserted one day to a maximum of one week (medium 3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Book Reviews

Book reviewed in this article:Atlas of Scrotal Ultrasound. By Brigitte Martin.Urinary Incontinence. (Societe Internationale d'Urologie Reports). Edited by A. Steg.Urinary Cytology. Manual and Atlas. Second edition. Edited by P. Rathert, S. Roth and M. S. Soloway.Non‐surgical Treatment of BPH. (Societe Internationale d'Urologie Reports). Edited by J. M. Fitzpa‐trick.Minimal Access Medicine and Surgery: Principles and Techniques. Edited by D. Rosin.Management and Biology of Carcinoma in situ and Cancer of the Testis. Proceedings of the 3rd Copenhagen Workshop, November 1–4, 1992. (Reprint of European Urology, 23, No. 1, 1993). Edited by N. E. Skakkebaek, K. M. Grigor, A. Giwerc‐man and M. Rerth.Kidney, Proteins and Drugs: An Update. (Contributions to Nephrology, Volume 101). Edited by C. Bianchi, V. Bocci, F. A. Carone and R. Rabkin.Prevention of Progressive Chronic Renal Failure. (Oxford Monographs on Clinical Nephrology–1).Edited by A. M. El Nahas, N. P. Mallick and Sharon Anderson.Rob and Smith's Operative Surgery: Genitourinary Surgery. Fifth edition. Edited by H. N. Whitfield.

Balloon dilatation of prostate: Keys to sustained favorable results

Seventy-seven patients with small prostates (< 40 g) and significant obstructive symptomatology were treated using balloon dilatation of the prostate (BDP) with a sized-to-fit intra-prostatec balloon. Eighty-seven percent of the patients experienced a 50 percent or greater decrease in symptom score at longest follow-up (12.0 months, average: 3–24 months, range). Forty-nine percent of the patients had a 50 percent or greater improvement in peak uroflow. An anterior coin missurotomy through the fibromuscular stroma was consistently found and is the hallmark of a technical and therapeutic success. No cases of incontinence, retrograde ejaculation, or impotence developed. When properly performed, BDP has a place in the spectrum of BPH treatment alternatives.

Transplantation of human benign hyperplastic prostate tissue into nude mice: first results of systemic therapy.

Xenografts of human benign hyperplastic prostate tissue (BPH) have been established as a model for the investigation of the etiology of BPH. In this paper it is our aim to answer the question of whether this model is useful for the established therapy of the disease. Additionally we try to evaluate the value of a commonly used plant extract for the therapy of BPH. Is there any influence of the extract from Sabal serrulatum on the BPH tissue in our model? Human BPH tissue from 2 patients was transplanted into athymic nude mice and treated with three different regimens. Animals of group I did not receive any treatment and served as control, in groups II and III the tissue was stimulated by application of silicone tubes containing crystalline 5 alpha-dihydrotestosterone and estradiol. Animals of group II additionally were treated orally with the lipophilic extract of S. serrulatum (contained in Prostagutt N), which is commonly used for the treatment of BPH clinically. Significant inhibition of tissue growth was observed in group III when compared to group II. In group I (control) atrophy of the graft was observed as expected. However, histologically no differences were visible between groups II and III. Our experiment shows a significant growth-inhibiting effect of the plant extract for human BPH tissue in our model (p less than 0.05). We conclude that the nude mouse model can be useful for the evaluation of systemic therapy modalities of human BPH and that the plant extract may have a certain value for clinical treatment, which is not only due to subjective criteria.

Endocrine treatment of benign prostatichypertrophy: Current concepts

To summarize the endocrine approach for the treatment of BPH: much clinical data have accumulated over the past forty years. Until recently, scientists and physicians mainly concentrated on the reduction of androgens as a possible solution. We have come a long way from surgical castration, through the administration of hormones such as estrogen and progesterone, gonadotropin-releasing hormone agonists to the inhibition of an enzymatic reaction reducing testosterone to DHT--the now recognized active intracellular androgen metabolite. Recently, the role of estrogens has been emphasized with the finding that stromal hyperplasia is the main change occurring in BPH. Lately, research has been initiated to examine the clinical effect aromatase inhibitors would have in the treatment of human BPH. Since there is enough evidence that both the epithelial and stromal components of the human prostate undergo hyperplasia in BPH, and individuals vary with respect to their relative epithelial/stromal components, both structures would have to be reduced for therapy to be successful. Therefore, the combination of an antiandrogenic and antiestrogenic effect is theoretically promising. Indeed, prostates of beagles shrunken after treatment with an aromatase inhibitor, further decreased in weight after additional treatment with cyproterone acetate, an antiandrogen. We are now approaching the stage where these "antihormones" are both enzyme inhibitors with actually no side effects that preclude the use of the earlier generation's "antihormonal" hormonal drugs. Furthermore, it has recently been reported that the aromatase inhibitor, 4-hydroxy-androstenedione also inhibits human prostatic 5-alpha reductase, at least in vitro. The in vivo relevance of this finding awaits further classification. Thus, a good hormonal treatment that will be both scientifically sound, and clinically safe and effective, seems feasible in the near future. Two main factors have encouraged our interest and research into methods of inhibiting prostatic growth or reducing its obstructive symptomatology: the enormous cost of prostatic operations for outlet obstruction secondary to BPH, and the natural aging process of the population accompanied by deteriorated health precluding anesthesia and prostatic surgery. Medical treatment of BPH has to result in symptomatic improvement, elimination of residual urine, and improvement of flow to be considered successful. These are usually accomplished by surgery and results at least as good as those obtained by operation should be aimed at, if medical treatment is to replace surgery. Although indications for surgery and outcome of operations are well-defined, this is not the case when alternatives to prostatectomy are chosen.(ABSTRACT TRUNCATED AT 400 WORDS)

The efficacy and safety of terazosin for the treatment of symptomatic BPH

At least 16 clinical investigations have documented the effectiveness of alpha blockade for BPH. In the present review, four clinical studies evaluating the efficacy and safety of terazosin, a selective long-acting alpha 1 blocker, for symptomatic BPH are reviewed. The unique features of these clinical investigations are: the study designs established detailed inclusion and exclusion criteria, the outcome assessments were based upon quantitative outcome parameters, large cohorts of homogeneous patients were enrolled, and appropriate statistical methods were utilized. The dose of terazosin was titrated to maximal doses ranging between 5-20 mg. Only four of the 163 patients developed orthostatic hypotension. Overall, the peak and mean uroflow rates increased 50% and 46%, respectively (P less than 0.001). The cumulative improvement in the mean obstructive, irritative, and total symptom scores was 67%, 35%, and 54%, respectively (P less than 0.001). The present review of terazosin in males with symptomatic BPH supports the following conclusions: (1) the dose of terazosin can be safely titrated to 10 mg in normotensive and hypertensive patients with symptomatic BPH; (2) the adverse events associated with doses of terazosin up to 10 mg are relatively mild and reversible; and (3) the improvements in the outcome parameters (symptom scores and urinary flow rates) are clinically and statistically significant. Although the ultimate role of terazosin for symptomatic BPH will be determined by multi-center randomized placebo-controlled studies, the present review provides further evidence that selective alpha 1 blockers are effective and safe for the treatment of symptomatic BPH.

Androgen Ablation and Blockade in the Treatment of Benign Prostatic Hyperplasia

Antiandrogen therapy appears to produce a 30 to 40 per cent decrease in the volume of the hyperplastic prostate after 3 to 6 months of therapy (Table 5). Longer treatment may result in further prostatic regression, although this remains to be seen. Biopsy studies suggest that epithelial regression occurs to a much more significant degree than does stromal regression, but this finding may simply reflect the relatively longer turnover of the stromal cell population. The significant placebo effect of oral medication in patients with BPH makes interpretation of clinical symptomatology and uro-flow data difficult. Analysis of symptom improvement is further complicated by the relatively slow improvement of patients on antiandrogen therapy, in contrast to surgery, in which relief is immediate. In addition to limited stromal involution and inadequate treatment duration, other biologic factors may limit the clinical efficacy of antiandrogen therapy. Most importantly, prostatic involution may not necessarily decrease urethral resistance. In addition, obstruction-induced detrusor dysfunction may persist after relief of outflow obstruction in some patients, as it does after surgery. Incomplete antiandrogen action of the compounds, as well as compliance issues, may likewise limit efficacy. Although there are no data to suggest that the 5 alpha-reductase inhibitor finasteride will be more effective than other antiandrogen compounds in the treatment of BPH, preliminary studies suggest that it has less toxicity. If long-term studies validate a modest but significant clinical response rate and preservation of sexual function, then finasteride therapy may well be acceptable to a subgroup of men presenting with the symptoms of BPH.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryologic Development of the Prostate: Insights into the Etiology and Treatment of Benign Prostatic Hyperplasia

Pharmacologic strategies for the treatment of BPH are at present directed toward relaxing prostate smooth muscle and reducing prostate volume. Historically, the primary limitation of pharmacotherapy for BPH has been that the symptomatic improvement achieved was overshadowed by the morbidity of treatment. However, the morbidity has been markedly diminished based on a more precise understanding of the embryology, physiology, and pharmacology of the prostate. The origins and pharmacologic properties of the smooth musculature of the prostate and bladder are unique. Therefore, drugs such as alpha blockers may relax the prostate selectively without altering bladder function. Although phenoxybenzamine, a nonselective alpha blocker, relieves infravesical obstruction secondary to BPH, the severity of the adverse reactions limits the use of this drug.3 The contractile properties of the prostate smooth muscle are mediated by alpha-1 adrenoceptors. The effectiveness of phenoxybenzamine and selective alpha-1 blockers such as prazosin and terazosin are similar. The side effects of the selective alpha-1 blockers are negligible. Androgen suppression, which lowers testosterone, produces intolerable side effects such as gynecomastia, erectile dysfunction, and impaired libido.35 The androgen dependency of the prostate provides the rationale for using 5α-reductase inhibitors for the treatment of BPH. Reduction of prostate volume can be achieved by blocking the action or synthesis of dihydrotestosterone without impotence, gynecomastia, and hot flashes. These recent advances in pharmacotherapy for BPH are based on understanding of the fundamental developmental properties of the prostate.

IN VITRO EFFECTS OF AN AROMATASE INHIBITOR ON 5α-REDUCTASE ACTIVITY IN HUMAN HYPERTROPHIC PROSTATIC TISSUE

To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT), 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstan-3 beta, 17 beta-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4-14C-T as substrate, in the presence of 4-OH-A (10(-8) to 10(-6) M); the amounts of the 5 alpha-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), a known inhibitor of the 5 alpha-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily. Both 4-OH-A and 4-MA induced significant and dose-related decreases in the formation of both DHT and the diols. The degree of inhibition induced by the different concentrations of 4-OH-A and 4-MA were 31, 41, 72% and 57, 87, 97%, respectively. The decreased formation of the diols was a consequence of the decreased availability of DHT (the immediate precursor of the diols) and was not due to direct effects of the inhibitors on the 3-hydroxysteroid dehydrogenases; both 4-OH-A and 4-MA were totally unable to modify the conversion of DHT to the diols, when 4-14C-DHT was used as substrate. Thus, 4-OH-A inhibits the process of 5 alpha-reduction of T in BPH tissue. This molecule might represent a potential new agent for the prevention and/or treatment of human BPH.

Dimensional renormalization

The analytic structure of a Feynman amplitude as a function of the number of space-time dimension (ν) is studied. A renormalization prescription by using ν as an analytic regularization parameter is given. It is shown its equivalence with BPH treatment for any graph in quantum field theory.