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[Pikamilone treatment of benign prostatic hyperplasia].

Pikamilone is an original drug of Russian produce having a central (vegetotropic and vascular) and peripheral (vasodilating) mechanisms of action. The drug was tried as monotherapy in elderly patients with benign prostatic hyperplasia who had symptoms of the lower urinary tracts to estimate its effect on local and general mechanisms of nervous and vascular regulation of detruzor function in infravesical obstruction. A positive trend in the clinical symptoms was observed (by IPSS scale), especially irritative symptoms. Urodynamics has also improved: maximal and mean urinary flow rate and total amount of urination increased. However, the residual urine volume remained the same. Further placebo-controlled and randomized studies are needed for precise estimation of pikamilone effects. Meanwhile, the drug can be used as a component of combined therapy of benign prostatic hyperplasia.

Administration, Oral↗

Long-term implications of medical therapy on benign prostatic hyperplasia end points.

There is a progression over time of relevant measurable benign prostatic hyperplasia (BPH) end points including symptoms, flow rates, prostate size, complications such as acute urinary retention (AUR), and surgical rates. Only two classes of medical therapy, the alpha-blockers and a 5-alpha-reductase inhibitor, have shown unequivocal and consistent efficacy over placebo in 1-year studies. Both of these classes of medications have demonstrated relative long-term safety. Finasteride has been shown in three large, 2-year, randomized, controlled studies to be superior to placebo, and both finasteride and the alpha-blockers have demonstrated long-term efficacy and safety in open-label studies. The efficacy of finasteride is significantly enhanced when it is used in patients with large prostates. Long-term finasteride therapy also results in a significant reduction in the incidence of AUR and the need for surgery. Long-term medical therapy for BPH is effective and safe. Data are now available that allow clinicians to analyze the long-term risks and benefits of the various medical options and subsequently rationalize long-term therapy for individual patients.

Acute Disease↗

Using a treatment satisfaction measure in an early trial to inform the evaluation of a new treatment for benign prostatic hyperplasia.

OBJECTIVE: This article describes the results of an exploratory analysis of treatment satisfaction data from a phase 2 study to inform the evaluation of a new treatment for benign prostatic hyperplasia (BPH). METHODS: The study was a randomized, placebo-controlled, double blind trial comparing three doses (low, medium, and high) of a new uro-selective alpha-blocker with an active comparator. A total of 536 men aged 40 years and older with lower urinary tract symptoms (LUTS) resulting from BPH were randomized into the study. Patients' perceptions of satisfaction with efficacy, dosing, and side effects were explored using a validated disease-specific instrument, the Treatment Satisfaction Scale-Benign Prostatic Hyperplasia (TSS-BPH). The TSS-BPH was administered at the end of the study or at withdrawal. RESULTS: Compared with placebo, the medium and high doses showed the greatest efficacy on the primary endpoint, the International Prostate Symptom Score (IPSS). Patient satisfaction with efficacy at these doses was significantly better than that for placebo. Nevertheless, adverse events were most frequent in the high dose group. Satisfaction with side effects was significantly worse than placebo for this group, and this was reflected in the total scores on the TSS-BPH, with patients being most satisfied overall with the medium dose. CONCLUSIONS: Exploring patients' treatment satisfaction with medication in early trials using multidimensional measures provides an overall evaluation of efficacy and side effects, and can be used to inform the selection of doses for later trials. This is especially useful for products that require adherence with medication over long periods of time.

Adrenergic alpha-Antagonists↗

Association between family history of benign prostatic hyperplasia and urinary symptoms: results of a population-based study.

Baseline measurements for a population-based prospective cohort study were used to assess the association between family history of enlarged prostate and urinary symptoms. Between December 1989 and March 1991, a group of randomly selected men aged 40-79 years from Olmsted County, Minnesota, was administered a previously validated questionnaire that included questions with wording close to that of the American Urological Association's Symptom Index. A detailed family history of an enlarged prostate was obtained by personal interview, and peak urinary flow rates were measured for each participant. Of the 2,119 men, 440 (21 percent) reported a family history of an enlarged prostate. The age-adjusted odds of having moderate or severe urinary symptoms were elevated among those with a family history relative to those without (odds ratio = 1.3, 95 percent confidence interval 1.1-1.7). With simultaneous control for effects of age and worry about urologic function, the odds ratio remained at 1.3 (95 percent confidence interval 1.0-1.6). Furthermore, this risk was greater for men with relatives diagnosed at a younger age (odds ratio = 2.5, 95 percent confidence interval 1.5-4.3). Men with a family history were also 1.3 times as likely to have an impaired peak urinary flow rate. These findings suggest that men with a family history of an enlarged prostate may be at increased risk for development of symptoms and signs suggestive of benign prostatic hyperplasia and that this risk is greater in men with relatives diagnosed at a younger age. Recognition of this association may help to target early interventions and may lead to further clues about the causes of benign prostatic hyperplasia.

Adult↗

Holmium and interstitial lasers for the treatment of benign prostatic hyperplasia: a laser revival.

With the introduction of the side-firing neodymium:yttrium-aluminum-garnet laser in the early 1990s laser prostatectomy became a widely used treatment for benign prostatic hyperplasia. However, because of prolonged postoperative catheterization times, the lack of immediate effect, and severe postoperative dysuria, many urologists became disinterested in this procedure. Recently, as a result of advances in laser technology, namely, the holmium laser and interstitial laser prostatectomy, interest in lasers for the treatment of benign prostatic hyperplasia has been rekindled. This paper will review published reports over the past year regarding these relatively new treatments.

Clinical Trials as Topic↗

Ultrasonic evaluation of age-related human prostatic growth and development of benign prostatic hyperplasia.

In 175 normal men aged 27-70 (median 40) years, the prostate was ultrasonically scanned by the transrectal route. Ultrasonic signs of adenoma were found in 26%. The earliest age at which signs of benign prostatic hyperplasia appeared was 27 years, and the incidence increased with age. Adenomatous prostates were significantly larger than nonadenomatous, with median volume 28.0 (14.5-62.1) ml versus 23.0 (11.3-39.1) ml (p less than 0.0005). The adenomatous prostates also had a larger median volume of the periurethral gland (4.1 ml vs. 3.0 ml; p less than 0.0005) and a larger peripheral zone (23.3 ml vs. 20.2 ml; p less than 0.005). The total prostatic volume increased statistically significantly with age and the growth rate was calculated to be 0.81 %/year +/- 0.25 (S.E.) corresponding to 0.2 ml/year. The growth rate of the periurethral zone was 1.5 %/year +/- 0.5 (S.E.). Volumetric correlation between periurethral gland and total prostatic volume depended on whether or not adenoma had developed. Prostatic volumes measured in vivo by ultrasound are slightly greater than values obtained at autopsy.

Adult↗

Relationship between the prostatic tissue components and natural history of benign prostatic hyperplasia.

OBJECTIVE: Few reports have been published on the relationship between prostatic tissue components and the natural history of benign prostatic hyperplasia (BPH). The present study was undertaken to evaluate this relationship. STUDY DESIGN: Forty-nine patients with BPH who underwent suprapubic prostatectomy were studied. Six infant prostates and 10 non-BPH specimens were obtained from autopsy. Specimens were stained with antibodies to alpha-smooth muscle actin, and the mean ratio of the stroma was determined with computer image analysis. Stromal ratios were evaluated according to resected prostate weight and age. RESULTS: The stroma comprised 82.6 +/- 8.4% of the prostate area at 0-1 year of age and 43.7 +/- 5.1% at 15-28 years of age. In BPH, the stromal proportion increased to 55.9 +/- 10.2%, but decreased with increases in prostate weight and/or age. CONCLUSION: The stromal component increased in patients with BPH and decreased with increased prostate weight and/or age, comprising approximately 42-47% of the prostate area, as in the non-BPH prostate, indicating a balance in prostatic tissue components in both patients with BPH and the non-BPH prostate.

Actins↗

Micturition problems in relation to quality of life in men with prostate cancer or benign prostatic hyperplasia: comparison with men from the general population.

The aim of the study was to investigate men with prostate cancer and benign prostatic hyperplasia (BPH) in comparison with men from the general population in aspects of presence and frequency of micturition problems in remembrance of prior to treatment and currently. Further, the aim was to investigate the impact of micturition problems on quality of life and the association with micturition problems, and quality of life and sense of coherence (SOC). The samples consisted of 155 men with prostate cancer, 131 with BPH, and 129 from the general population. Micturition problems were assessed with study-specific questions, modified International Prostate Symptom Score (IPSS), quality of life questionnare (QLQ C-30), and SOC questionnaires. Parametric and nonparametric statistics were applied. Most troublesome urinary problems were leakage, feelings of discomfort, and disrupted urinary function and frequency. Men with urological diagnosis had more micturition problems, fatigue, and sleeping difficulties than men from the general population, but the cancer diagnosis did not add to the problems. Role and social functioning (prostate cancer), emotional functioning (BPH), and grade of fatigue (general population) showed itself vital for overall quality of life. Thus, help in solving issues of micturition problems, fatigue, and sleeping disturbances may contribute to maintenance of role, social, and emotional aspects of life.

Activities of Daily Living↗

Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial.

In a randomized triple-blind multicentre study, injections with the anti-androgenic agent oxendolone were compared with placebo in the treatment of benign prostatic hyperplasia. Thirty patients were treated with weekly injections of oxendolone 200 mg during a 3 months' period, and 30 patients were allocated to placebo treatment. During oxendolone treatment the maximum urinary flow rate increased statistically significantly (from 6.8 ml/s to 8.2 ml/s). However compared to placebo, the oxendolone effect was statistically insignificant. A slight but statistically significant improvement of the symptoms "sensation of retention", "urgency" and "frequency", was observed following oxendolone treatment, but an almost identical effect was seen in the placebo group. Following either treatment no change was observed in the residual urine volumes, in prostatic volume as measured by transrectal ultrasonotomography, or in any other therapeutic parameters. Conservative treatment of benign prostatic hyperplasia with the antiandrogen oxendolone in a dose of 200 mg a week cannot be recommended for clinical use.

Aged↗

Role of alpha-adrenergic blockers in the treatment of benign prostatic hyperplasia.

The dynamic component of infravesical obstruction in men with symptomatic benign prostatic hyperplasia (BPH) is determined by alpha 1-adrenoceptor-mediated contractions of the prostatic capsule, prostate adenoma, and bladder neck. Since alpha 1-adrenoceptors are sparse in the bladder, medical therapy aimed at blocking the alpha receptor will relieve bladder outlet obstruction without inhibiting bladder function. Numerous clinical studies have evaluated the use of various alpha blockers for the treatment of BPH. Although the majority of these trials involved limited numbers of patients treated for only short periods, their results have consistently shown that alpha blockers improve urinary flow rates. Adverse reactions appear to be more frequent and more serious with the use of nonselective alpha blockers than with selective alpha 1 blockers, such as terazosin or prazosin. Terazosin offers the additional advantage of once-daily dosing. The common association of hypertension, hyperlipidemia, and symptomatic BPH in the aging male population may provide further impetus for initiating treatment with alpha blockers because alpha blockers are effective antihypertensive agents and may favorably alter lipid profiles.

Adrenergic alpha-Agonists↗

Effects of flutamide and hydroxy-flutamide on the growth of human benign prostatic hyperplasia cells in primary culture: a preliminary report.

Tissues from human benign prostatic hyperplasia [BPH] were collected from twelve patients undergoing routine transurethral resection of the prostate to relieve urine out-flow obstruction. Viable epithelial organoids were obtained after enzymatic digestion of the tissue. Primary cultures of epithelium were successfully maintained on collagen gel for up to 21 days. Immunocytochemical staining revealed that there was no expression of either desmin or vimentin in these cells; however, the anticytokeratin antibodies LP-34 (cytokeratins 4, 5, 6, 10, 13, 16, 17 and 18), LE-61 (cytokeratin 18) and CAM 5.2 (cytokeratins 7 and 8) all showed positive responses, indicating the epithelial nature of the cells. Cell growth was significantly increased in the presence of 3 x 10(-10) M testosterone propionate [TP] in the culture medium. The presence of the non-steroidal anti-androgens, Flutamide and Hydroxy-Flutamide [Flu-OH], in the concentration range 1.0-0.001 micrograms per ml of medium inhibited the growth in the presence of androgens in a dose-dependent manner. The anti-androgens failed to affect cell growth in the absence of TP. In view of these preliminary findings, it is postulated that the antiandrogens might be acting either by displacing the androgen from its receptor or alternately by inhibiting the activity of prostatic 5 alpha-reductase.

Aged↗

[Benign prostatic hyperplasia--choice of therapy in the elderly].

The incidence of benign prostatic hyperplasia of up to 80% in 80-year-old men raises question as to possible therapeutic consequences. For decades, the standard treatment has consisted in transurethral resection of the prostate (TUR-P) which results in subjective and objective improvement in up to 95% of the cases and has low morbidity and negligible mortality. With a view to establishing a minimally invasive form of treatment, the search for alternative therapies makes good sense. To date, however, various medical therapeutic approaches (phytotherapy, alpha-blockers, antiandrogens, 5-alpha-reductase inhibitors) and/or interventional measures (thermotherapy, stents, balloon dilatation) have failed to match the therapeutic efficacy of TUR. However, in individuals at a high risk of surgery, they represent practicable alternatives.

Aged↗

Transurethral microwave thermotherapy in symptomatic benign prostatic hyperplasia.

Since October 1990, 336 patients with symptoms due to benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). The technic of treatment, the inclusion and exclusion criteria for TUMT treatment are discussed. Temporary urinary retention, probably due to edema of the prostate, developed in about 25% of the patients. Results are presented with a follow-up period of up to 1 year. In the majority of patients a significant subjective response was shown. Objective improvement was less pronounced.

Aged↗

Progressive prostate hyperplasia in adult prolactin transgenic mice is not dependent on elevated serum androgen levels.

BACKGROUND: Transgenic mice overexpressing the rat prolactin (PRL) gene under control of the metallothionein-1 promoter (Mt-1) develop a dramatic prostatic enlargement. These animals also display significantly elevated testosterone serum levels. In this study, we aim to clarify the role of circulating androgen levels in the promotion of abnormal prostate growth in the adult PRL transgenic mouse prostate. METHODS: Prostate morphology and androgen-receptor distribution patterns were analyzed in castrated and testosterone substituted adult PRL transgenic and in wild-type males. RESULTS: Progressive prostatic hyperplasia in adult PRL transgenic males was not affected by substitution to serum testosterone levels corresponding to wild-type. Furthermore, prolonged testosterone treatment in adult wild-type males did not produce any significant changes in prostate growth or morphology compared with wild-type controls. Immunohistochemical studies revealed a significantly increased proportion of androgen receptor positive epithelial cells in all lobes of the PRL transgenic prostate versus wild-type. CONCLUSION: The present study demonstrates that progressive prostate hyperplasia in adult PRL transgenic mice is not dependent on elevated serum androgen levels. Furthermore, prolonged androgen treatment in adult wild-type male mice appears to have no significant effect on prostate growth. In addition, our results suggest that prolonged hyperprolactinemia results in changes in prostate epithelial and stromal cell androgen receptor distribution.

Animals↗

Benign prostatic hyperplasia.

In both ageing men and women, there is an increasing incidence of lower urinary tract symptoms (LUTS) which are increasing. These infections have many possible causes, including smooth muscle dysfunction, neurological factors and benign prostatic hyperplasia. Up to 15% to 25% of men aged 50-65 years have LUTS of sufficient severity to interfere with their quality of life. Although benign prostatic hyperplasia is an important cause of these symptoms, and can have serious consequences, clinicians should be aware of these other causes so that the appropriate diagnosis is made before invasive treatments are started. New medical treatments, including alpha-adrenergic blocking agents and 5 alpha-reductase inhibitors mean that many men without complications such as infection, bleeding, or chronic retention, and with mild to moderate symptoms, should be managed in primary care. Combined local protocols between primary and secondary care will help to establish which men with persistent symptoms or complications need referral for a urological opinion to determine the need for further investigation and more invasive forms of management. We review the pathophysiology of the disease, and current approaches to investigation and management of this common problem.

Cross-Sectional Studies↗

Thermal model for the local microwave hyperthermia treatment of benign prostatic hyperplasia.

A system for the noninvasive localized, hyperthermia treatment of benign prostatic hyperplasia was investigated. The system uses a microwave transrectal antenna with a water cooled jacket to achieve localized hyperthermia. The purpose of this study is to model the temperature rise in the prostate and in the surrounding tissue during treatment. The SAR distribution for the transrectal probe is measured in a muscle tissue equivalent phantom. The SAR information is used with a finite element solution of the bioheat transfer equation to give the temperature rise during the treatment. Also the finite element solution is further used to determine the effect of the microwave power, the cooling fluid temperature and the blood perfusion on the tissue temperature rise. The results of the solution are compared to temperature measurements in a canine protocol. It was found that the maximum temperature rise in the tissue during treatment is 44 degrees C at a depth of 2 cm from the rectal mucosa.

Animals↗

Benign prostatic hyperplasia: clinical overview and value of diagnostic imaging.

The term benign prostatic hyperplasia has traditionally been used to describe a constellation of obstructive and irritative voiding symptoms that occur in men as they age. Such symptomatology may be due to a variety of causes, including prostatic enlargement. Thus, the term lower urinary tract symptoms has replaced BPH to describe this symptom complex. The evaluation and treatment of LUTS continues to be a significant part of urology practice in the United States, as well as a significant component of medical resource utilization. Currently, indication for treatment in patients with LUTS is most often based on subjective measurements of symptom severity and bother. Consequently, imaging does not play a major role in the evaluation of such patients. Recent data suggest that the size of the prostate gland may predict which patients with LUTS will develop progressive symptoms and complications. Moreover, both prostate size and the histologic composition of BPH may help to select patients for specific treatment options. Thus, radiologic imaging may eventually play a larger role in the diagnosis and treatment of LUTS in the future. After review of the literature, it appears that routine upper urinary tract imaging in patients with LUTS or BPH is not warranted. Selective use of such imaging tests in patients with BPH and either hematuria, laboratory evidence of renal insufficiency (elevated BUN or creatinine), or a history of urinary tract infection, urolithiasis, previous urinary tract surgery, or congenital or acquired renal disease remains indicated. Local imaging of the prostate can be performed with either MR imaging or TRUS. Although MR imaging provides excellent resolution of internal prostatic anatomy, information with respect to the ratio of glandular to stromal tissue in the prostate, and an accurate estimate of prostate volume, its use in patients with BPH is limited by its high cost and limited availability. In contrast, TRUS remains an important tool in the evaluation of patients with prostatic disease. Similar to MR imaging, TRUS provides excellent images of internal prostatic anatomy and an accurate estimate of prostate volume prior to treatment. In addition, this imaging modality is noninvasive, cost-efficient, easily adapted to office use, and able to provide guidance for transrectal prostate biopsy.

Biopsy↗

Importance of the natural history of benign prostatic hyperplasia in the evaluation of pharmacologic intervention.

The variable natural history of untreated symptomatic benign prostatic hyperplasia (BPH) and the fact that therapeutic intervention is based more on subjective than objective criteria of progressive disease have important consequences for appropriately evaluating the effects of pharmacologic intervention on clinical BPH. To evaluate accurately the success of drug therapy for symptomatic BPH, any trial must include a placebo treatment arm for comparison. However, for such a placebo control to be legitimate, it must not affect the natural history of BPH. To evaluate the effect of placebo treatment on BPH, a large body of data following the natural history of untreated clinical BPH from a variety of independent studies was combined and compared to those from a large variety of independent studies in which a placebo-treated group of patients with clinical BPH also followed. These comparisons demonstrate that 1) placebo treatment does not affect the natural history of the disease; 2) spontaneous improvement usually occurs within the first 6 months of initial presentation of symptoms, if it is to occur at all; and 3) 3-6 months of follow-up are needed to determine if a patient is going to get worse. Thus, to evaluate accurately the potential benefit of any medical intervention for symptomatic BPH, placebo-controlled clinical trials will be required and should be of at least 6 month's duration.

Follow-Up Studies↗