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The role of dihydrotestosterone in benign prostatic hyperplasia.

This article examines the role of the androgen dihydrotestosterone (DHT) in the healthy and diseased prostate and considers the implications of the data on DHT for therapeutic approaches to benign prostatic hyperplasia (BPH). Development and maintenance of the normal prostate, as well as development of BPH, depend on a functional androgen-signaling axis, components of which include: (1) testosterone synthesis in the testes and adrenal glands; (2) conversion of testosterone to DHT; (3) transport of DHT to target tissues; and (4) binding of DHT to the androgen receptor with consequent modulation of genes. DHT plays a beneficial role in the developing prostate but it can be detrimental in the adult prostate in that it causes pathologic prostate growth. The role of DHT in other adult tissues is uncertain. DHT has not been shown to perform beneficial functions unique from testosterone in the adult male, and it is believed that its fundamental effect is to amplify testosterone's weaker hormonal signal. Increased understanding of the cellular mechanisms by which the androgen-signaling axis functions has led to advances in treatment for prostate disease. In BPH, the 5alpha-reductase inhibitors--the only class of therapy to act at the pathophysiologic substrate of the disease--arrest the disease process, reduce prostate volume, improve symptoms, and reduce the risk of acute urinary retention and BPH-related surgery. The availability of dutasteride, the first dual (Type 1/Type 2) 5alpha-reductase inhibitor, offers the opportunity for rapid and consistent inhibition of DHT.

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

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.

Aged↗

[Relationship between preoperative urine cultures and prostatic gland cultures in patients treated for benign prostatic hyperplasia].

OBJECTIVES: 1.--Investigate the bacteriuria preoperative in patients who will be operate on for Being Prostatic Hyperplasia (BPH). 2.--Define the prevalence of the prostatic colonization or infection. 3.--Try to correlate the bacteriological findings of urine and prostate, and find the degree of concordance between the microorganisms which can be commonly found in urine and prostatic tissue. METHOD AND MATERIALS: Prospective series of 175 patients undergoing prostatectomy for obstructive symptoms. The protocol revealed, among others variables: the preoperative urine culture; the presence or the absence of catheter; and the quantitative bacteriological culture of prostatic tissue. The information could be analised and its results could be obtained later on. The analysis stages consisted of both a descriptive and an analytic study. RESULTS AND CONCLUSIONS: 1.--Only 36 patients (20.6%) presented bacteriological increase of microorganisms (> or = 10(4) UFC/ml) in the preoperative urine culture. The Escherichia coli was the most common microorganism, followed by the Enterococcus faecalis, coagulase-negative Staphylococcus and the Pseudomona aeruginosa. A single microorganism grew in 31 out of the 36 positive cultures. 2.--The prevalence of the infection or colonization of the prostatic tissue was 25.1% (44 patients). The most common isolated microorganism was the coagulase-negative Staphylococcus followed by the Escherichia coli and the Enterococcus faecalis, in concentrations of at least 10(4) UFC/gr of tissue in the 79.6%. A single microorganism was isolated in 32 out of 44 patients. 3.--The proportion of positive prostatic cultures, in patients with positive urine culture (38.3%), was significantly higher than the one obtained in patients with negative urine cultures (16.5%) (p < 0.0001). Nevertheless, 52.3% of the 44 patients with positive prostatic cultures had negative urine culture, and only 21 (58.3%) out of the 36 patients with positive urine cultures presented a bacteriological growth in prostate. The degree of concordance (Kappa index) between the microorganisms which were found in preoperative urine and prostatic tissue is low or none for the majority of them.

Aged↗

Clinical results with microwave thermotherapy of benign prostatic hyperplasia.

Since October 1990, 414 patients with micturition complaints due to benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In this study 130 patients are presented who were treated according to a strict protocol. The technique of treatment as well as the inclusion and exclusion criteria for TUMT treatment are discussed. With a follow-up period of 1 year after TUMT, a clear subjective improvement was seen in 63% of the patients. Objective improvement, however, is less pronounced. The main complication of TUMT is a urinary retention, which can be treated with a transurethral catheter. This catheter can be removed in most patients after 1 week.

Aged↗

Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40 g.

OBJECTIVES: To compare the safety and efficacy of two alternatives for surgically treating symptomatic benign prostatic hyperplasia (BPH), i.e. transurethral vapour resection of the prostate (TUVRP) and holmium laser enucleation of the prostate (HOLEP), with transurethral resection of the prostate (TURP), the standard surgical therapy, as treating large prostates is associated with greater morbidity, and to date there is no simultaneous comparison of these three methods. PATIENTS AND METHODS: We prospectively randomized 150 patients (50 in each group) with BPH and glands of >40 g to undergo either TURP, TUVRP or HOLEP. The evaluation before treatment included urine culture, serum prostate specific antigen (PSA) level estimation, the International Prostate Symptom Score (IPSS), peak urinary flow rate (Q(max)), and transabdominal ultrasonography to estimate prostate size and postvoid urine residue (PVR). The operative duration, blood loss, resected tissue weight, change in levels of haemoglobin and serum sodium, nursing contact time, duration of catheterization, and complications were noted. After surgery patients were reassessed for the IPSS, Q(max) and PVR at 6 months and 1 year. RESULTS: The patients in all three groups had comparable characteristics before surgery. The mean operating duration and intraoperative irrigant used for TUVRP was less than for HOLEP or TURP, and blood loss with HOLEP and TUVRP was less than with TURP (all P < 0.001). Postoperative irrigation, nursing contact time, and catheter duration were significantly less for HOLEP than TURP or TUVRP, and for TUVRP than TURP. At follow-up, patients in all groups had a significant improvement from baseline in IPSS, Q(max,) and PVR, but the differences between the groups were not significant at 6 months or 1 year. CONCLUSIONS: HOLEP and TUVRP are both acceptable alternatives to TURP for treating large prostate glands, with less perioperative morbidity and comparable efficacy at 6 months and 1 year.

Adult↗

Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a more selective alpha1A-adrenergic antagonist.

Benign prostatic hyperplasia (BPH) is very common in older men, causing symptoms that can markedly impair quality of life. Surgical treatment, typically transurethral resection of the prostate (TURP), is highly effective but can be costly and is associated with the risk for significant morbidity. Medical treatments for BPH are targeted toward reducing bladder outlet obstruction either by androgen blockade to reduce prostatic volume or alpha-adrenergic blockade to relax the smooth muscle tone of the prostate. In recent years, understanding of the sympathetic innervation of the prostate has improved. This has been paralleled by the development of alpha-adrenergic blocking agents, from nonselective alpha-antagonists, to selective alpha1-antagonists, to the more selective alpha1A-antagonists. It is anticipated that more specific agents will optimize the therapeutic effectiveness of alpha-adrenergic blockade in the prostate while reducing the side effects associated with alpha-adrenergic blockade in other areas of the body, such as the vascular system. This article reviews the evolution of alpha-blockade therapy in management of BPH, focusing on tamsulosin, an agent targeted toward the alpha1A-adrenoceptor that predominates in the prostate. Clinical trials in Europe and the United States have provided evidence that tamsulosin is effective at doses of 0.4 and 0.8 mg/day. At both doses, tamsulosin is associated with significant improvements in the American Urological Association symptom score and the mean and peak urinary flow rates as compared with placebo. This once-daily alpha1A-adrenergic antagonist is well-tolerated, with a minimal potential for the side effects associated with alphas-blocker therapy.

Adrenergic alpha-Antagonists↗

Urodynamic implications of benign prostatic hyperplasia.

By the age of 60, about 70% of men have developed benign prostatic hyperplasia (BPH), and 85%-95% of these have symptomatic dysfunction of the lower urinary tract, 10%-20% undergoing prostatectomy. Although transurethral resection of the prostate is generally considered to be a safe and effective surgical procedure, it has recently been shown that immediate surgery, as opposed to a wait-and-see strategy, leads to a 1-month reduction in life expectancy. In 10%-15% of the patients who undergo surgery, the postoperative result is unsatisfactory as symptoms persist. Between 4% and 40% of patients undergoing prostatectomy become impotent. A urodynamic study with a scope extending beyond that of the standard urological examination is therefore needed to help reduce the number of treatment failures. The value of preoperative cystometry is questionable, since preoperative documentation of detrusor instability has no bearing on the postoperative result. Measurement of urinary flow, in contrast, is of predictive value in BPH, patients in whom the maximum urinary flow before surgery is more than 15 ml/s having significantly worse results of surgery than those with a maximum urinary flow of less than 15 ml/s before surgery. Further data relevant to the prognosis are yielded by pressure-flow investigations, which allow a quantitative estimate of the degree of obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Transurethral microwave thermotherapy versus transurethral catheter therapy for benign prostatic hyperplasia.

Transurethral microwave thermotherapy (TUMT) is a single outpatient treatment for benign prostatic hyperplasia. It produces good symptomatic relief but minimal objective improvement in mean flow rates. We wished to evaluate the placebo effect of the transurethral catheter. We evaluated 40 patients with outflow obstruction, 20 had TUMT for 1 h and 20 had a catheter placed in the urethra without treatment for 1 h. Urinary flow rates improved in both groups (12.8-14.6 with TUMT, 10.0-12.4 with catheter). Significant reduction from pretreatment values occurred in symptom scores and postvoid residual urine volume in both groups following treatment. The subjective results of TUMT and the placebo effect seen in the catheter group cast doubt on our understanding of the mechanism of action of TUMT.

Humans↗

Relations between circulating levels of testosterone, 17 beta-estradiol, androstenedione, dehydroepiandrosterone sulfate, and androgenic receptor content of cytosol in benign prostatic hyperplasia.

Cytoplasmic androgen receptor content was determined in 26 patients with benign prostatic hyperplasia using methyltrienolone (R 1881) as the radioactive ligand. Their concentrations were compared with patient age, adenoma weight, and total circulating concentrations of testosterone, 17 beta-estradiol (17 beta-E2), androstenedione (A) and dehydroepiandrosterone sulfate (DHEA-S). Statistically significant inverse correlations were noted between adenoma weight and receptor content (p less than 0.05) and significant direct correlations between DHEA-S and receptor concentration (p less than 0.05), although the levels of this androgen were similar to those observed in a 'normal' population of the same age. The possible implications of these findings relative to the pathogenesis of the disease are discussed.

Aged↗

Conservative treatment of benign prostatic hyperplasia.

A study was carried out in 30 male patients with benign prostate hyperplasia to assess the effectiveness of treatment with a progestational agent, gestonorone caproate (200 mg), given intramucularly every 7 days over a period of 2 to 3 months. The results showed definite subjective and objective improvement after treatment. Residual urine determination diminished significantly after therapy in 78% of the cases completing the study; uroflometry also showed improvement. There appeared to be some reduction in the degree of occlusion of the urethral lumen in at least 13(65%) out of 20 patients given follow-up cystopanendoscopy after 6 months. This result was further supported by improvement in urinary flow rates and uroflometrograms in the same patients. The only adverse effect of treatment noted was the development of impotency in 21 patients.

Aged↗

Effects of a new steroidal aromatase inhibitor, TZA-2237, and/or chlormadinone acetate on hormone-induced and spontaneous canine benign prostatic hyperplasia.

OBJECTIVE: It has been known for many years that human benign prostatic hyperplasia (BPH) is composed predominantly of hyperplastic stromal cells rather than epithelial cells. In the present study the effects of a new steroidal aromatase inhibitor on hormone-induced and spontaneous canine BPH were investigated. METHODS: (1) Effects of TZA-2237 on hormone-induced canine BPH. Ten castrated beagles were administered testosterone and androstenedione 6 days/week for 8 months, and divided randomly into three groups after 2 months of treatment as follows. Group I served as controls, Group II was given 0.5 and Group III was given 2.5 mg/kg/day TZA-2237 5 days/week for 6 months. (2) Effects of TZA-2237 on spontaneous canine BPH. Twenty aged beagles with BPH were divided into five groups, Group IV was untreated, Group V was treated with 1 and Group VI with 5mg/kg/day TZA-2237 5 days/week for 31 weeks. Group VII was treated with 5mg/kg/day Atamestane and Group VIII was treated with 0.3 mg/kg/day chlormadinone acetate (CMA) 5 days/week. (3) Effects of TZA-2237 combined with CMA on spontaneous canine BPH. Three aged beagles with BPH were treated with 1mg/kg/day TZA-2237 and 0.03 mg/kg/day CMA 5 days/week for 20 weeks (Group IX) and a further three aged beagles with BPH were treated with 0.3 mg/kg/day CMA alone 5 days/week (Group X). RESULTS: Hormone-induced prostatic growth was significantly suppressed in group III compared with that in other groups. In Group III, the intraprostatic aromatase activity, estradiol level and androgen receptor content decreased significantly in comparison with the values in Group I. The prostatic weights in Groups V, VI and VII increased significantly in comparison with the weight in Group IV. Serum LH and testosterone levels in Groups V, VI, and VII increased significantly in comparison with the level in Group IV. The prostatic weight in Group IX was decreased only slightly, but the smooth muscle component was decreased significantly. CONCLUSIONS: TZA-2237 is a new, unique and effective aromatase inhibitor that causes inhibition of both epithelial and stromal compartments in hormone-induced canine BPH. Dual inhibition of androgen and estrogen resulted in inhibition of smooth muscle growth, and should prove effective as a new method of treatment given the atrophic effects on not only the epithelium but also the stroma in human BPH.

5-alpha Reductase Inhibitors↗

Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia.

OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.

Adult↗

Medical therapy for benign prostatic hyperplasia: sexual dysfunction and impact on quality of life.

Therapies for benign prostatic hyperplasia (BPH) may either improve or exacerbate sexual function with an ensuing impact on quality of life. Here we review a total of 73 papers on medical therapies for BPH with a focus on the effects of different pharmacological agents on sexual function. For example, certain alpha(1)-adrenergic receptor blockers may improve erectile function; however, ejaculatory dysfunction with one of these agents, tamsulosin, occurs at a rate of 4-18%, rising to 30% with long-term use. In addition, treatment with the 5 alpha-reductase inhibitor finasteride is associated with problems of ejaculation (2.1-7.7%), erection (4.9-15.8%), and libido (3.1-5.4%). Such significant and undesirable complications in relation to sexual function produce a well-documented negative impact on quality of life. Thus, optimal treatment for men with BPH requires the use of agents that demonstrate efficacy and safety with fewer sexual side effects.

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

Benign prostatic hyperplasia in an XX man.

A sixty-nine-year-old white phenotypic male who was being investigated for a myeloproliferative disorder, was found to have an XX karyotype in all cells examined in bone marrow, lymphocytes, and skin fibroblast cultures. Despite essentially no testosterone in the plasma, he also suffered from severe prostatic hyperplasia, a finding not reported previously in patients with this genotype. While endocrine studies showed normal follicle-stimulating hormone, the luteinizing hormone level was twice the upper limit of normal and estrogens were in the normal female range. Except for complete absence of Leydig cells, testicular histology resembled that usually found in Klinefelter syndrome. The patient died of the combined effects of the myeloproliferative disease and urinary tract obstruction. The mechanism of occurrence of the sex chromosome anomaly as well as the cause and implication of the unusual finding of prostatic hyperplasia are discussed.

Aged↗

Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia.

The pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia (BPH) are incompletely understood; however, the development of reliable instruments to measure symptom severity, prostatic enlargement, and bladder outlet obstruction has allowed major advances in their elucidation. The development of lower urinary tract symptoms (LUTS) in the aging male is influenced to some degree by the severity of bladder outlet obstruction and prostatic enlargement. Although the development of LUTS, bladder outlet obstruction, and BPH are age-dependent, they are not necessarily causally related; there are many other factors involved in the pathophysiology of LUTS. The clinically important parameters of disease progression in men with moderate to severe LUTS and low peak flow rates are symptom progression and the development of acute urinary retention (AUR). The risk of AUR is related to both baseline serum prostate-specific antigen level and prostate volume. In men with moderate prostate enlargement, the risk of AUR appears to be high enough to justify intervention with a 5alpha-reductase inhibitor in order to reduce this risk.

Journal Article↗

[Disorders of kidney function in patients with benign prostatic hyperplasia].

The examination of 648 males aged 50 to 86 to conduct an early outpatient detection of renal dysfunction in the elderly men employed an original technique of renal function assessment based on the kinetics of urinary 5-NOK elimination. Renal dysfunctions were revealed in 165 patients, in 159 of them the underlying cause was benign prostatic hyperplasia. The results were compared with those obtained at radionuclide tracing and Reberg-Tareev test. The correlation found indicated the authors' technique informative value and its compatibility with the above methods. Identification of renal dysfunction at early stages of benign prostatic hyperplasia allowed their timely hospitalization and operative treatment which enables the physicians to prevent progression of chronic renal failure in these patients.

Aged↗

The epidemiology of benign prostatic hyperplasia: a study in Greece.

OBJECTIVE: To assess the epidemiology of benign prostatic hyperplasia (BPH) in a case-control study in greater Athens, Greece. PATIENTS AND METHODS: The study comprised 184 patients surgically treated for BPH within one year of its diagnosis (cases) and 246 patients with no symptoms of BPH who were treated in the same hospitals for minor diseases or conditions (controls). All cases and controls were permanent residents of the greater Athens area, Greece. The data were assessed using unconditional logistic regression. RESULTS: After controlling for age and education, cases and controls had similar distributions for height, body mass index, sibship size and birth order in the parental family, marital status, number of offspring and a series of previous medical diagnoses or surgical operations. The sole exception was surgery for haemorrhoids, that appeared to be related to the incidence of BPH, possibly by chance. There was no evidence that vertex baldness, tobacco smoking, alcohol consumption or coffee drinking increased the risk for BPH. Men who had spent most of their lives in a rural rather than an urban environment appeared to be at reduced risk for BPH. CONCLUSION: The lifestyle factors assessed here have no major effect on the aetiology of BPH.

Age Distribution↗

Outcome analysis of minimally invasive treatments for benign prostatic hyperplasia.

The armamentarium of minimally invasive treatment modalities for patients with benign prostatic hyperplasia has increased steadily during the past decade. The energy sources used range from microwaves and radiofrequency waves to high-intensity focused ultrasound, with laser vaporization/coagulation/resection and electrosurgical techniques. The large amount of data available allow some conclusions to be drawn concerning the present role of the "gold standard" TURP among the minimally invasive procedures. Although the subjective response after TURP and other minimally invasive procedures is comparable, improvements of flow and urodynamic parameters usually are more pronounced after TURP. Failure rates requiring reintervention (usually TURP) are considerable. Minimally invasive procedures lead to a shift of morbidity from the intraoperative phase, which is reduced (risk of bleeding, TUR syndrome, transfusion) to the postoperative phase. This period is characterized by prolonged urinary retention (ILC, VLAP), significant dysuria (VLAP, TUVP), and nycturia. Recent advances in electrosurgical techniques, such as band TURP loops that facilitate coagulation due to the longer contact time between the electrode and the tissue, have the potential to convert TURP into a less invasive procedure. Finally, high-energy TUMT seems to offer a truly minimally invasive treatment combining efficacy and the need for topical anesthesia only. However, due to a lack of homogeneity of criteria for patient recruitment, parameters of evaluation, and adequate follow-up; accurate guidelines for appropriate patient management have not been established yet.

Catheter Ablation↗