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PubMed2000

[Rebound of prostate specific antigen after discontinuation of antiandrogen therapy for benign prostatic hyperplasia].

We compared the prostate specific antigen (PSA) levels in benign prostatic hyperplasia (BPH) patients with antiandrogen chlormadinone acetate (CMA) or allylestrenol (AE) before and during the treatment. We also investigated the serial change of PSA levels before, during and after discontinuation of antiandrogen therapy. Fifty-one BPH patients with normal PSA levels were treated with CMA or AE for 16 weeks. The mean serum PSA level significantly decreased after the treatment from 1.9 +/- 1.0 ng/ml to 1.1 +/- 0.7 ng/ml (M +/- SD). We discontinued medication with informed consent and the patients were carefully monitored for another 16 weeks. Nineteen patients were followed for 32 weeks. The mean serum PSA level decreased significantly from 2.0 +/- 1.0 ng/ml to 1.1 +/- 0.5 ng/ml (M +/- SD) and recovered approximately to the pretreatment level (1.7 +/- 1.1 ng/ml) at the end of this study. We found only one patient whose PSA was slightly elevated to a subnormal range (4.3 ng/ml) after discontinuation of therapy. The other BPH patients with normal PSA levels showed no excessive increase in PSA levels beyond the normal limit after discontinuation of antiandrogen therapy compared with the pretreatment baseline. In conclusion, BPH patients with a marked increase in PSA after discontinuation of antiandrogen therapy should be checked for prostate cancer.

Aged↗
PubMed2004

[Serum PSA and transition zone index as predictors of acute urinary retention in benign prostate hyperplasia].

OBJECTIVE: To evaluate prostate specific antigen (PSA) and transition zone index (TZI) as predictors of acute urinary retention (AUR) in men with benign prostate hyperplasia(BPH). METHODS: The complete data of 602 cases of BPH were reviewed and analyzed. RESULTS: Mean serum PSA and TZI were (6.60 +/- 3.4) microgram/L and (0.71 +/- 0.14) in AUR group, (3.51 +/- 2.3) microgram/L and (0.46 +/- 0.21) in non-AUR group, respectively. There were significant differences in serum PSA and TZI between the two groups(P < 0.05). The difference in incidence of AUR between serum PSA < 4.0 micrograms/L, 4.0-10.0 micrograms/L and PSA > 10.0 micrograms/L was significant (P < 0.05). There was significant positive correlation between serum PSA and TZI(r = 0.213, P < 0.01). CONCLUSION: Serum PSA and TZI were powerful predictors of the risk of AUR in men with BPH.

Acute Disease↗
PubMed2006

Dioxin exposure and benign prostatic hyperplasia.

OBJECTIVE: Dioxins decrease prostate weight, reduce androgen responsiveness, and inhibit prostate morphogenesis in rats. We assessed the association of dioxins and benign prostatic hyperplasia (BPH) in participants in the National Health and Nutritional Examination Survey 1999-2000. METHODS: Forty-two participants were classified as having BPH and 99 were classified as controls. Dioxin exposure was expressed as dioxin toxic equivalents (TEQ). Age, body mass index, waist circumference, race/ethnicity, smoking, physical activity, and education were assessed as potential confounders. RESULTS: After age adjustment, men without BPH had 20.9% higher TEQs (95% confidence interval [CI] = 5.4-38.7%) as compared with men with BPH. On weighted, multivariate, logistic regression analyses, men with higher dioxin levels had lower odds of having BPH (odds ratio = 0.22, 95% CI = 0.08-0.62). CONCLUSIONS: Dioxin exposure in the general population may be associated with decreased odds of BPH. Our study findings need to be confirmed.

Aged↗
PubMed1996

Economics of different treatment options of benign prostatic hyperplasia in Turkey.

Benign prostatic hyperplasia (BPH) has an important impact on the national health economics and can be managed in a large spectrum of modalities from simple follow-up to surgery. In this study, we aimed to compare different treatment options of BPH in terms of cost effectiveness in Turkey. The first evaluation of a BPH patient has a cost of $200. The cost of TURP or open prostatectomy (OP) in our hospital including all the expenses is $740. Finasteride has an annual cost nearly equal to TURP and OP. Considering the expenses of the close follow-up studies and regular visits, one-year lasting Finasteride treatment is two times more expensive than surgery. In comparison with medical treatment options, TURP as the gold standard of treatment of BPH is cost effective when long-term expenses are considered.

Cost-Benefit Analysis↗
PubMed2004

Molecular and cellular pathogenesis of benign prostatic hyperplasia.

PURPOSE: Symptomatic benign prostatic hyperplasia (BPH) is one of the most common ailments seen by the urologist. Significant advances have occurred in medical and surgical therapy, and in the understanding of the biology of this disease. However, the basic science literature is often conflicting and confusing, without a unified voice. We report the current state of knowledge of the molecular and cellular basis of BPH. MATERIALS AND METHODS: We compiled and interpreted basic science studies relevant to BPH pathogenesis. RESULTS: Cellular alterations that include changes in proliferation, differentiation, apoptosis and senescence in the epithelium and stroma are implicated in BPH pathogenesis. Molecular analyses have yielded numerous candidate genes important in disease progression. Differential expression of cytokines and growth factors in BPH tissue suggests roles for inflammation and hypoxia. Through the use of cell culture models the complex regulatory mechanisms of growth control in BPH are becoming defined. CONCLUSIONS: The scientific endeavor has resulted in great strides in our understanding of BPH on a molecular and cellular level. It is hopeful that basic science and translational research will improve treatment and prevention strategies for this common disease of elderly men.

Apoptosis↗
PubMed1993

[Economic public health aspects of benign prostatic hyperplasia in Austria].

Benign prostatic hyperplasia (BPH) is one of the most frequent diseases in advanced aged men. The introduction of a new coding system (ICD-VESKA) in 1989 made it possible to analyze the number of hospitalized cases and to calculate the costs of inpatient care. In 1990 10,710 BPH cases were treated within Austrian hospitals. Controlling for multiple entries 9,742 individual patients (269.4 per 100,000) were treated 138,761 days. Case fatality was 0.5% (46 deaths). The number of inpatients comprises only the top 1,3% of morbidity, the total number is estimated with 770,000 patients. Based on the official nursing fees total costs in public affiliated hospitals were AS 250 millions. Including private hospitals total costs increase to AS 306 millions. The inpatient care of BPH represents only a small proportion of the total health and economic burden, which obviously mainly occurs in the outpatient system. Therefore BPH is one of the diseases of which social and economic importance is usually underestimated due to a lack of information.

Adolescent↗
PubMed1989

[Prognosis of the prostatectomy of benign prostatic hyperplasia].

Surgery of benign prostatic hyperplasia has been performed in 484 cases during a period of 10 years from January 1978 to December 1987; these 484 cases comprised 345 to transurethral resection, 130 of subcapsular extirpation and 9 of cryosurgery. Their period of prognosis was examined; 10-year survival rate was 88.9, 95.7, 60.4, 55.8 and 42.8% for 55-59, 60-64, 65-69, 70-74 and 75-79 years, respectively, 8-year and 7-year survival rates being 31.7 and 66.7% for 80-84 85-89 years, respectively. Survival rate by age bracket was compared in terms terms of electrocardiogram (ECG), pulmonary function and possible anomalies and operative blood transfusion. The group of patients with abnormal ECG and pulmonary function showed a significant decreasing survival rate with aging. The aged patients showed no difference in survival rate according to possible blood transfusion. Examination of the cause of death revealed predominant involvement of cardiopathy and cerebrovascular disorder, with comparatively less due to cancers. In terms of postoperative conditions of life of these patients and a long period prognosis of their urination, more 75% of them are living in good condition and 70% are in a state of satisfactory urination.

Age Factors↗
PubMed1995

Regional distribution of epidermal growth factor, testosterone and dihydrotestosterone in benign prostatic hyperplasia tissue.

In benign prostatic hyperplasia (BPH), basic fibroblast growth factor (bFGF) is found to have a regional distribution, with concentrations in the periurethral zone (where the primitive fibrostromal nodule originates) higher than those of the peripheral subcapsular zone. The aim of the present investigation was to verify whether androgens and epidermal growth factor (EGF) are uniformly distributed from the periurethral to the peripheral zone or whether they show regional differences. Tissue samples, removed by transvesical resection from nine untreated BPH patients, sectioned in periurethral, subcapsular, and intermediate zones, were examined. In the periurethral zone, dihydrotestosterone (DHT), testosterone, and EGF, determined by radioimmunoassay (RIA) techniques after purification on Celite microcolumns and Sep-pak C18 cartridge, showed values significantly higher (mean +/- SD: 1121 +/- 482 pg, 250 +/- 129 pg, and 6.89 +/- 3.28 ng/mg DNA, respectively; P < 0.01) than those of the subcapsular zone (489 +/- 190 pg, 114 +/- 70 pg, and 3.40 +/- 1.90 ng/mg DNA, respectively). A positive linear correlation between EGF, testosterone, and DHT was also observed. The regional distribution of EGF, testosterone, and DHT was similar to that found for bFGF: the highest levels of these factors in the periurethral region allow us to hypothesize on their possible involvement in the rewakening of mesenchymal tissue, leading to the formation of the primitive fibrostromal nodule and then to BPH development.

Data Interpretation, Statistical↗
PubMed2001

Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH).

Because benign prostatic hyperplasia (BPH) is relatively common, it is important to discover safe and effective means to treat this often debilitating perturbation. Accordingly, we examined the effectiveness of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) in treating symptoms of BPH. We undertook a randomized, placebo-controlled, double-blind study. Patients were enrolled from 3 urological practices in the USA. 144 subjects were randomized for study. 17 subjects eventually withdrew, leaving 70 patients in the test group and 57 in the placebo group to complete the study. Inclusion criteria consisted of a diagnosis of BPH, no evidence of cancer, and a maximal urinary flow rate between 5 and 15 ml/second. Patients received either placebo or the combined natural products for 3 months. Evaluations were performed via the American Urological Association (AUA) Symptom Index score, urinary flow rate, PSA measurement, and residual bladder volume. Nocturia showed a markedly significant decrease in severity in patients receiving the combined natural products compared to those taking placebo (p < 0.001). Daytime frequency was also lessened significantly (p < 0.04). When the average individual total AUA Symptom Index score in the test group was compared to that in the placebo group at the end of the study, the difference proved highly significant (p < 0.014). PSA measurements, maximal and average urinary flow rates, and residual volumes showed no statistically significant differences. When taken for 3 months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) compared to placebo can significantly lessen nocturia and frequency and diminish overall symptomatology of BPH as indicated by an improvement in the total AUA Symptom Index score. The combination of natural products caused no significant adverse side effects.

Androgen Antagonists↗
PubMed2006

Correlation between serum prostate specific antigen and prostate volume in Taiwanese men with biopsy proven benign prostatic hyperplasia.

PURPOSE: We studied the correlation between serum prostate specific antigen and the volume of different zones of the prostate in Taiwanese men with biopsy proven benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 233 patients with a mean age of 71.4 years (range 42 to 89), serum prostate specific antigen less than 10 ng/ml and pathologically confirmed benign prostatic hyperplasia were enrolled in this study. Total prostate and transitional zone volumes were measured with transrectal ultrasonography. Peripheral zone volume was determined by subtracting transitional zone volume from total prostate volume. Correlations between patient age, total serum prostate specific antigen and the volume of each prostate zone were analyzed with the Pearson correlation coefficient. A linear regression model was used to determine the relationship between prostate specific antigen and prostate volume. The prostate specific antigen-prostate volume relationship in our patients was compared with published data on white and Japanese men. RESULTS: Age did not significantly correlate with serum prostate specific antigen and prostate volume. Serum prostate specific antigen significantly correlated with the volume of each prostate zone. After log transformation the Pearson correlation coefficient between total prostate specific antigen and the volume of the whole prostate gland, the transitional zone and the peripheral zone were 0.369, 0.377 and 0.272, respectively (p <0.001). Taiwanese men had lower prostate volume per unit prostate specific antigen comparing with white men, while the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men was similar. CONCLUSIONS: In Taiwanese men with biopsy proven benign prostatic hyperplasia the volume of each prostate zone has significantly correlates with serum prostate specific antigen. The prostate specific antigen-total prostate volume relationship in Taiwanese men is different from that in white men. However, the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men is similar.

Adult↗
PubMed1987

The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia.

We examined the influence of androgens on benign prostatic hyperplasia, using nafarelin acetate, a potent luteinizing-hormone-releasing hormone agonist, to achieve reversible androgen deprivation in men with benign prostatic hyperplasia. Nine patients with bladder-outlet obstruction due to benign prostatic hyperplasia were treated with subcutaneous nafarelin acetate (400 micrograms per day) in an open trial for six months. In all patients, serum testosterone decreased to castrate levels. Objective observations included uroflowmetry, measurement of residual urine volume, determination of prostatic size by ultrasonography, and prostatic biopsy. In all patients, the prostate regressed to a mean (+/- SEM) of 75.8 +/- 3 percent of the initial size (range, 52 to 86; P less than 0.005); the regression reached a plateau after four months. Morphologic analysis of biopsy specimens showed regression of glandular epithelium. Three of nine patients had clinical improvement with treatment. Six months after the cessation of treatment, plasma testosterone levels had returned to normal and the size of the prostate had increased to 99 +/- 5.5 percent of the initial size. These findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients. However, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.

Aged↗
PubMed2000

Benign prostatic hyperplasia. The Saudi perspective in the year 2000.

All published data on benign prostatic hyperplasia in Saudi Arabia was reviewed. The age of presentation of the benign prostatic hyperplasia Saudi patient is between 60 and 70 years. Until the introduction of medical therapy for benign prostatic hyperplasia, presentation by complication was common, mainly by retention of urine in 40-50% of the cases. Diagnostic modalities are improving and both biochemical and imaging techniques are now available. Medical therapy for benign prostatic hyperplasia is widely used but studies on only 2 alpha adrenergic blocking agents out the 5 pharmacological preparations currently in the field were reported. Those are Prazosin and Terazosin. Several studies on the use of the 5-alpha reductase enzyme inhibitor Finastride were also reported. Minimally invasive surgery, other recent techniques including laser technology and standard surgical techniques such as open prostatectomy and Trans-urethral Resection of the Prostate are reported to be efficiently utilized. The workload due to benign prostatic hyperplasia is increasing and estimated currently to be 20-40% of the whole urological workload. Late and complicated presentations still pose a serious medical problem. Screening programs and enhancement of awareness are required to ensure early presentation. The diagnostic modalities have improved and need to further improve by making both PSA testing and ultrasonography as standard procedures. Most advanced methods of medical and surgical treatment are available. More studies researching all aspects of benign prostatic hyperplasia are needed to improve patient care.

5-alpha Reductase Inhibitors↗
PubMed2003

5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium.

PURPOSE: In the prostate testosterone is converted to the more potent androgen dihydrotestosterone by the enzymes 5alpha-reductase (5alphaR) types 1 (5alphaR1) and 2 (5alphaR2). Since 5alphaR2 is the dominant prostatic enzyme, the 5alphaR2 selective inhibitor finasteride has been widely used to treat benign prostatic hyperplasia (BPH). However, inhibition of both 5alphaR enzymes provides a greater decrease in serum dihydrotestosterone. We developed a specific antibody to 5alphaR1 and assessed expression in BPH and prostate cancer (pCa) tissue. The presence of this isoenzyme in localized prostate cancer would provide a rationale for assessing the efficacy of dual inhibition for prostate cancer prevention. MATERIALS AND METHODS: A polyclonal antibody to 5alphaR1 was developed and validated using 5alphaR1 and 5alphaR2 transfected COS-1 cells. A total of 26 BPH and 53 pCa specimens were assessed for 5alphaR1 protein expression using immunocytochemical methods. Also, 29 BPH and 37 pCa specimens were assayed for 5alphaR1 and 5alphaR2 enzyme activity. RESULTS: Specificity of the 5alphaR1 antibody was confirmed using transfected COS-1 cells. Cells transfected with 5alphaR1 showed specific staining in immunocytochemistry experiments and on Western blotting of cell lysates the expected 24 kDa band was observed. High intensity immunoreactivity for 5alphaR1 was observed in the tumor epithelium of 28% of pCa specimens. No high intensity epithelial staining was observed in BPH specimens. In 19% of pCa and 7% of BPH specimens 5alphaR1 enzyme activity was detected. CONCLUSIONS: The presence of increased 5alphaR1 in some prostatic malignancies suggests that it is worthwhile to investigate the use of a dual 5alphaR inhibitor to prevent or treat early stage prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1989

Beta-glucuronidase activity in prostatic carcinoma and benign prostatic hyperplasia.

Beta-glucuronidase activity was extracted from prostatic carcinomas and hyperplastic prostates. It was 3.6-fold higher (P less than 0.0001) in prostatic carcinoma than in prostatic hyperplasia. Analysis for isoenzymes of prostatic beta-glucuronidase by disc-gel electrophoresis in nondenaturing polyacrylamide gels demonstrated only one form of the enzyme. Histochemically, enzymatic activity was observed almost entirely in epithelial cells in both prostatic carcinoma and benign prostatic hyperplasia.

Aged↗
PubMed1997

Cell kinetic in epithelium and stroma of benign prostatic hyperplasia.

The induction of benign prostatic hyperplasia (BPH) from normal prostate is obviously associated with a distinct increase in epithelial and stromal proliferation. We have shown previously that the further increase of BPH volume in aging men is not associated with a further increase in proliferation. We studied whether an imbalance between programmed cell death (apoptosis) and cell proliferation may explain continuing growth in aging men. In prostates of 17 men with BPH removed by open prostatectomy proliferating cells were localized immunohistochemically with the Ki-67 antibody. Apoptotic cells were detected with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. Proliferation and apoptotic index was calculated with a computer assisted image analysis system. Mean proliferation index +/- standard deviation in epithelium (0.142 +/- 0.097) and stroma (0.121 +/- 0.082) was nearly identical. Mean apoptotic index in epithelium (0.172 +/- 0.156) was negligibly higher than the corresponding proliferation index. In stroma, however, no apoptotic cells were detectable. Proliferation index and apoptotic index in epithelium and proliferation index in stroma showed no correlation to patient age or prostate volume. In the epithelium of BPH, obviously the cell kinetic is balanced. On the other hand, our results indicate stromal growth due to cell proliferation in the absence of cell death. This may explain the continuous increase of BPH volume in aging men.

Adult↗
PubMed1990

Clinical and experimental studies of benign prostatic hyperplasia.

The canine prostate appears to be a suitable model for investigating many aspects of abnormal prostate growth related to BPH. This model has indicated that BPH is a complex pathologic process that varies with age and produces a gland that is composed of a mixture of glandular, cystic, and stromal hyperplasia juxtapositioned with foci of atrophy. Canine BPH first occurs very early in life as a glandular hyperplasia before the onset of more complex BPH. As the prostate increases in size with age, the tissue dihydrotestosterone content falls, as does the secretory capacity of the gland. The fall in glandular dihydrotestosterone content is counterbalanced by a concomitant increase in the metabolism of androgens toward dihydrotestosterone and an increase in nuclear androgen receptors. As the prostate ages, it thus becomes more sensitive to androgens, which are required for maintaining the abnormal size of the gland. Established BPH can be maintained in the absence of the testes in the presence of normal testosterone levels, and it appears that the abnormal growth is primarily attributable to an inherent change that has occurred in the aged prostate. In the dog and man, both the normal prostate and BPH are rich in growth factors and dihydrotestosterone receptor in the nucleus, yet mitotic cells are rare. Established BPH is not growing rapidly; the abnormal size of the aged prostate is maintained, not by an increase in the rate of cell replication, but rather by an apparent decrease in the rate of cell death. It appears that a combination of estrogens and 5 alpha-reduced androgens can cause this decrease in the rate of cell death and replication and that this imbalance can produce abnormal cell accumulation and an experimental prostatic hyperplasia. Besides affecting cell death and replication, estradiol has a marked effect in stimulating the stroma and collagen synthesis. Current investigations are focusing on determining the distribution of stem cells for both the epithelial and the stromal elements of the prostate, how these stem cells are recruited to form transiently proliferating cells, and how they mature and subsequently are programmed for cell death. It is believed that steroid imprinting in the neonatal and prepubertal period may be of great importance in determining the ultimate growth of the prostate. Preliminary attempts to control abnormal canine prostate growth by forcing maturation with retinoic acid, or by interfering with growth factors through the use of suramin, have not proved effective; only androgen ablation is. Important leads in the search for the etiology and control of BPH can be studied in the canine model. These concepts must ultimately be tested and confirmed for human BPH in well-controlled clinical investigations.

Aging↗
PubMed2003

Prostate-specific antigen and transition zone index - powerful predictors for acute urinary retention in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the efficacy of prostate-specific antigen and various parameters obtained by transrectal ultrasonography as predictors of acute urinary retention in patients with benign prostatic hyperplasia. METHODS: Eighty-nine men with symptoms of benign prostatic hyperplasia were enrolled in this study from February 2002 to June 2003. Among them, 21 patients presented with acute urinary retention. Transrectal ultrasonography was used to calculate the total prostate volume, transition zone volume and transition zone index. Sample of prostate-specific antigen was taken in outpatient clinic or in clinic before first insertion of the catheter into the bladder, because of urinary retention. If the patient presented with inserted catheter, we used latest prostate-specific antigen date from the medical notes of outpatient clinic. To compare the usefulness of the various indexes, the area under the receiver-operator characteristic curve was calculated for each index. RESULTS: There were significant differences between patients with and without acute urinary retention in the total prostate volume (58.16 cm(3) and 44.28 cm(3), p=0.0028), transition zone volume (36.62 cm(3) and 23.70 cm(3), p=0.0001), transition zone index (0.62 and 0.51, p=0.00022), prostate-specific antigen (4.96 ng/ml and 2.97 ng/ml, p=0.00069), age and quality of life score, but no significant difference in International Prostate Symptom Score. In patients with acute urinary retention, the area under the receiver-operator characteristic curve was 0.775 for transition zone index, 0.742 for prostate-specific antigen, 0.737 for transition zone volume, 0.696 for total prostate zone volume and 0.633 for International Prostate Symptom Score. CONCLUSIONS: The transition zone index and prostate-specific antigen are accurate predictors of acute urinary retention in patients with benign prostatic hyperplasia and may be useful for deciding between surgical intervention and medical treatment.

Acute Disease↗
PubMed1983

Estrogen receptor in human benign prostatic hyperplasia.

Estrogens have been proposed as a major etiological factor in the pathogenesis of benign prostatic hyperplasia in man. The presence of estrogen receptor in benign prostatic hyperplasia would support this concept. Using the receptor stabilizer, sodium molybdate, and a hydroxylapatite assay we assayed human benign prostatic hyperplasia for the presence of cytosolic estrogen receptor. For comparison, we assayed estrogen receptor in cytosols of prostatic cancer and normal tissue, and we also measured androgen receptor and progesterone receptor concentrations in the 3 tissue types. Estrogen receptor was present in 8 of 15 benign prostatic hyperplasia specimens at a mean concentration of 9.2 fmol./mg. protein for the estrogen-receptor-positive samples. Sucrose gradient analysis of the estrogen receptor of benign prostatic hyperplasia revealed that it sedimented in the region of 8S, and steroid specificity studies confirmed that the binding to estrogen receptor was estrogen-specific. Estrogen receptor was also found in normal (3 of 3) and malignant (4 of 6) tissues, and all tissues were positive for androgen receptor. The presence of estrogen receptor in human benign prostatic hyperplasia supports the proposal that circulating estrogens may have a role in the pathogenesis of this disorder.

Adolescent↗