Etiology Of Benign Prostatic Hyperplasia Research Articles

The role of sex steroid hormones in benign prostatic hyperplasia

Introduction: The etiology of benign prostatic hyperplasia (BPH) remains a mystery to scientists; estrogen/androgen imbalance in aged men has been implicated.Methods: Thirty (30) apparently healthy men and newly diagnosed BPH patients were recruited from the Ghana Police Hospital. Lower urinary tract syndrome (LUTS) and prostate volume were assessed via the prostate symptom score sheet (IPSS) and abdominopelvic scan, respectively. Laboratory assays for total prostate specific antigen (tPSA) and hormones [androstenedione (AED), testosterone (T), dihydrotestosterone (DHT), androstanedioladiol (3α-adiol), androstanediol (3β-diol), estrone (E1) and estradiol (E2)] were performed via ELISA techniques. Non-parametric analyses were employed. p < 0.05 was considered significant.Results: AED was significantly higher in controls compared to the BPH patients. AKRIC2 (3α-diol/DHT) was significantly higher in the BPH group (p < 0.001) whiles AKRIC1 (3β-diol/DHT) was significantly lower. Estradiol was significantly higher in BPH (p= 0.029). Age correlated negatively with T, while a negative correlation was observed between TIPSS and 3β-diol and AKRIC1. Also, prostate volume correlated negatively with fT.tPSA correlated positively with E2 and aromatase activity (E2/T) and negatively with fT. On multiple linear regression, DHT and 3β-diol remained independent predictors for TIPSS and fT for tPSA.Conclusion: Estrogens and androstanediols seem to play a role in BPH development.

Comparative analysis of resected prostate weight in diabetic and non-diabetic benign prostatic hyperplasia Patients.

Background:Benign prostatic hyperplasia (BPH) is the most common benign tumor in men. The etiology of BPH is still unresolved and multiple systems are likely to be involved. The effects of diabetes on urinary system are a risk factor for BPH. We then assessed the effects of diabetes on the parameters related to BPH, especially weight and volume.Methods:This study was conducted on patients with BPH who underwent surgery during 2010-2013. The patients’ demographic and clinical data including age, height, weight, history of diabetes, abdominal sonography, prostate-specific antigen(PSA), fasting blood sugar (FBS), triglyceride, and cholesterol, resected sample weight, and pathological diagnosis were extracted.Results:The mean age of all 225 patients (35 (15.6%) diabetic patients and 190 (84.4%) non-diabetic patients) who entered the study was 71.5±8.7 years. The patients were divided in to 3 body mass index (BMI) groups: 48 (21.3%) were normal, 151 (67.1%) were overweight and 26 (11.6%) were obese. The mean weight of resected prostate was higher in diabetic patients (22.9±6.9 vs 21.7±14.3, P=0.02). The resected prostate weight had a significant relationship with BMI (P=0.001), prostate–specific antigen (PSA) level (P=0.001), and prostate volume sonography (P=0.001). No significant relationship was detected between resected prostate weight with age, FBS and triglyceride however, it is significant with cholesterol.Conclusion:We concluded that diabetes has a role in the development and progression of BPH with effect on prostate weight and volume. As well, BMI is a risk factor in BPH progression.

P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate.

Prostate smooth muscle tone and hyperplastic growth are involved in the pathophysiology and treatment of male lower urinary tract symptoms (LUTS). Available drugs are characterized by limited efficacy. Patients’ adherence is particularly low to combination therapies of 5α-reductase inhibitors and α1-adrenoceptor antagonists, which are supposed to target contraction and growth simultaneously. Consequently, molecular etiology of benign prostatic hyperplasia (BPH) and new compounds interfering with smooth muscle contraction or growth in the prostate are of high interest. Here, we studied effects of p21-activated kinase (PAK) inhibitors (FRAX486, IPA3) in hyperplastic human prostate tissues, and in stromal cells (WPMY-1). In hyperplastic prostate tissues, PAK1, -2, -4, and -6 may be constitutively expressed in catecholaminergic neurons, while PAK1 was detected in smooth muscle and WPMY-1 cells. Neurogenic contractions of prostate strips by electric field stimulation were significantly inhibited by high concentrations of FRAX486 (30 μM) or IPA3 (300 μM), while noradrenaline- and phenylephrine-induced contractions were not affected. FRAX486 (30 μM) inhibited endothelin-1- and -2-induced contractions. In WPMY-1 cells, FRAX486 or IPA3 (24 h) induced concentration-dependent (1–10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486 or IPA3. Cytotoxicity of FRAX486 and IPA3 in WPMY-1 cells was time- and concentration-dependent. Stimulation of WPMY-1 cells with endothelin-1 or dihydrotestosterone, but not noradrenaline induced PAK phosphorylation, indicating PAK activation by endothelin-1. Thus, PAK inhibitors may inhibit neurogenic and endothelin-induced smooth muscle contractions in the hyperplastic human prostate, and growth of stromal cells. Targeting prostate smooth muscle contraction and stromal growth at once by a single compound is principally possible, at least under experimental conditions.

Cross-sectional analysis between prostate volumes and serum sex hormones in Japanese men attending a urological clinic

Aim: To evaluate epidemiologically the association between measured prostate volume and sex hormones.Methods: Between December 2012 and September 2014, 226 patients attending the urological clinic were assessed for the relationship between prostate volume (PV) and, serum sex hormones, physical size, personal habits, etc. Prostate volume was measured by using transabdominal ultrasonography. Statistically, the Pearson correlation coefficients test was used.Results: Total cases, the cases of PV ≤ 25 ml, and the cases of PV > 25 ml were evaluated respectively. Total cases and the cases of PV > 25 ml showed a positive significant correlation with testosterone (T), but the cases of PV ≤ 25 ml showed no such correlation. The cases of PV > 25 ml had a positive significant correlation with estradiol (E2), but total cases and cases of PV ≤ 25 ml did not. Dehydroepiandrosterone sulfate (DHEAS) showed no correlation with any case of PV, however it decreased significantly with age and had a correlation with alopecia. The E2/T ratio had no correlation with any case of PV, but on the other hand, the T/DHEAS and E2/DHEAS ratios had significant positive correlation with PV > 25 ml.Conclusions: Serum T and E2 had significant positive correlation with measured PV especially in larger prostates. This result seems to correspond with the conventional theory that T and E2 have an etiological effect on benign prostatic hyperplasia. DHEAS did not show direct correlation with PV, however it appeared to suppress the role of T and E2 on benign prostatic hyperplasia growth. DHEAS might be a key to understanding the etiology of benign prostatic hyperplasia with aging.

EPIDEMIOLOGY OF BENIGN PROSTATIC HYPERPLASIA (BPH)

ABSTRACT: Several mechanisms appear to be involved in the pathophysiology of Benign Prostatic Hyperplasia. These represent tissue modifications such as age related to hormonal disorders and metabolic syndrome as well as inflammation (Briganti et al, 2009, Vignozzi et al, 2016, Sebastianelli et al, 2018). The Tsimane are a key case study to understand the etiology of Benign Prostatic Hyperplasia as they have low levels of obesity and metabolic syndrome as well as lower levels of Testosterone compared to men of similar age in the US lacking BPH. In general, these data suggest that BPH may not be an inevitable part of male aging during human evolutionary history (Trumble et al, 2015). Given the high prevalence of BPH both in the world and in Peru, it is necessary to investigate what are its factors associated with therapeutic and preventive purposes. Material and methods This cross-sectional study included 162 patients aged ≥ 60 years of the clinical history of the Sermedial Clinic laboratory with and without BPH. The results of standard biochemical and cardiological tests (Glucose, Triglycerides, HDL - Cholesterol, Uric Acid, Systolic Blood Pressure and Diastolic Blood Pressure) and their body composition (Age, Weight, Size, Waist Circumference, Index of each patient were recorded for each patient). Body Mass and Conicity Index). The SPSS statistical program was used and the data will be expressed as means  DS. Your will apply ANOVA as well as the Scheffe specificity test to determine differences between quantitative variables between locations, chi square between categorical variables; and Pearson's correlation coefficients (r) to describe association between variables. In all tests p &lt;0.05 will be considered significant. The statistical analysis will be executed with Statistica software (version 7.0; StatSoft Inc, Tulsa, USA). To evaluate the relationship or association between biochemical, cardiac and body factors with BPH Results With statistical significance (p &lt;0.05) BPH is associated with abnormal values of glucose, triglycerides, HDL-cholesterol, uric acid Diastolic Blood Pressure, Body Mass Index and Circumference Waist in men with age ranges from 60 to ≥ 90 years. Conclusion The main finding of our work is the independent, statistically significant association (p &lt;0.05) with biochemical, cardiac and body values that could be reversed with diet and exercise

The Variation with Age of 67 Macro- and Microelement Contents in Nonhyperplastic Prostate Glands of Adult and Elderly Males Investigated by Nuclear Analytical and Related Methods.

To clarify age-related changes of 67 macro- and microelement contents in prostate gland of adult and geriatric males, a quantitative measurement by five analytical methods was performed. The nonhyperplastic prostate glands of 65 subjects (European-Caucasian aged 21-87years) were investigated by energy dispersive X-ray fluorescence (EDXRF), instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides (INAA-SLR), instrumental neutron activation analysis with high resolution spectrometry of long-lived radionuclides (INAA-LLR), inductively coupled plasma atomic emission spectrometry (ICP-AES), and inductively coupled plasma mass spectrometry (ICP-MS). The prostates were obtained at autopsy from subjects who died from acute illness (cardiac insufficiency, stroke, embolism of pulmonary artery, alcohol poisoning) and trauma. None of the subjects had any symptoms of prostatic disease, and all prostates were classified as histologically normal. The combination of nuclear (EDXRF, INAA-SLR, and INAA-LLR) and inductively coupled plasma (ICP-AES and ICP-MS) analytical methods allowed estimation of the contents of 67 chemical elements and precisely determined the mass fraction of 54 elements in the tissue samples of nonhyperplastic adult and geriatric prostate glands. This work's results reveal that there is a significant increase with age of Bi, Cd, Co, Fe, Hg, Pb, Sc, Sn, Th, U, and Zn mass fractions in the prostate tissue of healthy individuals of ages from 21 to 60years, as well as an increase in Ba from age 61 up to 87years. It implies that an age-related increase and excess in Ba, Bi, Cd, Co, Fe, Hg, Pb, Sc, Sn, Th, U, and Zn mass fraction in prostatic tissue may be one of the main factors in the etiology of benign prostatic hyperplasia (BPH) and prostate carcinoma (PCa).

Challenging the Inevitability of Prostate Enlargement: Low Levels of Benign Prostatic Hyperplasia Among Tsimane Forager-Horticulturalists.

Often considered an inevitable part of male aging, benign prostatic hyperplasia (BPH) is the most common non-life threatening disease to affect men in Western populations. We examine age-related change in prostate size and BPH risk and related serum biomarkers among the Tsimane Amerindians of the Bolivian Amazon who live a traditional lifestyle of hunting and small-scale horticulture. The Tsimane are a critical case study for understanding the etiology of BPH as they have low levels of obesity and metabolic syndrome, as well as lower levels of testosterone than age matched U.S. males, factors associated with BPH in previous research. Ultrasounds were conducted on 348 men aged 28-89 years (median age 56 years). Testosterone, prostate specific antigen, sex hormone binding globulin, and glycosylated hemoglobin were examined in relationship to prostate size and BPH. Tsimane have less than half of the BPH prevalence experienced by U.S. men, and prostate volumes 62.6% smaller. While Tsimane have low levels of testosterone and subclinical levels of metabolic syndrome compared to U.S. men, Tsimane with high testosterone were more likely to experience BPH, as were those with higher glycosylated hemoglobin, suggesting targets for clinical interventions to reduce BPH. These results have clinical significance for the growing number of men taking testosterone supplementation; even at low levels the additional testosterone exposure could be placing these men at higher risk of BPH. Overall, these data suggest that BPH may not have been an inevitable part of male aging throughout human evolutionary history.

Protective effect of tadalafil on the functional and structural changes of the rat ventral prostate caused by chronic pelvic ischemia.

BackgroundThe etiology of Benign Prostatic Hyperplasia (BPH), a common among aged men, is not fully understood, however, in addition to androgens and aging, chronic ischemia has been proposed to contribute. Using an established rat model, we investigated whether chronic ischemia alters the structural and functional properties of the ventral rat prostate, and whether phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) may have a protective action.MethodsAdult male Sprague-Dawley rats were divided into control, arterial endothelial injury (AI), and AI with tadalafil treatment (AI-tadalafil) groups. AI and AI-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-tadalafil rats were treated with tadalafil (2 mg/kg/day) orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, animals were sacrificed, and pharmacological and morphological studies on prostate tissues were performed.ResultsIliac arteries from AI rats displayed neo-intimal formation and luminal occlusion, an effect that was not prevented by tadalafil treatment. In the AI group, there was an obvious epithelial atrophy and a statistically significant increase in collagen fibers compared with the controls. Immunohistochemically, there was an up-regulation of smooth muscle α-actin (SMA). Contractile responses of prostate strips to KCl, electrical field stimulation (EFS), and phenylephrine (PE) were significantly higher after AI than in controls. Chronic treatment with tadalafil prevented the increase in contractile responses in ischemic tissue, and decreased the collagen deposition compared with the AI group.ConclusionsIn this rat model, chronic pelvic ischemia caused distinct functional and morphological changes in the prostate. Prostatic tissue from ischemic animals showed an increased contractile response to electrical and pharmacological stimulation, an increase in SMA, and an increased deposition of collagen. All these changes could be prevented by treatment with the PDE5 inhibitor, tadalafil, suggesting an involvement of cyclic guanosine monophosphate (cGMP). Prostate 75:233–241, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Epithelial-to-mesenchymal transition and estrogen receptor α mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia.

Epithelial-to-mesenchymal transition (EMT) has been reported involved in the pathogenesis of fibrotic disorders and associated with stemness characteristics. Recent studies demonstrated that human benign prostatic hyperplasia (BPH) development involves accumulation of mesenchymal-like cells derived from the prostatic epithelium. However, the inductive factors of EMT in the adult prostate and the cause-and-effect relationship between EMT and stemness characteristics are not yet resolved. EMT expression patterns were immunohistochemically identified in the human epithelia of normal/BPH prostate tissue and in a rat BPH model induced by estrogen/androgen (E2/T, ratio 1:100) alone or in the presence of the ER antagonist raloxifene. Gene expression profiles were analyzed in micro-dissected prostatic epithelia of rat stimulated by E2/T for 3 days. Two main morphological features both accompanied with EMT were observed in the epithelia of human BPH. Luminal cells undergoing EMT dedifferentiated from a cytokeratin (CK) CK18(+) /CK8(+) /CK19(+) to a CK18(-) /CK8(+) /CK19(-) phenotype and CK14 expression increased in basal epithelial cells. ERα expression was closely related to these dedifferentiated cells and the expression of EMT markers. A similar pattern of EMT events was observed in the E2/T induced rat model of BPH in comparison to the prostates of untreated rats, which could be prevented by raloxifene. Epithelial and mesenchymal phenotype switching is an important mechanism in the etiology of BPH. ERα mediated enhanced estrogenic effect is a crucial inductive factor of epithelial dedifferentiation giving rise to activation of an EMT program in prostate epithelium.

Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet obstruction

Benign prostatic hyperplasia (BPH) is a histological diagnosis associated with unregulated proliferation of connective tissue, smooth muscle and glandular epithelium. BPH may compress the urethra and result in anatomic bladder outlet obstruction (BOO); BOO may present as lower urinary tract symptoms (LUTS), infections, retention and other adverse events. BPH and BOO have a significant impact on the health of older men and health-care costs. As the world population ages, the incidence and prevalence of BPH and LUTS have increased rapidly. Although non-modifiable risk factors – including age, genetics and geography – play significant roles in the etiology of BPH and BOO, recent data have revealed modifiable risk factors that present new opportunities for treatment and prevention, including sex steroid hormones, the metabolic syndrome and cardiovascular disease, obesity, diabetes, diet, physical activity and inflammation. We review the natural history, definitions and key risk factors of BPH and BOO in epidemiological studies.

White blood cell count is positively associated with benign prostatic hyperplasia

To determine whether low-grade systemic inflammation is associated with prostatic enlargement/benign prostatic hyperplasia. Prostate volume was measured by transrectal ultrasonography in 576 Japanese men. The association between prostate volume and routine clinical inflammatory markers (C-reactive protein level, white blood cell count, or the differential white cell count [neutrophils, lymphocytes, basophils, eosinophils, and monocytes]) were analyzed. Contributors to prostate volume were identified in univariate and multivariable linear regression models. Prostate volume was found to have a positive association with serum prostate-specific antigen level (P < 0.001), white blood cell count (P = 0.027) and absolute neutrophil count (P = 0.010). In univariate linear regression models, a large prostate volume was associated with older age, higher prostate-specific antigen, and higher white blood cell and neutrophil counts. A multivariable model adjusted for age, prostate-specific antigen, and C-reactive protein showed that the white blood cell count and the neutrophil count were independently associated with prostate volume. An increased white blood cell count was also associated with higher total International Prostatic Symptom Scores (P < 0.001). White blood cell count seems to be associated with the degree of prostate enlargement and lower urinary tract symptoms. Chronic low-grade systemic inflammation might be involved in the etiology of benign prostatic hyperplasia.

Antimicrobial Activity of Willowherb (Epilobium angustifolium L.) Leaves and Flowers

Since the aetiology of benign prostatic hyperplasia (BHP) is still unknown, the use of medicinal herb extracts and products prepared thereof are recommended due to their antimicrobial activity, especially during early stages of BHP. A comparison was performed of the in vitro antimicrobial activity (using broth microdilution assay) of flowers and leaves of willowherb (Epilobium angustifolium L., Onagraceae) from Mt. Velebit (Croatia). The strains (standard ATCC and clinical isolates) of Staphylococcus aureus (including MRSA), Bacillus subtilis, Escherichia coli (including p-fimbriae positive strain), Pseudomonas aeruginosa, Proteus mirabilis, Candida albicans, C. tropicalis, C. dubliniensis and Saccharomyces cerevisiae were susceptible with MIC values between 4.6±0.2 and 18.2±0.8 mg/mL. The results of in vitro studies showed that no differences were found in the antimicrobial activity between the ethanol extracts of leaves and flowers of E. angustifolium. Using the quantitative fluorescent assay with ethidium bromide and acridine orange, the viability of C. albicans ATCC 10231 was assessed after in vitro exposure to E. angustifolium leaf and flower ethanol extracts. Apoptosis of C. albicans blastospores dominated over necrosis in all treated samples after short-term exposure with 6 to 12 mg/mL of extracts. In addition to the valuable biological activity of E. angustifolium extracts, the data obtained from the in vitro diffusion, the dilution assay and antifungal viability fluorescent assay suggest that leaf and flower ethanol extracts of E. angustifolium L. are a promising complementary herbal therapy of conditions such as BHP.

Effects of selenium status, dietary glucosinolate intake and serum glutathione S‐transferase α activity on the risk of benign prostatic hyperplasia

Study Type--Prognosis (case control) Level of Evidence 2. What's known on the subject? and What does the study add? Geographical and ethnic differences in the distribution of BPH and the results of migrant studies indicate that not only age, androgens and genetics, but also modifiable factors may play a role in the aetiology of BPH. Oxidative stress induced by chronic inflammation could be a cause and antioxidants, including selenoproteins, may reduce the risk. The published data related to this topic are scarce and are mainly based on cross-sectional and case-control studies. In a nested case-control study, we observed a significant inverse association between serum selenium concentrations and the risk of BPH. These results need to be confirmed in larger, prospective epidemiological studies. Prostate enlargement is an increasing health problem as a result of an ageing population in many countries. Modifiable factors may also play a role. In the present study, before this antioxidant can be recommended as a preventive measure. • To determine whether geographical differences in the distribution of benign prostatic hyperplasia (BPH) and migrant studies indicate that modifiable factors play a role in the aetiology of BPH. Oxidative stress produced by chronic inflammation could represent one of the causes, and antioxidants, including selenoproteins, may reduce the risk. • Conditional logistic regression was used to examine the associations of serum selenium and selenoprotein P concentrations and glutathione peroxidase activity with respect to the risk of BPH in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort, including 111 cases and 214 matched controls. • In addition, dietary glucosinolate intake and the serum glutathione S-transferase α concentration was investigated. • The risk of BPH significantly decreased with an increasing serum selenium concentration; the risk estimate was 0.83 (35% CI 0.69-0.99) per 10 µg/L increase in serum selenium concentration. • However, no significant association was present for serum selenoprotein P concentration or glutathione peroxidase activity. Risk estimates for BPH decreased with a higher intake of glucosinolates, although the results were not statistically significant. • A low serum selenium concentration may increase the risk of BPH, although the findings reported in the present study need to be confirmed in larger, well-designed epidemiological studies.

Benign Prostatic Hyperplasia: from Bench to Clinic

Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options.

Relationships between Prostate-Specific Antigen, Prostate Volume, and Components of Metabolic Syndrome in Healthy Korean Men

PurposeMetabolic syndrome (MS) plays a potential role in the etiology of benign prostatic hyperplasia (BPH). Recent studies have reported on an association between MS and BPH. However, there has been no consensus on recent results. This study was conducted to evaluate the associations among prostate-specific antigen (PSA), prostate volume (PV), and metabolic components in men who visited our health promotion center.Materials and MethodsDuring the period from January 2005 to December 2010, 521 consecutive men (age range, 40 to 70 years) who underwent transrectal ultrasonography were enrolled in this retrospective study. The health screening program includes blood pressure, body measurements (height, weight, waist circumference, body mass index), biochemical analysis (serum glucose, total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol, fasting plasma glucose, tumor markers), stool and urine analysis, and a detailed clinical examination.ResultsThe serum PSA level and PV were significantly higher in patients with MS than in patients without MS, retrospectively (p<0.001, p<0.001). Patients with more than one metabolic component were significantly more likely to have a larger PV and higher serum PSA level. The serum PSA level and PV were increased in a similar manner with the increasing sum of MS components (p<0.0001, p<0.0001).ConclusionsThe MS components were associated with larger PV and higher serum PSA level. Therefore, each MS component could be an important factor in BPH development and management.

Benign Prostatic Hyperplasia and Male Lower Urinary Tract Symptoms: Epidemiology and Risk Factors.

The epidemiology of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS) has evolved considerably during the past several years. The term LUTS describes a distinct phenotype and allows for a broad epidemiologic description of urinary symptoms at a population level. Although it is becoming the preferred term for studying urinary symptoms in populations, LUTS remains interconnected with BPH in the literature. The incidence and prevalence of BPH and LUTS are increasing rapidly as the US population ages. BPH and LUTS are associated with serious medical morbidities, an increased risk of falls, depression, diminished health-related quality of life, and billions of dollars in annual health care costs. Although age and genetics play important roles in the etiology of BPH and LUTS, recent insights at the population level have revealed that modifiable risk factors are likely key components as well. Serum dihydrotestosterone, obesity, elevated fasting glucose, diabetes, fat and red meat intake, and inflammation increase the risk; vegetables, regular alcohol consumption, exercise, and NSAIDs decrease the risk.

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

The precise aetiology of benign prostatic hyperplasia (BPH) remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 (NOS2) inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms (SNPs) in the NOS2 gene, including rs2779248 (promoter, -278 T/C), rs10459953 (5'-untranslated region) and rs2297518 (exon 16, missense, Ser608Leu), using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP (rs10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P < 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P < 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model) was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP (rs10459953) between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.

Emerging drugs for the treatment of benign prostatic obstruction

Importance of the field: Benign prostatic enlargement (BPE) leading to benign prostatic obstruction (BPO) affects an increasing number of men as they grow older. They can affect quality of life and cause lower urinary tract symptoms (LUTS) including urinary retention. The currently available pharmacotherapies are α-blockers and 5-α reductase inhibitors which may be effective but can have adverse effects and long-term compliance problems. Therefore, it is important to find new medical treatments for LUTS/BPO and this review aims to identify the potential future drugs undergoing clinical trials in this field.Areas covered in this review: Articles were identified by means of a computerized Google, PubMed and Cochrane Library search over the last 10 years (using the following keywords: benign prostate hyperplasia, enlargement and obstruction) and a search of the PharmaProjects database.What the reader will gain: An insight into the currently available and future potential treatments for benign prostatic obstruction.Take home message: The exact etiology of benign prostatic hyperplasia (BPH) and its consequences, BPE and BPO, are not known; however, ageing and functioning testes have been implicated. Several classes of drugs are currently undergoing clinical trials such as phosphodiesterase inhibitors and leutenizing hormone-releasing hormone antagonists. Others include phytoestrogens, progestogens, NX1207 and PRX302. Some of these work by affecting testosterone level and, therefore, on the static component of BPO, while it is not known how the rest work. Until the exact etiology of BPH/BPE/BPO is known, we are unlikely to have the cure for this ageing male phenomenon.

Expression patterns of survivin and cuspuse-3 in dissymmetric enlarged prostate

Objective To compare the different expression patterns of survivin and caspase-3 between the larger part and the smaller part of the dissymmetric enlarged prostates in BPH patients, and to clarify the role of apoptosis in BPH etiology. Methods BPH tissues from 25 patients were embedded in paraffin. The specimens constituted of two prostate parts from each patient. One part was from the larger enlarged gland and the other was from the smaller enlarged counterpart. 50 paraf-fin blocks were cut into sections and stained with survivin and caspase-3 polyclonal antibodies against human. All the data was analyzed by SPSS13.0 software. Results Survivin immunoreactivity was localized in prostatic cell nuclei. Survivin expression in larger enlarged parts (22.08±16. 33)0% was significantly higher than the smaller parts (7. 645±5. 45)%(P 0. 05). Conclusions Survivin and caspase-3 expression patterns are different in the two parts of the dissymmetric enlarged prostates. These different patterns indicate apoptosis playing an important role in BPH development. Key words: Benign prostatic hyperplasia (BPH); Apoptosis; Survivin; Caspase-3

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGF-beta signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA. Androgen receptor and estrogen receptor beta (ERbeta)1 and ERbetacx were abundant in both stromal and epithelial compartments but cells expressing ERalpha were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGF-beta is thought to play a key role in EMT. Our data suggests that TGF-beta/Smad should be considered as targets for treatment of BPH.