Intrinsic and extrinsic factors causing hyperplasia of the prostate.

Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity.

Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. METHODS: We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. RESULTS: The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. CONCLUSION: This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.

Magnetic resonance imaging-guided transurethral ultrasound ablation for benign prostatic hyperplasia: 12-month clinical outcomes of a phase I study.

OBJECTIVES: To investigate the safety and feasibility of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) for the treatment of benign prostatic obstruction (BPO). PATIENTS AND METHODS: An investigator-initiated, prospective, registered (NCT03350529), phase I study enrolled men with lower urinary tract symptoms due to benign prostatic hyperplasia in need of surgical intervention. Patients were followed for 12 months after TULSA. Uroflowmetry, prostate-specific antigen (PSA) level, and a comprehensive set of functional questionnaires including the Expanded Prostate cancer Index Composite-26, International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function were obtained at baseline and every 3 months afterwards. MRI was obtained at baseline, and at 3 and 12 months after TULSA. Medication use before and after TULSA were recorded. Adverse events (AEs) were reported using the Clavien-Dindo classification. RESULTS: A total of 10 men underwent TULSA with no severe AEs encountered. The baseline median (interquartile range [IQR]) age and prostate volume were 68 (63-72) years and 53 (45-66) mL, respectively. At baseline, six patients were moderately symptomatic and four patients severely symptomatic. Nine patients at baseline were on BPO medication. The median (IQR) improvement in the IPSS was 82%, from 17.5 (15.3-23.0) at baseline to 4.0 (2.3-6.3) at 12 months. Similarly, the median maximum urinary flow rate improved by 101%, from a median (IQR) of 12.4 (8.8-17.6) mL/s at baseline to 21.8 (17.6-26.5) mL/s at 12 months. Improvements were already seen at 3 months. The median prostate volume and PSA reduction at 12 months were 33% and 48%, respectively. There were no changes in continence, sexual, erectile or bowel functions. At 12 months, five out of six men with normal ejaculatory function before TULSA reported normal antegrade ejaculations. All patients taking BPO medication before TULSA discontinued medication after TULSA. CONCLUSION: TULSA appears to be a safe and effective treatment for BPO, with promising 12-month follow-up outcomes. Further studies with larger cohorts are needed to confirm the observed results.

Challenging cases in high-risk prostate cancer patients treated with Retzius-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To evaluate the relationship between enlarged prostate, bulky median lobe (BML) or prior benign prostatic hyperplasia (BPH) surgery and perioperative functional, and oncological outcomes in high-risk (HR) prostate cancer (PCa) patients treated with Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). METHODS: 320 HR-PCa patients treated with RS-RARP between 2011 and 2020 at a single high-volume center. The relationship between prostate volume, BML, prior BPH surgery and perioperative outcomes, Clavien-Dindo (CD) grade ≥ 2 90-day postoperative complications, positive surgical margins (PSMs), and urinary continence (UC) recovery was evaluated respectively in multivariable linear, logistic and Cox regression models. Complications were collected according to the standardized methodology proposed by EAU guidelines. UC recovery was defined as the use of zero or one safety pad. RESULTS: Overall, 5.9% and 5.6% had respectively a BML or prior BPH surgery. Median PV was 45 g (range: 14-300). The rate of focal and non-focal PSMs was 8.4% and 17.8%. 53% and 10.9% patients had immediate UC recovery and CD ≥ 2. The 1- and 2-yr UC recovery was 84 and 85%. PV (p = 0.03) and prior BPH surgery (p = 0.02) was associated with longer operative time. BML was independent predictor of time to bladder catheter removal (p = 0.001). PV was independent predictor of PSMs (OR: 1.02; p = 0.009). Prior BPH surgery was associated with lower UC recovery (HR: 0.5; p = 0.03). CONCLUSION: HR-PCa patients with enlarged prostate have higher risk of PSMs, while patients with prior BPH surgery have suboptimal UC recovery. These findings should help physicians for accurate preoperative counseling and to improve surgical planning in case of HR-PCa patients with challenging features.

Incidence and risk factors for postoperative urinary incontinence after various prostate enucleation procedures: systemic review and meta-analysis of PubMed literature from 2000 to 2021.

PURPOSE: To evaluate the risk of urinary incontinence (UI) after various prostate enucleation procedures (PEP). METHODS: PubMed was searched from January 2000 to July 2021 for studies investigating UI after PEP. The articles were divided into 5 subgroups: holmium, thulium, greenlight laser, electrocautery, and simple prostatectomy. Meta-analysis was performed to examine rate of stress (SUI), urge (UUI) or unspecified UI at short (< 3 months), intermediate (3-6 months), and long-term (> 6 months). The impact of age, prostate size, surgery time, laser time, postoperative nadir PSA level and technical modifications on UI was analyzed. RESULTS: Most (69.4%) of 49 articles included employed holmium laser. There was no significant difference in incidence of short-, intermediate-, and long-term UI, SUI and UUI between five sub-groups and within different technical modifications. Although not statistically significant, the incidence of UI was higher (15%) at short-term with green-light and simple prostatectomy (95% CI 9-23 and 1-84), and higher (4%) at intermediate-term with holmium laser (95% CI 2-8). SUI was more prevalent at short-term with holmium laser (4%; 95% CI 2-5%), and at intermediate term with simple prostatectomy (3%; 95% CI 1-14). UUI was higher in the thulium group (10%, 95% CI 7-16). Increased age, surgery time, laser time and prostate size up to 80 cc were associated with higher UI. There was no correlation between postoperative PSA and UI. CONCLUSIONS: There is no significant difference in incidence of UI, SUI and UUI after various PEP. Patients age, prostate size, surgery and laser time are linearly associated with UI.

Urethral and bladder neck stenosis after thulium laser enucleation of the prostate: Analysis of risk factors in a series of 1003 patients.

We assessed the incidence and risks factors of bladder neck and urethral stenosis after Thulium laser enucleation of the prostate. Patients who underwent surgery at two centres were retrospectively reviewed (December 2014-June 2020). Exclusion criteria: previous urethral/prostatic surgery, pelvic irradiation, prostate cancer, neurogenic bladder, history of bladder neck and urethral stenosis, concomitant transurethral surgery, active urinary tract infection. Significant variables at univariate analysis (p < 0.05) were included in a multivariate logistic regression analysis to establish their association with bladder neck/urethral stenosis. One thousand and three patients were included. Median age was 69.0 (63.0-75.0) years. Median prostate volume was 65.0 (46.3-82.0) ml. Median follow-up was 31 (25-75) months. Thirty patients (2.99%) developed bladder neck stenosis [median time after surgery: 15 (11-17.75) months], 50 patients (4.98%) urethral stenosis [median time after surgery: 9 (7-11) months]. Men with bladder neck and urethral stenosis had significantly smaller prostate volume (median volume 43.5 ml vs. 66.0 ml, p = 0.008, and 52.0 ml vs. 66.0 ml, p = 0.009, respectively). At multivariable analysis, short surgical time predicted for bladder neck stenosis (OR 0.973; 95% CI 0.957-0.994, p = 0.002), and re-catheterization (OR 3.956; 95% CI 1.867-8.382, p < 0.001) for urethral stenosis, whereas prostate volume was significantly associated with a lower incidence of US (OR 0.984, 95% CI 0.972-0.998, p = 0.03).

Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer.

Two out of three diseases of the prostate gland affect aging men worldwide. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement affecting millions of men. Prostate cancer (PCa) in turn is the second leading cause of cancer death. The factors influencing the occurrence of BPH and PCa are different; however, in the course of these two diseases, the overexpression of heat shock proteins is observed. Heat shock proteins (HSPs), chaperone proteins, are known to be one of the main proteins playing a role in maintaining cell homeostasis. HSPs take part in the process of the proper folding of newly formed proteins, and participate in the renaturation of damaged proteins. In addition, they are involved in the transport of specific proteins to the appropriate cell organelles and directing damaged proteins to proteasomes or lysosomes. Their function is to protect the proteins against degradation factors that are produced during cellular stress. HSPs are also involved in modulating the immune response and the process of apoptosis. One well-known factor affecting HSPs is the androgen receptor (AR)-a main player involved in the development of BPH and the progression of prostate cancer. HSPs play a cytoprotective role and determine the survival of cancer cells. These chaperones are often upregulated in malignancies and play an indispensable role in tumor progression. Therefore, HSPs are considered as one of the therapeutic targets in anti-cancer therapies. In this review article, we discuss the role of different HSPs in prostate diseases, and their potential as therapeutic targets.

Joint effect between bisphenol A and alcohol consumption on benign prostatic hyperplasia: A case-control study in Hong Kong Chinese males.

BACKGROUND: Whether bisphenol A (BPA) exposure is a contributing factor to benign prostatic hyperplasia (BPH) remains unclear. This study evaluated the association between chronic BPA exposure and BPH risk, and explored whether this association was modified by alcohol drinking. METHODS: This study included a total of 650 BPH cases and 650 controls recruited from the same hospital in Hong Kong during 2011-2016. Chronic BPA exposure level was estimated by a validated cumulative BPA exposure index (CBPAI). We performed unconditional logistic regression model to examine the association of BPH risk with potential sources of BPA exposure via oral intake and CBPAI. We further tested the interactions between CBPAI and alcohol consumption habits on BPH risk. RESULTS: A positive exposure-response relationship was observed between CBPAI and BPH risk. Frequent BPA exposure via oral intake of foods heated in a plastic box/bag (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.51-8.22), cooling water in a plastic bottle (OR = 2.65, 95% CI: 1.33-5.27), or using a plastic cup to contain hot water (OR = 4.14, 95% CI: 1.02-16.89), was significantly associated with increased BPH risk. Compared with nonalcohol drinkers, alcohol drinkers was insignificantly associated with BPH risk (OR = 1.10, 95% CI: 0.77-1.57), but it demonstrated a more remarkable positive gradient between CBPAI exposure and BPH risk among alcohol drinkers, indicating an additive interaction between CBPAI and alcohol on BPH risk (synergy index = 4.24, 95% CI: 1.21-14.94). CONCLUSIONS: Chronic oral BPA exposure increased BPH risk with a positive exposure-response relationship among Hong Kong Chinese, and alcohol drinking amplified the effect of BPA on BPH. Hence, minimizations of containing food or water/beverage in plastic containers and drinking alcohol are recommended in the community to mitigate BPH risk. Future larger and designated studies are warranted.

Benign prostatic hyperplasia - what do we know?

OBJECTIVES: To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies. METHODS: The literature on BPH was reviewed. BPH is a prevalent disease with significant health and economic impacts on patients and health organisations across the world, whilst the cause/initiation of the disease process has still not been fully determined. RESULTS: In BPH, pathways involving androgens, oestrogens, insulin, inflammation, proliferative reawakening, stem cells and telomerase have been hypothesised in the pathogenesis of the disease. A number of pathways first described >40 years ago have been first rebuked and then have come back into favour. A system of an inflammatory process within the prostate, which leads to growth factor production, stem cell activation, and cellular proliferation encompassing a number of pathways, is currently in vogue. This review also highlights the physiology of the prostate cell subpopulations and how this may account for the delay/failure in treatment response for certain medical therapies. CONCLUSION: BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.

Marijuana, Alcohol, and ED: Correlations with LUTS/BPH.

PURPOSE OF REVIEW: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) is a disease complex with enormous societal burden and yet the pathogenesis of LUTS/BPH is poorly understood. We set out to review the literature on the relationship between depression, marijuana usage, and erectile dysfunction (ED) to LUTS/BPH. RECENT FINDINGS: LUTS/BPH has independent associations with depression as well as with ED. In each case, the causality and mechanistic relationship is unknown. The impact of marijuana, as it increasingly pervades the general population, on the disease complex of LUTS/BPH is not well studied but recent results support short-term benefit and long-term caution. Depression, a form of central nervous dysfunction, and ED, which is likely mediated via endothelial dysfunction, are independently associated with LUTS/BPH. The presence of cannabinoid receptors in urologic organs, coupled with recent population studies, supports a modulatory effect of marijuana on voiding although an enormous knowledge gap remains.

Effects of inflammatory prostatitis on the development and progression of benign prostatic hyperplasia: A literature review.

Benign prostatic hyperplasia is a major disease that affects the quality of life of middle-aged and older men. Although >70% of men aged >70 years have pathological benign prostatic hyperplasia, its pathogenesis and progression remain unclear. In this article, we reviewed the scientific literature on this condition and examined the development of lower urinary tract symptoms. Clinically, the weight of the prostate is not always proportional to the severity of the symptoms, and many factors can influence the progression of benign prostatic hyperplasia. Other than androgens, chronic inflammation can play an essential role in its development and the induction of symptoms, especially in symptomatic hyperplasia, because inflammatory cell infiltration is frequently observed in the prostate. Inflammation-induced changes in the prostate environment lead to changes in gene expression and subsequent chronicity of inflammation. It has been suggested that chronic asymptomatic prostatitis might be associated with changes in prostate structure and subsequent symptoms. In animal studies, the administration of anti-inflammatory drugs in rats with chronic prostatitis prevented the infiltration of inflammatory cells and increased the gland-to-stroma ratio. It is hoped that future research on the molecular biology of asymptomatic prostatitis might help to develop new therapeutic strategies for lower urinary tract symptoms associated with symptomatic prostatitis. Our conclusions provide a comprehensive insight into the prevalence and development of benign prostate hyperplasia and the treatment methods that can be used to treat it.

Chronic inflammation promotes proliferation in the prostatic stroma in rats with experimental autoimmune prostatitis: study for a novel method of inducing benign prostatic hyperplasia in a rat model.

OBJECTIVE: Inflammation plays an important role in the development of benign prostatic hyperplasia (BPH). The aim of the present study was to reference the study of the pathological changes in the prostate gland of rats with experimental autoimmune prostatitis (EAP), for the development of experimental models of BPH. METHODS: Experimental autoimmune prostatitis was induced in rats by the intradermal injection of rat prostate antigen with immunoadjuvants. In case of the positive BPH group, BPH was induced by the subcutaneous injection of testosterone propionate. At the end of the 45-day model period, prostate weights were measured, and the histopathological analysis of the prostate glands was performed. The levels of cytokines, TGF-ß1/RhoA/ROCK signals, and the oxidative stress status were also examined. RESULTS: Rats from the EAP group had a higher histological score than those from the control group. Compared to the samples from rats in the hormone-induced group, those from the EAP group showed a more pronounced increase in the size of the stromal compartment; this was characterized by the formation of reactive stroma and the deposition of a greater amount of extracellular matrix (ECM). Significant increases in the numbers of CD3-positive cells and CD68-positive cells, as well as a significant upregulation in the cytokine levels, and an increase in the TGF-ß1 levels and activation of RhoA/ROCK signaling, were observed in the samples from rats in the EAP group. CONCLUSION: Chronic inflammation can induce BPH in rats via EAP model method. When performing drug experiments on the stroma compartments of BPH, the use of the EAP model is a recommendation of the authors based on this study.

Can second to fourth finger ratio play a role in determining the risk of benign prostatic enlargement.

Benign prostatic enlargement (BPE) is a disease that testosterone plays a role in its aetiology. Second to fourth finger ratio is a marker of prenatal androgenic exposure and may be a risk factor for several androgen-related diseases such as BPE. In this study, we investigated the relationship between the second to fourth finger ratio and BPE. A total of 63 patients with BPE were included for study group, and age-matched 63 healthy patients were included as a control group. Finger was measured by the distance from the proximal crease to the tip by using a digital caliper. The mean age of patients with BPE and non-BPE was 62 ± 8.9 and 61.5 ± 7.1 years respectively. There was statistically significant difference between groups in terms of prostate-specific antigen levels, prostate volumes and international prostate symptom scores. The mean finger ratios for right and left hand were 0.97 ± 0.03, 0.99 ± 0.03(p = .001) and 0.93 ± 0.15, 0.98 ± 0.03(p < .001) for BPE and non-BPE groups respectively. Men with a lower second to fourth finger ratio have higher risk of developing BPE than men without BPE. Therefore, the second to fourth finger ratio, which is indicative of prenatal androgen exposure, can be used as a marker of BPE risk.

Anti-Proliferative Effects of Standardized Cornus officinalis on Benign Prostatic Epithelial Cells via the PCNA/E2F1-Dependent Cell Cycle Pathway.

Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.

Long-lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically-induced prostatic inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the major causes of lower urinary tract symptoms (LUTS), including storage LUTS such as urinary frequency and urgency. Recently, a growing number of clinical studies indicate that prostatic inflammation could be an important pathophysiological mechanism inducing storage LUTS in patients with BPH. Here we aimed to investigate whether nonbacterial prostatic inflammation in a rat model induced by intraprostatic formalin injection can lead to long-lasting bladder overactivity and changes in bladder afferent neuron excitability. METHODS: Male Sprague-Dawley rats were divided into four groups (n = 12 each): normal control group, 1-week prostatic inflammation group, 4-week inflammation group, and 8-week inflammation group. Prostatic inflammation was induced by formalin (10%; 50 µL per lobe) injection into bilateral ventral lobes of the prostate. Voiding behavior was evaluated in metabolic cages for each group. Ventral lobes of the prostate and the bladder were then removed for hematoxylin and eosin (HE) staining to evaluate inflammation levels. Continuous cystometrograms (CMG) were recorded to measure intercontraction intervals (ICI) and voided volume per micturition. Whole-cell patch clamp recordings were performed on dissociated bladder afferent neurons labeled by fluorogold injected into the bladder wall, to examine the electrophysiological properties. RESULTS: Results of metabolic cage measurements showed that formalin-treated rats exhibited significantly (P < 0.05) increases in micturition episodes/12 hours and decrease in voided volume per micturition at every time point post injection. Continuous CMG illustrated the significant ( P < 0.05) higher number of nonvoiding contractions per void and shorter ICI in formalin-treated rats compared with control rats. HE staining showed significant prostatic inflammation, which declined gradually, in prostate tissues of formalin-induced rats. In patch clamp recordings, capsaicin-sensitive bladder afferent neurons from rats with prostatic inflammation had significantly ( P < 0.05) lower thresholds for spike activation and a "multiple" firing pattern compared with control rats at every time point post injection. CONCLUSIONS: Formalin-induced prostatic inflammation can lead to long-lasting bladder overactivity in association with bladder afferent neuron hyperexcitability. This long-lasting model could be a useful tool for the study of inflammation-related aspects of male LUTS pathophysiology.

Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model.

BACKGROUND: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. RESULTS: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. CONCLUSIONS: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.

Impact of Metabolically Healthy Obesity in Patients with Andrological Problems.

BACKGROUND: Although the pathogenic role of metabolically complicated obesity (MCO) in erectile dysfunction (ED), major adverse cardiovascular events (MACE), and male infertility has been widely studied, that of metabolically healthy obesity (MHO) has been poorly investigated. AIM: To assess the role of MHO in the pathogenesis of ED, prediction of MACE, and male reproductive health. METHODS: A consecutive series of 4,945 men (mean age, 50.5 ± 13.5 years) with sexual dysfunction (SD) (cohort 1) and 231 male partners of infertile couples (mean age, 37.9 ± 9.1 years; cohort 2) were studied. A subset of men with SD (n = 1,687) was longitudinally investigated to evaluate MACE. All patients underwent clinical, biochemical, erectile function, and flaccid penile color Doppler ultrasound (PCDU) assessment. Infertile men also underwent scrotal and transrectal ultrasound; semen analysis, including interleukin (IL-) 8; and prostatitis-like symptom assessment. MHO was defined as body mass index >30 kg/m2 with high-density lipoprotein cholesterol level >40 mg/dL and absence of diabetes or hypertension. The rest of the obesity sample was defined as MCO. MHO or MCO were compared with the rest of the sample, defined as normal weight (NW) individuals. OUTCOMES: Clinical, biochemical, erectile, and PCDU assessment in MHO, MCO and NW men in both cohorts; longitudinal MACE incidence assessment in cohort 1. RESULTS: In cohort 1, 816 men (16.5%) were obese, 181 (3.7%) were MHO, and 635 (12.8%) were MCO. In cohort 2, 68 men (28.4%) were obese, 19 (8.2%) were MHO, and 49 (21.2%) were MCO. After adjusting for confounders, in both samples, the men with MHO and MCO had lower total testosterone levels and worse PCDU parameters compared with the NW men. However, only MCO men had worse erectile function compared with NW men. In the longitudinal study, both MHO and MCO men independently had a higher incidence of MACE compared with NW men (P < .05 for both). In cohort 2, MHO and MCO men had a larger prostate volume, and MCO men also had higher ultrasound and biochemical (IL-8) features of prostatic inflammation compared with NW men, but no differences in prostatitis-like symptoms or seminal parameters. CLINICAL IMPLICATIONS: MHO men should be considered at high cardiovascular risk like MCO men and followed-up for erectile dysfunction and prostate abnormalities overtime. STRENGTHS & LIMITATIONS: The study simultaneously examined several endpoints with validated instruments within 2 different male populations, 1 with SD and 1 with infertility. As for limitations, there is no consensus in the scientific community regarding the definition of MHO, and the results are derived from patients with SD or infertility, which could have different characteristics than the general male population. CONCLUSION: MHO is associated with subclinical ED, increased cardiovascular risk, and prostate enlargement. Lotti F, Rastrelli G, Maseroli E, et al. Impact of Metabolically Healthy Obesity in Patients with Andrological Problems. J Sex Med 2019:16;821-832.

The effect of diet on BPH, LUTS and ED.

OBJECTIVE: Benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are common conditions that increase in the aging population. Several environmental factors have been linked to the development and progression of BPH and ED. Several studies have shown potential direct and indirect influences of several micronutrients and macronutrients on the risk of developing these conditions. We reviewed the available published literature of the effect of diet on BPH and ED. METHODS: A comprehensive search was performed to identify studies that evaluated how diet affected males with BPH and ED. Searches were run on July 5th, 2018 in the following databases: Ovid MEDLINE®; Ovid EMBASE; and The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). There were no language restrictions, publication date restrictions, or article type restrictions on the search strategy. RESULTS: We retrieved a total of 1670 results across all databases. After removing any duplicated results, 2 independent reviewers screened a total of 1325 citations. A total of 35 articles were selected for inclusion in this review. Diet is an important factor affecting the risk of development of BPH and ED. Several studies have shown the effect of dietary interventions for BPH and ED. DISCUSSION: A better understanding diet and its relative effects on the development, treatment and prevention of these diseases are an important area of further research for the given aging male population.

Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: What Is the Role and Significance of Inflammation?

PURPOSE OF REVIEW: The purpose of this review is to summarize the role and significance of inflammation as a putative additional factor contributing to lower urinary tract symptoms and the progression of benign prostatic hyperplasia. We review (1) the histologic definition of prostatic inflammation and its prevalence, (2) the effects inflammation in the prostate including on risk of acute urinary retention, and (3) the effects of systemic inflammation on the prostate and on voiding. RECENT FINDINGS: Inflammation is a highly prevalent finding in the prostate, both on a histological and biochemical level. Men with inflammation have higher IPSS scores and increased prostate size; however, these differences appear to be imperceptibly small. Men with inflammation do experience a significantly increased risk of developing acute urinary retention, an event that is associated with significant morbidity. Recently, attempts have been made to identify more specific biochemical markers of local inflammation, and to identify regional patterns of inflamed tissue within the prostate which may be associated with higher IPSS scores, accelerated progression, and AUR. The effects of systemic inflammatory states, most notably MetS, and their role in LUTS have also been examined. Inflammation is a common finding in prostates of aging men, but its contribution to lower urinary tract symptoms and benign prostatic hyperplasia progression appears to be small when considered as a clinically relevant entity. Advances in the understanding of different forms of inflammation, and their impact when experienced in different locations within the prostate, may refine this knowledge. Systemic inflammation affects voiding, including in the absence of a prostate, but again significant effects of systemic inflammation on the prostate itself are also difficult to demonstrate. Prostatic inflammation is associated with a significantly increased risk of acute urinary retention.

Obesity in benign prostatic enlargement: A cross-sectional study comparing sonographic and anthropometric indices of adiposity in a tertiary hospital in Southwestern Nigeria.

BACKGROUND: Findings from studies on obesity and benign prostatic enlargement (BPE) have been inconsistent. With a previous study done in our facility showing no correlation between anthropometric indices of obesity and BPE, this study aimed at reevaluating the association between obesity and BPE using sonographic indices of abdominal/central obesity. MATERIALS AND METHODS: Ninety consenting subjects with clinically confirmed BPE had their height and weight [(to calculate body mass index (BMI)] as well as waist and hip circumference [to calculate waist-hip ratio (WHR)] done. The subcutaneous, preperitoneal, and visceral fat thicknesses (SFT, PFT, and VFT, respectively) of these subjects and their prostate volumes were measured on transabdominal Ultrasonography (USS). Transrectal USS was also done to measure the total prostate and transitional zone volumes. Data were analyzed using SPSS version 22. RESULTS: WHR and waist circumference correlated positively with SFT (r = 0.325, P = 0.002 and r = 0.370, P = 0.000, respectively) and PFT (r = 0.209, P = 0.048 and r = 0.313, P = 0.003, respectively). While BMI correlated positively (r = 0.23, P = 0.029) with transrectal transitional zone volume, all three sonographic indices of adiposity correlated negatively (SFT: r = -0.223, P = 0.035; PFT: r = -0.321, P = 0.002; VFT: r = -0.242, P = 0.021) with transrectal total prostate volume. In addition, PFT correlated negatively with transabdominal prostate volume (r = -0.222, P = 0.037) and transrectal transitional zone volume (r = -0.211, P = 0.046). CONCLUSION: The relationship of BMI with transrectal transitional zone volume was a direct one, while that of SFT, PFT, and VFT with transrectal total prostate volume as well as PFT with transabdominal prostate volume and transrectal transitional zone volume was an inverse one.