Future aspects of plant derived bioactive metabolites as therapeutics to combat benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Benign prostatic hyperplasia (BPH), characterized by prostate enlargement due to cell proliferation, is a common urinary disorder in men over 50, manifesting as lower urinary tract symptoms (LUTS). Currently, several therapeutic options are accessible for treating BPH, including medication therapy, surgery and watchful waiting. Conventional drugs such as finasteride and dutasteride are used as 5α-reductase inhibitors for the treatment of BPH. However long-term use of these drugs is restricted due to their unpleasant side effects. Despite the range of available medical therapies, the effective treatment against BPH is still inadequate. Certain therapeutic plants and their phytochemicals have the aforementioned goals and work by regulating this enzyme. AIM OF THE STUDY: This review aims to provide a comprehensive insight to advancements in diagnosis of BPH, modern treatment methods and the significance of ethnobotanically relevant medicinal plants as alternative therapeutics for managing BPH. MATERIAL AND METHODS: A thorough and systematic literature search was performed using electronic databases and search engines such as PubMed, Web of Science, NCBI and SciFinder till October 2023. Specific keywords such as "benign prostatic hyperplasia", "medicinal plants", "phytochemicals", "pharmacology", "synergy", "ethnobotany", "5-alpha reductase", "alpha blocker" and "toxicology". By include these keywords, a thorough investigation of pertinent papers was assured, and important data about the many facets of BPH could be retrieved. RESULTS: After conducting the above investigation, 104 herbal remedies were found to inhibit Phosphodiesterase-5 (PDE-5) inhibition, alpha-blockers, or 5α -reductase inhibition effects which are supported by in vitro, in vivo and clinical trial studies evidence. Of these, 89 plants have ethnobotanical significance as alpha-blockers, alpha-reductase inhibition, or PDE-5 inhibition, and the other fifteen plants were chosen based on their ability to reduce BPH risk factors. Several phytocompounds, including, rutaecarpine, vaccarin, rutin, kaempferol, ß-sitosterol, quercetin, dicaffeoylquinic acid, rutaevin, and phytosterol-F have been reported to be useful for the management of BPH. The use of combination therapy offers a strong approach to treating long-term conditions compare to single plant extract drugs. Furthermore, several botanical combinations such as lycopene and curcumin, pumpkin seed oil and saw palmetto oil, combinations of extracts from Funtumia africana (Benth.) Stapf and Abutilon mauritianum (Jacq.) Medik., and Hypselodelphys poggeana (K.Schum.) Milne-Redh. and Spermacoce radiata (DC.) Sieber ex Hiern are also supported through in vitro and in vivo studies for managing BPH through recuperation in patients with chronic long-term illnesses, as measured by the International Prostate Symptom Score. CONCLUSION: The review proposes and endorses careful utilization of conventional medications that may be investigated further to discover possible PDE-5, 5 alpha-reductase, an alpha-blocker inhibitor for managing BPH. Even though most conventional formulations, such as 5 alpha-reductase, are readily available, systemic assessment of the effectiveness and mechanism of action of the herbal constituents is still necessary to identify novel chemical moieties that can be further developed for maximum efficacy. However, there exist abundant botanicals and medicinal plants across several regions of Africa, Asia, and the Americas, which can be further studied and developed for utilization as a potential phytotherapeutic for the management of BPH.

[Natural 5α-reductase inhibitors in treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia(BPH) is a common disease of the male urinary system, and its incidence rate in China is increasing. However, the mechanism underlying the pathogenesis of BPH remains unclear. Some studies demonstrated that the incidence of BPH was related to the change in the levels of steroid hormones. Too high content of dihydrotestosterone(DHT) in the body may cause BPH and other related diseases. Testosterone(T) is converted to DHT by 5α-reductase(SRD5A). By inhibiting the activity of this enzyme, the production of DHT can be reduced, and then the incidence of BPH can be lowered. Therefore, it has drawn great attention to screen and discover safer and more effective 5α-reductase inhibitors from natural medicines to treat prostatic hyperplasia without affecting the physiological function of men. This review summarizes the characteristics and tissue distribution of 5α-reductase, the discovery of 5α-reductase inhibitors in traditional Chinese medicine and natural medicines, 5α-reductase inhibitors commonly used in clinical practice and their side effects, as well as the animal models of prostatic hyperplasia and common detection indicators, aiming to provide a reference for more in-depth understanding and research about BPH and development of drugs.

How I Do It: Teaching holmium laser enucleation of the prostate (HoLEP).

Holmium laser enucleation of the prostate (HoLEP) is considered a size-independent technique to treat benign prostatic hyperplasia. This safe and effective procedure is increasingly being adopted in urology training programs worldwide, yet limited teaching strategies have been described. Endoscopic handling during HoLEP allows for a simultaneous interaction between the surgeon and trainee, facilitating a guided teaching strategy with increasing difficulty as experience grows. In this article, we describe our stepwise approach for teaching HoLEP as part of a structured surgical training curriculum. We also evaluate the association of our method with intraoperative efficiency parameters and immediate postoperative surgical outcomes of 200 HoLEP procedures.

In vitro inhibition of 5-α reductase and in vivo suppression of benign prostatic hyperplasia by Physalis angulata ethyl acetate extract.

The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 µg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of -9.3 and - 9.2 kcal/mol, respectively compared with finasteride (- 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.

Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Cost-effectiveness analysis of minimally invasive surgical treatments for benign prostatic hyperplasia: implications for Japan's public healthcare system.

AIMS: Benign prostatic hyperplasia (BPH) represents a significant public health issue in Japan. This study evaluated the lifetime cost-effectiveness of water vapor energy therapy (WAVE) versus prostatic urethral lift (PUL) for men with moderate-to-severe BPH from a public healthcare payer's perspective in Japan. MATERIALS AND METHODS: A decision analytic model compared WAVE to PUL among males in Japan. Clinical effectiveness and adverse event (AE) inputs were obtained from a systematic literature review. Resource utilization and cost inputs were derived from the Medical Data Vision database and medical service fee national data in Japan. Experts reviewed and validated model input parameters. One-way and probabilistic sensitivity analyses were conducted to determine how changes in the values of uncertain parameters affect the model results. RESULTS: Throughout patients' lifetimes, WAVE was associated with higher quality-adjusted life years (0.920 vs. 0.911 year 1; 15.564 vs. 15.388 lifetime) and lower total costs (¥734,134 vs. ¥888,110 year 1; ¥961,595 vs. ¥1,429,458 lifetime) compared to PUL, indicating that WAVE is a more effective and less costly (i.e. dominant) treatment strategy across all time horizons. Lifetime cost-savings for the Japanese healthcare system per patient treated with WAVE instead of PUL were ¥467,863. The 32.7% cost difference between WAVE and PUL was predominantly driven by lower WAVE surgical retreatment rates (4.9% vs. 19.2% for WAVE vs PUL, respectively, at 5 years) and AE rates (hematuria 11.8% vs. 25.7%, dysuria 16.9% vs. 34.3%, pelvic pain 2.9% vs. 17.9%, and urinary incontinence 0.4% vs. 1.3% for WAVE vs PUL, respectively, at 3 months). Model findings were robust to changes in parameter input values. LIMITATIONS: The model represents a simplification of complex factors involved in resource allocation decision-making. CONCLUSIONS: Driven by lower retreatment and AE rates, WAVE was a cost-effective and cost-saving treatment for moderate-to-severe BPH in Japan compared to PUL, providing better outcomes at lower costs to the healthcare system.

Benign prostatic hyperplasia (BPH) is an important public health issue in Japan, given its high prevalence and potential morbidity in a rapidly aging population. This study compared the clinical and economic outcomes of two minimally invasive surgical treatments for BPH (water vapor energy therapy [WAVE] vs. prostatic urethral lift [PUL]) for patients in Japan. Clinical effectiveness and adverse event (AE) information from published medical literature, and real-world health services and cost data from Japan, were used to estimate the impact of the two treatments. Compared to PUL, WAVE was found to provide better clinical outcomes and quality-of-life for patients whilst costing less to the Japanese healthcare system. Patients treated with WAVE had higher lifetime quality-adjusted life years vs. patients treated with PUL (15.564 vs. 15.388). Lifetime cost-savings for the Japanese healthcare system per patient treated with WAVE instead of PUL were estimated to be ¥467,863. The 32.7% cost difference between WAVE and PUL was predominantly driven by lower retreatment rates for WAVE (surgical retreatment rate was 4.9% vs. 19.2% for WAVE vs. PUL, respectively, at 5 years) and AE rates (AE rates at 3 months for WAVE vs. PUL, respectively, were: hematuria 11.8% vs. 25.7%, dysuria 16.9% vs. 34.3%, pelvic pain 2.9% vs. 17.9%, and urinary incontinence 0.4% vs. 1.3%). These findings provide evidence-based insights for clinicians, payers, and health policymakers to further define the role of WAVE for BPH in Japan.

Clinical outcome and safety of holmium laser prostate enucleation after transrectal prostate biopsies for benign prostatic hyperplasia.

PURPOSE: This study aimed to assess the clinical outcome and safety of holmium laser enucleation of the prostate (HoLEP) following transrectal ultrasound-guided prostate biopsy (TR biopsy) in the treatment of benign prostate hyperplasia. MATERIALS AND METHODS: We retrospectively analyzed data from 556 patients who underwent HoLEP between 2014 and 2021. The patients were categorized into six groups: Group 1-A (n=45) underwent HoLEP within four months post TR biopsy. Group 1-B (n=94) underwent HoLEP more than four months post TR biopsy. Group 1-C (n=120) underwent HoLEP after a single TR biopsy. Group 1-D (n=19) underwent HoLEP after two or more TR biopsies. Group 1-total (n=139, group 1-A+group 1-B or group 1-C+group 1-D) underwent HoLEP post TR biopsy. Group 2 (control group, n=417) underwent HoLEP without prior TR biopsy. We examined perioperative parameters, safety, and functional outcomes. RESULTS: The age, body mass index, International Prostate Symptom Score (IPSS), uroflowmetry, and comorbid diseases between group 1-total and group 2 were comparable. However, group 1-total exhibited significantly elevated prostate-specific antigen levels and larger prostate volumes (p<0.01). Perioperative factors like enucleation time, enucleation weight, and catheterization duration were notably higher in group 1-total (p<0.01). All groups showed significant improvements in IPSS, postvoid residual urine, and maximum flow rate during the 1-year postoperative period (p<0.05). The rates of postoperative complications were similar between group 1-total and group 2. CONCLUSIONS: Enucleation time and catheterization duration were significantly longer in the TR biopsy group. However, postoperative complications were not significantly different between TR biopsy and non-TR biopsy groups.

Propensity score-matched analysis comparing perioperative, functional, and safety outcomes between thulium fiber laser and bipolar enucleation of the prostate performed by a single surgeon with two years of follow-up.

PURPOSE: To compare perioperative, functional, and safety outcomes between thulium fiber laser enucleation of the prostate (ThuFLEP) and bipolar enucleation of the prostate performed by a single surgeon with use of propensity score (PS)-matched analysis. MATERIALS AND METHODS: Data were from 675 patients, 422 of whom underwent ThuFLEP and bipolar enucleation by a single highly experienced surgeon. ThuFLEP was performed with Fiberlase U1 (IRE Polus Ltd.). Perioperative parameters, safety, and functional outcomes, such as International Prostate Symptom Score (IPSS), quality of life (QoL), postvoid residual volume (PVR), and maximum urinary flow rate (Qmax) were assessed. To control for selection bias, a 1:1 PS-matched analysis was carried out using the following variables as covariates: total prostate volume, preoperative IPSS and early sphincter release. RESULTS: Of 422 patients, 370 (87.7%) underwent ThuFLEP and 52 (12.3%) underwent bipolar enucleation. Operation, enucleation, and morcellation time were comparable between groups before and after PS-matched analysis (p=0.954, p=0.474, p=0.362, respectively). Functional parameters (IPSS, QoL, PVR, Qmax) were also comparable between groups at every time point before and after PS matching. Significant improvements in IPSS, QoL score, Qmax, and PVR were observed during the 24-month follow-up period for both ThuFLEP and bipolar enucleation without any significant differences between groups. Early and late postoperative complications before and after PS-matched analysis were similar. CONCLUSIONS: ThuFLEP was comparable to bipolar enucleation in perioperative characteristics, improvement in voiding parameters, and complication rates. Both procedures were shown to be effective and safe in the management of benign prostatic hyperplasia.

Elucidation of active components and target mechanism in Jinqiancao granules for the treatment of prostatitis and benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases. MATERIALS AND METHODS: Jinqiancao granules were commercially available and purchased. Database-driven data mining and networking were utilized to establish a general correlation between Jinqiancao granules and the two diseases above. Ultra-performance liquid chromatography-mass spectrometry was used for compound separation and characterization. The characterized compounds were evaluated on four G-protein coupled receptors (GPCRs: GPR35, muscarinic acetylcholine receptor M3, alpha-1A adrenergic receptor α1A and cannabinoid receptor CB2). A dynamic mass redistribution technique was applied to evaluate compounds on four GPCRs. Nitric acid (NO) inhibition was tested on the macrophage cell line RAW264.7. Molecular docking was conducted on GPR35-active compounds and GPR35 crystal structure. Statistical analysis using GEO datasets was conducted. RESULTS: Seventy compounds were isolated and twelve showed GPCR activity. Three compounds showed potent GPR35 agonistic activity (EC50 < 10 µM) and the GPR35 agonism action of PAL-21 (Scutellarein) was reported for the first time. Docking results revealed that the GPR35-targeting compounds interacted at the key residues for the agonist-initiated activation of GPR35. Five compounds showed weak antagonistic activity on M3, which was confirmed to be a disease target by statistical analysis. Seventeen compounds showed NO inhibitory activity. Several compounds showed multi-target properties. An experiment-based network reflected a pharmacological relationship between Jinqiancao granules and the two diseases. CONCLUSIONS: This study identified active compounds in Jinqiancao granules that have synergistic mechanisms, contributing to anti-inflammatory effects. The findings provide scientific evidence for the potential use of Jinqiancao granules as a treatment for prostatitis and BPH.

Incidence of complications and urinary incontinence following endoscopic enucleation of the prostate in men with a prostate volume of 80 ml and above: results from a multicenter, real-world experience of 2512 patients.

PURPOSE: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV). METHODS: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023). INCLUSION CRITERIA: prostate volume ≥ 80 ml. EXCLUSION CRITERIA: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy. PRIMARY OUTCOME: complication rate. SECONDARY OUTCOMES: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence. RESULTS: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence. CONCLUSIONS: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.

Pulse modulation in En-Bloc HoLEP: does it really matter? A propensity score matched analysis.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is an established option in the surgical treatment of benign prostatic hyperplasia. Pulse modulation, such as MOSES® technology, has recently been introduced and may offer potential advantages in HoLEP. METHODS: Perioperative data from 117 patients who underwent MOSES® laser enucleation of the prostate (MoLEP) were collected. Propensity score matching using prostate volume, age, body mass index (BMI), and anticoagulant intake was performed using a database of 237 patients treated with HoLEP. In total, 234 patients were included in the analysis. RESULTS: Prostate volume (104 vs. 102 ml), age (70 vs. 71 years), BMI (27 vs. 27), and anticoagulant intake (34 vs. 35%) did not differ significantly between the groups. There were no significant differences in operation time (61.5 vs. 58.1 min, p = 0.42), enucleation efficiency (2.5 vs. 2.6 g/min, p = 0.74), hemostasis time (7.8 vs. 8 min, p = 0.75) and hemoglobin drop (0.9 vs. 0.7 mg/dl, p = 0.48). The complication rates were low in both groups (16.2% for HoLEP and 17.1% for MoLEP). No differences were noted in the Clavien-Dindo Classification (p = 0.63) and the Comprehensive Complication Index (p = 0.24). The rate of complications > CDC IIIa was 0.9% for HoLEP (endoscopic coagulation) and 1.7% for MoLEP (2 cases of endoscopic coagulation). No transfusions were administered. CONCLUSION: Overall, the enucleation efficiency was high in both groups and the procedure time was short. HoLEP is an efficient and safe treatment option in experienced hands, regardless of the use of pulse modulation technology.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

National Trends in Surgical Management for Benign Prostatic Hyperplasia From 2013 to 2019 in the United States.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common urologic pathology for older men. The prevalence and effect on quality of life have prompted the development of new surgical procedures to manage BPH while attempting to minimize treatment side effects. The objective of this study is to utilize TriNetX, a third-party database, to investigate temporal trends in BPH procedures from 2013 to 2019 in the United States. METHODS: Male patients aged 18 to 100 who were diagnosed with BPH from 2013 to 2019 were filtered from the TriNetX Diamond Network. Yearly cohorts undergoing a BPH-related procedure were searched using Current Procedural Terminology and International Classification of Diseases 10th Revision codes. Temporal and descriptive analytics were utilized to describe trends in treatment utilization. RESULTS: There were 302,646 BPH procedures recorded on the TriNetX Diamond Network. Transurethral resection of the prostate was the most commonly performed procedure, accounting for 47.2% of procedures in 2013 and 44.9% in 2019. Photoselective vaporization of the prostate remained a popular treatment but showed the greatest decrease in utilization over time (31.8% in 2013, 21.5% in 2019). Prostatic urethral lift (UroLift) was rapidly embraced as a treatment modality, as usage increased by 18.3% over a 6-year period (0.0% in 2014, up to 18.3% in 2019). Other procedures such as Rezum (5.8%) and holmium laser enucleation of the prostate (5.1%) made up greater proportions of BPH procedures by 2019. CONCLUSIONS: Transurethral resection of the prostate was the most common procedure from 2013 to 2019. However, minimally invasive surgeries represent an increased percentage of BPH surgeries every year.

Early investigational agents for the treatment of benign prostatic hyperplasia'.

INTRODUCTION: Benign prostatic hyperplasia (BPH), as a clinical entity that affects many people, has always been in the forefront of interest among researchers, pharmaceutical companies, and physicians. Patients with BPH exhibit a diverse range of symptoms, while current treatment options can occasionally cause adverse events. All the aforementioned have led to an increased demand for more effective treatment options. AREAS COVERED: This review summarizes the outcomes of new medications used in a pre-clinical and clinical setting for the management of male lower urinary tract symptoms (LUTS)/BPH and provides information about ongoing trials and future directions in the management of this condition. More specifically, sheds light upon drug categories, such as reductase­adrenoceptor antagonists, drugs interfering with the nitric oxide (NO)/cyclic guanosine monophosphate (GMP) signaling pathway, onabotulinumtoxinA, vitamin D3 (calcitriol) analogues, selective cannabinoid (CB) receptor agonists, talaporfin sodium, inhibitor of transforming growth factor beta 1 (TGF-ß1), drugs targeting the hormonal control of the prostate, phytotherapy, and many more. EXPERT OPINION: Clinical trials are being conducted on a number of new medications that may emerge as effective therapeutic alternatives in the coming years.

Natural Products in the Treatment of Lower Urinary Tract Dysfunction and Infection.

The popularity of natural products for the treatment of lower urinary tract symptoms (LUTS) differs considerably between countries. Here we discuss the clinical evidence for efficacy in two indications, male LUTS suggestive of benign prostatic hyperplasia and urinary tract infections, and the mechanistic evidence from experimental studies. Most evidence for male LUTS is based on extracts from saw palmetto berries, stinging nettle roots, and pumpkin seeds, whereas most evidence for urinary tract infection is available for European golden rod and combined preparations although this field appears more fragmented with regard to extract sources. Based on differences in sample collection and extraction, extracts from the same plants are likely to exhibit at least quantitative differences in potential active ingredients, which makes extrapolation of findings with one extract to those of others potentially difficult. While only limited information is available for most individual extracts, some extracts have been compared to placebo and/or active controls in adequately powered trials.

Therapeutic efficacy of 180-W GreenLight laser photoselective vaporization of the prostate for storage symptoms concomitant with benign prostatic obstruction and a search for outcome predictors.

PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.

Serenoa repens for the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement: An Updated Cochrane Review.

PURPOSE: To assess the effects of Serenoa repens in the treatment of men with lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We performed a comprehensive search using multiple databases up to September 2022 with no language or publication status restrictions. We included parallel-group randomized controlled trials of participants with BPH who were treated with Serenoa repens or placebo/no treatment. We used standard Cochrane methods, including a GRADE assessment of the certainty of the evidence (CoE). RESULTS: We included 27 studies involving a total of 4,656 participants. Serenoa repens results in little to no difference in urologic symptoms at short-term follow-up (International Prostate Symptom Score [IPSS]: mean difference [MD] -0.90, 95% confidence interval [CI] -1.74 to -0.07; I²=68%; 9 studies, 1,681 participants; high CoE). Serenoa repens results in little to no difference in the quality of life at short-term follow-up (high CoE). Serenoa repens probably results in little to no difference in adverse events (moderate CoE). Different phytotherapeutic agents that include Serenoa repens may result in little to no difference in urologic symptoms compared to placebo at short-term follow-up (IPSS: MD -2.41, 95% CI -4.54 to -0.29; I²=67%; 4 studies, 460 participants; low CoE). We are very uncertain about the effects of these agents on quality of life (very low CoE). These agents may result in little to no difference in the occurrence of adverse events (low CoE). CONCLUSIONS: Serenoa repens alone provides little to no benefits for men with LUTS due to benign prostatic enlargement. There is more uncertainty about the role of Serenoa repens in combination with other phytotherapeutic agents.

[Minimally invasive treatment of benign prostatic hyperplasia : The German S2e guideline 2023-part 4]. / Minimalinvasive Therapien des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 4/4.

BACKGROUND: Lower urinary tract symptoms suggestive for benign prostatic obstruction (LUTS/BPO) are one of the most frequent diseases in men and can have a significant impact on quality of life. Instrumental therapies are common, and many patients seek minimally invasive treatment options. OBJECTIVE: Presentation and evidence-based evaluation of the minimally invasive therapy for benign prostatic syndrome. MATERIALS AND METHODS: Summary and overview of chapters 11-13 on minimally invasive therapies for LUTS/BPO of the current long version of the German S2e guideline. RESULTS: In case of absolute indication for surgery or after unsatisfactory or undesired medical therapy, minimally invasive treatments such as UroLift® (Neotract Inc., Pleasanton, CA, USA), Rezá¿¡m™ (Boston Scientific, Malborough, MA, USA), iTIND™ (Olympus America Inc., Westborough, MA, USA), and prostatic artery embolization (PAE) can be considered. These indirect/delayed ablative therapies offer lower morbidity and the possibility of performing them under local anesthesia, but they are inferior to direct ablative/resective techniques in terms of effectiveness and sustainability. CONCLUSIONS: The updated German S2e guideline summarizes evidence-based recommendations for new minimally invasive therapies for LUTS/BPO, which present alternative treatment options for selected patients.

Minimally invasive techniques in quest of Holy Grail of surgical management of enlarged prostates: a narrative review.

PURPOSE: Past decade has seen a renewed interest in minimally invasive surgical techniques (MISTs) for management of enlarged prostate. This narrative review aims to explore newer MIST for benign prostatic hyperplasia (BPH) which are not yet integrated into established societal guidelines. METHODS: We conducted a literature search across PubMed, Google Scholar, and FDA ClinicalTrials.gov databases on June 1st, 2023, to identify studies published within the past decade exploring various MISTs for BPH. Additionally, we gathered insights from abstracts presented in meetings of professional associations and corporate websites. We broadly classified these procedures into three distinct categories: energy-based, balloon dilation, and implant/stent treatments. We collected detail information about the device, procedure details, its inclusion and exclusion criteria, and outcome. RESULTS: Our review reveals that newer energy-based MISTs include Transperineal Laser Ablation, Transurethral Ultrasound Ablation, and High-Intensity Focused Ultrasound. In the sphere of balloon dilation, Transurethral Columnar Balloon Dilation and the Optilume BPH Catheter System were gaining momentum. The noteworthy implants/stents that are on horizon include Butterfly Prostatic Retraction Device, Urocross Expander System, Zenflow Spring System, and ProVee Urethral Expander System. CONCLUSION: The exploration of various MISTs reflects ongoing efforts to enhance patient care and address limitations of existing treatments. This review provides a bird-eye view and valuable insights for urologists and researchers seeking to navigate the dynamic landscape of MISTs in the quest for effective and minimally invasive solutions for enlarged prostates.

New fusidane-type nortriterpenoids from the Arctic marine-derived fungus Simplicillium lamellicola culture medium with their inhibitory effect on benign prostatic hyperplasia.

Three new fusidane-type nortriterpenoids, simplifusinolide A, 24-epi simplifusinolide A, and simplifusidic acid L (1-3), were isolated from the EtOAc extract of the Arctic marine-derived fungus Simplicillium lamellicola culture medium, together with fusidic acid (4) and 16-O-deacetylfusicid acid (5). The structures of the isolated compounds were elucidated by NMR and MS analyses. The absolute configurations of compounds 1-3 were established by the quantum mechanical calculations of electronic circular dichroism and gauge-including atomic orbital NMR chemical shifts, followed by DP4 + analysis. Benign prostatic hyperplasia (BPH) is a major urological disorder in men worldwide. The anti-BPH potentials of the isolated compounds were evaluated using BPH-1 and WPMY-1 cells. Treatment with simplifusidic acid L (3) and fusidic acid (4) significantly downregulated the mRNA levels of the androgen receptor (AR) and its downstream effectors, inhibiting the proliferation of BPH-1 cells. Specifically, treatment with 24-epi simplifusinolide A (2) significantly suppressed the cell proliferation of both BPH-1 and DHT-stimulated WPMY-1 cells by inhibiting AR signaling. These results suggest the potential of 24-epi simplifusinolide A (2), simplifusidic acid L (3) and fusidic acid (4) as alternative agents for BPH treatment by targeting AR signaling.