Search Results (27)

Background and Objectives: While α1-blockers like silodosin are the mainstay for treating lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), combination therapy with phytotherapeutics may provide enhanced symptom control. Xipag^® is a novel formulation containing Graminex^® G96 (pollen extract) and Teupol^® 25P (teupolioside), offering anti-inflammatory and antiandrogenic effects. This study aimed to evaluate the efficacy of Xipag^® versus hexanic extract of Serenoa repens (HESr), both in combination with silodosin, in patients with LUTS/BPH. Materials and Methods: We conducted a single-center, prospective, observational, comparative study involving male patients with moderate-to-severe LUTSs undergoing treatment with silodosin. Patients were allocated to receive either Xipag^® or HESr in addition to silodosin, with follow-up every 3 months for 12 months. Primary outcomes included changes in symptom scores such as IPSS, QoL, and functional improvements such as peak urinary flow rate (Qmax). Multivariable regression analyses were used to assess predictors of the response. Results: Patients receiving Xipag^® showed significantly greater improvements in Qmax at all follow-up points (p < 0.05), with earlier and more sustained benefits compared to the HESr group. QoL index scores and PSA levels were also significantly better in the Xipag^® group starting from month six onward. IPSS scores improved in both groups but were significantly lower in the Xipag^® group only at 12 months (p = 0.04). No differences in erectile function (IIEF-5) or adverse events were observed. Conclusions: Xipag^® in combination with silodosin provides superior improvement in urinary flow, symptom-related QoL, and PSA reduction compared to HESr plus silodosin, with a favorable safety profile. These findings support the use of multi-target nutraceuticals like Xipag^® as a valuable adjunct in the management of LUTS/BPH. Larger randomized trials are warranted to confirm these results and explore underlying mechanisms. Full article

Selected phenotypes of dried maca (Lepidium peruvianum) hypocotyls and supercritical CO₂ extract (USPlus^®) of saw palmetto (Serenoa repens) were used to determine their targeted, cytotoxic action in prostate cancer cells. Fingerprinting by HPLC-MS and PCA analysis showed compositional differences in glucosinolates, amides, macamides, and other alkaloids, which varied based on the color and the size of hypocotyls. These phytochemical differences translated into a higher antioxidant potential of red maca than black maca samples. The greatest COX-2 inhibition was demonstrated with a combination of red maca: saw palmetto (67%:33%) and red maca: saw palmetto: black maca (25%:50%:25%). The LNCaP androgen-dependent prostate cancer cell line was the most sensitive to the three-component mixture of black, red maca, and saw palmetto treatment. This combination provided the most abundant set of high-activity metabolites, and is worthy of consideration in further clinical applications and future in-depth study. Full article

Background: We aimed to evaluate the impact of two different phytotherapeutic agents on decision making regarding prostate biopsy for patients with higher-than-normal prostate-specific antigen (PSA) levels. Methods: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B) for 3 months. At the follow-up visit after 3 months, all patients underwent PSA tests and multiparametric magnetic resonance imaging (mpMRI). Results: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction in total PSA compared to forty-nine in Group B (64.4%) (p < 0.001). Twenty-eight patients had PI-RADS III or higher in mpMRI: twelve in Group A and fourteen in Group B. Twenty-three patients (34.8%) in Group A and fifty-nine (77.6%) in Group B (p < 0.001) underwent prostate biopsy based on the mpMRI findings and PSA values. Three patients in Group A showed a significant reduction in total PSA values while having positive mpMRI findings (6%) compared with nine in Group B (19.5%) (p < 0.001). On the contrary, 7 patients in Group A did not show significant reduction in total PSA values and had negative mpMRI findings (43%) compared to 22 in Group B (81.4%) (p < 0.001). Conclusions: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica seems to be an interesting tool to avoid unnecessary prostate biopsies among men with higher-than-normal PSA levels. Full article

Leydig cells are essential for steroidogenesis and spermatogenesis. An imbalance in the production of reactive oxygen species (ROS) and the cellular antioxidant level brings about oxidative stress. Oxidative stress (OS) results in the dysfunction of Leydig cells, thereby impairing steroidogenesis, spermatogenesis, and ultimately, male infertility. To prevent Leydig cells from oxidative insults, there needs to be a balance between the ROS production and the cellular protective capacity of antioxidants. Evidence indicates that medicinal plants could improve Leydig cell function at specific concentrations under basal or OS conditions. The increased usage of medicinal plants has been considered a possible alternative treatment for male infertility. This review aims to provide an overview of the impact of oxidative stress on Leydig cells as well as the effects of various medicinal plant extracts on TM3 Leydig cells. The medicinal plants of interest include Aspalathus linearis, Camellia sinensis, Moringa oleifera, Morinda officinale, Taraxacum officinale, Trichilia emetica, Terminalia sambesiaca, Peltophorum africanum, Ximenia caffra, Serenoa repens, Zingiber officinale, Eugenia jambolana, and a combination of dandelion and fermented rooibos (CRS-10). According to the findings obtained from studies conducted on the evaluated medicinal plants, it can, therefore, be concluded that the medicinal plants maintain the antioxidant profile of Leydig cells under basal conditions and have protective or restorative effects following exposure to oxidative stress. The available data suggest that the protective role exhibited by the evaluated plants may be attributed to their antioxidant content. Additionally, the use of the optimal dosage or concentration of the extracts in the management of oxidative stress is of the utmost importance, and the measurement of their oxidation reduction potential is recommended. Full article

Background: Chronic Prostatitis/Chronic Pelvic Pain syndrome NIH-class III is a widespread condition affecting men universally, with existing treatments showing limited success. This study evaluated the efficacy and safety of a natural supplement, composed of Serenoa repens, Solanum lycopersicum, lycopene, and bromelain, in managing symptoms of this condition among a substantial patient group. Methods: In this prospective study, 245 patients diagnosed with Chronic Prostatitis/Chronic Pelvic Pain syndrome NIH-class III were treated with the aforementioned supplement, alongside lifestyle alterations, such as refraining from spicy foods, alcohol, caffeine, and cycling, for a duration of three months. Patients’ progress was assessed at one and three months using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptom Index (IPSS), quality of life (QoL) scores, and changes in total prostate-specific antigen (PSA) levels. Results: The supplement was well received with no serious adverse events reported. Significant improvements were observed in NIH-CPSI scores, IPSS, QoL scores, and a substantial decrease in total PSA levels at three months compared to baseline, with a positive trend noted from one-month to three-month evaluations. This was consistent in either patients with predominantly voiding or storage urinary symptoms. Conclusions: Our results suggest that this natural supplement in conjunction with lifestyle changes could offer a safe and effective alternative treatment for patients suffering from Chronic Prostatitis/Chronic Pelvic Pain syndrome NIH-class III. However, these findings require validation through further large-scale randomized controlled trials. Full article

Benign prostatic hyperplasia (BPH) describes the non-malignant enlargement of the prostate. It is both common and growing in incidence. Treatment is multimodal, involving conservative, medical, and surgical interventions. This review aims to examine the evidence base for phytotherapies, specifically analyzing their role in treating lower urinary tract symptoms (LUTS) attributable to BPH. A literature search was completed, specifically looking for randomized control trials (RCTs) and systematic reviews involving phytotherapy treating BPH. Specific emphasis was placed on exploring substance origin, the proposed mechanism of action, evidence of efficacy, and the side-effect profile. Several phytotherapeutic agents were evaluated. These included serenoa repens, cucurbita pepo, and pygeum Africanum, among others. For most of the reviewed substances, only modest effectiveness was reported. Generally, though, all treatments were tolerated well with minimal side effects. None of the treatments discussed in this paper form part of the recommended treatment algorithm in either European or American guidelines. We, therefore, conclude that phytotherapies, in the treatment of LUTS attributable to BPH, do provide a convenient option for patients, with minimal side effects. At present, however, the evidence for the usage of phytotherapy in BPH is inconclusive, with some agents having more backing than others. This remains an expansive field of urology whereby there is still more research to be done. Full article

Inhibition of 5α-reductase (5αR), which blocks the conversion of testosterone to its active metabolite, dihydrotestosterone, has been shown to impact further prostate enlargement (benign prostatic hyperplasia, or BPH). Clinical trials of standardized lipidosterolic extracts of Serenoa repens (LSESr), also known as standardized extracts of saw palmetto, have demonstrated improvement in lower urinary tract symptoms (LUTS) and delayed progression of BPH. The aim of this preclinical study was to compare two standardized LSESr, a proprietary ultrahigh-pressure supercritical carbon dioxide extract of S. repens (UHP-sCESr) and the well-established hexanic extract of S. repens (HESr), for both 5αR inhibition activity and lipid profiles. UHP-sCESr and HESr had nearly identical inhibition curves and comparable IC₅₀ values for 5αR-1 (9.25 ± 0.87 and 9.86 ± 0.11 μg/mL, respectively; p = 0.43) and 5αR-2 (7.47 ± 0.07 and 7.72 ± 0.05 μg/mL, respectively; p = 0.0544). UHP-sCESr and HESr also had comparable lipid profiles based on similar total fatty acid levels (87.7% and 91.5%, respectively), weight/weight comparisons of individual fatty acids, and individual fatty acid ratios to lauric acid. In addition, UHP-sCESr meets the standard set by the United States Pharmacopeia (USP) monograph for authenticity and purity for a supercritical carbon dioxide (SCCO₂) extract of saw palmetto, whereas HESr meets the standard set by the European Medicines Agency (EMA) for a well-established medicinal product. In conclusion, based on enzyme inhibition curves and IC₅₀ values, a standardized lipid profile is important to achieve comparable mechanisms of action for lipidosterolic extracts of saw palmetto. UHP-sCESr offers a comparable, standardized LSESr for men with LUTS/BPH in regions where the proprietary HESr is not available. Full article

The hexanic extract of Serenoa repens (HESr) has been in use for decades as an effective, safe and well-tolerated therapy for relieving bothersome lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). This manuscript gives an overview of HESr as monotherapy for LUTS/BPH treatment and focuses on the currently available literature investigating the possible clinical benefits of HESr combination therapy with α-blockers. Combination therapy of HESr with α-blockers has been gaining significant interest in recent years, as an increasing body of evidence shows the beneficial pharmacological effects that HESr treatment can add to standard first-line treatment with α-blockers. By reducing persistent Prostatic Inflammatory Status (PIS), commonly present in LUTS/BPH patients, HESr complements the relaxation of prostate smooth muscle induced by α-blockers, thus providing additional symptom relief. Data suggest that patients harbouring PIS and having a specific clinical profile might especially benefit from the combination therapy. Future therapeutic efforts may take advantage of more personalised strategies for LUTS/BPH management. Full article

Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH etiology is still unclear. Recent works highlighted a relevant inflammation role in BPH onset and development. Consequently, to complement the 5-α reductase (and α-adrenergic receptor agonists-based therapy, an anti-inflammatory therapy should be devised. To reduce potential adverse effects of multi-drug treatment, plant extract-based therapies are becoming increasingly common. Serenoa repens, the main phytotherapic treatment for BPH, is not sufficient to front the multi-faceted etiology of BPH. In response to this, a novel, multiple phytotherapic agents-based formulation, LENILUTS^®, was developed. In the present work, we compared, using an in vitro approach, the prostatic safety and efficacy of LENILUTS^® with a commercial formulation, based only on Serenoa repens, and a 5αR inhibitor, Dutasteride. Furthermore, preliminary in vitro experiments to investigate the active principles, bioaccessibility and bioavailability of LENILUTS^® were performed. Our results showed a better prostatic safety and therapeutic efficacy of LENILUTS^® compared to the commercial formulation and Dutasteride, with increased anti-inflammatory, and pro-apoptotic activity, and a stronger inhibitory effect on the release of the key enzyme 5αR and Prostatic-Specific Antigen (PSA). The limited bioaccessibility and bioavailability of the active principles of LENILUTS^® were highlighted. Considering the results obtained, the LENILUTS^® formulation is more promising for BPH and LUTs therapy compared to formulations based on Serenoa repens only, but further efforts should be made to improve the bioaccessibility and bioavailability of the active principles. Full article

Objectives: The aim of this study was to establish a tool to identify patients at risk for pharmaceutical and surgical interventions for benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) over a 10 year follow-up. Methods: The data of patients with mild to moderate male LUTS undergoing phytotherapy from January to December 2010 were reviewed. Patients were followed for 10 years through medical visits and telephone consultations. The outcomes were (1) treatment switch from phytotherapy or no therapy to alpha-blockers or 5α-reductase inhibitors (5-ARI), and (2) clinical progression (acute urinary retention or need for surgery). Two calibrated nomograms (one for each outcome) were constructed on significant predictors at multivariate analysis. Results: A total of 107 patients with a median age of 55 years at presentation were included; 47% stopped or continued phytotherapy, while 53% switched to alpha-blockers and/or 5-ARI after a median time of 24 months. One-third in the second group experienced clinical progression after a median time of 54 months. Age, symptom score, peak flow rate (Qmax), prostate-specific antigen (PSA), and post-void residual volume were significantly associated with the outcomes. According to our nomograms, patients switching therapy or progressing clinically had average scores of 75% and 40% in the dedicated nomograms, respectively, as compared to 25% and <5% in patients who did not reach any outcome. Conclusions: We developed a nomogram to predict the risk of pharmaceutical or surgical interventions for BPH-related LUTS at 10 years from presentation. On the basis of our models, thresholds of >75% and >40% for high risk and <25% and <5% for low risk of pharmaceutical or surgical interventions, respectively, can be proposed. Full article

The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability. Full article

Introduction: The effect of the lipidosterolic extract derived from Serenoa repens (commonly known as “saw palmetto extract” or LSESr) berries on benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS) has been extensively studied in the global literature. However, a lack of global consensus with regard to its effectiveness remains, resulting in differing recommendations on the role of LSESr in the BPH/LUTS treatment paradigm. Here, we describe the consensus reached by an international panel of urology experts. Methods: In an independent meeting on 24 April 2021, an international panel of urology experts convened with the goal of developing consensus statements to address the following: the differences between the AUA and EAU guidance regarding the use of LSESr for the treatment of BPH/LUTS, the proposed mechanism of action of LSESr, and data examining the efficacy and safety of LSESr. These consensus statements were developed over the course of several months after an extensive review of the global literature and a discussion thereof. Results: A total of seven consensus statements were agreed upon by the panel. These statements addressed the proposed mechanism of action of LSESr, LSESr quality, and the results from clinical trials examining the efficacy and safety of various LSESrs. Conclusion: Based on the reviewed evidence, the panel recommends that LSESr should be considered as a treatment option for men with mild-to-moderate BPH/LUTS as an alternative to watchful waiting. Full article

We investigated changes in symptoms and quality of life (QoL) in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving the hexanic extract of Serenoa repens (HESr) and compared results with a matched group on watchful waiting (WW). Data was from a real-world, open-label, prospective, multicenter study. This sub-group analysis included patients with moderate-to-severe symptoms receiving either the HESr 320 mg/daily for six months (HESr) or who remained untreated for LUTS/BPH (WW). Changes in urinary symptoms and QoL were measured by IPSS and BII questionnaires. Two statistical approaches (iterative matching and propensity score pairing) were used to maximize between-group comparability at baseline. Tolerability was assessed in the HESr group. After iterative matching, data for analysis was available for 783 patients (102 WW, 681 HESr). IPSS scores improved by a mean (SD) of 3.8 (4.4) points in the HESr group and by 2.2 (4.5) points in the WW group (p = 0.002). Changes in BII score were 1.8 (2.4) points and 1.0 (2.2) points, respectively (p < 0.001). Three patients (0.9%) treated with the HESr reported mild adverse effects. Moderate-severe LUTS/BPH patients treated for six months with the HESr showed greater improvements in symptoms and QoL than matched patients on WW, with a very low rate of adverse effects. Full article

Background: Phytotherapeutic agents aroused an increasing interest either as alternative or in addition to conventional therapy in the management of BPH. The aim of the article was to evaluate the clinical and functional changes after add-on treatment with Serenoa repens associated with Solanum lycopersicum, lycopene and bromelain in patients with BPH presenting with mild to moderate LUTS and previously treated only with Alfuzosin over a 6–12 months period. Materials and methods: Between January and July 2019, patients with symptomatic BPH already on treatment with Alfuzosin (Al) 10 mg for at least 6–12-month were enrolled at three academic referral centres, included in a prospective treatment group, and managed with a combination treatment of Al and 6-month daily oral single-tablet supplementation of Serenoa repens and Solanum lycopersicum + lycopene + bromelain (SeR + SL + Ly + Br). A retrospective control group with comparable baseline characteristics was obtained by performing a propensity score matching from a database of 434 patients managed with Alfuzosin 10 mg/day only over a 6–12 months period between March 2015 and December 2018. IPSS, QoL questionnaires, voiding diary assessment, postvoid residual volume (PVR), maximal (Qmax) and average (Qave) urinary flow rates were evaluated at baseline in the treatment group at the moment of patient accrual, in the control group after 6-month of treatment with alfuzosin, and thereafter at 3 and 6 months in both groups. Results: Overall, 250 patients entered the study (n = 125 treatment group; n = 125 control group). Total IPSS score significantly decreased at 6-month assessment from baseline in the treatment vs control group (17 [IQR: 12–20] vs 12 [IQR: 9–14], p = 0.02) with a significative storage symptoms improvement detected both at 3- (p = 0.03) and 6-month evaluation (p = 0.001). PVR significantly improved at each follow-up visit with the most relevant reduction at 6-month assessment (125 cc vs. 102 cc; p = 0.02). Moreover, a significative improvement in LUTS-related quality of life (QoL) was recorded at 3- and 6-month assessment with a median decrease of −1 and −2 (p = 0.05 and p = 0.001 respectively) from baseline. Conclusions: Combination treatment with AB and SeR + SL + Ly + Br led to meaningful improvements in LUTS severity compared to AB as monotherapy, after a 6-month treatment period in men with mild to moderate LUTS/BPH. Full article

Parts I and II of this three-part series indicated how a global review of both English-language and non-English language papers, plus a focus on a lipidosterolic extract of Serenoa repens (LSESr) having a standardized fatty acid profile, have together engendered new insights about the biological activity of LSESr vs. LUTS. In this last part, data from the world literature is presented that confirms that LSESr efficacy is the predominant finding in clinical trials. Despite two placebo-controlled clinical trials performed in the U.S. that failed to confirm a benefit of LSESr vs. placebo in LUTS, the global body of the peer-reviewed literature attests not only to efficacy but also to safety. Results will be presented of important trials that compare LSESr to alpha-blockers such as tamsulosin (Flomax^®) as well as to 5α-reductase inhibitors such as finasteride (Proscar^®) that demonstrate consistent findings of near equivalency between LSESr and these pharmacologic agents. Studies relating data indicative of an additive effect or synergy between LSESr and tamsulosin will also be presented. The heightened effectiveness of LSESr in men with severe LUTS vs. moderate LUTS expands the importance of our scrutiny of the global literature concerning LSESr. Of great consequence are the contributions of non-English language peer-reviewed publications that have consistently provided evidence of LSESr efficacy in treating LUTS/BPH. These peer-reviewed articles have shown that the effect of LSESr is not that of a placebo. Finally, a comparison of the LSESr extraction products used in the treatment of LUTS, and a discussion of the milieu factors that affect the natural history of LUTS and influence the outcome of clinical trials, complete this detailed analysis of LSESr vs. LUTS. Full article