Article

Effects of Pumpkin Seed in Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in the One-Year, Randomized, Placebo-Controlled GRANU Study

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Abstract

Introduction: The German Research Activities on Natural Urologicals (GRANU) study was a randomized, partially blinded, placebo-controlled, parallel-group trial that investigated the efficacy of pumpkin seed in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). Subjects and methods: A total of 1,431 men (50-80 years) with BPH/LUTS were randomly assigned to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or matching placebo. The primary response criterion was a decrease in International Prostate Symptom Score (IPSS) of ≥5 points from baseline after 12 months. Secondary outcome measures included IPSS-related quality of life, IPSS single items and diary-recorded nocturia. Results: After 12 months, the response rate (intention-to-treat/last-observation-carried-forward approach) did not differ between pumpkin seed extract and placebo. In the case of pumpkin seed (responders: 58.5%), the difference compared with placebo (responders: 47.3%) was descriptively significant. The study products were well tolerated. Overall, in men with BPH, 12 months of treatment with pumpkin seed led to a clinically relevant reduction in IPSS compared with placebo. Conclusion: In order to fully justify a recommendation for the use of pumpkin seed to treat moderate LUTS, these findings need to be substantiated in a confirmatory study or systematic review.

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... To date, no more than five randomized placebo-controlled long-term studies in patients with LUTS/BPH have been reported [6]. Notably, two of these 12-month studies investigated pumpkin seed soft extract (PSE) 1 [16,17]. ...
... The second study (GRANU study) was a three-arm trial testing the efficacy and safety of pumpkin seed (open study arm) and PSE capsules against matching placebo. This study showed no difference between PSE and placebo [17]. ...
... Nonetheless, these two placebo-controlled studies have established the long-term safety of the extract; less than 1% of more than 700 patients treated with PSE reported adverse events with a possible causal relationship to treatment [16,17]. The reactions were nonserious, and most of them were gastrointestinal complaints. ...
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Background In clinical practice, plant extracts are an option to treat mild-to-moderate lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH). However, only a few herbal extracts have been investigated in long-term placebo-controlled studies. The safety and efficacy of a well-tolerated proprietary pumpkin seed soft extract (PSE) were investigated in two randomized placebo-controlled 12-month studies (Bach and GRANU study). Both trials studied LUTS/BPH patients with an International Prostate Symptom Score (IPSS) ≥13 points at baseline. The Bach study demonstrated positive effects of PSE compared to placebo, but no difference between treatments was observed in the GRANU study. We aimed to assess the efficacy of PSE in a meta-analysis using the patient-level data of these two studies. Methods Pooled analysis was performed in the intention-to-treat set using last-observation-carried-forward (ITT-LOCF). An IPSS improvement of ≥5 points after 12 months of therapy was the predefined response criterion. Logistic regression and ANCOVA models included the covariables treatment group, study, center size, and baseline IPSS. Each analysis was repeated for the per-protocol (PP) set. Results The ITT/PP analysis sets consisted of 687/485 and 702/488 patients in the PSE and placebo groups, respectively. At the 12-month follow-up, the response rates in the PSE group were 3% (ITT) and 5% (PP) higher than those in the placebo group. The odds ratio of response obtained by logistic regression analysis for comparing PSE versus placebo was 1.2 (95% CI 0.9, 1.5), favoring PSE (ITT- LOCF). For the IPSS change from baseline to 12 months, the ANCOVA estimated difference between the treatment groups was 0.7 points (95% CI 0.1, 1.2) in favor of PSE. The variables study, baseline IPSS, and center size had a relevant influence on treatment response. Conclusion Although the Bach and the GRANU study showed contradictory results, the analysis in a pooled form still pointed towards an advantage of PSE; namely, more patients in the PSE group showed an IPSS improvement of at least 5 points after 12 months. Therefore, the results of this meta-analysis suggest that patients with moderate LUTS/BPH may benefit from PSE treatment in terms of symptomatic relief.
... PSA was non-significantly improved in 2 articles: P>0.05 (Karami et al., 2020;Marks et al., 2000), PVR significantly improved in 1 article: P<0.05 (Krzeski et al., 1993), and QoL non-significantly improved in 1 article; P>0.05 (Melo et al., 2002). Of the 4 articles (14%) investigating C. pepo as intervention either in isolation (n = 2) or in combination with other herbs/components (n = 2), IPSS/AUASI was significantly improved in 3 articles; P<0.05 (Coulson et al., 2013;Hong et al., 2009;Vahlensieck et al., 2015), and Qmax improved in 3 articles: P<0.05 (n = 2); p-value not provided (n = 1) (Carbin et al., 1990;Hong et al., 2009;Vahlensieck et al., 2015). PSA improved in 2 articles: P<0.05 (n = 1); p-value not provided (n = 1) (Coulson et al., 2013;Hong et al., 2009). ...
... PSA was non-significantly improved in 2 articles: P>0.05 (Karami et al., 2020;Marks et al., 2000), PVR significantly improved in 1 article: P<0.05 (Krzeski et al., 1993), and QoL non-significantly improved in 1 article; P>0.05 (Melo et al., 2002). Of the 4 articles (14%) investigating C. pepo as intervention either in isolation (n = 2) or in combination with other herbs/components (n = 2), IPSS/AUASI was significantly improved in 3 articles; P<0.05 (Coulson et al., 2013;Hong et al., 2009;Vahlensieck et al., 2015), and Qmax improved in 3 articles: P<0.05 (n = 2); p-value not provided (n = 1) (Carbin et al., 1990;Hong et al., 2009;Vahlensieck et al., 2015). PSA improved in 2 articles: P<0.05 (n = 1); p-value not provided (n = 1) (Coulson et al., 2013;Hong et al., 2009). ...
... PSA improved in 2 articles: P<0.05 (n = 1); p-value not provided (n = 1) (Coulson et al., 2013;Hong et al., 2009). QoL scores improved: P<0.05 (n = 1); p-value not provided (n = 1), PRV improved P<0.05 (n = 1); p-value not provided (n = 1), and PV improved: p-value not provided (n = 2) (Carbin et al., 1990;Coulson et al., 2013;Vahlensieck et al., 2015). ...
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Background : The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a treatment for BPH in clinical trials based on PRISMA guidelines. Methods : A literature search was conducted using PubMed, Cochrane, Medline, and Scopus databases, including English language clinical trials (Jadad score of ≥ 4) that investigated herbal medicine as a sole intervention, reporting at least one of the following outcomes: International Prostate Symptom Score (IPSS); American Urological Association Symptom Index (AUASI); Maximum Urinary Flow Rate (Qmax); Post-void residual volume (PRV); Prostate volume (PV); Serum Prostatic Specific Antigen (PSA); Quality of Life (QoL) Scores. Results : Following article screening, 28 articles were included. The most frequently studied herbs in isolation or in combination were Serenoa repens (54%), Urtica dioica (14%), Cucurbita pepo (14%), lycopene (14%), Pygeum africanum (14%) and Linum usitatissimum (7%). These herbal-based formulations mostly improved the symptoms associated with BPH (IPSS/AUASI, Qmax, PSA, QoL scores, PRV and PV). This review further discusses these herbs and the outcomes, with a focus on the potential mechanisms of action. Conclusions : There are limited high quality clinical trials investigating herbal medicine on BPH, where S. repens is significantly more represented than other popular herbs for BPH, such as C. pepo, U. dioica, P. africanum, and lycopene. Although the included studies broadly found positive positive results for standardised outcomes for LUTS and urinary flow, there was great variability in the study designs requires caution in interpretation. As these herbs are supported by in vivo and in vitro studies on potential mechanisms of actions, comparison of efficacy of mono-herbal and poly-herbal approaches, standardized extract based on identification of active constituents, as well as dosage and long-term safety.
... terrestris), Maghz tukhm-i-kaddu shireen (Cucurbita pepo), Babuna (Matricaria recutita), Alsi (Linum usitatissimum), Anisoon (Pimpinella anisum), and Khayareen (Cucumis sativus) have been found to reduce symptoms and improve QoL in BPH patients [64]. Flaxseed and pumpkin seed have also been observed to be effective when used individually [65,66]. Acupuncture is also contributing for better prostate health, improving BPH symptoms and QoL [67]. ...
... Medicines such as C. pepo (Maghz tukhm-i-kaddu shireen) [66], Linum usitatissimum (Alsi) [65], T. terrestris (Kharkhask), P. anisum (Anisoon), C. sativus (Maghz tukhm-ikhyarein), and M. recutita (Babuna) are considered to be effective in alleviating these symptoms [64]. Most of these medicines were also found to have anti-inflammatory, 5alpha-reductase inhibitor, and anti-tumor properties [64]. ...
... U Trial 1dC. pepo seed vs. placebo [66]: This is a doubleblind study comparing the effect of C. pepo seeds, their extract and placebo with each other, and our study has shown the comparison between pumpkin seed (C. pepo) and placebo only in order to simplify it. ...
Article
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Objective: Conventional treatments for benign prostatic hyperplasia (BPH) like 5alpha-reductase inhibitors and invasive surgery are associated with some obvious side effects. Conversely, evidence, though limited, has shown that alternative medicines are safer and have potential to improve the lower urinary tract symptoms (LUTS) and quality of life in addition to improving sexual dysfunction in patients with BPH. The current article aimed to include an overview of BPH, different ways of its management, and particularly its appreciation in Greco-Arab (Unani) system of medicine, one of the alternative medicinal systems. Methods: PubMed, Scopus, ScienceDirect, Web of Sciences, Google Scholar databases and classical texts of Greco-Arab medicine were searched for data collection. Results: In Unani system of medicine, BPH, traced under the headings of Waram unuq al-mathana (bladder neck swelling) and Insidad majra-i-mathana (bladder outlet obstruction), has been managed for centuries with herbal medicines yet demanding a comprehensive scientific validation. Among the herbs, Cucurbita pepo, Tribulus terrestris, Urtica dioica, and Linum usitatissimum are worth mentioning. Conclusion: For achieving the goal of LUTS-free ageing men, and safer and cost-effective future management of BPH, Unani herbal medicine could hopefully prove beneficial.
... The main fatty acids that constitute about 90% of PSOs are palmitic acid, oleic acid, and linoleic acid [15][16][17][18]. The few studies available on PSOs involved in vivo research and indicated a positive effect on the prostate through the prevention of testosterone-induced hyperplasia [2,[19][20][21]. This endogenous effect could be attributed to the physiological effect of PSO on the inhibition of 5-α-reductase, which converts testosterone into DHT (dihydrotestosterone), the active form of testosterone. ...
... This is a statistically significant finding, as it indicates a compound with greater efficacy against hyperplastic cells, including cancer cells and other rapidly growing cells that are present in hyperplastic tissue and only slightly impact non-hyperplastic cells [24]. Therefore, this extract is a possible treatment option [2,[19][20][21]. Similar results obtained in vivo would indicate the significance of this compound as a supportive treatment for conditions, such as BPH, which frequently occurs in males aged 50 and over [25][26][27]. ...
... PDE5 inhibitors, as TDL, have been reported to decrease the proliferation of prostate cells, while also decreasing the number of smooth muscle cells (SMCs) in the prostate, bladder, neck, and supporting vasculature [5,9,10]. In addition, a previous study has revealed improvement in symptoms of BPH for patients receiving PSO and/or saw palmetto oil [20,21,24]. The efficacy of PSO for improved BPH symptoms is attributed to its reported 5-α-reductase inhibition activity [19]. ...
Article
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The FDA has approved tadalafil (TDL) for the treatment of benign prostatic hyperplasia (BPH)-associated symptoms. Pumpkin seed oil (PSO) has shown promise for the relief of prostatitis-related lower urinary tract symptoms. The aim was to improve TDL delivery to the prostate and assess the combined effect of TDL with a PSO-based formula in the management of BPH. PSO, Tween 80, and polyethylene glycol 200 were selected for the optimization of self nano-emulsified drug delivery system (SNEDDS). The formed vesicles were assessed for their globule size and zeta potential. A rat in vivo study was carried out to investigate prostate weight and index, histopathology, and pharmacokinetics. The average globule size for the optimized TDL-PSO SNEDDS was 204.8 ± 18.76 nm, with a zeta-potential value of 7.86 ± 1.21 mV. TDL-PSO SNEDDS produced a marked drop in prostate weight by 35.51% and prostate index by 36.71% compared to the testosterone-only group. Pharmacokinetic data revealed a 2.3-fold increase of TDL concentration, from optimized TDL-PSO SNEDDS, in the prostate compared with the raw TDL group. This study indicated that the combination of TDL and PSO in an optimized TDL PSO SNEDDS formula improved the efficacy of TDL in the management of BPH.
... Pumpkin seed and its soft extract provide symptomatic relief in men with moderate LUTS/BPH and have good tolerability [18,19]. One objective of treating such patients should be to improve or stabilize their quality of life, physically, psychologically, and sexually. ...
... Consistent with previous findings [19], relief of LUTS/ BPH under treatment with PSE resulted in better IPSS-QoL scores. The proportion of patients who felt at least "mostly satisfied" (IPSS-QoL < 3) increased to 61% and 73% after 12 and 24 months, respectively, from only 11% initially. ...
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Purpose To assess the symptoms, quality of life and sexual well-being in patients with lower urinary tract symptoms due to benign prostatic hyperplasia LUTS/BPH treated with pumpkin seed soft extract (PSE) in routine practice. Methods This noninterventional study included 130 men treated for up to 24 months. The International Prostate Symptom Score (IPSS) and related quality of life, Aging Males’ Symptoms Scale (AMS), and International Index of Erectile Function (IIEF-5) were recorded. Descriptive statistical methods were applied. The mean with 95% confidence interval (CI) was calculated for the primary end point (change in IPSS after 12-month treatment). Results Analysis at 12 months included 83 patients [mean (SD) age 65.2 (8.7) years and IPSS (15.6 (3.4), IPSS-QoL 3.4 (0.9)]. AMS and IIEF-5 indicated mild or mild to moderate disorder regarding sexual well-being and erectile dysfunction, respectively. After 12 months, the mean IPSS change from baseline was − 4.7 (95% CI − 5.4 to − 3.9), with 83% (95% CI 65.3 to 84.1) and 53% (95% CI 42.3 to 63.7) of the patients achieving reductions by at least 3 and 5 points, respectively. The proportion of patients with IPSS-QoL below 3 points (mostly satisfied) was 11% (9/83) at baseline and rose to 62% (51/83) and 73% (40/55) at 12 and 24 months, respectively. AMS and IIEF-5 scores did not indicate a negative impact on sexual function during treatment. Conclusion In men with a moderate LUTS suggestive of BPH, a low progression risk and an active sex life, treatment with pumpkin seed soft extract provided symptomatic relief, improved IPSS-QoL, and maintained sexual well-being. Trial registration DRKS00010729, June 22, 2016.
... Seven patients were lost to follow-up. Details of patient enrollment are demonstrated in Fig. 1 [13,14]; however, with the available dose per capsule in our study, taking 3 capsules (1080 mg) could have reduced patient compliance. Thus, patients in the pumpkin group received 2 capsules a day (720 mg). ...
... This effect has been confirmed by other in vitro and animal studies [21][22][23]. In line with our findings, Vahlensieck et al. demonstrated a clinically relevant reduction of IPSS compared to placebo after 12 months of taking pumpkin seed extract [13]. They used 500 mg Cucurbita pepo seed oil extract capsules twice a day. ...
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Background Benign prostatic hyperplasia (BPH) is very common in aging men. We aimed to compare the effects of tamsulosin and pumpkin (Cucurbita pepo) seed oil on BPH symptoms. Methods This single-blind randomized clinical trial included patients with BPH aged ≥ 50 years referred to the Urology Clinic of Shahid Beheshti Hospital, Hamadan, Iran, from August 23, 2019 to February 19, 2020. Patients were randomized into two groups. One group received 0.4 mg tamsulosin every night at bedtime and the other received 360 mg pumpkin seed oil twice a day. Patients’ age, weight, height, and body mass index (BMI) were recorded. The International Prostate Symptom Score (IPSS) was filled out by the patients at baseline and then 1 month and 3 months after the initiation of treatment. The BPH-associated quality of life (QoL), serum prostate-specific antigen, prostate and postvoid residual volume, and maximum urine flow were also assessed at baseline and 3 months later. Drug side effects were also noted. Results Of the 73 patients included in this study with a mean age of 63.59 ± 7.04 years, 34 were in the tamsulosin group and 39 in the pupkin seed oil group. Patients were comparable with respect to age, weight, height, BMI, and baseline principal variables in both groups. Also, there was no significant difference between groups in terms of principal variables at any time point. However, there was a significant decrease in IPSS and a significant improvement in QoL in both groups. Although the decrease in IPSS from baseline to 1 month and 3 months was significantly higher in the tamsulosin group compared to the pumpkin group (P = 0.048 and P = 0.020, respectively), the decrease in IPSS from 1 to 3 months was similar (P = 0.728). None of the patients in the pumpkin group experienced drug side effects, while dizziness (5.9%), headache (2.9%), retrograde ejaculation (2.9%), and erythema with pruritus occurred in the tamsulosin group. Conclusions Pumpkin (Cucurbita pepo) seed oil relieved BPH symptoms with no side effects, but was not as effective as tamsulosin. Further studies are required to confirm the role of pumpkin seed oil as an option for the treatment of BPH symptoms. Trial registration Iranian Registry of Clinical Trials, IRCT20120215009014N340. Registered 19.02.2020. Retrospectively registered, https://en.irct.ir/trial/45335.
... A systematic review of data on pumpkin seed or its oil for benign prostatic hyperplasia (BPH) or lower urinary tract symptoms identified six clinical studies (Damiano et al., 2016). Among three studies conducted for 12 months, the pumpkin seed treatments (as extracts, oil, or powder) reduced International Prostatic Symptoms Scores (IPSS) of treatment (Bach, 2000;Hong et al., 2009;Vahlensieck et al., 2015). In a trial for BPH, men aged 50 to 80 years (n = 1,431) consumed ground pumpkin seed (5 g), pumpkin seed extract (500 mg), or a placebo (Vahlensieck et al., 2015). ...
... Among three studies conducted for 12 months, the pumpkin seed treatments (as extracts, oil, or powder) reduced International Prostatic Symptoms Scores (IPSS) of treatment (Bach, 2000;Hong et al., 2009;Vahlensieck et al., 2015). In a trial for BPH, men aged 50 to 80 years (n = 1,431) consumed ground pumpkin seed (5 g), pumpkin seed extract (500 mg), or a placebo (Vahlensieck et al., 2015). The intent-to-treat basis response was not different between the extract and placebo. ...
Article
Seeds play important roles in human nutrition and health since ancient time. The term “specialty” has recently been applied to seeds to describe high‐value and/or uncommon food products. Since then, numerous studies have been conducted to identify various classes of bioactive compounds, including polyphenols in specialty seeds. This review discusses nutrients, fat‐soluble bioactives, polyphenols/bioactives, antioxidant activity, bioavailability, health benefits, and safety/toxicology of commonly consumed eight specialty seeds, namely, black cumin, chia, hemp, flax, perilla, pumpkin, quinoa, and sesame. Scientific results from the existing literature published over the last decade have been compiled and discussed. These specialty seeds, having numerous fat‐soluble bioactives and polyphenols, together with their corresponding antioxidant activities, have increasingly been consumed. Hence, these specialty seeds can be considered as a valuable source of dietary supplements and functional foods due to their health‐promoting bioactive components, polyphenols, and corresponding antioxidant activities. The phytochemicals from these specialty seeds demonstrate bioavailability in humans with promising health benefits. Additional long‐term and well‐design human intervention trials are required to ascertain the health‐promoting properties of these specialty seeds.
... In another 12-month, randomized, placebo-controlled, parallel-group trial enrolled 1,431 men (of average 65 years old) with BPH. The group treated with PSE led to a clinically relevant reduction in IPSS compared with the placebo group [140] . Only preliminary studies were carried out on PSO and PSE on its potential to treat BPH. ...
... Vahlensieck et al. [140] A randomized clinical trial study involved 100 BPH male patients. ...
Article
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Pumpkin seeds may be tiny, but they are densely packed with useful nutrients and nutraceuticals such as amino acids, phytosterols, unsaturated fatty acids, phenolic compounds, tocopherols, cucurbitacins, and valuable minerals. All these bioactive compounds are important to a healthy life and well-being. The purpose of this review is to merge the evidence-based information on the potential use of pumpkin seeds as a functional food ingredient and associated biological mechanisms, collected from electronic databases (Sci-enceDirect, ResearchGate, PubMed, Scopus and Google Scholar) up to January 2020. Bioactive compounds in pumpkin seeds exhibit promising activities such as anthelmintic, antidiabetic, antidepressant, antioxidant, antitumor, and cytoprotective. Furthermore, these bioactives carry potential in ameliorating microbiological infections, hepatic, and prostate disorders. As evidenced from literature, pumpkin seeds show potential to be used as both a traditional and functional food ingredient provided further animal and clinical investigations are carried out to establish the respective molecular mechanisms and safety profile.
... Patients had a baseline median IPSS score of 15 (12)(13)(14)(15)(16)(17), significantly decreasing to 11 (8)(9)(10)(11)(12)(13)(14) at 1month visit and then to 9 (6-12) at 3-month visit (p < 0.001). Post hoc analysis using pairwise comparisons showed a significant difference between visit 1 and visit 2 (p < 0.001), visit 2 and visit 3 (p < 0.001), and visit 1 and visit 3 (p < 0.001) (Figure 2(a)). ...
... Hong et al. showed, in a placebo-controlled study, a decrease of the IPSS score and an improvement in the urologic quality of life, in patients treated with pumpkin seed extract [9]. Vahlensieck et al. showed that treatment with pumpkin seed results in a significant improvement in BPH/LUTS and a clinically significant improvement in IPSS-related QoL [10]. Advances in Urology 3 e soy germ isoflavones showed good effect in treating BPH in men, via their antioxidative properties. ...
Article
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Phytotherapy for lower urinary tract symptoms (LUTSs) due to benign prostate hyperplasia (BPH) is progressively demanded by patients and trusted by physicians. The aim was to assess the efficacy of a mix of pumpkin seed extract, soy germ isoflavonoids, and cranberry (Novex®) in the management of mild to moderate LUTS in BPH patients. Male patients aged ≥40 years, who had had mild to moderate LUTS for >6 months at screening, with no previous therapy or who are still symptomatic despite current use of alpha-blockers, were recruited. Exclusion criteria were an IPSS >19 and an age >80 years. The mixed compound was administered orally, daily, for 3 months. Patients were evaluated by means of IPSS, urological quality of life (uQoL) index, and International Index of Erectile Function (IIEF-5) at 3 visits: baseline (visit 1), 30 days (visit 2), and 90 days after treatment (visit 3). Among 163 screened patients, 128 patients (61.8 ± 9.9 years) were recruited. IPSS improved from 15 (Q1 : 12–Q3 : 17) in visit 1, to 11 (Q1 : 8–Q3 : 14) in visit 2, and to 9 (Q1 : 6–Q3 : 12) in visit 3 ( p<0.001 ). uQoL improved from 4 (3–4) in visit 1, to 3 (2–3) in visit 2, and to 2 (1–2) in visit 3 ( p<0.001 ). The patients had an IIEF-5 score of 15 (12–18.7) in visit 1, 15 (12–18) in visit 2, and 17 (13–19) in visit 3 ( p=0.99 visits 1 vs. 2, p=0.004 visits 2 vs. 3, and p=0.001 visits 1 vs. 3). Treating mild to moderate LUTS/BPH patients with Novex® might therefore relieve symptoms, improve the quality of life, and have a mild beneficial effect on erectile function.
... Pumpkin seed extract has been found to have no benefit when compared to placebo after 12 months of use [28]. A study of 1431 men aged 50-80 years were randomized to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or a placebo group were found to have similar response rate (decrease in IPSS score of > 5 points) [28]. ...
... Pumpkin seed extract has been found to have no benefit when compared to placebo after 12 months of use [28]. A study of 1431 men aged 50-80 years were randomized to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or a placebo group were found to have similar response rate (decrease in IPSS score of > 5 points) [28]. While this could be the result of an absent active compound in the extract, other potential explanations could be the use of a suboptimal dose. ...
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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.
... It was also found that the use of a hydroalcoholic extract of pumpkin seeds exhibited a protective effect against hyperplastic and cancerous cells, and the findings strengthened the antihyperplastic role of PSO (Leibbrand et al., 2019). Studies have also shown that PSO exhibited a protective effect against testosterone-induced prostate hyperplasia via the inhibition of 5-α-reductase (Vahlensieck et al., 2015). The chemical composition of PSO includes phytosterol, fatty acids (oleic acids, palmitic acid, linoleic acid), triterpene, and tocopherols (Nawirska-Olszańska et al., 2013). ...
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Benign prostatic hyperplasia (BPH) is a nonmalignant growth of the prostate tissue and causes urinary tract symptoms. To provide effective treatment, tamsulosin (TM), saw palmetto oil (SP), and pumpkin seed oil (PSO) were combined and fabricated a nanostructured lipid carrier (NLC) as TM-S/P-NLC using experimental design. The purpose was to enhance the permeation and therapeutic activity of TM; combining TM with SP and PSO in an NLC generates a synergistic activity. An optimized TM-S/P-NLC was obtained after statistical analysis, and it had a particle size, percentage of entrapment efficiency, and steady-state flux of 102 nm, 65%, and 4.5 μg/cm².min, respectively. Additionally, the optimized TM-S/P-NLC had spherical particles with a more or less uniform size and a stability score of 95%, indicating a high level of stability. The in vitro release studies exhibited the optimized TM-S/P-NLC had the maximum release profile for TM (81 ± 4%) as compared to the TM-NLCs prepared without the addition of S/P oil (59 ± 3%) or the TM aqueous suspension (30 ± 5%). The plasma TM concentration–time profile for the TM-S/P-NLC and the marketed TM tablets indicated that when TM was supplied in a TM-S/P-NLC, the pharmacokinetic profile of the drug was improved. Simultaneously, in vivo therapeutic efficacy studies also showed favorable results for the TM-S/P-NLC in terms of the prostate weight and prostate index following treatment of BPH. Based on the findings of present study, we suggest that in the future, the TM-S/P-NLC could be a novel drug delivery system for treating BPH.
... Its unique bioactivity seems related to ∆7 sterols, providing protection against hypertension and carcinogenic diseases [14]. Moreover, oils from Cp seeds are used in combination with Serenoa repens fruit extracts for the treatment of the same pathologies and to prevent prostatic cancer [16,17]. ...
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The valorization of biomass residuals constitutes a key aspect of circular economy and thus a major challenge for the scientific community. Among industrial wastes, plant residuals could represent an attractive source of bioactive compounds. In this context, a residue from the industrial extraction of Cucurbita pepo L. seeds, whose oil is commercialized for the treatment of genito-urinary tract pathologies, has been selected. Supercritical CO2 technology has been employed as a highly selective “green” methodology allowing the recovery of compounds without chemical degradation and limited operational costs. Free fatty acids have been collected in mild conditions while an enrichment in sterols has been selectively obtained from sc-CO2 extracts by appropriate modulation of process parameters (supercritical fluid pressure and temperature), hence demonstrating the feasibility of the technique to target added-value compounds in a selective way. Obtained fatty acids were thus converted into the corresponding ethanol carboxamide derivatives by lipase-mediated biocatalyzed reactions, while the hydroxylated derivatives of unsaturated fatty acids were obtained by stereoselective hydration reaction under reductive conditions in the presence of a selected FADH2-dependent oleate hydratase.
... 55 Pumpkin seeds have also been shown to inhibit testosterone conversion to DHT, preventing testosterone-induced BPH in a rat model and treating BPH. 56 ...
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Benign prostatic hyperplasia (BPH) is a severe illness affecting middle-aged and geriatric male patients. This disease normally occurs at the age of 40 or above and is also associated with sexual dysfunction. Alpha-blockers and 5α-reductase inhibitors are the preferred drugs practiced to treat BPH. However, invasive surgical therapy remains the gold standard for managing the condition in the case of refractory and intricate BPH conditions. Due to the fear of sexual dysfunction and the detrimental influence on their quality of life, most patients seek to avoid synthetic drugs and surgery. For this reason, several patients turn to phytotherapy and other alternative therapies. The authors looked at the existing perceptions of epidemiology, etiology, and pathophysiology associated with BPH in this review article. In addition, this article contained basic information on the pathological roles of inflammation in BPH and various diagnoses and treatment options. It was well reported that the administration of medicinal herbs played a vital role in managing BPH. In recent years, many researchers worldwide have reported the efficiency and safety of phytochemicals in managing numerous pathological disorders in-vivo and in-vitro conditions and the prevention of illness.
... The worldwide male population above 50 years mostly suffers through an outgrowth of stromal and epithelial cells, usually in the periurethral area and in the transition zone [142,143]. Many researches support the claim that pumpkin seed extract has also been reported to overcome lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), such as saw palmetto and prazosin [144,145]. In addition to treating LUTS, pumpkin administered for a whole month at a 14 mg/kg dose is a really useful strategy in controlling testosterone-induced hyperplasia [17]. ...
Article
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Pumpkin is a well-known multifunctional ingredient in diet, full of nutrients, has opened up new vistas for scientists in past years. Not just the fruit of pumpkin, but the flower, seed as well as peel are rich source of primary and secondary metabolites including proteins, carbohydrates, monounsaturated fatty acids, polyunsaturated fatty acids, carotenoids, tocopherols, tryptophan, delta-7-sterolsand many other phytochemicals. This climber is being used traditionally in many countries such as Austria, Hungary, Mexico, Slovenia, China, Spain, and several Asian as well as African countries as functional food and to promote health promising properties. Other benefits of pumpkin such as improving spermatogenesis, wound healing, anti-microbial, anti-inflammatory, anti-oxidative, anti-ulcerative properties and treatment of benign prostatic hyperplasia have also been confirmed by researchers. For better drug delivery, nanoemulsions and niosomes made by pumpkin seeds have also been reported as a health promising tool but still more researches need to be done in this field. This review mainly focuses on compiling and summarizing most relevant literature to highlight the nutritional value, phytochemical potential and therapeutic benefits of pumpkin.
... Семена тыквы и продукты их переработки оказывают противоязвенное, гепатопротекторное, желчегонное действие и обладают противогельминтной активностью 11 [3][4][5][6]. Их применяют при гепатите, жировой дистрофии печени, холецистохолангите, дискинезии желчевыводящих путей, гастрите, изжоге, язвенной болезни желудка и двенадцатиперстной кишки, колите, энтероколите, геморрое, атеросклерозе, простатите, доброкачественной гиперплазии предстательной железы, эрозии шейки матки, а также для лечения герпеса, дерматита, диатеза, псориаза, экземы, ожогов и пародонтоза [6][7][8][9]. Имеются данные о заметном противовоспалительном и анальгетическом действии производных семян тыквы [10], а также об их положительном эффекте при сахарном диабете 2-го типа и андрогенной алопеции [11]. Поэтому актуально изучение особенностей накопления ЭТ в данном виде нативных растительных продуктов. ...
Article
Pumpkin seeds belong to the so-called native products. Their characteristic feature is that they can be consumed directly, without prior extraction of the starting material. All elemental toxicants contained in pumpkin seeds are transferred in full to the native product. Therefore, it is important to study specific aspects of elemental toxicant accumulation by pumpkin seeds. The aim of the study was to determine the content of heavy metals, As, and Al in pumpkin seed herbal substance and native products, and to assess the degree of accumulation of these elements, depending on the vegetation area. Materials and methods : the study evaluated pumpkin seed native products by Russian manufacturers as well as pumpkin seeds harvested in areas with different anthropogenic load. The sample preparation was performed by microwave digestion, and the determination of the elemental toxicants was perfomed by inductively coupled plasma mass spectrometry. Results : the pumpkin seeds were shown to contain essential, probably essential, potentially toxic, and toxic elements. The authors performed comparative analysis of the elemental composition of pumpkin seeds as well as seeds, grains, and beans of various oil-bearing, grain, and leguminous crops. Conclusions : the content of the specified elemental toxicants (As, Cd, Hg, Pb) in the tested samples of pumpkin seed herbal substance and herbal medicinal products did not exceed the limits established by the Russian Pharmacopoeia. The unspecified toxic elements were either absent in pumpkin seeds (Tl) or found in trace amounts (Al). The content of a number of essential elements (Zn, Fe, Mn, Cu, Mo, Cr) in pumpkin seeds was higher than in the seeds of many oil-bearing crops. The vegetation area had no significant influence on the content of the tested elements in the pumpkin seeds. Pumpkin seeds are capable of accumulating abnormally high amounts of Cd, Co, and Ni in areas with high environmental pollution.
... In a randomized, placebocontrolled, parallel-group trial, which enrolled 1431 men (of average 65 years old) with BPH, the treated group used pumpkin seed extract for 12 months. The treatment showed that the symptoms of BPH were relieved compared to the placebo group [62]. In a study by Leibbrandt and Coulson, pumpkin seed extract was used for 12 weeks by BPH patients in a randomized, double blind, placebo-controlled clinical trial that included 57 males aged 40-80 years. ...
Article
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Benign prostatic hyperplasia (BPH) is one of the most common urinary diseases affecting men, generally after the age of 50. The prevalence of this multifactorial disease increases with age. With aging, the plasma level of testosterone decreases, as well as the testosterone/estrogen ratio, resulting in increased estrogen activity, which may facilitate the hyperplasia of the prostate cells. Another theory focuses on dihydrotestosterone (DHT) and the activity of the enzyme 5α-reductase, which converts testosterone to DHT. In older men, the activity of this enzyme increases, leading to a decreased testosterone/DHT ratio. DHT may promote prostate cell growth, resulting in hyperplasia. Some medicinal plants and their compounds act by modulating this enzyme, and have the above-mentioned targets. This review focuses on herbal drugs that are most widely used in the treatment of BPH, including pumpkin seed, willow herb, tomato, maritime pine bark, Pygeum africanum bark, rye pollen, saw palmetto fruit, and nettle root, highlighting the latest results of preclinical and clinical studies, as well as safety issues. In addition, the pharmaceutical care and other therapeutic options of BPH, including pharmacotherapy and surgical options, are discussed, summarizing and comparing the advantages and disadvantages of each therapy.
... These authors conducted a randomized clinical trial in which a placebo, 300, or 600 mg/day of secoisolariciresinol diglucoside, a flaxseed extract, were administered to 87 patients affected by BPH and found a decrease in IPSS and improvement of quality of life score and LUTSs, respectively [69]. Conversely, it has been shown that pumpkin seed extract did not have any benefits on BPH compared to the placebo over a 1-year period [70]. ...
Article
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Interest in the role of dietary patterns has been consistently emerging in recent years due to much research that has documented the impact of metabolism on erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH). We conducted a non-systematic review of English articles published from 1964 to September 2021. The search terms were: (“dietary patterns” OR “diet”) AND/OR (“erectile dysfunction”) AND/OR (“benign prostatic hyperplasia”). In the present review, we have highlighted how the association between dietary patterns and two of the most frequent pathologies in urology, namely erectile dysfunction and benign prostatic hyperplasia, is present in the literature. The data suggested that a diet that is more adherent to the Mediterranean diet or that emphasizes the presence of vegetables, fruits, nuts, legumes, and fish or other sources of long-chain (n-3) fats, in addition to reduced content of red meat, may have a beneficial role on erectile function. At the same time, the same beneficial effects can be transferred to BPH as a result of the indirect regulatory effects on prostatic growth and smooth muscle tone, thus determining an improvement in symptoms. Certainly, in-depth studies and translational medicine are needed to confirm these encouraging data.
... 13 Herbal medicine, though in use for centuries in treating LUTS, is still lacking a comprehensive scientific validation except a few. 23,24 However, some common side effects like loss of libido and retrograde ejaculation associated with the conventional medicine become strong factors for patients choosing herbal medicine. ...
Experiment Findings
INTRODUCTION Benign prostatic hyperplasia (henceforth BPH) is one of the commonest non-malignant neoplasms to affect men beyond middle age. 1 The incidence of BPH increase with age so that it affects approximately 20% of men in their 40s reaching up to 90% in 9 th decade. 2 Despite multiple treatment innovations, BPH still remains a nightmare for the ageing men, mostly due to its distressing lower urinary tract symptoms (LUTS) affecting quality of life (QOL) and sexual functions. 3 Dihydrotestosterone (DHT) derived from testosterone through the action of 5-α reductase seems to be the major stimulus for proliferation of prostate in men with nodular hyperplasia. 3,4 Inflammatory mediators and local growth factors are also considered to be responsible for prostatic hyperplasia. 5-7 Moreover, inheritance, metabolic syndrome, obesity and decreased physical activity increase the risk factors of prostatic hyperplasia. 8 Unani, an age-old traditional system of medicine, which is based on the 'humoral theory' proposed by Hippocrates (480-370 BC), the father of medicine, states that any disturbance in the ratio of four humors is responsible for the disease. One of the major humor to which our hormones also belong is phlegm (Balgham). 9 So, according to this very system of medicine ABSTRACT Background: Benign prostatic hyperplasia (BPH) affects a significant number of men beyond the age of 40 years with its incidence reaching up to 90% in 80's. Despite multiple treatment innovations, BPH still remains a nightmare for ageing men, mostly due to its distressing lower urinary tract symptoms (LUTS) and sexual dysfunction. The severity of LUTS is graded by international prostate symptom score or American urological association symptom index (AUA-SI) along with impact on quality of life (QOL). The objective of this study was to evaluate the efficacy of an Unani polyherbal formulation, Habb-i-muqil, in improving the AUA-SI and QOL in patients with BPH. Methods: In an open, standard controlled study, 76 men, diagnosed with clinical BPH, aged between 40 and 80 years were randomly allocated for treatment for duration of 90 days with Habb-i-muqil (test drug) or Tamsulosin (standard control) after ethical approval. AUA-SI and QOL were assessed at baseline (0 day) and days 15, 30, 45, 60, 75 and 90. Results: Analysis of 60 men showed that after 90 days of treatment the percentage changes in the AUA-SI from baseline were 59.4 and 49.4% by Habb-i-muqil and tamsulosin, respectively. The test drug produced statistically significant improvement (p<0.001) in overall AUA-SI and QOL compared with standard control. Conclusions: The Unani polyherbal formulation, Habb-i-muqil, was effective in improving AUA-SI and QOL in men with BPH in comparison to tamsulosin. Both the treatments were generally well tolerated.
... 13 Herbal medicine, though in use for centuries in treating LUTS, is still lacking a comprehensive scientific validation except a few. 23,24 However, some common side effects like loss of libido and retrograde ejaculation associated with the conventional medicine become strong factors for patients choosing herbal medicine. ...
Experiment Findings
Full-text available
Background: Benign prostatic hyperplasia (BPH) affects a significant number of men beyond the age of 40 years with its incidence reaching up to 90% in 80’s. Despite multiple treatment innovations, BPH still remains a nightmare for ageing men, mostly due to its distressing lower urinary tract symptoms (LUTS) and sexual dysfunction. The severity of LUTS is graded by international prostate symptom score or American urological association symptom index (AUA-SI) along with impact on quality of life (QOL). The objective of this study was to evaluate the efficacy of an Unani polyherbal formulation, Habb-i-muqil, in improving the AUA-SI and QOL in patients with BPH.Methods:In an open, standard controlled study, 76 men, diagnosed with clinical BPH, aged between 40 and 80 years were randomly allocated for treatment for duration of 90 days with Habb-i-muqil (test drug) or Tamsulosin (standard control) after ethical approval. AUA-SI and QOL were assessed at baseline (0 day) and days 15, 30, 45, 60, 75 and 90.Results: Analysis of 60 men showed that after 90 days of treatment the percentage changes in the AUA-SI from baseline were 59.4 and 49.4% by Habb-i-muqil and tamsulosin, respectively. The test drug produced statistically significant improvement (p<0.001) in overall AUA-SI and QOL compared with standard control.Conclusions:The Unani polyherbal formulation, Habb-i-muqil, was effective in improving AUA-SI and QOL in men with BPH in comparison to tamsulosin. Both the treatments were generally well tolerated.
... A more recent study reported similar findings (Wong et al., 2019); thus, evidence suggests that Cucurbita provides health benefits for postmenopausal women. Likewise, a survey conducted by Vahlensieck et al. (2015) found that patients with benign prostate hyperplasia treated with C. pepo seed ( ...
Article
Oxidative stress is the imbalance between reactive oxygen species (ROS) production, and accumulation and the ability of a biological system to clear these reactive products. This imbalance leads to cell and tissue damage causing several disorders in human body, such as neurodegeneration, metabolic problems, cardiovascular diseases , and cancer. Cucurbitaceae family consists of about 100 genera and 1,000 species of plants including mostly tropical, annual or perennial, monoecious, and dioecious herbs. The plants from Cucurbita species are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacins, saponins, carotenoids, phytosterols, and
... 43 Other phytotherapeutic compounds have shown beneficial effects on BPH symptoms. [44][45][46][47] The product tested in our study is a dietary supplement formulation combining b-sitosterol, pygeum africanum bark extract, lycopene, boron, and melatonin to support prostate health. b-sitosterol is a phytosterol derived from pine tree and found in saw palmetto berry. ...
Article
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Background Nocturia is the most bothersome lower urinary tract symptoms (LUTS) and can significantly reduce men's quality of life. It is often poorly managed with conventional treatments. Objective The purpose of this study was to evaluate the self-assessed benefits of a prostate health dietary combination formulation on mild LUTS, especially nocturia in healthy males. Methods In an open label clinical study, thirty healthy male subjects with mild LUTS took one daily capsule of the product for 60 days. The primary outcome was self-assessed severity of LUTS using the International Prostate Symptoms Score (IPSS) questionnaire at Day 1 (baseline), Day 30 and Day 60. Safety and compliance were also evaluated. Results At Day 60, IPSS significantly decreased from baseline by 16.3% (3.6 ± 2.1 vs. 4.3 ± 1.5, p < 0.05). Although the reduction in IPSS did not reach statistical significance at Day 30, it was mostly driven by a 30.7% decrease (p < 0.05) in the nocturia sub-score compared with baseline. While 37% of subjects reported at baseline waking up 2‒3 times/night to void, none did so after taking the study product for 60 days. Compliance was very high throughout the study. No adverse events related to the study product were reported. Conclusions The study product might be a safe alternative for individuals willing to explore a non-conventional approach to manage their nocturia. A larger randomized placebo-controlled clinical trial is warranted to confirm these results. Clinical trial registry: Clinical Trials.gov. Registration number (September 1st, 2016): NCT02886832.
... A recent German study has investigated the efficiency of C. pepo seeds in men with BPH (Vahlensieck et al., 2015). About 1431 elderly men, with BPH symptoms, were daily treated with pumpkin seed (5 g) and placebo (500 mg (Table 01). ...
Article
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Prostatic adenoma, or benign prostate hypertrophy (BPH), is a natural and common disease in elderly men. Its etiology is multifactorial. BPH is associated with annoying symptoms and morbid complications. The treatment of BPH with drugs, or synthetic chemicals, damages hepatic and renal tissues developing cirrhosis and kidney failure. As an alternative, there has been recourse to the use of medicinal plants or natural health. Pumpkin seeds, nettle leaves and soybeans have been proven to be potent against pain and discomfort in BPH patients. Moreover, plants used at high doses during a long period as treatment, may be toxic and complicate the lifestyle of BPH patients. Both, drugs and plants, used without precaution is a dilemma of prevention and toxicity. The patients simultaneously consume the drug and plants to anticipate healing. Combined drug-plant therapy could have harmful effects on health due to an accumulating antagonistic synergy of chemical and natural.
... The IPSS and QoL improved by 41.4% and 46.1%, respectively, the average rate of urination declined during the day and during the night as well[39]. Previously, 1-year studies demonstrated that pumpkin seeds led to a significant reduction in IPPS, prostate volume, improved micturition flow rate compared with placebo[40,41]. Recently, Leibbrand et al. performed a pilot study in humans and investigated the effect of oil-free hydroethanolic pumpkin seed extract in men with BPH. ...
Article
Full-text available
Benign prostatic hyperplasia (BPH) is a common disease that can cause uncomfortable lower urinary tract symptoms. The occurrence of symptomatic BPH develops after the age of 40 years and increases gradually with age to reach more than 50% at the age of 60 years and severely disturbs the quality of life of the patients. Alpha-blockers and 5-alpha reductase inhibitors are first-line agents used for the treatment of BPH. Due to the adverse effects of these conventional therapies, many patients turn to phytotherapy and other alternative therapies. This review covers alternative therapies, i.e., phytotherapy (cernilton, eviprostat, quercetin, saw palmetto and pumpkin seed) and physical therapy (acupuncture, aquablation, pulsed electromagnetic field, prostate urethral lift, radial extracorporeal shock wave therapy, thermobalancing therapy, and transurethral needle ablation) commonly used in the management of BPH.
... According to this definition, 55.4% of participants could be classified as responders. In the study of Vahlensieck et al. 17 the primary outcome was a decrease in IPSS of >5 points from baseline after 12 months. The response rate differed significantly between pumpkin seed and placebo (58% vs. 47%). ...
... According to this definition, 55.4% of participants could be classified as responders. In the study of Vahlensieck et al. 17 the primary outcome was a decrease in IPSS of >5 points from baseline after 12 months. The response rate differed significantly between pumpkin seed and placebo (58% vs. 47%). ...
Article
Full-text available
Majority of men are affected by symptomatic benign prostatic hyperplasia (BPH) from a certain age. Botanical extracts are frequently used in the early management of the symptoms. In a single-arm, mono-center pilot study, the effects of a proprietary oil-free hydroethanolic pumpkin seed extract on the symptoms of BPH were investigated. A total of 60 men (62.3 years [95% confidence interval (CI): 60.3-64.3 years]) with a total International Prostate Symptom Score (IPSS) of 14.8 (95% CI: 13.5-16.1) participated between January 2017 and October 2017 in the study by ingesting the oil-free hydroethanolic pumpkin seed extract once daily before going to bed during 3 months. Change in IPSS within treatment period was assessed. Frequency of nocturia was recorded by bladder diary, and postvoid residual urine volume was determined through ultrasound. Between baseline and after 12 weeks of supplementation, a significant symptom reduction of an average 30.1% (95% CI: 23.1-37.1) was seen for the total IPSS. Symptom alleviation had a high impact on quality of life (P < .0001) and was significant after 8 and 12 weeks of intervention (P < .001). Nocturia significantly decreased over time (P < .0001), as confirmed by IPSS questionnaire and bladder diary. Postvoid residual urine volume was significantly reduced at the end of intervention (baseline: 83.67 mL [95% CI: 58.02-109.3]; after 12 weeks: 63.11 mL [95% CI: 45.37-80.85]; P = .0394). These results indicate that the oil-free hydroethanolic pumpkin seed extract seems to be a very well tolerable, appropriate plant extract to support health benefits in a collective suffering from BPH related symptoms without the need of medical treatment.
... Pumpkin oil and seeds display antiandrogen activity that may be beneficial for BPH (Damiano et al., 2016). Importantly, in a one-year, randomized, placebo-controlled study involving 1431 men with LUTS suggestive of BPH, treatment with pumpkin seed led to a clinically relevant reduction in International Prostate Symptom Score compared to placebo (Vahlensieck et al., 2015). ...
Article
Ethno-pharmacological relevance: Phytotherapeutic approaches have been widely proposed to improve male health. Despite the well-touted effects of tribulus (Tribulus terrestris L) on men's health, an optimal phytotherapy remains an elusive challenge. Aim of the review: We sought to critically analyze the evidence in the phytotherapic literature beyond the effects of tribulus on testosterone (T) concentration and sperm analysis to also include indications for prostate health. Materials and methods: A focused literature search was conducted to include studies published in Cochrane, Pubmed, and Web of Science databases between the years 2002 and 2018. Results: The use of tribulus and maca (Lepidium meyenii Walp, Brassicaceae) were not scientifically supported to improve serum T levels in men. Moderate evidence supports the use of long Jack (Eurycoma longifolia Jack, Simaroubaceae), mucuna (Mucuna pruriens (L.) DC., Fabaceae), ashwagandha (Withania somnifera (L.) Dunal, Solanaceae), fenugreek (Trigonella foenum-graceum L., Fabaceae), and black seeds (Nigella sativa L., Ranunculaceae) to increase total T and improve seminal parameters. Data suggests an increase in total T with the use of 5000 mg/d of powdered mucuna seed and ashwagandha root (151 and 143 ng/dL, respectively) over a 12-week period in patients with oligozoospermia. The use of mucuna was supported for patients with oligozoospermia to improve sperm parameters, with an increase of 83.3 million/mL observed after use of 5000 mg/d of powdered mucuna seed over a 12-week period. Evidence supporting the use of saw palmetto (Serenoa repens, (W.Bartram) Small, Arecaceae) to improve prostate health remains equivocal; whereas, evidence supporting the use of Pygeum africanum Hook.f., Rosaceae, Urtica dioica L., Urticaceae, beta-sitosterols, pollen extract, onion, garlic, and tomato, appears favorable and promising. Conclusion: Scientific evidence supports the use of mucuna and ashwagandha as phytotherapics for improving serum T concentrations and semen parameters. Despite inconclusive evidence for use of tribulus as a T booster, it may provide advantageous effects on sperm parameters in men with idiopathic infertility. Nutraceutical strategies and some phytotherapics may also be effective to promote prostate health. Popular foodstuffs (onion, garlic, and tomato), nutraceutical agents (pollen extract and beta-sitosterols), and herbal medicines (Pygeum africanum and Urtica dioica) are rational approaches.
... Rare ∆ 7 -sterols ( Figure 1), previously isolated from the roots of the plant [4], have been reported to possess antitumor activity. They also have a positive effect in cases of prostate hyperplasia [5]. ...
Article
Species from the genus Gypsophila are known for their medicinal, industrial and decorative applications. G. trichotoma Wend. is an endangered plant species for the Bulgarian flora according to the Red Data Book. Δ⁷-Sterols, which are unusual and rare in the plant kingdom, are present in the roots of this species. In previous studies different in vitro cultures were established from aerial parts of the species. The objective of this study was to explore the possibility for production of Δ⁷-sterols from in vitro cultured roots of G. trichotoma. The root cultures were grown on six modified MS media and the quantity of sterols was analyzed. These findings will serve to solve the important matter of the role of nutrients on sterols biosynthesis.
... Moreover, according to Friedrich et al. [334] and Hong et al. [335] administration of pumpkin seed oil in patients with benign prostatic hyperplasia (BPH) may significantly improve symptoms based on the international prostate symptom score (IPPS), without however reducing prostate volume and prostate specific antigen. Similar results have been reported by Vahlensieck et al. who observed a clinical reduction of IPPS after one year of pumpkin seed oil administration in patients with lower urinary tract symptoms [336]. Other studies, also highlight the beneficial effects of pumpkin seed oil against prostate hyperplasia in testosterone-induced rats [337,338]. ...
... These sterols have not been found in any other sterol-containing plant extracts used in the treatment of benign prostatic hyperplasia (BPH). 11 Pumpkin seeds contain considerable amounts of D7-phytosterols, either in the free form or bound to sugar molecules. Furthermore, a lipid-steroidal extract has also been confirmed to have an inhibitory effect on 5-α-reductase in cultured human prostate fibroblasts. ...
... These sterols have not been found in any other sterol-containing plant extracts used in the treatment of benign prostatic hyperplasia (BPH). 11 Pumpkin seeds contain considerable amounts of D7-phytosterols, either in the free form or bound to sugar molecules. Furthermore, a lipid-steroidal extract has also been confirmed to have an inhibitory effect on 5-α-reductase in cultured human prostate fibroblasts. ...
Article
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Background A significant number of men who are younger than 50 years visit urologists for interminable prostatitis. This study aimed to thoroughly investigate the effect of pumpkin seed oil (PSO) phonophoresis on chronic nonbacterial prostatitis (CNBP). Subjects and methods Sixty patients with CNBP were randomly assigned to three groups: Group A, wherein patients were treated with PSO using phonophoresis; Group B, where patients underwent transperineal continuous low-intensity ultrasound (LIUS); and Group C, wherein patients underwent placebo LIUS. All three groups received their corresponding treatments daily for up to 3 weeks. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), residual urine determined by urodynamic measurements, and flow rate were used to analyze study outcomes. The white blood cell (WBC) count in the prostatic secretion was determined. Results Comparisons of the intragroup mean values of all measurements in Groups A and B before and after the end of the treatment showed a significant improvement in residual urine, flow rate, WBC count, and NIH-CPSI (p < 0.05), whereas no significant change was found in Group C (p > 0.05). Between-group comparisons of all variables showed a significant difference was found after intervention (p < 0.05). Postintervention comparisons between Groups A and B showed a significant difference in all measurements, except for WBC, in favor of Group A. Comparing the changes between Groups A and C, a significant difference was found in all measurements (p < 0.05). Furthermore, all parameters differed significantly when comparing Groups B and C (p < 0.05). Conclusion The current study showed that PSO phonophoresis can produce a significant effect in the management of CNBP and can, therefore, be considered a safe, noninvasive method for the treatment of CNBP.
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Functional medicine
Article
Benign prostatic hyperplasia affects men from the age of 40 and its prevalence increases with age. Millions of men worldwide suffer from this disease, with many of them choosing an alternative treatment approach using phytotherapeutics, which are available in the form of registered preparations or food supplements. These preparations contain extracts that have been tested in clinical studies. Many of these studies have been critically evaluated by systematic reviews and meta-analyses. Recent data shows that saw palmetto (Serenoa repens) has a significant effect. Other drugs used in the treatment of BPH/LUTS include stinging nettle, lycopene, pumpkin, pygeum and rye pollen. However, the results of studies cannot be extrapolated to specific products unless proper extraction techniques, phytochemical analysis and dosage have been followed. The present paper aims to provide an overview of the latest know­ledge in the field of BPH/LUTS phytotherapy with an emphasis on the clinical effect, side effects, interactions and rational dosage.
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Pumpkin (Cucurbita maxima), belonging to family Cucurbitaceae, is a well-known edible plant, cultivated and abundantly used as herbal medicine and functional food. This review aimed to investigate functional and nutraceutical constituents present in all three parts (peel, flesh and seeds) of pumpkin, and health benefits of these nutrients. Pumpkin fractions are rich source of nutritional components like oils, proteins, carbohydrates and minerals. Certain classes of phytochemical compounds including, phenolics, flavonoids, tocopherols, carotenoids, terpenoids, cucurbitacin, moschatin and phytosterols have been discovered from pumpkin fractions. Considerable evidences from several epidemiological studies upon animals and human trials have been present about pharmacological actions of pumpkin bio actives. Therapeutically, pumpkin peel, flesh and seeds contain active ingredients, acting as effective antioxidants and antimicrobial agents. No part of pumpkin fruit should be discarded during processing as these parts possess excellent phytochemistry, capable of impacting positive health impacts. All these parts of pumpkin can be used in the form of powders or extracts to isolate and characterize bio-actives and to utilize them in food and pharmaceutical industries as therapeutic agents. Instead of consumption in raw form, technologies should be implemented to develop novel and innovative nutraceuticals and pharma foods from health beneficial constituents of pumpkin.
Article
Background Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) in older men. Nowadays, there are several plant extracts used for the treatment of LUTS due to BPH. Objective The aim of this study is to compare the effect of combining silodosin 8 mg with Serenoa repens, Urtica dioica, Cucurbita pepo (Rotaprost 530 mg) compared to silodosin 8 mg and Rotaprost 530 mg alone in patients with LUTS/BPH. Methods Four hundred five men with symptomatic BPH were recruited for the study from June 2020 to January 2021. Three hundred eighty-nine patients were followed up for 6 months. All participants provided written informed consent. This prospective study included analysis of three treatment groups: Group I patients (n = 130) received a combination of silodosin 8 mg and Rotaprost 530 mg (containing a dry extract of Serenoa repens 80 mg, a dry extract of Urtica dioica 150 mg, a dry extract of Cucurbita pepo seeds 200 mg, zinc (in the form of zinc picolinate) 0.105 mg, and selenium (as sodium selenite) 22.5 µg); the group II (n = 129) received silodosin 8 mg alone, and the group III (n = 130) received Rotaprost 530 mg alone. Outcomes were measured by changes from baseline in International Prostate Symptom Score (IPPS) total score, PSA value, prostate volume, residual urine after urination, and maximum flow rate. Statistical significance was set at P < 0.05. Results In group I, IPSS, prostate volume, and maximum urinary flow rate (Qmax) improved significantly (P < 0.05) compared with groups II and III during follow-up. Prostate volume in group I showed a significant decrease only during 6 months of therapy (P < 0.05). No serious adverse effects were registered in the three groups. Conclusion Combination therapy with silodosin 8 mg significantly reduced LUTS/BPH, Qmax, and prostate volume compared with silodosin 8 mg alone. Rotaprost 530 mg can also reduce PSA by at least 20.6−25.7% after 6-months of treatment.
Article
Patients using nutraceuticals represent a diverse patient population with a keen potential interest and/or adherence to healthy lifestyle changes. BPH nutraceuticals, including saw palmetto were as safe, but not more effective than placebo in the STEP and CAMUS clinical trials, but another high-quality saw palmetto product could be tested in a phase 3 trial. Several other BPH supplements need more recent robust clinical data, environmental oversight, or safety data. ED supplements, including Panax ginseng, and the notable nitric oxide (NO) enhancing amino acids arginine and citrulline have positive preliminary short-term efficacy data with and without PDE-5 inhibitors, but herbal quality control (QC) or safety signals with some of these agents in specific patient populations need to be resolved. "Less is more" should be the current mantra in the prostate cancer milieu, and potentially in some men with male infertility based on the FAZST trial because it is plausible some antioxidants are exhibiting prooxidant activity in some settings. Some prescription anthelmintic medications are being studied, others are being purchased over-the-counter (OTC), but their preliminary safety and efficacy against cancer have been concerning and questionable. In fairness, ongoing additional objective clinical trial data should become available soon, especially with mebendazole. DHEA or DHEA enhancing products have multiple concerns including HDL reductions, and their questionable use in men with BPH or prostate cancer based on the limited data. Some of these concerns should also be addressed in long-term robust clinical trials of prescription testosterone agents. Regardless, more attention should be directed toward heart-healthy lifestyle changes for most urologic men's health conditions, whether they are used in a preventive or synergistic setting with other acceptable clinical treatment options.
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Nowadays there is a growing demand for nutraceuticals to prevent diseases related to redox imbalances, such as atherosclerosis and diabetes, being crucial to search for new matrixes rich in bioactive compounds. This work aims to characterize the value-added compounds extracted from Curcubita pepo seeds using green methodologies, namely microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), employing water as an extracting solvent for two ratios (condition 1: 1 mg/20 mL; condition 2: 2.5 mg/20 mL). The extract with the best antioxidant/antiradical activity in FRAP (71.09 μmol FSE/g DW) and DPPH (5.08 mg TE/g DW) assays was MAE condition 1, while MAE condition 2 exhibited the highest activity in the ABTS assay (13.29 mg AAE/g DW) and TPC (16.89 mg GAE/g DW). A remarkable scavenging capacity was observed, particularly for HOCl, with IC50 values ranging from 1.88–13.50 μg/mL. A total of 21 phenolic compounds were identified, being catechin (4.567–7.354 mg/g DW), caffeine (1.147–2.401 mg/g DW) and gallic acid (0.945–1.337 mg/g DW) predominant. No adverse effects were observed on Caco-2 viability after exposure to MAE extracts, while the other conditions led to a slight viability decrease in NSC-34. These results highlighted that the extract from MAE condition 2 is the most promising as a potential nutraceutical ingredient.
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This study aimed to determine the prophylactic and curative effects of pumpkin seed ethanolic extract (PSEE) in adult male rats with testosterone-induced BPH. Two study group were designed for this study; the first study examined the protective effect of (PSEE) against testosterone-induced BPH in five rats divided into three equal groups (control negative group (C1) received only drinking water; protective group (P) received testosterone enanthate concurrently with regular oral administration of (PSEE) for 30 days, and control positive group (CP) received only testosterone enanthate; although the second study examined the extract's therapeutic effect on testosterone-induced BPH, it used two equal groups (control negative group (C2) (injected testosterone enanthate only for 30 days) and therapeutic group (T) (injected testosterone enanthate for 30 days, then the injection stopped, and the rats received 100mg of pumpkin seed ethanolic extract orally for 27 days). Serum dihydrotestosterone(DHT) levels, 5α-reductase, and PSA were estimated, and prostates were histologically studied. Results showed a significant reduction in all examined parameters and histopathological improvement in protective and therapeutic groups compared to control groups. In conclusion, the pumpkin seed ethanolic extract has curative and protective activity on testosterone-induced BPH in rats, with a potential protective effect compared to curative activity.
Chapter
Reproductive and developmental disorders or abnormalities that occur in male and female reproductive tracts and fetal development are induced by infectious and noninfectious agents and various other conditions. Currently, environmental pollution, and the common use of synthetic chemicals in cosmetics and other items for domestic day-to-day uses undoubtedly contribute to the noninfectious causes of reproductive abnormalities and developmental disorders. In both animals and humans, modern drugs are used to treat reproductive disorders. However, unwanted side effects that follow often pose severe problems and concerns, consequently increasing the global use of natural products including nutraceuticals to treat reproductive and developmental abnormalities. In this chapter, use of nutraceuticals in the treatment and management of female and male reproductive tract abnormalities and developmental problems is briefly highlighted.
Chapter
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A wide variety of plant species provide edible seeds. Seeds are the dominant source of human calories and protein. The most important and popular seed food sources are cereals, followed by legumes and nuts. Their nutritional content of fiber, protein, and monounsaturated/polyunsaturated fats make them extremely nutritious. They are important additions to our daily food consumption. When consumed as part of a healthy diet, seeds can help reduce blood sugar, cholesterol, and blood pressure.
Article
Background: Practice guidelines hardly recommend herbal extracts for male lower urinary tract symptoms (LUTS). However, many patients are unsatisfied with first-line synthetic drugs and often prefer herbal medicines because of good tolerability. To improve the decision-making process, which should consider the patients' expectations, it is crucial to reflect on the role of phytotherapy in the treatment of LUTS. We (panel experts) reflected on current guideline recommendations and real practice across various European countries and debated the potential role of plant extracts with a focus on pumpkin seed soft extract investigated over 12 months in two randomised placebo-controlled trials. Summary: Most guidelines give no clear recommendations on phytotherapy due to the heterogeneity of clinically investigated extracts. Nevertheless, plant extracts are prescribed to patients with mild-to-moderate LUTS. Also, self-medicating patients often handle their complaints with herbal products. Many patients aim to avoid synthetic drugs for fear of sexual functional side effects and a negative impact on their quality of life. For the elderly, vasoactive comedications might become an issue. When taking plant extracts, patients experience an acceptable symptomatic relief similar to that achieved with synthetics but without side effects. Key Messages: In shared decision-making for purely symptomatic treatment, a low risk of side effects takes priority. We propose to consider patient preferences in the treatment of mild-to-moderate LUTS in men with a low risk of disease progression. We found a consensus that pumpkin seed soft extract adds to the therapeutic armamentarium for patients who cannot or do not want to apply synthetic drugs.
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During the last years, pharmaceutical innovations in primary care are dramatically less frequent and will be even more rare in the next future. In this context, preclinical and clinical research oriented their interest toward natural compounds efficacy and safety, supporting the development of a new “nutraceutical” science. Medicinal plants, in the form of plant parts or extracts of them, are commonly used for the treatment of prostate diseases such as benign hypertrophy, prostatitis and chronic pelvic pain syndrome. The pharmacological properties searched for the treatment of prostatic diseases are anti-androgenic, anti-estrogenic, antiproliferative, antioxidant and anti-inflammatory. The most studied and used medicinal plants are Serenoa repens, Pygeum africanum and Urtica dioica. Other promising plants are Cucurbita pepo, Epilobium spp, Lycopersum esculentum, Secale cereale, Roystonea regia, Vaccinium macrocarpon. In parallel, epidemiological studies demonstrated that diet may play an important role on incidence and development of prostatic diseases. The Mediterranean diet is rich of elements with anti-oxidant properties that act as a protective factor for prostatic cancer. Similarly, low intake of animal protein, high intake of fruits and vegetable, lycopene and zinc are a protective factor for benign prostatic hyperplasia (BPH). Serenoa repens in the treatment of symptoms of BPH has been tested either alone or, more frequently, in combination with other medicinal plants, alpha-blockers and inhibitors of 5- alpha reductase (5-ARI). Recent meta-analyses found the effectiveness of Serenoa repens similar or inferior of that of finasteride and tamsulosin but clearly higher than that of placebo in the treatment of mild and moderate low urinary tract symptoms (LUTS), nocturia and discomfort. Clinical trials showed potential synergistic effect of Serenoa repens with other medicinal plants and drugs. In addition to Serenoa repens, there are many other medicinal plants for which clinical evidence is still controversial. Urtica dioica, Pygeum africanum and Curcubita pepo can be considered as an adjunct to the common therapies and their use is supported by studies showing improvement of symptoms and flowmetric indices. Lycopene and selenium are natural products with antioxidant and anti-inflammatory action. The combination of lycopene and selenium with Serenoa repens was able to reduce inflammation in histological prostate sections and to further improve symptom scores and urinary flow in patients with BPH on tamsulosin treatment. Similar effects could be obtained with the use of other carotenoids, such as astaxanthin, and/or zinc. Efficacy on symptoms of patients with BPH of some polyphenols such as quercitin, equol and curcumin have been demonstrated by clinical studies. Pollen extract is a mixture of natural components able to inhibit several cytokines and prostaglandin and leukotriene synthesis resulting in a potent anti-inflammatory effect. Pollen extracts significantly improve symptoms, pain, and quality of life in patients affected by chronic pelvic pain syndrome and chronic prostatitis. Beta-sitosterol is a sterol able to improve urinary symptoms and flow measures, but not to reduce the size of the prostate gland. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide-signaling molecule with anti-inflammatory and neuroprotective effects that can have an interesting role in the management of chronic pelvic pain syndrome and chronic urological pain. Finally, several plant-based products have been subjected to preclinical, in vitro and in vivo, investigations for their potential pharmacological activity against prostate cancer. Some epidemiological studies or clinical trials evaluated the effects of beverages, extracts or food preparations on the risk of prostate cancer. Some plant species deserved more intense investigation, such as Camelia sinensis (green or black tea), Solanum lycopersicum (common tomato), Punica granatum (pomegranate), Glycine max (common soy) and Linum usitatissimum (linen).
Article
Purpose The purpose of this paper is to review the nutritional and food value of pumpkin Cucurbita , along with different health benefits. Cucurbita (pumpkin) is an herbaceous vine, member of Cucurbitaceae family. It is an edible, heat-sensitive plant, which has an abundant amount of active compounds such as carotenoids, alkaloids, flavonoids, polyphenols, tannins, tocopherols, phytosterols and cucurbitacin, accounted for numerous health benefits, namely, antidiabetic, antioxidant, anticarcinogenic, hypotensive, hyper protective activities. Design/methodology/approach Major well-known bibliometric information sources such as Web of Science, Scopus, Mendeley and Google Scholar were searched with keywords such as nutrition value of Cucurbita , Cucurbita utilization, bioactive compounds of pumpkin, health benefits, processing, food formulations and current scenarios were chosen to obtain a large range of papers to be analyzed. A final inventory of 105 scientific sources was made after sorting and classifying them according to different criteria based on topic, academic field, country of origin and year of publication. Findings The comprehensive review of different literature, data sources and research papers seeks to find and discuss various nutritional benefits of pumpkin. It contains all necessary macro- and micro-nutrients, amino acids, vitamins, antioxidants and bioactive compounds with a relatively low amount of antinutrients. The recent upsurge in consumer interest for health-promoting products has opened up new vistas for plant products containing bioactive compounds in different food formulations. Originality/value This paper contains information regarding the chemical composition, nutritive value, phytochemical studies, pharmacological properties, bio-accessibility, food and industrial applications of pumpkin. Worldwide, pumpkin is used as food additive in various food products such as candy, weaning mix, corn grits, kheer, jam, crackers, bread, etc. Effect of different processing methods such as high temperature, pH, blanching, oven drying, freeze-drying to retain or minimize its losses in case of color, texture, flavor, and the carotenoids are of concern. The review paper highlights the nutritional, therapeutic, potential and processing attributes.
Article
Benign prostatic hyperplasia (BPH) is a common disorder in men aged over 60 years and significantly contributes to the distressing lower urinary tract symptoms. Cucurbitacins are triterpene derivatives with diverse medicinal uses including prostate diseases. Cucurbitacin E glucoside was evaluated against testosterone-induced prostatic hyperplasia in mice. Our data indicate that it significantly inhibited the increase in prostate weight and prostate index. The compound ameliorated histopathological changes in prostatic architecture and inhibited the increase in glandular epithelial length induced by testosterone. These results were confirmed by decreased expression of cyclin D1 in prostatic tissues compared to those obtained from the testosterone-alone group. Also, it showed significant antioxidant activity as evidenced by inhibiting lipid peroxides accumulation, glutathione depletion and superoxide exhaustion. Further, it exhibited anti-inflammatory activity as it decreased cyclooxygenase-2 and interleukin-1β protein expression in prostatic tissues. Masson's trichrome staining of prostate sections indicated obvious antifibrotic activity that was supported by decreased α-smooth muscle actin expression. In conclusion, Cucurbitacin E glucoside inhibits testosterone-induced experimental BPH in mice due to, at least partly, its antiproliferative, antioxidant, anti-inflammatory, and antifibrotic effects.
Chapter
Reproductive disorders or abnormalities that occur in male and female reproductive tracts are induced by infectious and noninfectious agents and various other conditions. In the contemporary world, common use of synthetic chemicals in cosmetics and other items for domestic day-to-day uses undoubtedly contributes to the noninfectious causes of reproductive abnormalities. In both animals and humans, modern drugs are used to treat reproductive disorders. However, unwanted side effects that follow often pose severe problems and concerns, consequently increasing global use of natural products including nutraceuticals to treat reproductive abnormalities. In this chapter, the use of nutraceuticals in the treatment and management of female and male reproductive tract abnormalities is briefly highlighted.
Article
Full-text available
Benign prostatic hyperplasia (BPH) is a common disease in elderly men. Although it is a nonmalignant disease, it can have a significant impact on the quality of life of elderly men. The pumpkin seed is claimed to be useful in the management of BPH. This investigation analysed the chemical composition of pumpkin seeds and examined its effect on citral-induced hyperplasia of the prostate in Wistar rats. Citral was administered orally into stomachs of male rats to induce BPH to all rats except negative control group. A rat from each group was sacrificed after 15 days from study, protein binding prostate was determined in ventral prostate gland in order to ensure that BPH has been induced. Fifty adult Wistar male rats were divided into five groups as follows: negative control group that have no BPH and fed on basal diet (C-), positive group rats have BPH and fed on basal diet only (C+), the remaining groups had BPH and were fed on different level of pumpkin seeds, 2.5, 5 and 10%. Four weeks later all rats were sacrificed and several investigations have been conducted such as ventral prostatic growth, protein binding prostate (PBP) and the histology of testis. Citral significantly increased prostate weight (P<0.05). However, pumpkin seeds significantly inhibited enlarged prostate especially at high concentrations seed dose (10%) (P < 0.02). Results indicate that pumpkin seeds can alleviate the signs of BPH such as decrease of PBP levels, weight of ventral prostate size, improve histology of testis that may be beneficial in the management of mild stage of benign prostatic hyperplasia. For the first time we found a link between BPH and testis histopathology that needs more investigation.
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The oil from the pumpkin (Cucurbita pepo) seed is claimed to be useful in the management of benign prostatic hyperplasia. This investigation seeks to examine the effect of pumpkin seed oil on testosterone-induced hyperplasia of the prostate of rats. Hyperplasia was induced by subcutaneous administration of testosterone (0.3 mg/100 g of body weight) for 20 days. Simultaneous oral administration of either pumpkin seed oil (2.0 and 4.0 mg/100 g of body weight) or corn oil (vehicle) was also given for 20 days. The weights of the rats were recorded weekly, and the influence of testosterone and pumpkin seed oil on the weight gain of the rats was examined. On day 21, rats were sacrificed, and the prostate was removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. Neither testosterone nor pumpkin seed oil had any significant influence on the weight gain of the rats. Testosterone significantly increased prostate size ratio (P < .05), and this induced increase was inhibited in rats fed with pumpkin seed oil at 2.0 mg/100 g of body weight. The protective effect of pumpkin seed oil was significant at the higher pumpkin seed oil dose (P < .02). We conclude pumpkin seed oil can inhibit testosterone-induced hyperplasia of the prostate and therefore may be beneficial in the management of benign prostatic hyperplasia.
Article
Nocturia, which is especially frequent among older men, adversely affects the individual's quality of life. It is regarded as one of the most bothersome lower urinary tract symptoms (LUTS). The aim of the study was to investigate factors contributing to the frequency of nocturia. Men ≥ 40 years with LUTS were enrolled in this study. After medical histories were taken and physical examinations conducted, biochemical tests and measures for LUTS were carried out. Anthropometric measurements were performed and Epworth scores (ES) were examined. Patients were divided into two groups with respect to nocturia: the first group having no nocturia or one incident of nocturia per night, and the second group with two or more nightly incidents of nocturia. The data were analyzed statistically; p < 0.05 was considered significant. A total of 118 consecutive patients (56 ± 10 years) were enrolled in the study. The first group consisted of 31 participants, while the second group contained 87 patients. The groups differed significantly with respect to age, body height, body weight, waist circumference and body mass index (BMI). ES, prostatic volumes, maximum flow rates (Qmax) and international prostate symptom scores (IPSS) were significantly different. Fasting blood glucose levels were similar for both groups. Homeostasis model assessment (HOMA) scores showed borderline significance. Insulin levels were different, while insulin resistance (IR) was similar between the groups. Nocturnal polyuria was associated with nocturia, systolic blood pressure and IPSS. Age, nocturnal polyuria, metabolic syndrome and sleep disturbances have been shown to be contributing factors in the frequency of nocturia and LUTS. Therefore, steps taken to alleviate factors that can be altered - such as hypertension, weight gain, sleep disturbances and IPSS - may improve the individual's quality of life.
Article
Objective: To evaluate the efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Methods: A comprehensive search was done to identify randomized controlled trials comparing the efficacy and safety of tadalafil for LUTS/BPH with placebos. Meta-analytical techniques were applied to evaluate the differences in the study results. Results: Eight studies were identified and analyzed. Compared with placebo, tadalafil was associated with significant improvements in the International Prostate Symptom Score (IPSS) (mean difference = -2.19, p < 0.00001) and the International Index of Erectile Function (IIEF) score (mean difference = +4.66, p < 0.00001), despite the concomitant presence of erectile dysfunction. Significant differences were also observed in the IPSS irritative and obstructive subscores, IPSS quality of life index and BPH impact index. After pooling four doses (2.5, 5, 10 and 20 mg), tadalafil failed to produce a significant outcome in maximal urinary flow rate (Qmax) (mean difference = +0.26 ml/s, p = 0.14), but 5 mg of tadalafil significantly improved Qmax (mean difference = +0.63 ml/s, p = 0.04). No significant difference was detected in the incidence of serious adverse events (risk ratio = 1.00, p = 1.00) after tadalafil treatment. Conclusions: Tadalafil showed good efficacy and safety for improving LUTS and erectile dysfunction in men with BPH, and 5 mg of tadalafil significantly improved Qmax.
Article
For decades sterol containing plant extracts have found wide applications in the treatment of benign prostate enlargement. Especially in Germany, the extracts of Cucurbita spec. (pumpkin seeds), Sabal fructus and Urtica dioica, as well as other poorly defined „phytosterol“ preparations are widely used. In contrast to phytosterols from other plants of interest, the extracts of pumkin seeds contain significant amounts of Δ7-phytosterols and their glucosides, which are claimed to be responsible for the therapeutic effects due to their structural similarity to 5α-dihydrotestosteron. In continuation of our research on sterol analysis we worked out a methodology for the determination of phytosterols in different pharmaceutical formulations. The method includes a sample cleanup of the unsaponifiables and the glucoside hydrolysates by a modified QuEChERS approach and the identification and determination of the sterol aglyca by GC-MS analysis of the corresponding trimethylsilyl ethers. In a number of phytosterol preparations from local pharmacies, supermarkets and internet shops the sterol patterns were analyzed with special attention to the content of Δ5- and Δ7-phytosterols. Only in two pharmacy products (GRANU FINK PROSTA and PROSTA FINK FORTE) we found relevant amounts of Δ7-phytosterols. All other products without pumpkin seed contained no Δ7-phytosterols. Lowest content of phytosterols were found in a pumpkinseed oil product from a discounter.
Article
Objective: To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). Evidence acquisition: We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. Evidence synthesis: Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1-blockers. Men with enlarged prostates, especially those >40ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1-blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1-blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment-resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30-80ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. Conclusions: These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online (www.uroweb.org/gls/pdf/12_Male_LUTS.pdf).
Article
Objective: This study aims to examine the relationship between chronic prostatic inflammation and prostatic calculi, and clinical parameters of benign prostatic hyperplasia (BPH). Materials and methods: This study was based on 225 patients who underwent transurethral resection of the prostate for BPH. Chronic inflammation was graded as 0 (n = 44), I (n = 54), II (n = 88) or III (n = 39) according to severity. Prostatic calculi were classified into types A (n = 66), B (n = 44), M (n = 77) and N (n = 38). The relationship between inflammation and calculus type was analyzed, and clinical parameters of BPH were compared for each group. Results: There was no correlation between severity of inflammation and calculus type. Prostatic volume increased with the severity of inflammation and showed significant differences between G2, G3 and G0. The International Prostate Symptom Score also increased with increasing inflammation. There was no significant difference between each clinical parameter according to calculus type. Conclusions: Prostatic calculi had no significant association with chronic inflammation and clinical parameters of BPH. Chronic inflammation was associated with the volume of the prostate and storage symptoms; thus, it is not only presumed to be related to the progression of BPH, but may also be one of the causes of lower urinary tract symptoms.
Article
Objective: To evaluate the efficacy and safety of fesoterodine extended-release (ER) plus tamsulosin in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Patients and methods: Men aged ≥50 years, with LUTS, prostate volume ≤60 ml and International Prostate Symptom Score (IPSS) ≥13 were enrolled in this study. 173 consecutive patients were treated initially with tamsulosin (0.4 mg) for 1 week. At the second visit, 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were randomized into two groups. The first group received a therapy with tamsulosin and fesoterodine combination (group 1, n = 24) while the second continued the therapy with the single administration of tamsulosin (group 2, n = 23) for an additional 4-week period. Results: There was no statistically significant difference in age, prostate volume, Q, and postvoid residual urine between the two groups. A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits (10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively). Conclusion: Regarding bothersome LUTS and storage symptoms, fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin.
Article
Zum Thema Die Wirksamkeit und Vertrglichkeit von Krbissamen wurde erstmals als Monosubstanz in einer randomisierten, doppelblinden, placebokontrollierten Studie nach GCP bei benigner Prostatahyperplasie ber einen Zeitraum von 12 Monaten geprft. Entsprechend den Empfehlungen des "Internationalen Konsensus Komitees" und der "Arbeitsgruppe BPH der Deutschen Gesellschaft fr Urologie" wurde der "Internationale Prostata Symptomen Score" (IPSS) als Hauptzielparameter zur berprfung der Wirksamkeit auf die Miktionssymptomatik gewhlt.
Article
Pumpkin seeds were prepared into oil n-butyle alcohol and ether extracts. The effects of the three extracts on the urodynamics of rabbits were observed. It was concluded that the oil preparation could remarkably reduce the bladder pressure, increase the bladder compliance, reduce the urethral pressure. Other two kinds of preparations had no effect in this experimental. The mechanisms of the effect of oil preparation on the urodynamics and the prospect of clinical use was discussed.
Article
What's known on the subject? and What does the study add? For the past 30 years Serenoa repens has become a widely used phytotherapy in the USA and in Europe, mostly because of positive comparisons to α-blockers and 5α-reductase inhibitors. During the last 4 years we have seen two very high quality trials comparing Serenoa repens to placebo and up to 72 weeks' duration. These trials found Serenoa repens no better than placebo, even (in one trial) at escalating doses. • To estimate the effectiveness and harms of Serenoa repens monotherapy in the treatment of lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH). • We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other sources through to January 2012 to identify randomised trials. • Trials were eligible if they randomised men with symptomatic BPH to receive Serenoa repens extract monotherapy for at least 4 weeks in comparison with placebo, and assessed clinical outcomes and urodynamic measurements. • Our primary outcome was improvement in LUTS, based on change in urological symptom-scale scores. • In all, 17 randomised controlled trials (N= 2008) assessing Serenoa repens monotherapy (typically 320 mg/day) vs placebo met inclusion criteria, although only five reported American Urological Association Symptom Index (AUASI) or International Prostate Symptom Scores (IPSS). Trial lengths ranged from 4 to 72 weeks. The mean age of all enrolees was 64.3 years and most participants were of White race. The mean baseline total score was 14 points, indicating moderately severe symptoms. In all, 16 trials were double blinded and adequate treatment allocation concealment was reported in six trials. • In a meta-analysis of three high quality long-to-moderate term trials (n= 661), Serenoa repens therapy was no better than placebo in reducing LUTS based on the AUASI/IPSS (weighted mean difference [WMD]-0.16 points, 95% confidence interval [CI]-1.45 to 1.14) or maximum urinary flow rate (Q(max) ; WMD 0.40 mL/s, 95% CI -0.30 to 1.09). Based on mostly short-term studies, Q(max) measured at study endpoint were also not significantly different between treatment groups (WMD 1.15 mL/s, 95% CI -0.23 to 2.53) with evidence of substantial heterogeneity (I(2) 58%). • One long-term dose escalation trial (72 weeks) found double and triple doses of Serenoa repens extract did not improve AUASI compared with placebo and the proportions of clinical responders (≥ 3 point decrease in the AUASI) were nearly identical (43% vs 44% for Serenoa repens and placebo, respectively) with a corresponding risk ratio of 0.96 (95% CI 0.76-1.22). • Long-term, Serenoa repens therapy was no better than placebo in improving nocturia in one high-quality study (P= 0.19). Pooled analysis of nine short-term Permixon® trials showed a reduction in the frequency of nocturia (WMD -0.79 times/night, 95% CI-1.28 to -0.29), although there was evidence of heterogeneity (I(2) 76%) • Adverse events of Serenoa repens extracts were few and mild, and incidences were not statistically significantly different vs placebo. Study withdrawals occurred in ≈ 10% and did not differ between Serenoa repens and placebo. • Serenoa repens therapy does not improve LUTS or Q(max ) compared with placebo in men with BPH, even at double and triple the usual dose. • Adverse events were generally mild and comparable to placebo.
Article
ObjectivesSince decades plant extracts belong to the most popular drugs for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE). Herein we review biological mechanisms, the placebo effect, results of clinical trials, the role of meta-analyses and guideline recommendations.MethodsReview of the literature with particular reference to long-term (study period ≥6 months) controlled trials and of BPH-guideline recommendations.ResultsOnly few of the large number of available studies meet the criteria defined by the WHO-BPH consensus conference. The few, placebo-controlled, long-term (study period ≥6 months) studies suggest a positive effect of some extracts (saw palmetto, ß-sitosterol, urtica, saw palmetto/urtica combination) on LUTS, an effect on uroflow, post-void residual volume, prostate volume and PSA was not consistently demonstrable. Randomised trials against active comparators (α1-blocker, 5α-reductase inhibitors) are difficult to interpret. Due to the lack of prospective studies, several meta-analyses have been published that can not replace prospective studies according to WHO-BPH recommendations. None of the BPH-guidelines currently recommends plant extracts, yet universally conclude that this is an interesting approach.ConclusionsFurther prospective studies according to WHO-standards are required to reliably determine the role of plant extracts in contemporary LUTS-management.
Article
Pumpkin seeds were prepared into oil n-butyle alcohol and ether extracts. The effects of the three extracts on the urodynamics of rabbits were observed. It was concluded that the oil preparation could remarkably reduce the bladder pressure, increase the bladder compliance, reduce the urethral pressure. Other two kinds of preparations had no effect in this experimental. The mechanisms of the effect of oil preparation on the urodynamics and the prospect of clinical use was discussed.
Article
Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone.
Article
Various treatment modalities for benign prostatic hyperplasia (BPH) have emerged and are now in use or await evaluation of clinical usefulness. It is difficult, however, to compare their efficacies on a single scale, because standardized criteria for therapeutic efficacy of BPH treatments have not been established. A total of 692 BPH patients from 8 institutions in Japan received various treatments, and were judged by specialized physicians for overall efficacy, and for efficacy in 4 domains: symptom, function, anatomy, and quality of life (QOL). Efficacy of treatment was graded as excellent, good, fair or poor, and assessed using items based on conventional clinical measurements. These items included 1) the difference (post-pretreatment value), 2) relative ratio (post/pre) and, 3) the individual values of pre- or posttreatment measurements. The cut off levels for each grade were heuristically selected by Spearman's rank correlation and multiple regression analysis so that the results accurately predicted physicians' judgement, while the feasibility was maintained. The results for each efficacy grade (range of excellent, range of good, range of fair, range of poor) were summarized as follows: Symptom: (post/pre treatment ratio of I-PSS) < or = 0.25, < or = 0.5, < or = 0.75, > 0.75. Function: (post-pre of Qmax) > or = 10 mL/s, > or = 5 mL/s, > or = 0.25 mL/s, < 0.25 mL/s. Anatomy: (post/pre ratio of prostate volume) < or = 0.5, < or = 0.75, < or = 0.9, > 0.9. QOL: (pre-post of QOL index) > or = 4, 3, 2 and 1, < or = 0. The overall efficacy grade was defined as the median of efficacy grades of 3 domains: symptom, function and QOL. The agreement rates between the criteria and physicians' judgement on the dichotomous efficacy (either excellent plus good, or fair plus poor) were approximately 80% in individual domains and overall estimate, and consistent among various treatments. The proposed criteria are fairly accurate, simple, and practical, and thus may be useful as a standard method for assessing the clinical efficacy of BPH treatments.
Article
Phytotherapy of BPS has a long tradition in Germany; nevertheless, data referring to single phytotherapeutic agents are rare. We therefore performed a randomized, double-blind, placebo-controlled multicenter study for 1 year with Bazoton uno (459 mg dry extract of stinging nettle roots) with 246 patients. The IPSS decreased on average from 18.7+/-0.3 to 13.0+/-0.5 with a statistically significant difference compared to placebo (18.5+/-0.3 to 13.8+/-0.5; p=0.0233). The median Q(max) increased by 3.0+/-0.4 ml/s in comparison to 2.9+/-0.4 ml/s (placebo), thus not statistically significantly different, as well as the median volume of residual urine, which changed from 35.5+/-3.4 ml before therapy to 20.0+/-2.8 ml and from 40.0+/-4.0 ml to 21.0+/-2.9 ml under placebo application. The number of adverse events (29/38) as well as urinary infections etc. (3/10 events) was smaller under Bazoton uno therapy compared to placebo. Treatment with Bazoton uno can therefore be considered a safe therapeutic option for BPS, especially for reducing irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects of the stinging nettle extract. A strong increase of Q(max) or reduction of residual urine are not to be expected.
Article
This paper profiles the usage and effectiveness of various LUTS/BPH drugs in real-life practice. The TRIUMPH study recorded the treatment and outcomes of 2351 newly-presenting LUTS/BPH patients in 6 European countries over a 1-year follow-up period. At each visit the clinician recorded the treatment, co-morbidities, complications and drugs prescribed, and the patient completed an IPSS questionnaire. The results were analysed using change in IPSS as the primary outcome measure. Over the study period 74.9% of patients were prescribed medication, the majority (83% of those medicated) were prescribed only a single drug. Tamsulosin was the most commonly prescribed drug in all countries (38% of medicated cases), although with national variation from 24% in Poland to 70% in Italy. The alpha-blockers were the most effective, with a mean reduction of 6.3 IPSS points. Finasteride was slightly less effective (4.1 points). Significant improvements were seen in 43% of patients on phytotherapy with Serenoa repens or Pygeum africanum compared to 57% of those on finasteride and 68% on alpha-blockers. The only combination therapy found to produce a statistically significant improvement over the use of individual drugs was finasteride+tamsulosin (8.1 points compared to 6.7 for tamsulosin alone and 4.2 for finasteride alone). All drug treatments showed some improvement over watchful-waiting for most patients over the study period: the alpha-blockers were found to be the most effective. There were marked national differences in prescribing patterns, both in individual drug choice and in the use of combination therapies.
Article
Benign prostatic hyperplasia (BPH) is a condition that is common among older men. It causes a variety of clinically significant lower urinary tract signs and symptoms. BPH is rarely life-threatening; the decision to seek treatment is frequently based on the degree to which patients find the symptoms bothersome and disruptive of daily activities. Recently developed reliable and valid outcome measures to evaluate treatments for BPH are clinical tools that urologists can use to determine the extent of bother and make treatment decisions. A single question used to determine the "bother score" provides a widely used and statistically valid measure of the need for treatment of BPH. Validation data support the argument that the bother score is a statistically reliable measure of treatment outcome in patients with BPH who view their symptoms as bothersome.
Article
This study was undertaken to investigate the effects of pumpkin seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T-P) prostate growth in rats. Forty adult Wistar rats were divided into five groups, including: one control group, rats treated with vehicle only, one group treated with T-P, and two groups of T-P-treated rats, one receiving orally pumpkin seed oil alone and one group receiving orally pumpkin seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to-body weight ratio was determined after sacrifice. The total protein concentration was measured by using a protein assay. Some ventral prostatic tissues were histologically examined after hematoxylin-eosin staining. Histological sections of the ventral prostate showed that the architecture of the prostate glands became hyperplastic in the T-P rats, but not in the control or vehicle-treated animals. As compared with the control or vehicle group, T-P rats had a significantly higher prostatic weight-to-body weight ratio for the ventral prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001, respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or pumpkin seed oil combined with Phytosterol-F had a significantly lower weight ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and significantly lower protein levels within both lobes (p=0.03 and p=0.003, respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had some additive effect on the total protein synthesis within the ventral prostate (p=0.02). Pumpkin seed oil alone or combined with Phytosterol-F can block the T-P-induced increases in prostatic weight-to-body weight ratio and protein synthesis.
Article
The lack of cure with medical therapy implies life-long treatment emphasising the need for a thorough understanding of the long-term outcome. We review the natural history, markers for progression, placebo effect, efficacy, pharmacoeconomic aspects, and preventive measures. Literature review with particular reference to long-term controlled studies using plant extracts, alpha1-blockers, 5alpha-reductase inhibitors (5-ARIs), and combination therapy. There is a long-lasting (>or=12 mo) placebo response of symptoms (20% decrease) and maximum flow rate (10% rise). The five long-term controlled trials of plant extracts are inconclusive and therefore their role in contemporary medical management is still controversial. The alpha1-blockers provide fast amelioration of symptoms yet have no relevant impact on the risk of acute urinary retention or surgery. Combination therapy should be reserved for moderately or severely symptomatic patients with a high risk of progression; in the majority of patients the alpha1-blocker can be safely stopped after 6-12 mo. The preventive use of 5-ARIs in men with no or mild symptoms at risk of progression is scientifically sound yet not generally accepted mainly for economic reasons. A sharp contrast exists between the duration of the longest controlled trial (4.5 yr) and the situation in real life with treatment periods up to one or two decades of life. Real-life and registry data will be the only source of this important information in the future.
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