Phytotherapy in urology. Current scientific evidence of its application in benign prostatic hyperplasia and prostate adenocarcinoma | Actas Urológicas Españolas (English Edition)

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Current scientific evidence of its application in benign prostatic hyperplasia and prostate adenocarcinoma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "114" "paginaFinal" => "119" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "E. Morán, A. Budía, E. Broseta, F. Boronat" "autores" => array:4 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Morán" "email" => array:1 [ 0 => "edumoran@comv.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Budía" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Broseta" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Boronat" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Urología, Hospital Universitario y Politécnico La Fe, Valencia, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fitoterapia en Urología. Evidencia científica actual de su aplicación en hiperplasia benigna de próstata y adenocarcinoma de próstata" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1228 "Ancho" => 1320 "Tamanyo" => 71422 ] ] "descripcion" => array:1 [ "en" => "Differences in Qmax but not in IPSS." ] ] ] "textoCompleto" => "IntroductionProstatic disease is probably one of the main reasons for consulting a urologist. The PAC is in fact the most common cancer and the second leading cause of cancer death in men. The use of phytotherapy in BPH was based primarily on the treatment, while in the PAC, the studies are based especially on prevention.The aim of this review is to analyze the usefulness of phytotherapy in routine clinical practice.Material and methodThere has been a systematic review of the evidence collected in the published literature from January 1990 to January 2011. In order to carry out the review, we introduced a search of the scientific terms: phytotherapy, benign prostatic hyperplasia, prostate adenocarcinoma, and prostate cancer. We searched in PubMed and The Cochrane Library. To search for the phytotherapeutic components, we used the scientific names following the rules of the International Code of Botanical Nomenclature.Inclusion criteria: articles published until January 2011 written in Spanish and English were included. We included in vitro or in vivo studies both in animal models and in humans.Exclusion criteria: Not Spanish/English literature or articles with serious defects in their design were excluded (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Benign prostatic hyperplasiaThere are more than 100 preparations derived from available plants for the treatment of BPH, the most used being Serenoa repens and Pygeum africanum. Despite this large number of products, the studies conducted show conflicting results and some are methodologically incorrect.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Serenoa repens has an anti-inflammatory, anti-androgenic, and anti-proliferative effect.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Even an inhibitory effect on type II 5-alpha-reductase has been shown in vitro<a class="elsevierStyleCrossRef" href="#bib0015">3</a>, demonstrating clinical improvement.Other studies, like the one by Bent et al.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), with double-blind design, placebo group, and 12-month follow-up, do not appreciate the superiority of Serenoa repens versus placebo in the American Association of Urology Symptom Index (AUASI) score, urinary flow, prostate volume, postvoid residue, quality of life, or PSA. However, Shi et al.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) in their study, methodologically similar but with shorter follow-up period (12 weeks), do obtain improvement in the Qmax, but not in other parameters, such as the IPSS between the groups. Studies with similar designs but in the longer term (3 years), such as the one by Djavan et al.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>), do show an improvement in the IPSS scores, quality of life, and urinary flow. However, this study did not have a placebo group, but it compared Serenoa repens versus watchful waiting.<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>The PERMAL study compared Serenoa repens versus tamsulosin in patients with moderate and severe BPH symptoms.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a> This study, on 811 patients and with a follow-up of 12 months, did not obtain differences in terms of IPSS or Qmax improvement between tamsulosin and Serenoa repens in patients with IPSS greater than 10 (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). In a subanalysis of the PERMAL study, the same authors found no statistically significant differences between both treatments in patients with severe symptoms (IPSS greater than 19), treatment with Serenoa repens<a class="elsevierStyleCrossRef" href="#bib0045">9</a> being economically more profitable. Among the limitations of this study, and of its sub-analysis, we can highlight not including a calculation of sample size, so the statistical power and the lack of placebo group cannot be assessed. There were no differences either with respect to placebo in patients with moderate to severe BPH (IPSS ≥8) in a double-blind study with random distribution conducted by Gerber et al.<a class="elsevierStyleCrossRef" href="#bib0050">10</a><elsevierMultimedia ident="fig0025"></elsevierMultimedia>A recently published study where Serenoa repens was administered for 2 months prior to BPH surgery showed shorter surgical time, fewer complications, shorter hospital stay, and shorter length of urethral catheterization.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> These results were contradictory with regard to those published by Tuncel et al.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> in a similar study.Pygeum africanum presents a mechanism of action that has not yet been clarified, although it seems that the prostate cells of BPH patients are more sensitive to the antiproliferative and apoptotic action of Pygeum africanum than the cells of patients without BPH.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In a meta-analysis<a class="elsevierStyleCrossRef" href="#bib0070">14</a> we observed how the patients who received the compound had improvement in the symptoms compared to placebo. However, the follow-up time is barely over 2 months, and the sample size is small. Furthermore, the selection criteria are somewhat lax as studies in which the treatment arm allows for treatment with Pygeum africanum alone or in combination with other compounds are included, so that the real efficiency of the product could be masked. Furthermore, in some of these studies, the methods of evaluating results do not have validated questionnaires.Madersbacher et al.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> assess the long-term results of medical therapy on the BPH. In this review, we observe that the published studies have failed to demonstrate either greater efficacy over placebo or other compounds or the impact on the natural history of the disease. Hutchison et al.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> study the effect of the various therapies for BPH so that, after treatment with phytotherapy, improvements in the IPSS were obtained in 73% of the patients (>4 points in 42%). Unfortunately, this study had no placebo control arm.In short, most of the recognized clinical guidelines coincide in not recommending treatment with phytotherapy for BPH, despite the large number of studies and meta-analyses published, mainly on Serenoa repens, due to the lack of consistency and the methodological weaknesses, and because of the absence of an extended follow-up. Recent papers leave the door open to treatment with phytotherapy, although new studies, better designed and in the longer term, are underway to elucidate the question. In spite of that, as described by Djavan<a class="elsevierStyleCrossRef" href="#bib0085">17</a>, phytotherapy is the treatment of choice for 16% of patients in Europe, with differences between countries, from 25% in Germany to 7% in Spain. Its use is based, primarily, on the safety of its use and the results related to the placebo effect. In our country, a decrease in the use of phytotherapy has been shown, given the data from the study by Unda et al.,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> since in 1999, 21% of the patients received treatment with phytotherapy compared to less than 10% today.Prostate cancerThe plant extracts with an effect on prostate cancer are red wine, green tea, and soy. The idea of studying these compounds was based on the differences in the prevalence of prostate cancer according to geographical areas that for high-grade prostate cancer in Asian countries – with a high rate of intake of soy and green tea – are clearly inferior.Green tea (Camellia sinensis) is the second most consumed beverage in the world, its main component being epigallocatenin-3-gallate. One of its antitumor mechanisms is its synergistic action with drugs that inhibit the COX-2<a class="elsevierStyleCrossRef" href="#bib0095">19</a> enzyme, as it occurs with soy.We studied patients diagnosed with high-grade PIN, randomly allocated to receive 600mg/day of green tea polyphenols versus placebo.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> After a year of follow-up, only 3% of the patients who received green tea were diagnosed with cancer compared to 30% in the placebo group. The problem is that the amount needed to produce this effect is close to 20 cups of tea a day. Conversely, Kikuchi et al.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> found no benefit with respect to the incidence of prostate cancer in general.A new target is MCM7, a gene that seems to be involved in the growth and invasion by prostate tumor cells, given that it is part of the complex of genes that allow for cell replication. The green tea catenins are capable of inhibiting its expression and, therefore, they could alter the behavior of the tumor, although this has only been shown in in vitro studies.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Red wine has an anti-tumor effect (antioxidant, immunomodulatory, anti-androgenic, anti-inflammatory, and inhibitor of angiogenesis) thanks mainly to resveratrol. This polyphenol is specifically found in red wine and not in other alcoholic beverages. In fact, a prospective study showed an association between moderate alcohol consumption from other spirits and the onset of prostate cancer, but with beer and red wine.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Moreover, this compound is capable, in cell lines, of increasing apoptosis in tumor cells by activating caspases 3 and 9, so that some studies support its therapeutic use, and not only as a preventive measure.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> It has been described how resveratrol is capable of inhibiting the production of PSA, of kallikrein-2, of the specific coactivator of the androgenic receptors (ARA70) and many other compounds involved in carcinogenesis.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>Despite all this, its relation to the incidence of prostate cancer remains controversial. Thus, in a paper by Velicer et al.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> a greater risk of prostate cancer was observed in patients who drank more than one glass of alcohol a day, with the exception of red wine. Other studies, however, found no evidence of association<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and others get an increase in the incidence of prostate cancer.<a class="elsevierStyleCrossRef" href="#bib0140">28</a>Piceatannol, another compound of red wine, has proved, in vitro, to increase the apoptosis of neoplastic cells.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> Along with the latter, other elements that have been studied contained in red wine are gallic acid, quercetin, rutin, morin, and tannic acid, demonstrating its efficacy at the level of cultures of tumor cell lines.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>Another phytoterapic product containing isoflavones is red clover. This compound has shown to reduce the PSA by more than 30%, although the studies that support it do not have an optimal methodological design. In an observational study, the apoptosis of tumor cells increased in tumors of low and intermediate risk, not of high risk<a class="elsevierStyleCrossRef" href="#bib0155">31</a>. Studies like that by Gray et al.,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> recently published, found that, in cell cultures, the genistein and daidzein that red clover contains are able to modify the microenvironment in which prostate cancer is developed inhibiting the function of TGFβ-1 (enhancer of the effect of dehydroepiandrosterone).The last of the compounds studied in this section is soy that, containing genistein and daidzein, has a weak estrogenic effect at the cellular level, although the overall effect of soy is greater than the isolated effect of isoflavones contained therein. These compounds have anti-angiogenic, cytotoxic, inhibitor of proliferation and tumor invasion, induction of apoptosis, and COX-2 inhibition.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> Kumar et al.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> conducted a prospective, randomized, double-blind, and controlled analysis versus watchful waiting. It showed a trend to lower levels of PSA and testosterone in the group of patients who received treatment with soy. However, neither in this study nor in others<a class="elsevierStyleCrossRef" href="#bib0175">35</a> was there a statistically significant benefit of PSA reduction in patients with prostate cancer and treatment with soy derivatives.Nevertheless, an inverse relation between localized prostate cancer and soy intake has been shown. This can be explained because one of the effect pathways of soy is on the (-estrogen receptor, which is present in cancers with low metastatic potential but which is partially or entirely absent in those that have great potential to spread.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> Another route of action has been postulated by which genistein would inhibit the HDAC6-Hsp90 protein, which is the one that stabilizes and allows for the function of the androgenic receptors.<a class="elsevierStyleCrossRef" href="#bib0185">37</a>As for the type of soy consumed, in a recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0190">38</a> on 24 papers, it was shown that in its fermented forms such as tofu or soy milk, it was more beneficial than those non-fermented products.Another application described is in patients with biochemical relapse after treatment with surgery or radiotherapy for a localized prostate adenocarcinoma,<a class="elsevierStyleCrossRef" href="#bib0195">39</a> showing a delay in the rise of the PSA curve. Moreover, the radiosensitizer role of soy has been demonstrated for the patients who are going to receive prostate radiotherapy, which results in an increased rate of cell death from radiation.<a class="elsevierStyleCrossRef" href="#bib0200">40</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the main compounds and their mechanism of action.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In summary, all the products evaluated in this section have shown in vitro and on tumor cell lines, their anticarcinogenic application. We studied multiple therapeutic targets and there are applications for the phytotherapic products in different and complicated pathways or cascades of cellular reactions. However, clinical trials to support their use are not as abundant. Those found in the literature are mostly retrospective reviews or, in the case of being prospective, they have a small sample size or reach conclusions opposing each other. Therefore, more studies are needed and, so far, we cannot recommend these therapies as prevention and, even less, as a treatment for a disease as prevalent as prostate cancer.ConclusionsStudies on phytotherapy in BPH have shown in some cases subjective (IPSS) and objective (Qmax) improvement, although the studies are short-term, with few patients or incorrect methodological designs. There is no evidence for the recommendation of phytotherapy in the PAC.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres192063" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Acquisition of evidence" 3 => "Synthesis of the evidence" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec179295" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres192064" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Adquisición de la evidencia" 3 => "Síntesis de la evidencia" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec179296" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and method" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Benign prostatic hyperplasia" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Prostate cancer" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-04-04" "fechaAceptado" => "2012-07-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec179295" "palabras" => array:3 [ 0 => "Phytotherapy" 1 => "Benign prostate hyperplasia" 2 => "Prostatic adenocarcinoma" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec179296" "palabras" => array:3 [ 0 => "Fitoterapia" 1 => "Hiperplasia benigna de próstata" 2 => "Adenocarcinoma prostático" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo evaluate the usefulness of phytotherapy in the treatment of the benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (ADCP). Acquisition of evidenceSystematic review of the evidence published until January 2011 using the following scientific terms: phytotherapy, benign prostate hyperplasia, prostatic adenocarcinoma, prostate cancer and the scientific names of compounds following the rules of the International Code of Botanical Nomenclature. The databases used were Medline and The Cochrane Library. We included articles published until January 2011 written in English and Spanish. We included studies in vitro/in vivo on animal models or human beings. Exclusion criteria were literature not in English and Spanish or articles with serious methodological flaws. Synthesis of the evidenceWe included 65 articles of which 40 met the inclusion criteria. BPH: the most studied products are serenoa repens and pygeum africanum. There are many studies in favor of the use of phytotherapy but its conclusions are inconsistent due to the small number of patients, the lack of control with placebo or short follow-up. However, the use of these products is common in our environment. ADCP: there is no evidence to recommend phytotherapy in the treatment of the ADCP. There are works on prevention but only at experimental level so there is no evidence for its recommendation. ConclusionsThe scientific evidence on the use of phytotherapy in prostatic pathology is conclusive not recommending the use of it for BPH or the ADCP." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivoEvaluar la utilidad de la fitoterapia en el tratamiento de la hiperplasia benigna de próstata (HBP) y el adenocarcinoma prostático (ADCP). Adquisición de la evidenciaSe realizó una revisión sistemática de la evidencia publicada hasta enero del 2011, empleando los términos científicos fitoterapia, hiperplasia benigna de próstata, adenocarcinoma prostático, cáncer de próstata, y los nombres científicos de los compuestos siguiendo las normas del Código Internacional de Nomenclatura Botánica. Las bases de datos utilizadas fueron Medline y The Cochrane Library. Se incluyeron artículos publicados hasta enero del 2011, escritos en español e inglés. Se incluyeron estudios in vitro/in vivo sobre modelos animales o seres humanos. Los criterios de exclusión fueron literatura no española/inglesa o artículos con graves defectos metodológicos. Síntesis de la evidenciaSe incluyeron 65 artículos, de los cuales se seleccionaron 40 que cumplieron los criterios de inclusión. HBP: los productos más estudiados son la Serenoa repens y Pygeum africanum. Existen muchos estudios a favor del empleo de la fitoterapia; no obstante, sus conclusiones son poco consistentes debido al escaso número de pacientes, la falta de control con placebo o el escaso seguimiento. A pesar de ello el empleo de estos productos es habitual en nuestro medio. ADCP: no existe evidencia para recomendar la fitoterapia en el tratamiento del ADCP. Existen trabajos respecto de la prevención, aunque únicamente a nivel experimental, por lo que tampoco existe evidencia para su recomendación. ConclusionesLa evidencia científica acerca del empleo de la fitoterapia en la afección prostática es concluyente a la hora de no recomendarla en el empleo de la HBP o el ADCP." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Morán E, et al. Fitoterapia en Urología. Evidencia científica actual de su aplicación en hiperplasia benigna de próstata y adenocarcinoma de próstata. Actas Urol Esp. 2013;37:114–9." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1000 "Ancho" => 1606 "Tamanyo" => 58870 ] ] "descripcion" => array:1 [ "en" => "Flow of inclusion of papers in the review." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 991 "Ancho" => 1284 "Tamanyo" => 63169 ] ] "descripcion" => array:1 [ "en" => "No differences in Qmax or in AUASI score." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1228 "Ancho" => 1320 "Tamanyo" => 71422 ] ] "descripcion" => array:1 [ "en" => "Differences in Qmax but not in IPSS." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1249 "Ancho" => 1333 "Tamanyo" => 81210 ] ] "descripcion" => array:1 [ "en" => "Differences in IPSS and Qmax comparing phytotherapy vs. watchful waiting." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1322 "Ancho" => 1254 "Tamanyo" => 73446 ] ] "descripcion" => array:1 [ "en" => "Results PERMAL study." ] ] 5 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Name \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Compound \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Effect \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Green tea (Camellia sinensis) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epigallocatenin-3-gallate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-inflamatoryMCM7 inhibition \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Red wine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ResveratrolPiceatannol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Angiogenesis inhibitionIncreasing cellular apoptosisCaspase activationIncreasing cellular apoptosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Red clover \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GenisteinDaidzein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGFβ-1 inhibition \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Soy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Isoflavones \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AntiangiogenicCytotoxicHDAC6-Hsp90 inhibition \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab328687.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Phytotherapeutic products in prostate cancer." ] 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Phytotherapy in urology. Current scientific evidence of its application in benign prostatic hyperplasia and prostate adenocarcinoma

Fitoterapia en Urología. Evidencia científica actual de su aplicación en hiperplasia benigna de próstata y adenocarcinoma de próstata

E. Morán

Corresponding author

edumoran@comv.es

Corresponding author.

, A. Budía, E. Broseta, F. Boronat

Servicio de Urología, Hospital Universitario y Politécnico La Fe, Valencia, Spain

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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Differences in <span class="elsevierStyleItalic">Q</span><span class="elsevierStyleInf">max</span> but not in IPSS&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prostatic disease is probably one of the main reasons for consulting a urologist&#46; The PAC is in fact the most common cancer and the second leading cause of cancer death in men&#46; The use of phytotherapy in BPH was based primarily on the treatment&#44; while in the PAC&#44; the studies are based especially on prevention&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of this review is to analyze the usefulness of phytotherapy in routine clinical practice&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and method</span><p id="par0015" class="elsevierStylePara elsevierViewall">There has been a systematic review of the evidence collected in the published literature from January 1990 to January 2011&#46; In order to carry out the review&#44; we introduced a search of the scientific terms&#58; phytotherapy&#44; benign prostatic hyperplasia&#44; prostate adenocarcinoma&#44; and prostate cancer&#46; We searched in PubMed and The Cochrane Library&#46; To search for the phytotherapeutic components&#44; we used the scientific names following the rules of the International Code of Botanical Nomenclature&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Inclusion criteria&#58; articles published until January 2011 written in Spanish and English were included&#46; We included in vitro or in vivo studies both in animal models and in humans&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58; Not Spanish&#47;English literature or articles with serious defects in their design were excluded &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Benign prostatic hyperplasia</span><p id="par0030" class="elsevierStylePara elsevierViewall">There are more than 100 preparations derived from available plants for the treatment of BPH&#44; the most used being <span class="elsevierStyleItalic">Serenoa repens</span> and <span class="elsevierStyleItalic">Pygeum africanum</span>&#46; Despite this large number of products&#44; the studies conducted show conflicting results and some are methodologically incorrect&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Serenoa repens</span> has an anti-inflammatory&#44; anti-androgenic&#44; and anti-proliferative effect&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Even an inhibitory effect on type II 5-alpha-reductase has been shown in vitro<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#44; demonstrating clinical improvement&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Other studies&#44; like the one by Bent et al&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; with double-blind design&#44; placebo group&#44; and 12-month follow-up&#44; do not appreciate the superiority of <span class="elsevierStyleItalic">Serenoa repens</span> versus placebo in the American Association of Urology Symptom Index &#40;AUASI&#41; score&#44; urinary flow&#44; prostate volume&#44; postvoid residue&#44; quality of life&#44; or PSA&#46; However&#44; Shi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; in their study&#44; methodologically similar but with shorter follow-up period &#40;12 weeks&#41;&#44; do obtain improvement in the <span class="elsevierStyleItalic">Q</span><span class="elsevierStyleInf">max</span>&#44; but not in other parameters&#44; such as the IPSS between the groups&#46; Studies with similar designs but in the longer term &#40;3 years&#41;&#44; such as the one by Djavan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; do show an improvement in the IPSS scores&#44; quality of life&#44; and urinary flow&#46; However&#44; this study did not have a placebo group&#44; but it compared <span class="elsevierStyleItalic">Serenoa repens</span> versus watchful waiting&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The PERMAL study compared <span class="elsevierStyleItalic">Serenoa repens</span> versus tamsulosin in patients with moderate and severe BPH symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> This study&#44; on 811 patients and with a follow-up of 12 months&#44; did not obtain differences in terms of IPSS or <span class="elsevierStyleItalic">Q</span><span class="elsevierStyleInf">max</span> improvement between tamsulosin and <span class="elsevierStyleItalic">Serenoa repens</span> in patients with IPSS greater than 10 &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; In a subanalysis of the PERMAL study&#44; the same authors found no statistically significant differences between both treatments in patients with severe symptoms &#40;IPSS greater than 19&#41;&#44; treatment with <span class="elsevierStyleItalic">Serenoa repens</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> being economically more profitable&#46; Among the limitations of this study&#44; and of its sub-analysis&#44; we can highlight not including a calculation of sample size&#44; so the statistical power and the lack of placebo group cannot be assessed&#46; There were no differences either with respect to placebo in patients with moderate to severe BPH &#40;IPSS &#8805;8&#41; in a double-blind study with random distribution conducted by Gerber et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">A recently published study where <span class="elsevierStyleItalic">Serenoa repens</span> was administered for 2 months prior to BPH surgery showed shorter surgical time&#44; fewer complications&#44; shorter hospital stay&#44; and shorter length of urethral catheterization&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> These results were contradictory with regard to those published by Tuncel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> in a similar study&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pygeum africanum</span> presents a mechanism of action that has not yet been clarified&#44; although it seems that the prostate cells of BPH patients are more sensitive to the antiproliferative and apoptotic action of <span class="elsevierStyleItalic">Pygeum africanum</span> than the cells of patients without BPH&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In a meta-analysis<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> we observed how the patients who received the compound had improvement in the symptoms compared to placebo&#46; However&#44; the follow-up time is barely over 2 months&#44; and the sample size is small&#46; Furthermore&#44; the selection criteria are somewhat lax as studies in which the treatment arm allows for treatment with <span class="elsevierStyleItalic">Pygeum africanum</span> alone or in combination with other compounds are included&#44; so that the real efficiency of the product could be masked&#46; Furthermore&#44; in some of these studies&#44; the methods of evaluating results do not have validated questionnaires&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Madersbacher et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> assess the long-term results of medical therapy on the BPH&#46; In this review&#44; we observe that the published studies have failed to demonstrate either greater efficacy over placebo or other compounds or the impact on the natural history of the disease&#46; Hutchison et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> study the effect of the various therapies for BPH so that&#44; after treatment with phytotherapy&#44; improvements in the IPSS were obtained in 73&#37; of the patients &#40;&#62;4 points in 42&#37;&#41;&#46; Unfortunately&#44; this study had no placebo control arm&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In short&#44; most of the recognized clinical guidelines coincide in not recommending treatment with phytotherapy for BPH&#44; despite the large number of studies and meta-analyses published&#44; mainly on <span class="elsevierStyleItalic">Serenoa repens</span>&#44; due to the lack of consistency and the methodological weaknesses&#44; and because of the absence of an extended follow-up&#46; Recent papers leave the door open to treatment with phytotherapy&#44; although new studies&#44; better designed and in the longer term&#44; are underway to elucidate the question&#46; In spite of that&#44; as described by Djavan<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44; phytotherapy is the treatment of choice for 16&#37; of patients in Europe&#44; with differences between countries&#44; from 25&#37; in Germany to 7&#37; in Spain&#46; Its use is based&#44; primarily&#44; on the safety of its use and the results related to the placebo effect&#46; In our country&#44; a decrease in the use of phytotherapy has been shown&#44; given the data from the study by Unda et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> since in 1999&#44; 21&#37; of the patients received treatment with phytotherapy compared to less than 10&#37; today&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Prostate cancer</span><p id="par0070" class="elsevierStylePara elsevierViewall">The plant extracts with an effect on prostate cancer are red wine&#44; green tea&#44; and soy&#46; The idea of studying these compounds was based on the differences in the prevalence of prostate cancer according to geographical areas that for high-grade prostate cancer in Asian countries &#8211; with a high rate of intake of soy and green tea &#8211; are clearly inferior&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Green tea &#40;<span class="elsevierStyleItalic">Camellia sinensis</span>&#41; is the second most consumed beverage in the world&#44; its main component being epigallocatenin-3-gallate&#46; One of its antitumor mechanisms is its synergistic action with drugs that inhibit the COX-2<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> enzyme&#44; as it occurs with soy&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We studied patients diagnosed with high-grade PIN&#44; randomly allocated to receive 600<span class="elsevierStyleHsp" style=""></span>mg&#47;day of green tea polyphenols versus placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> After a year of follow-up&#44; only 3&#37; of the patients who received green tea were diagnosed with cancer compared to 30&#37; in the placebo group&#46; The problem is that the amount needed to produce this effect is close to 20 cups of tea a day&#46; Conversely&#44; Kikuchi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> found no benefit with respect to the incidence of prostate cancer in general&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">A new target is MCM7&#44; a gene that seems to be involved in the growth and invasion by prostate tumor cells&#44; given that it is part of the complex of genes that allow for cell replication&#46; The green tea catenins are capable of inhibiting its expression and&#44; therefore&#44; they could alter the behavior of the tumor&#44; although this has only been shown in in vitro studies&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Red wine has an anti-tumor effect &#40;antioxidant&#44; immunomodulatory&#44; anti-androgenic&#44; anti-inflammatory&#44; and inhibitor of angiogenesis&#41; thanks mainly to resveratrol&#46; This polyphenol is specifically found in red wine and not in other alcoholic beverages&#46; In fact&#44; a prospective study showed an association between moderate alcohol consumption from other spirits and the onset of prostate cancer&#44; but with beer and red wine&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Moreover&#44; this compound is capable&#44; in cell lines&#44; of increasing apoptosis in tumor cells by activating caspases 3 and 9&#44; so that some studies support its therapeutic use&#44; and not only as a preventive measure&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> It has been described how resveratrol is capable of inhibiting the production of PSA&#44; of kallikrein-2&#44; of the specific coactivator of the androgenic receptors &#40;ARA70&#41; and many other compounds involved in carcinogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Despite all this&#44; its relation to the incidence of prostate cancer remains controversial&#46; Thus&#44; in a paper by Velicer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> a greater risk of prostate cancer was observed in patients who drank more than one glass of alcohol a day&#44; with the exception of red wine&#46; Other studies&#44; however&#44; found no evidence of association<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and others get an increase in the incidence of prostate cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Piceatannol&#44; another compound of red wine&#44; has proved&#44; in vitro&#44; to increase the apoptosis of neoplastic cells&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Along with the latter&#44; other elements that have been studied contained in red wine are gallic acid&#44; quercetin&#44; rutin&#44; morin&#44; and tannic acid&#44; demonstrating its efficacy at the level of cultures of tumor cell lines&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Another phytoterapic product containing isoflavones is red clover&#46; This compound has shown to reduce the PSA by more than 30&#37;&#44; although the studies that support it do not have an optimal methodological design&#46; In an observational study&#44; the apoptosis of tumor cells increased in tumors of low and intermediate risk&#44; not of high risk<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46; Studies like that by Gray et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> recently published&#44; found that&#44; in cell cultures&#44; the genistein and daidzein that red clover contains are able to modify the microenvironment in which prostate cancer is developed inhibiting the function of TGF&#946;-1 &#40;enhancer of the effect of dehydroepiandrosterone&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The last of the compounds studied in this section is soy that&#44; containing genistein and daidzein&#44; has a weak estrogenic effect at the cellular level&#44; although the overall effect of soy is greater than the isolated effect of isoflavones contained therein&#46; These compounds have anti-angiogenic&#44; cytotoxic&#44; inhibitor of proliferation and tumor invasion&#44; induction of apoptosis&#44; and COX-2 inhibition&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Kumar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> conducted a prospective&#44; randomized&#44; double-blind&#44; and controlled analysis versus watchful waiting&#46; It showed a trend to lower levels of PSA and testosterone in the group of patients who received treatment with soy&#46; However&#44; neither in this study nor in others<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> was there a statistically significant benefit of PSA reduction in patients with prostate cancer and treatment with soy derivatives&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nevertheless&#44; an inverse relation between localized prostate cancer and soy intake has been shown&#46; This can be explained because one of the effect pathways of soy is on the &#40;-estrogen receptor&#44; which is present in cancers with low metastatic potential but which is partially or entirely absent in those that have great potential to spread&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Another route of action has been postulated by which genistein would inhibit the HDAC6-Hsp90 protein&#44; which is the one that stabilizes and allows for the function of the androgenic receptors&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">As for the type of soy consumed&#44; in a recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> on 24 papers&#44; it was shown that in its fermented forms such as tofu or soy milk&#44; it was more beneficial than those non-fermented products&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Another application described is in patients with biochemical relapse after treatment with surgery or radiotherapy for a localized prostate adenocarcinoma&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> showing a delay in the rise of the PSA curve&#46; Moreover&#44; the radiosensitizer role of soy has been demonstrated for the patients who are going to receive prostate radiotherapy&#44; which results in an increased rate of cell death from radiation&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the main compounds and their mechanism of action&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In summary&#44; all the products evaluated in this section have shown in vitro and on tumor cell lines&#44; their anticarcinogenic application&#46; We studied multiple therapeutic targets and there are applications for the phytotherapic products in different and complicated pathways or cascades of cellular reactions&#46; However&#44; clinical trials to support their use are not as abundant&#46; Those found in the literature are mostly retrospective reviews or&#44; in the case of being prospective&#44; they have a small sample size or reach conclusions opposing each other&#46; Therefore&#44; more studies are needed and&#44; so far&#44; we cannot recommend these therapies as prevention and&#44; even less&#44; as a treatment for a disease as prevalent as prostate cancer&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">Studies on phytotherapy in BPH have shown in some cases subjective &#40;IPSS&#41; and objective &#40;<span class="elsevierStyleItalic">Q</span><span class="elsevierStyleInf">max</span>&#41; improvement&#44; although the studies are short-term&#44; with few patients or incorrect methodological designs&#46; There is no evidence for the recommendation of phytotherapy in the PAC&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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            0 => "Resumen"
            1 => "Objetivo"
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          "titulo" => "Benign prostatic hyperplasia"
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          "titulo" => "Prostate cancer"
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    "fechaRecibido" => "2012-04-04"
    "fechaAceptado" => "2012-07-28"
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            0 => "Phytotherapy"
            1 => "Benign prostate hyperplasia"
            2 => "Prostatic adenocarcinoma"
          ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec179296"
          "palabras" => array:3 [
            0 => "Fitoterapia"
            1 => "Hiperplasia benigna de pr&#243;stata"
            2 => "Adenocarcinoma prost&#225;tico"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the usefulness of phytotherapy in the treatment of the benign prostatic hyperplasia &#40;BPH&#41; and prostatic adenocarcinoma &#40;ADCP&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Acquisition of evidence</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Systematic review of the evidence published until January 2011 using the following scientific terms&#58; phytotherapy&#44; benign prostate hyperplasia&#44; prostatic adenocarcinoma&#44; prostate cancer and the scientific names of compounds following the rules of the International Code of Botanical Nomenclature&#46; The databases used were Medline and The Cochrane Library&#46; We included articles published until January 2011 written in English and Spanish&#46; We included studies in vitro&#47;in vivo on animal models or human beings&#46; Exclusion criteria were literature not in English and Spanish or articles with serious methodological flaws&#46;</p> <span class="elsevierStyleSectionTitle">Synthesis of the evidence</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 65 articles of which 40 met the inclusion criteria&#46; <span class="elsevierStyleItalic">BPH</span>&#58; the most studied products are serenoa repens and pygeum africanum&#46; There are many studies in favor of the use of phytotherapy but its conclusions are inconsistent due to the small number of patients&#44; the lack of control with placebo or short follow-up&#46; However&#44; the use of these products is common in our environment&#46; <span class="elsevierStyleItalic">ADCP</span>&#58; there is no evidence to recommend phytotherapy in the treatment of the ADCP&#46; There are works on prevention but only at experimental level so there is no evidence for its recommendation&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The scientific evidence on the use of phytotherapy in prostatic pathology is conclusive not recommending the use of it for BPH or the ADCP&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la utilidad de la fitoterapia en el tratamiento de la hiperplasia benigna de pr&#243;stata &#40;HBP&#41; y el adenocarcinoma prost&#225;tico &#40;ADCP&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Adquisici&#243;n de la evidencia</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una revisi&#243;n sistem&#225;tica de la evidencia publicada hasta enero del 2011&#44; empleando los t&#233;rminos cient&#237;ficos fitoterapia&#44; hiperplasia benigna de pr&#243;stata&#44; adenocarcinoma prost&#225;tico&#44; c&#225;ncer de pr&#243;stata&#44; y los nombres cient&#237;ficos de los compuestos siguiendo las normas del C&#243;digo Internacional de Nomenclatura Bot&#225;nica&#46; Las bases de datos utilizadas fueron Medline y The Cochrane Library&#46; Se incluyeron art&#237;culos publicados hasta enero del 2011&#44; escritos en espa&#241;ol e ingl&#233;s&#46; Se incluyeron estudios in vitro&#47;in vivo sobre modelos animales o seres humanos&#46; Los criterios de exclusi&#243;n fueron literatura no espa&#241;ola&#47;inglesa o art&#237;culos con graves defectos metodol&#243;gicos&#46;</p> <span class="elsevierStyleSectionTitle">S&#237;ntesis de la evidencia</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 65 art&#237;culos&#44; de los cuales se seleccionaron 40 que cumplieron los criterios de inclusi&#243;n&#46; <span class="elsevierStyleItalic">HBP&#58;</span> los productos m&#225;s estudiados son la <span class="elsevierStyleItalic">Serenoa repens</span> y <span class="elsevierStyleItalic">Pygeum africanum</span>&#46; Existen muchos estudios a favor del empleo de la fitoterapia&#59; no obstante&#44; sus conclusiones son poco consistentes debido al escaso n&#250;mero de pacientes&#44; la falta de control con placebo o el escaso seguimiento&#46; A pesar de ello el empleo de estos productos es habitual en nuestro medio&#46; <span class="elsevierStyleItalic">ADCP&#58;</span> no existe evidencia para recomendar la fitoterapia en el tratamiento del ADCP&#46; Existen trabajos respecto de la prevenci&#243;n&#44; aunque &#250;nicamente a nivel experimental&#44; por lo que tampoco existe evidencia para su recomendaci&#243;n&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La evidencia cient&#237;fica acerca del empleo de la fitoterapia en la afecci&#243;n prost&#225;tica es concluyente a la hora de no recomendarla en el empleo de la HBP o el ADCP&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Mor&#225;n E&#44; et al&#46; Fitoterapia en Urolog&#237;a&#46; Evidencia cient&#237;fica actual de su aplicaci&#243;n en hiperplasia benigna de pr&#243;stata y adenocarcinoma de pr&#243;stata&#46; Actas Urol Esp&#46; 2013&#59;37&#58;114&#8211;9&#46;</p>"
      ]
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Results PERMAL study&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Name&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Green tea &#40;<span class="elsevierStyleItalic">Camellia sinensis</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Epigallocatenin-3-gallate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Anti-inflamatoryMCM7 inhibition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Red wine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ResveratrolPiceatannol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Angiogenesis inhibitionIncreasing cellular apoptosisCaspase activationIncreasing cellular apoptosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Red clover&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">GenisteinDaidzein&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">TGF&#946;-1 inhibition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">Soy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Isoflavones&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">AntiangiogenicCytotoxicHDAC6-Hsp90 inhibition&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Phytotherapeutic products in prostate cancer&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:40 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Criterios de referencia de la HBP en antenci&#243;n primaria&#46; Sociedad Espa&#241;ola de M&#233;dicos de Atenci&#243;n Primaria&#44; Sociedad Espa&#241;ola de Medicina General&#44; Sociedad Espa&#241;ola de Medicina de Familia y Comunitaria&#44; Asociaci&#243;n Espa&#241;ola de Urolog&#237;a"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Casti&#241;eiras Fern&#225;ndez"
                            1 => "J&#46;M&#46; Cozar Olmo"
                            2 => "A&#46; Fern&#225;ndez-Pro"
                            3 => "J&#46;A&#46; Mart&#237;n"
                            4 => "F&#46;J&#46; Brenes Berm&#250;dez"
                            5 => "E&#46; Naval Pulido"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Urol Esp"
                        "fecha" => "2010"
                        "volumen" => "34"
                        "paginaInicial" => "24"
                        "paginaFinal" => "34"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20223130"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "BPH and inflammation&#58; pharmacological effects of Permixon on histological and molecular inflammatory markers&#46; Results of a double blind pilot clinical assay"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Vela Navarrete"
                            1 => "J&#46;V&#46; Garcia Cardoso"
                            2 => "A&#46; Barat"
                            3 => "F&#46; Manzarbeitia"
                            4 => "A&#46; L&#243;pez Farr&#233;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol"
                        "fecha" => "2003"
                        "volumen" => "44"
                        "paginaInicial" => "549"
                        "paginaFinal" => "555"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14572753"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Potency of a novel saw palmetto ethanol extract&#44; SPET-085&#44; for inhibition of 5alpha-reductase II"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46; Pais"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Adv Ther"
                        "fecha" => "2010"
                        "volumen" => "8"
                        "paginaInicial" => "555"
                        "paginaFinal" => "563"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Saw palmetto for benign prostatic hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Bent"
                            1 => "C&#46; Kane"
                            2 => "K&#46; Shinohara"
                            3 => "J&#46; Neuhaus"
                            4 => "E&#46;S&#46; Hudes"
                            5 => "H&#46; Goldberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa053085"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "557"
                        "paginaFinal" => "566"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16467543"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of saw palmetto soft gel capsule on lower urinary tract symptoms associated with benign prostatic hyperplasia&#58; a randomized trial in Shanghai&#44; China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Shi"
                            1 => "Q&#46; Xie"
                            2 => "X&#46; Gang"
                            3 => "J&#46; Lun"
                            4 => "L&#46; Cheng"
                            5 => "A&#46; Pantuck"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.juro.2007.09.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Urol"
                        "fecha" => "2008"
                        "volumen" => "179"
                        "paginaInicial" => "610"
                        "paginaFinal" => "615"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18082217"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Progression delay in men with mild symptoms of bladder outlet obstruction&#58; a comparative study of phytotherapy and watchful waiting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46; Djavan"
                            1 => "Y&#46;K&#46; Fong"
                            2 => "A&#46; Chaudry"
                            3 => "A&#46; Reissigl"
                            4 => "T&#46; Anagnostou"
                            5 => "F&#46; Bagheri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00345-005-0005-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Urol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "253"
                        "paginaFinal" => "256"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16175413"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of a phytotherapeutic agent &#40;Permixon&#41; with an alpha-blocker &#40;Tamsulosin&#41; in the treatment of benign prostatic hyperplasia&#58; a 1-year randomized international study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Debruyne"
                            1 => "G&#46; Koch"
                            2 => "P&#46; Boyle"
                            3 => "F&#46;C&#46; Da Silva"
                            4 => "J&#46;G&#46; Gillenwater"
                            5 => "F&#46;C&#46; Hamdy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol"
                        "fecha" => "2002"
                        "volumen" => "41"
                        "paginaInicial" => "497"
                        "paginaFinal" => "506"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12074791"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of the clinical benefit of permixon and tamsulosin in severe BPH patients-PERMAL study subset analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Debruyne"
                            1 => "P&#46; Boyle"
                            2 => "F&#46; Calais Da Silva"
                            3 => "J&#46;G&#46; Gillenwater"
                            4 => "F&#46;C&#46; Hamdy"
                            5 => "P&#46; Perrin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.eururo.2004.01.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol"
                        "fecha" => "2004"
                        "volumen" => "45"
                        "paginaInicial" => "773"
                        "paginaFinal" => "779"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15149751"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
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Article information

ISSN: 21735786
Original language: English

DOI:10.1016/j.acuroe.2012.07.014

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Year/Month	Html	Pdf	Total

2018 February	133	2	135
2018 January	20	5	25
2017 December	155	1	156
2017 November	19	3	22
2017 October	15	4	19
2017 September	18	1	19
2017 August	23	0	23
2017 July	24	2	26
2017 June	40	6	46
2017 May	22	12	34
2017 April	23	0	23
2017 March	24	37	61
2017 February	22	3	25
2017 January	21	3	24
2016 December	16	4	20
2016 November	26	7	33
2016 October	28	8	36
2016 September	28	12	40
2016 August	16	3	19
2016 July	16	1	17
2016 June	15	9	24
2016 May	20	11	31
2016 April	22	19	41
2016 March	25	11	36
2016 February	27	14	41
2016 January	32	8	40
2015 December	23	8	31
2015 November	23	5	28
2015 October	25	7	32
2015 September	24	7	31
2015 August	22	5	27
2015 July	13	5	18
2015 June	16	2	18
2015 May	16	3	19
2015 April	27	9	36
2015 March	18	3	21
2015 February	18	2	20
2014 July	1	0	1
2014 May	3	1	4
2014 January	3	1	4
2013 December	12	4	16
2013 November	13	5	18
2013 October	27	10	37
2013 September	14	7	21
2013 July	0	1	1

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