phytoestrogens profile

Phytoestrogens: Compounds derived from plants, primarily ISOFLAVONES that mimic or modulate endogenous estrogens, usually by binding to ESTROGEN RECEPTORS. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	56842207
MeSH ID	M0068568

Synonym
phytoestrogens
D048789000

Excerpt	Reference	Relevance
"Phytoestrogens are a large family of plant-derived molecules possessing various degrees of estrogen-like activity; they exhibit agonist or antagonist estrogenic properties depending on the tissue."	( Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress. Li, N; Liu, T; Liu, Y; Liu, ZD; Xia, QM; Xiong, K; Yan, YQ; Zhang, H, 2020)	1.54
"Phytoestrogens are a class of plant produced polyphenolic compounds with diphenolic structure, which is similar to 17β-estradiol. "	( Biotransformation of dietary phytoestrogens by gut microbes: A review on bidirectional interaction between phytoestrogen metabolism and gut microbiota. Liu, W; Meng, X; Rawat, PS; Seyed Hameed, AS, 2020)	2.29
"Phytoestrogens are an important class of compounds which have known estrogenic potential; studies have also indicated the anticancer potentials of these molecules in cell culture and animal models of BC."	( Natural Bioactive Compounds as Emerging Therapeutic Molecules Against Breast Cancer: Emphasis on the Role of Phytoestrogens. Malayil, AS; Narayanankutty, A; Poothaadammal, AK, 2021)	1.56
"Phytoestrogens are a group of non-steroidal polyphenolic plant-based substances, commonly used for the treatment of menopause-related conditions. "	( The effects of phytoestrogens on postmenopausal health. Baber, RJ; Rowe, IJ, 2021)	2.42
"Phytoestrogens are a group of plant-derived compounds that have been studied in the case of metabolic disorders treatment."	( The effect of enterolactone on sphingolipid pathway and hepatic insulin resistance development in HepG2 cells. Berk, K; Chabowski, A; Charytoniuk, T; Drygalski, K; Iłowska, N; Konstantynowicz-Nowicka, K, 2019)	1.24
"Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. "	( Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro. Briese, V; Friese, K; Jeschke, U; Mylonas, I; Richter, DU; Scholz, C; Toth, B, 2009)	2.19
"Phytoestrogens are a class of endocrine disruptors found in plants."	( Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats. Ball, ER; Burr, MJ; Caniglia, MK; Overton, KA; Sanders, BJ; Wilcox, JL; Wisniewski, AB; Wolfe, BD; Wrenn, CC, 2010)	1.08
"Phytoestrogens are a group of non-steroidal compounds of plant origin that present structural and functional similarities with estradiol. "	( Phytotherapy as alternative to hormone replacement therapy. Hidalgo-Mora, JJ; Molla, MD; Soteras, MG, 2011)	1.81
"Phytoestrogens are a class of bioactive compounds derived from plants and exert various estrogenic and antiestrogenic effects. "	( Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Chiang, SS; Pan, TM, 2013)	2.15
"Phytoestrogens are a diverse class of non-steroidal compounds that have an affinity for estrogen receptors α and β, for the peroxisome proliferator-activated receptor (PPAR) family and for the aryl hydrocarbon receptor. "	( Phytoestrogens and the metabolic syndrome. Jungbauer, A; Medjakovic, S, 2014)	3.29
"Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. "	( Effects of phytoestrogens on the trophoblast tumour cell lines BeWo and Jeg3. Briese, V; Bruer, G; Friese, K; Jeschke, U; Plessow, D; Richter, DU; Waldschläger, J, )	1.96
"Phytoestrogens are a group of compounds present in human diet that display estrogenic-like properties. "	( Identification and characterization of a phytoestrogen-specific gene from the MCF-7 human breast cancer cell. Gray, WG; Ramanathan, L, 2003)	1.76
"Phytoestrogens are a diverse group of plant-derived compounds that structurally or functionally mimic mammalian estrogens and show potential benefits for human health. "	( Phytoestrogens: a review of the present state of research. Kennelly, EJ; Ososki, AL, 2003)	3.2
"Phytoestrogens are a group of plant-derived substances that are structurally or functionally similar to estradiol. "	( Phytoestrogens: potential benefits and implications for breast cancer survivors. Cyr, M; Duffy, C, 2003)	3.2
"Phytoestrogens are a family of plant-derived compounds with weak estrogenic and antiestrogenic properties. "	( Phytoestrogens possess a weak antioxidant activity on low density lipoprotein in contrast to the flavonoid quercetin in vitro in postmenopausal women. Arteaga, E; Bianchi, M; Marshall, G; Rojas, A; Villaseca, P, 2004)	3.21
"Phytoestrogens appear to be an effective treatment during perimenopause where symptoms, such as hot flashes are reduced."	( Effects of dietary phytoestrogens on core body temperature during the estrous cycle and pregnancy. Bu, LH; Lephart, ED, 2005)	1.38
"Phytoestrogens are a diverse group of non-steroidal compounds that occur naturally in many plants. "	( Effects of phytoestrogens genistein and daidzein on production of human chorionic gonadotropin in term trophoblast cells in vitro. Briese, V; Bruer, G; Friese, K; Jeschke, U; Mylonas, I; Plessow, D; Richter, DU; Waldschläger, J, 2005)	2.16
"Phytoestrogens are a diverse group of non-steroidal plant compounds. "	( Effects of phytoestrogen extracts isolated from rye, green and yellow pea seeds on hormone production and proliferation of trophoblast tumor cells Jeg3. Abarzua, S; Briese, V; Effmert, U; Hartmann, AM; Jeschke, U; Kragl, U; Kupka, MS; Matscheski, A; Piechulla, B; Richter, DU; Ruth, W, 2006)	1.78
"Phytoestrogens are a group of plant-derived biologically active substances with a chemical structure that resembles that of 17beta-estradiol (E2). "	( In vitro effects of genistein and resveratrol on the production of interferon-gamma (IFNgamma) and interleukin-10 (IL-10) by stimulated murine splenocytes. Rachoń, D; Rimoldi, G; Wuttke, W, 2006)	1.78
"Phytoestrogens are a wide variety of chemical compounds, mainly isoflavonoids, from a vegetable source. "	( Gonadotrophin levels and morphological testicular features in rats after different doses of the phytoestrogen coumestrol. Diaz-Sánchez, V; García-Lorenzana, CM; Tarragó-Castellanos, CR; Velázquez-Moctezuma, J, 2006)	1.78
"Phytoestrogens are a diverse group of plant-derived compounds structurally or functionally mimicking mammalian oestrogens. "	( How isoflavone levels in common rodent diets can interfere with the value of animal models and with experimental results. Jensen, MN; Ritskes-Hoitinga, M, 2007)	1.78
"Phytoestrogens are a diverse group of plant-derived compounds that structurally or functionally mimic mammalian estrogens and show potential benefits for human health. "	( Molecular aspects of phytoestrogen selective binding at estrogen receptors. Agatonovic-Kustrin, S; Glass, BD; Turner, JV, 2007)	1.78
"Phytoestrogens are a diverse group of nonsteroidal plant compounds which have similar effects to endogenous estrogens in humans and have been ascribed potential anticarcinogenic activities. "	( Effects of phytoestrogen extracts from Linum usitatissimum on the Jeg3 human trophoblast tumour cell line. Abarzua, S; Briese, V; Gailus, S; Piechulla, B; Richter, DU; Ruth, W; Szewczyk, M, )	1.57
"Soy phytoestrogens, isoflavones, are a primary class of plant-based estrogen alternatives being sold over the counter nowadays. "	( Comparison of the estrogenic potencies of standardized soy extracts by immature rat uterotrophic bioassay. Campos, LM; de Lima Toccafondo Vieira, M; Duarte, RF; Nunan, Ede A, 2008)	0.9
"Phytoestrogens are a group of plant-derived substances that are structurally or functionally similar to estradiol. "	( Implications of phytoestrogen intake for breast cancer. Duffy, C; Partridge, A; Perez, K, )	1.57
"Phytoestrogens are a group of polyphenolic plant metabolites that can induce biological responses. "	( Extraction and quantification of phytoestrogens in foods using automated solid-phase extraction and LC/MS/MS. Bingham, SA; Dell'aquila, C; Kuhnle, GG; Kussmaul, M; Low, YL, 2007)	2.06
"Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. "	( Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study. Bingham, S; Chapelais, G; Khaw, KT; Kuhnle, GG; Luben, R; Ward, H, 2008)	1.79
"Phytoestrogens are a group of naturally occurring diphenolic compounds present in legumes, whole grains, fruits, and vegetables. "	( Induction of NADPH:quinone reductase by dietary phytoestrogens in colonic Colo205 cells. Chen, H; Higuchi, CM; Liu, LQ; Wang, W, 1998)	2
"Phytoestrogens are a normal constituent of soy protein and have been shown to have anti-inflammatory activity in various in vitro and in vivo models. "	( Dietary phytoestrogens have anti-inflammatory activity in a guinea pig model of asthma. Fraser, DG; Greenberg, NA; Regal, JF; Weeks, CE, 2000)	2.18
"Phytoestrogens are a chemically diverse group of compounds made by plants that can have estrogenic effects in animals. "	( Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Andò, S; Bonofiglio, D; Cenni, B; Maggiolini, M; Marsico, S; Panno, ML; Picard, D, 2001)	1.97

Excerpt	Reference	Relevance
"Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. "	( Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial. Ahlin, R; Hedelin, M; Josefsson, A; Landberg, R; Nybacka, S; Nørskov, NP; Skokic, V; Steineck, G; Stranne, J, 2023)	2.35
"Phytoestrogens have been proposed as a natural therapy for prevention of bone loss. "	( The isoflavone genistein enhances osteoblastogenesis: signaling pathways involved. Cepeda, SB; Crescitelli, MC; Massheimer, VL; Rauschemberger, MB; Sandoval, MJ, 2020)	2
"Phytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. "	( In vitro estrogenic, cytotoxic, and genotoxic profiles of the xenoestrogens 8-prenylnaringenine, genistein and tartrazine. Nasri, A; Pohjanvirta, R, 2021)	2.06
"Phytoestrogens have been investigated for their potential anti-tumorigenic effects in various cancers including breast cancer. "	( Identification of Potential Therapeutic Genes and Pathways in Phytoestrogen Emodin Treated Breast Cancer Cell Lines via Network Biology Approaches. Guray, NT; Sakalli-Tecim, E; Uyar-Arpaci, P, 2022)	2.16
"Phytoestrogens have been identified as a natural, plant-based alternative to synthetically derived estrogens, to supplement the absence of endogenous estrogens in post-menopausal women, and attenuate the progression of pathologies and side-effects associated with menopause. "	( The controversy on the beneficial effect of phytoestrogens in diabetic treatment in postmenopausal women. Romani, AMP, 2021)	2.33
"Phytoestrogens have been found to delay signs of skin aging in post-menopausal women, in a way similar to the effects of estrogens. "	( Development and evaluation of topical films containing phytoestrogenic diaryheptanoids from Curcuma comosa extract. Jaipakdee, N; Limpongsa, E; Sripanidkulchai, B; Tuntiyasawasdikul, S, 2018)	1.92
"Phytoestrogens have shown estrogenic effects, which may involve in the etiology of MetS."	( The associations between plasma phytoestrogens concentration and metabolic syndrome risks in Chinese population. Du, L; Gao, Y; Jia, K; Li, P; Li, X; Liu, J; Mi, S; Zhang, H; Zhao, J; Zhao, W, 2018)	1.49
"Phytoestrogens have been shown to be neuroprotective in neurotoxicity models; however, their effect on microglia has not been well established."	( Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia. Jantaratnotai, N; Sanvarinda, P; Sanvarinda, Y; Thampithak, A; Utaisincharoen, P, 2013)	2.55
"Phytoestrogens have been shown to exert anti-proliferative effects on different cancer cells. "	( Phytoestrogens regulate the proliferation and expression of stem cell factors in cell lines of malignant testicular germ cell tumors. Hasibeder, A; Radzun, HJ; Schweyer, S; Thelen, P; Venkataramani, V, 2013)	3.28
"Phytoestrogens have been implicated in the prevention of bone loss in postmenopausal osteoporosis. "	( Bone sparing effect of a novel phytoestrogen diarylheptanoid from Curcuma comosa Roxb. in ovariectomized rats. Chairoungdua, A; Chuncharunee, A; Piyachaturawat, P; Suksamrarn, A; Tantikanlayaporn, D; Weerachayaphorn, J; Wichit, P, 2013)	1.83
"Phytoestrogens have been associated with subtle hormonal changes, although effects on fecundity are unknown. "	( Higher urinary lignan concentrations in women but not men are positively associated with shorter time to pregnancy. Barr, DB; Louis, GM; Maisog, JM; Mumford, SL; Parker, DL; Pfeiffer, CM; Rybak, ME; Schisterman, EF; Sundaram, R; Sweeney, AM, 2014)	1.85
"Phytoestrogens have been investigated as natural alternatives to hormone replacement therapy and their potential as chemopreventive agents. "	( Breast cancer cell apoptosis with phytoestrogens is dependent on an estrogen-deprived state. Fan, P; Jordan, VC; Obiorah, IE, 2014)	2.12
"Phytoestrogens have been suggested as alternative treatment for postmenopausal osteoporosis. "	( Equol promotes rat osteoblast proliferation and differentiation through activating estrogen receptor. Chen, K; Mi, MT; Shu, FR; Wang, B; Wang, J; Xu, J, 2014)	1.85
"Phytoestrogens have been applied for compensation of hormone deficiency in the menopause."	( Soy and phytoestrogens: possible side effects. Jargin, SV, 2014)	1.56
"Phytoestrogens have been associated with subtle hormonal changes, although effects on male fecundity are largely unknown."	( Urinary Phytoestrogens Are Associated with Subtle Indicators of Semen Quality among Male Partners of Couples Desiring Pregnancy. Boyd Barr, D; Buck Louis, GM; Chen, Z; Kim, S; Mumford, SL, 2015)	2.29
"Phytoestrogens have been associated with subtle hormonal changes, but their effects on endometriosis are largely unknown."	( Urinary Phytoestrogen Concentrations Are Not Associated with Incident Endometriosis in Premenopausal Women. Buck Louis, GM; Kannan, K; Mumford, SL; Weck, J, 2017)	1.9
"Phytoestrogens have been shown to ameliorate various menopausal symptoms."	( The phytoestrogens daidzein and genistein enhance the insulin-stimulated sulfate uptake in articular chondrocytes. Briese, V; Claassen, H; Kurz, B; Manapov, F; Nebe, B; Schünke, M, 2008)	1.63
"Phytoestrogens have been shown to exert anti-estrogenic and estrogenic effects in some tissues, including the breast. "	( Phytoestrogen consumption and endometrial cancer risk: a population-based case-control study in New Jersey. Bandera, EV; Bayuga, S; Olson, SH; Pulick, K; Sima, C; Soslow, R; Wilcox, H; Williams, MG; Zauber, AG, 2009)	1.8
"Phytoestrogens have been promoted as healthy alternatives to synthetic estrogens and are found in many dietary supplements."	( Reproductive consequences of developmental phytoestrogen exposure. Jefferson, WN; Patisaul, HB; Williams, CJ, 2012)	1.1
"Phytoestrogens have been implicated as promising therapeutic agents to treat the vascular impairment seen in menopausal women. "	( Long-term effect of phytoestrogens from Curcuma comosa Roxb. on vascular relaxation in ovariectomized rats. Chokchaisiri, R; Chuncharunee, A; Intapad, S; Piyachaturawat, P; Prasannarong, M; Saengsirisuwan, V; Suksamrarn, A; Suvitayawat, W, 2012)	2.15
"Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake."	( Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women. Bots, ML; Grobbee, DE; Lamberts, SW; Lebrun, CE; Peeters, PH; Pijpe, A; van der Schouw, YT; van Staveren, WA, 2002)	2.04
"Phytoestrogens have been shown to inhibit platelet activation by blocking platelet calcium channels. "	( Dietary phytoestrogens and their synthetic structural analogues as calcium channel blockers in human platelets. Blackmore, PF; Dobrydneva, Y; Morris, GZ; Williams, RL, 2002)	2.19
"Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. "	( Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Grobbee, DE; Keinan-Boker, L; Kreijkamp-Kaspers, S; Peeters, PH; Rimm, EB; van der Schouw, YT, 2005)	1.77
"Phytoestrogens have been described to be weak estrogens, SERMs or exhibit antiestrogenic properties. "	( Combinatory effects of phytoestrogens and 17beta-estradiol on proliferation and apoptosis in MCF-7 breast cancer cells. Diel, P; Michna, H; Schmidt, S, 2005)	2.08
"Phytoestrogens have been suggested to reduce the risk of prostate cancer (CaP), but no data exists on how oral phytoestrogen supplementation influences phytoestrogen concentrations in prostate tissue."	( Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation. Adlercreutz, H; Petas, A; Rannikko, A; Rannikko, S, 2006)	1.78
"Phytoestrogens have been hypothesized to protect against prostate cancer via modulation of circulating androgen concentrations. "	( Polymorphisms in the CYP19 gene may affect the positive correlations between serum and urine phytoestrogen metabolites and plasma androgen concentrations in men. Bingham, SA; Day, NE; Doody, D; Dowsett, M; Dunning, AM; Folkerd, E; Grace, PB; Khaw, KT; Low, YL; Luben, RN; Mulligan, AA; Scollen, S; Taylor, JI; Wareham, NJ; Welch, AA, 2005)	1.77
"Phytoestrogens have been described as weak estrogens, selective estrogen receptor mediators (SERMs) or to exhibit antiestrogenic properties. "	( Hormonal activity of combinations of genistein, bisphenol A and 17beta-estradiol in the female Wistar rat. Degen, GH; Diel, P; Hertrampf, T; Schmidt, S; Seibel, J; Vollmer, G, 2006)	1.78
"Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. "	( A high soy diet reduces programmed cell death and enhances bcl-xL expression in experimental stroke. Glendenning, M; Lovekamp-Swan, T; Schreihofer, DA, 2007)	0.9
"Phytoestrogens have been reported to exhibit antiproliferation to human breast cancer cells in vitro. "	( Pretreatment with phytoestrogen-rich plant decreases breast tumor incidence and exhibits lower profile of mammary ERalpha and ERbeta. Cherdshewasart, W; Panriansaen, R; Picha, P, 2007)	1.78
"Phytoestrogens have been thought to have favorable effects on women's health and perhaps in offsetting cancers. "	( Adverse effects of phytoestrogens on reproductive health: a report of three cases. Chandrareddy, A; McFarlane, SI; Muneyyirci-Delale, O; Murad, OM, 2008)	2.12
"Phytoestrogens have been investigated in a similar manner."	( Monitoring of estrogen mimics by a recombinant yeast assay: synergy between natural and synthetic compounds? Breithofer, A; Graumann, K; Jungbauer, A, 1999)	1.02
"Phytoestrogens (PE) have been proposed as the responsible agents of the hypocholesterolemic effect of soy foods."	( The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. Bruce, B; Dewell, A; Hollenbeck, CB, 2002)	1.33
"Phytoestrogens have been investigated at the epidemiological, clinical and molecular levels to determine their potential health benefits. "	( Phytoestrogens: a review of recent findings. Madar, Z; Stark, A, 2002)	3.2
"Phytoestrogens have been proposed as potential alternatives to ERT."	( Neuroprotective and neurotrophic efficacy of phytoestrogens in cultured hippocampal neurons. Chen, Q; Diaz Brinton, R; Zhao, L, 2002)	1.3

Excerpt	Reference	Relevance
"Phytoestrogens lower the risk of menopausal symptoms and osteoporosis, as well as cardiovascular disease."	( The Potential Effects of Phytoestrogens: The Role in Neuroprotection. Bartosz, G; Gorzkiewicz, J; Sadowska-Bartosz, I, 2021)	1.65
"Phytoestrogens inhibit carbachol-induced colonic contractility."	( Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta. Baird, AW; Collins, D; Hogan, AM; Sheehan, K; Winter, DC; Zierau, O, 2010)	1.42
"Phytoestrogens are known to cause hormonal and gonadal changes in male fish, but few studies have connected these effects to outcomes relevant to reproductive success."	( Reproductive consequences of exposure to waterborne phytoestrogens in male fighting fish Betta splendens. Brown, AC; Clotfelter, ED; Montgomery, TM; Stevenson, LM, 2011)	1.34
"Phytoestrogens also enhance bone formation and increase bone mineral density and levels of alkaline phosphatase, osteocalcin, osteopontin, and α1(I) collagen."	( Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Chiang, SS; Pan, TM, 2013)	1.43
"Phytoestrogens did not cause stimulation of the endometrium. "	( A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium. Balk, JL; DeFerrari, E; Naus, G; Roberts, JM; Whiteside, DA, )	1.57
"Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans, although little is known about the mechanisms and the role of direct action on oestrogen receptors (ER) in this process. "	( The effects of the phytoestrogen, coumestrol, on gonadotropin-releasing hormone (GnRH) mRNA expression in GT1-7 GnRH neurones. Bowe, J; Katzenellenbogen, BS; Katzenellenbogen, JA; Li, XF; O'Byrne, KT; Sugden, D, 2003)	1.76
"Phytoestrogens, can cause growth arrest and in some cases apoptosis in prostate cancer cells in vivo and in vitro."	( Phytoestrogens and prostate cancer. Morrissey, C; Watson, RW, 2003)	2.48
"Phytoestrogens did not inhibit or stimulate protein degradation or synthesis (P > .05)."	( In vitro effects of soy phytoestrogens on rat L6 skeletal muscle cells. Banz, WJ; Harty, J; Jones, KL; Roeder, MJ; Winters, TA, 2005)	1.36
"Phytoestrogens did not cause any sensitive and worrisome stimulation of the endometrial mucosa. "	( [The effects of phytoestrogen therapy on the endometrium in postmenopausal women]. Caserta, L; Caserta, R; De Lucia, D; Nappo, C; Panariello, S; Torella, M, 2005)	1.77
"Phytoestrogens may lower LDL-cholesterol levels without increasing triglyceride levels, they have shown antioxidannt properties as well as favorable effects on vascular reactivity."	( [Primary and secondary prevention of cardiovascular events through hormone replacement therapy (HRT)]. Pilz, H, 2005)	1.05
"Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans. "	( Phytoestrogens and gonadotropin-releasing hormone pulse generator activity and pituitary luteinizing hormone release in the rat. Brooks, A; Cates, PA; Coen, CW; McGarvey, C; Milligan, SR; O'Byrne, KT; Swanson, IA, 2001)	3.2

Excerpt	Reference	Relevance
"Treatment with phytoestrogens increased procaspase-1 expression in Jurkat and U937 cells while no changes were detected in K562 cells."	( Evaluation of phytoestrogens in inducing cell death mediated by decreasing Annexin A1 in Annexin A1-knockdown leukemia cells. Azmi, N; Hasan, M; Jamal, JA; Jasamai, M; Kumolosasi, E; Rajab, NF, 2020)	1.26
"Treatment with phytoestrogens induced improved bone quality."	( Effects of isoflavones equol and genistein on bone quality in a rat osteopenia model. Erren, M; Kolios, L; Sehmisch, S; Seidlova-Wuttke, D; Stuermer, EK; Stuermer, KM; Tezval, M; Wuttke, W, 2010)	0.7

Excerpt	Reference	Relevance
"Amyloid beta protein (Abeta) elicits a toxic effect on neurons in vitro and in vivo."	( The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. Chen, CF; Chi, CW; Lin, YL; Shiao, YJ; Wang, CN, 2001)	0.6
"It has been shown that numerous natural and synthetic chemicals with estrogenic activities are reproductive or developmental toxic factors in humans or animals by epidemiological investigations and animal experiments."	( [Molecular mechanisms of environmental estrogens on reproductive and developmental toxicity]. Chen, F; Li, Y; Long, D, 2002)	0.31
" To date, no adverse effects of short- or long-term use of soy proteins have been observed in humans and exposure to soy-based infant formulas does not appear to lead to different reproductive outcomes than exposure to cow milk formulas."	( Soy-based formulas and phyto-oestrogens: a safety profile. Armenio, L; Granieri, L; Miniello, VL; Moro, GE; Natile, M; Tarantino, M, 2003)	0.32
" Although there are still open questions regarding in utero or early postnatal exposure, the low potencies and concentrations of manmade chemicals as compared with the endogenous hormones in humans make it unlikely that adverse effects occur at common exposure."	( The endocrine and reproductive system: adverse effects of hormonally active substances? Greim, HA, 2004)	0.32
" There were no relevant group differences in adverse events, laboratory findings, or tolerability."	( Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Freudenstein, J; Friede, M; Henneicke-von Zepelin, HH; Liske, E; Osmers, R; Schnitker, J, 2005)	0.33
" Although soy and its constituents, such as genistein, have been consumed at high levels in several Asian populations without apparent adverse effects, concern has been raised about potential adverse effects due to estrogenic and other activities."	( Subchronic and chronic safety studies with genistein in dogs. Bausch, J; Davidovich, A; McClain, RM; Pfannkuch, F; Wolz, E, 2005)	0.33
" However, adverse health effects of phytoestrogens have often been ignored."	( Genotoxicity of phytoestrogens. Kobras, K; Schmitt, E; Stopper, H, 2005)	0.95
"Genistein, an isoflavone and phytoestrogen predominantly found in soy, is considered a potentially safe therapeutic option to prevent postmenopausal bone loss."	( Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers. Cohn, W; Frank, T; Metzner, J; Riegger, C; Ullmann, U, )	0.13
" Although soy, and its constituents such as genistein, have been consumed at high levels in several Asian populations without apparent adverse effects, concern has been raised about potential adverse effects due to the estrogenic and other activities."	( Acute, subchronic and chronic safety studies with genistein in rats. Bausch, J; Davidovich, A; Edwards, JA; Michael McClain, R; Pfannkuch, F; Wolz, E, 2006)	0.33
" Having various mechanisms of action, phytoestrogens display both beneficial and adverse effects on physiological processes."	( [Phytoestrogens: are they really safe?]. Macura, B; Sliwa, L, 2004)	1.5
" The common treatment up to the 1990's has been the oral hormone replacement therapy (HRT), but this treatment has been consequently re-considered due to its adverse effects."	( Open, non-controlled clinical studies to assess the efficacy and safety of a medical device in form of gel topically and intravaginally used in postmenopausal women with genital atrophy. Magnani, P; Marrè, GB; Mascarucci, P; Metelitsa, EN; Morali, G; Polatti, F, 2006)	0.33
" To determine the probability of endometrial hyperplasia and more serious adverse endometrial outcome, the point estimator and upper limit of 95% CI were calculated."	( First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Brucker, C; Gorkow, C; Raus, K; Wuttke, W, )	0.13
"The lack of endometrial proliferation and improvement of climacteric complaints as well as only few gynecologic organ-related adverse events are reported for the first time after a treatment period of 1 year."	( First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Brucker, C; Gorkow, C; Raus, K; Wuttke, W, )	0.13
" Soy, and hence its constituents, such as genistein, have been consumed at high levels in several Asian populations for many centuries without any apparent adverse effects and to the contrary, many health benefits have been associated with the ingestion of soy based foods."	( Reproductive safety studies with genistein in rats. Bausch, J; Davidovich, A; Edwards, J; McClain, RM; Wolz, E, 2007)	0.34
" Only eight women reported some kind of bleeding as an adverse event during the study."	( Endometrial safety assessment of a specific and standardized soy extract according to international guidelines. Aubert, L; Bergeron, C; Chantre, P; Eden, J; Mares, P; Nogales, F; Palacios, S; Pornel, B; Vazquez, F, )	0.13
"Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal."	( Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women. Chandeying, V; Lamlertkittikul, S, 2007)	0.34
"Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index."	( [The safety and tolerance of isoflavones (Soyfem) administration in postmenopausal women]. Drews, K; Kaluba-Skotarczak, A; Kazikowska, A; Malec, M; Puk, E; Seremak-Mrozikiewicz, A, 2007)	0.34
" To date, no adverse effects of short- or long-term use of soy proteins are known in humans, and the only adverse effects known are those reported in animals."	( Soy isoflavones as safe functional ingredients. Chun, OK; Hwang, I; Kim, BG; Kim, KS; Lee, SG; Lee, SY; Shin, D; Shin, HS; Song, WO, 2007)	0.34
" There were no significant differences in adverse effects on breast tissue, complete blood count, and liver and renal function tests between the Pueraria mirifica and placebo groups in this study."	( Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women. Chittacharoen, A; Manonai, J; Theppisai, H; Theppisai, U; Udomsubpayakul, U, )	0.13
" Mild adverse effects occurred after Pueraria mirifica and placebo treatment."	( Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women. Chittacharoen, A; Manonai, J; Theppisai, H; Theppisai, U; Udomsubpayakul, U, )	0.13
" The adverse event profile was similar across all red clover isoflavone and placebo groups."	( Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Affen, J; Ashley, S; Evans, DG; Flook, LA; Greenhalgh, R; Howell, A; McCloskey, EV; Powles, TJ; Tidy, A, 2008)	0.35
"This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women."	( Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Affen, J; Ashley, S; Evans, DG; Flook, LA; Greenhalgh, R; Howell, A; McCloskey, EV; Powles, TJ; Tidy, A, 2008)	0.35
" The possible adverse effects of phytoestrogens have not been evaluated."	( Adverse effects of phytoestrogens on reproductive health: a report of three cases. Chandrareddy, A; McFarlane, SI; Muneyyirci-Delale, O; Murad, OM, 2008)	0.96
"01 to 5 mM was toxic to these cultures."	( The phytoestrogenic isoflavones from Trifolium pratense L. (Red clover) protects human cortical neurons from glutamate toxicity. Circosta, C; De Pasquale, R; Occhiuto, F; Palumbo, DR; Pino, A; Samperi, S; Zangla, G, 2008)	0.35
" There were no differences in discomfort or adverse events between groups."	( Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. Adamo, EB; Adamo, V; Altavilla, D; Atteritano, M; Bitto, A; Burnett, BP; Cancellieri, F; Cannata, ML; Corrado, F; D'Anna, R; Di Stefano, V; Frisina, A; Frisina, N; Levy, RM; Lubrano, C; Marini, H; Marini, R; Mazzaferro, S; Minutoli, L; Polito, F; Sansotta, C; Squadrito, F, 2008)	0.35
" The risk of adverse effects of this treatment, however, is unknown."	( Side effects of phytoestrogens: a meta-analysis of randomized trials. Bentz, EK; Froese, G; Hefler, LA; Heinze, G; Huber, JC; Tempfer, CB, 2009)	0.7
" Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=."	( Side effects of phytoestrogens: a meta-analysis of randomized trials. Bentz, EK; Froese, G; Hefler, LA; Heinze, G; Huber, JC; Tempfer, CB, 2009)	0.7
"Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects."	( Side effects of phytoestrogens: a meta-analysis of randomized trials. Bentz, EK; Froese, G; Hefler, LA; Heinze, G; Huber, JC; Tempfer, CB, 2009)	0.7
"The current investigations were undertaken to study the mechanism of the adverse effect of phytoestrogens on the function of bovine granulosa (follicles >1< cm in diameter) and luteal cells from day 1-5, 6-10, 11-15, 16-19 of the oestrous cycle."	( The adverse effect of phytoestrogens on the synthesis and secretion of ovarian oxytocin in cattle. Kotwica, J; Mlynarczuk, J; Wrobel, MH, 2011)	0.9
" Black cohosh use appears safe in women with previous breast cancer."	( Safety of herbal medicinal products in women with breast cancer. Roberts, H, 2010)	0.36
" Increased pharmacovigilance practices for herbal medicines are required with initiatives to stimulate reporting of suspected adverse reactions."	( Safety of herbal medicinal products in women with breast cancer. Roberts, H, 2010)	0.36
"Our results indicate that genistein is a safe intravitreal drug in the rabbit model up to 540 mg."	( Retinal toxicity of intravitreal genistein in a rabbit model. Androudi, S; Brazitikos, P; Cagini, C; Cavaliere, A; Coltella, R; Fiore, T; Giansanti, F; Iaccheri, B; Mameli, MG; Pietrolucci, F, 2010)	0.36
" The present study shows that beneficial plant symbionts, such as mycorrhizal fungi, can lead to the production of safe and high-quality food, which is an important societal issue strongly demanded by both consumers and producers."	( Nutraceutical value and safety of tomato fruits produced by mycorrhizal plants. Avio, L; Barale, R; Ceccarelli, N; Cristofani, R; Giovannetti, M; Iezzi, A; Mignolli, F; Picciarelli, P; Pinto, B; Reali, D; Sbrana, C; Scarpato, R, 2012)	0.38
" On November 8, 2006 (71 FR 65537), CERHR staff released draft NTP Briefs on Genistein and Soy Formula that provided the NTP's interpretation of the potential for genistein and soy infant formula to cause adverse reproductive and/or developmental effects in exposed humans."	( NTP-CERHR expert panel report on the developmental toxicity of soy infant formula. Bhatia, J; Chambers, C; Clarke, R; Etzel, R; Foster, W; Hoyer, P; Leeder, JS; McCarver, G; Peters, JM; Rissman, E; Rybak, M; Sherman, C; Toppari, J; Turner, K, 2011)	0.37
" This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT."	( The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. Dueregger, A; Eder, IE; Heidegger, I; Klocker, H; Ofer, P; Perktold, B; Ramoner, R, 2014)	0.4
" This is, however, an oversimplification because several botanicals have been found to contain toxic compounds in concentrations harmful to human health."	( European medicinal and edible plants associated with subacute and chronic toxicity part I: Plants with carcinogenic, teratogenic and endocrine-disrupting effects. Kreft, S; Kristanc, L, 2016)	0.43
"Daidzein has become increasingly popular as a dietary supplement, particularly for postpeak-estrus animals, as a safe and natural alternative estrogen-like compound."	( Safety evaluation of daidzein in laying hens: Effects on laying performance, hatchability, egg quality, clinical blood parameters, and organ development. Dou, TC; Hu, YP; Li, SM; Lu, J; Qu, L; Shen, MM; Wang, KH, 2017)	0.46
" No adverse events were elicited."	( Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor β-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women. Brinton, RD; Chen, YL; Franke, AA; Hernandez, G; Mack, WJ; Schneider, LS; Zhao, L, 2018)	0.48
"A single-dose oral administration of the phytoSERM formulation was well-tolerated and did not elicit any adverse events."	( Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor β-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women. Brinton, RD; Chen, YL; Franke, AA; Hernandez, G; Mack, WJ; Schneider, LS; Zhao, L, 2018)	0.48

Excerpt	Reference	Relevance
"A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate neoplasia."	( Clinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasia. Boan, J; Crowell, JA; Fischer, L; Jeffcoat, AR; Koch, MA; Mahoney, C; Stinchcombe, T; Thomas, BE; Valentine, JL; Zeisel, SH, 2004)	0.32
"4% synthetic genistein aglycone was investigated in a phase 1 clinical study to assess safety and tolerability in healthy volunteers as well as to obtain pharmacokinetic data."	( Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers. Cohn, W; Frank, T; Metzner, J; Riegger, C; Ullmann, U, )	0.13
" We developed a physiologically-based pharmacokinetic (PBPK) model to quantify the internal, target-tissue dosimetry of genistein in adult rats."	( Physiologically-based pharmacokinetic modeling of genistein in rats, Part I: Model development. Borghoff, SJ; Coldham, NG; David, JA; Ghosh, SK; Schlosser, PM, 2006)	0.33
" The pharmacokinetic profile of 8-PN was characterized by rapid and probably complete enteral absorption, high metabolic stability, pronounced enterohepatic recirculation and tight dose linearity."	( Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women. Burggraaf, J; Cohen, AF; Hümpel, M; Rad, M; Schaefer, O; Schleuning, WD; Schoemaker, RC, 2006)	0.33
" Genistein also increased the peak concentration (C(max)) of paclitaxel significantly (p<0."	( Effect of genistein on the pharmacokinetics of paclitaxel administered orally or intravenously in rats. Choi, JS; Li, X, 2007)	0.34
" A reliable sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV detection for the pharmacokinetic study of taxifolin in rabbit plasma after enzymatic hydrolysis was developed and validated for the first time."	( Determination and pharmacokinetic study of taxifolin in rabbit plasma by high-performance liquid chromatography. Karlina, MV; Kosman, VM; Makarov, VG; Makarova, MN; Pozharitskaya, ON; Shikov, AN, 2009)	0.35
" The rapid absorption and pharmacokinetic parameters show that S-equol exposure is linear with dose."	( Single-dose and steady-state pharmacokinetic studies of S-equol, a potent nonhormonal, estrogen receptor β-agonist being developed for the treatment of menopausal symptoms. Desai, PB; Greiwe, JS; Jackson, RL; Schwen, RJ, 2011)	0.37
"73% for higher dose with a terminal half-life (t(1/2)) of 10."	( Pharmacokinetics and organ distribution of diarylheptanoid phytoestrogens from Curcuma comosa in rats. Hu, Y; Piyachuturawat, P; Sripanidkulchai, B; Sripanidkulchai, K; Su, J; Suksamrarn, A, 2012)	0.62
" Daidzein has a wide range of pharmacodynamic properties in the treatment of cancer, neurodegenerative disorders, cardiac disorders, diabetes and its complication, osteoporosis, and skin disorders."	( Pharmacokinetics, pharmacodynamics, toxicity, and formulations of daidzein: An important isoflavone. Kulkarni, YA; Laddha, AP, 2023)	0.91

Excerpt	Reference	Relevance
" The lignans do not exert adverse effects on any tissue, however, when combined with GEN, they exert an adverse effect on the uterus."	( Genistein alone and in combination with the mammalian lignans enterolactone and enterodiol induce estrogenic effects on bone and uterus in a postmenopausal breast cancer mouse model. Chen, JM; Power, KA; Saarinen, NM; Thompson, LU; Ward, WE, 2006)	0.33
" Because estrogen up-regulates this receptor, estrogen therapy combined with exercise training may be optimal for increasing bone mineral density."	( Effect of estrogenic compounds (estrogen or phytoestrogens) combined with exercise on bone and muscle mass in older individuals. Chilibeck, PD; Cornish, SM, 2008)	0.61
" Based on previous research, we hypothesized that phytoestrogens combined with exercise could have a synergic effect on women's health."	( Effect of exercise combined with phytoestrogens on quality of life in postmenopausal women. Audet, M; Choquette, S; Dionne, IJ; Riesco, E; Tessier, D, 2011)	0.9
"While phytoestrogens combined with mixed exercise were not sufficient to improve menopausal symptoms, it seemed to be a better strategy than exercise alone to improve the general quality of life in postmenopausal women."	( Effect of exercise combined with phytoestrogens on quality of life in postmenopausal women. Audet, M; Choquette, S; Dionne, IJ; Riesco, E; Tessier, D, 2011)	1.13
" The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women."	( Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial. Audet, M; Choquette, S; Dionne, IJ; Lebon, J; Riesco, E; Tessier, D, 2012)	0.87
"To evaluate the effects of different doses of phytoestrogen (genitein) combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized (OVX) mice."	( [Effects of phytoestrogen, genistein combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized mice]. Gao, L; Wang, Q; Xue, Y; Zhang, Y, 2011)	0.37
"It was lower stimulative effect of low dose of phytoestrogen (genitein) combined with calcium and vitamin D3 on elevating uterine weight in ovariectomized mice."	( [Effects of phytoestrogen, genistein combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized mice]. Gao, L; Wang, Q; Xue, Y; Zhang, Y, 2011)	0.37
"01 nM) in combination with low concentrations of GEN, DAI and EQ (0."	( Estrogenic in vitro evaluation of zearalenone and its phase I and II metabolites in combination with soy isoflavones. Betschler, A; Früholz, R; Grgic, D; Marko, D; Novak, B; Varga, E, 2022)	0.72

Excerpt	Reference	Relevance
" We also quantified the levels of phytoestrogens in extracts of some common foods, herbs, and spices and in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans."	( Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture. Blen, M; Duwe, G; Zava, DT, 1997)	0.58
" The bioavailability of phytoestrogens and phytoprogestins in vivo were studied by quantitating the ER-binding and PR-binding capacity of saliva following consumption of soy milk, exogenous progesterone, medroxyprogesterone acetate, or wild mexican yam products containing diosgenin."	( Estrogen and progestin bioactivity of foods, herbs, and spices. Blen, M; Dollbaum, CM; Zava, DT, 1998)	0.61
"The bioavailability in human subjects of non-nutrient plant factors, including dietary flavonoids and phyto-oestrogens, is of great importance relative to their reported health protective effects."	( The bioavailability of non-nutrient plant factors: dietary flavonoids and phyto-oestrogens. Wiseman, H, 1999)	0.3
" From these data, it is suggested that hSHBG binding may transport some contaminant xenoestrogens into the plasma and modulate their bioavailability to cell tissues."	( Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG). Claustrat, F; de la Perrière, AB; Déchaud, H; Pugeat, M; Ravard, C, 1999)	0.3
" In addition to their estrogenic activity, many of these plant compounds can interfere with steroid metabolism and bioavailability and can also inhibit enzymes, such as tyrosine kinase or topoisomerase, which are important for cellular proliferation."	( [Chemoprevention of prostatic carcinoma]. Graefen, M; Hammerer, P; Huland, H; Steuber, T, 2000)	0.31
" Investigations of phytoestrogen metabolism and bioavailability are also of great relevance."	( The therapeutic potential of phytoestrogens. Wiseman, H, 2000)	0.6
" If calcium supplements are required, the best absorption rate is from a dose of 500-600 mg of calcium once or twice daily."	( What strategies can women use to optimise bone health at this stage of life? Kerr, DA; Prince, RL, 2000)	0.31
" The bioavailability of phytoestrogens was studied by measuring red blood cell (RBC) uptake and serum protein binding ability."	( Composition, red blood cell uptake, and serum protein binding of phytoestrogens extracted from commercial kudzu-root and soy preparations. Baker, JI; Benlhabib, E; Keyler, DE; Singh, AK, 2002)	0.86
" Recently, it was shown, however, that the bioavailability of potential antioxidants from plant foods is generally too low to have any substantial direct effect on reactive oxygen species."	( Bioactive substances of plant origin in food--impact on genomics. Berwid, SJ; Jank, M; Orzechowski, A; Ostaszewski, P, )	0.13
" Isoflavones are present predominantly as glucosides in most commercially available soya products; there is evidence that they are not absorbed in this form and that their bioavailability requires initial hydrolysis of the sugar moiety by intestinal beta-glucosidases."	( Bioavailability of phyto-oestrogens. Cassidy, A; Faughnan, M; Hoey, L; Rowland, I; Wähälä, K; Williamson, G, 2003)	0.32
" That being said, the oral bioavailability of only a few soy phytoestrogens such as Daidzein and Genestein have been previously estimated."	( Determination of rat oral bioavailability of soy-derived phytoestrogens using an automated on-column extraction procedure and electrospray tandem mass spectrometry. Harris, HA; Mallis, LM; McConnell, OJ; Sarkahian, AB; Zhang, MY, 2003)	0.81
" More research is warranted to determine the bioavailability of lignins in the human diet."	( Dietary lignins are precursors of mammalian lignans in rats. Adlercreutz, H; Begum, AN; Fukushima, K; Heinonen, SM; Lapierre, C; Mila, I; Nagano, K; Nicolle, C; Rémésy, C; Scalbert, A, 2004)	0.32
" Hence, dietary flavonoids may be able to influence the bioavailability of endogenous estrogens, and disrupt endocrine balance, by increasing the ratio of active estrogens to inactive estrogen sulfates in human tissues."	( Phytoestrogens are potent inhibitors of estrogen sulfation: implications for breast cancer risk and treatment. Blagg, S; Bottomley, L; Harris, RM; Hughes, PJ; Kirk, CJ; Owen, K; Waring, RH; Wood, DM, 2004)	1.77
" The absorption rate ranges from 20-55%."	( [Soy isoflavones--a therapy for menopausal symptoms?]. Hahn, A; Wolters, M, 2004)	0.32
" Decreased bioavailability of endothelial derived nitric oxide (NO) is recognized as an important promoter in cardiovascular disease."	( The soy isoflavone genistein induces a late but sustained activation of the endothelial nitric oxide-synthase system in vitro. Dirsch, VM; Leikert, JF; Räthel, TR; Vollmar, AM, 2005)	0.33
" Bioavailability of IF requires an initial hydrolysis of the sugar moiety by intestinal beta-glucosidases to allow the following uptake by enterocytes and the flow through the peripheral circulation."	( Health effects of phytoestrogens. Branca, F; Lorenzetti, S, 2005)	0.66
" Based on consecutive administration of single oral doses of genistein, dose linearity was assumed for extent of absorption [AUC(0-infinity)] for all doses (30-300 mg) and for rate of absorption (Cmax) up to 150 mg."	( Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers. Cohn, W; Frank, T; Metzner, J; Riegger, C; Ullmann, U, )	0.13
" The bioavailability of phytochemicals can be influenced by intrinsic factors in food and/or in human, in general the substances are little adsorbed, largely metabolized and rapidly eliminated."	( [Biologically-active phytochemicals in vegetable food]. Carratù, B; Sanzini, E, 2005)	0.33
" Although a number of health effects are attributed to these compounds, only a few reports are available about the bioavailability of prenylflavonoids and the transformation potency of the intestinal microbial community."	( Activation of proestrogens from hops (Humulus lupulus L.) by intestinal microbiota; conversion of isoxanthohumol into 8-prenylnaringenin. De Keukeleire, D; Heyerick, A; Possemiers, S; Robbens, V; Verstraete, W, 2005)	0.33
" The pharmacokinetic characteristics of Bonistein revealed comparable results for extent and rate of absorption on Days 1 and 14."	( Repeated oral once daily intake of increasing doses of the novel synthetic genistein product Bonistein in healthy volunteers. Grossmann, M; Oberwittle, H; Riegger, C; Ullmann, U, 2005)	0.33
" The bioavailability and metabolism of isoflavones (daidzein in particular) were also examined to clarify the mechanism of their bone-protective effects in humans."	( Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Fujioka, M; Fuku, N; Higuchi, M; Ishimi, Y; Oka, J; Okuhira, T; Tabata, I; Teramoto, T; Toda, T; Uchiyama, S; Ueno, T; Urata, K; Wu, J; Yamada, K, 2006)	0.33
"Although orally administered 8-PN should be readily absorbed from the intestine, its bioavailability should be reduced significantly by intestinal and hepatic metabolism."	( In vitro studies of intestinal permeability and hepatic and intestinal metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus L.). Chadwick, LR; Li, Y; Nikolic, D; van Breemen, RB, 2006)	0.33
" Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones."	( The effects of fructo-oligosaccharides in combination with soy protein on bone in osteopenic ovariectomized rats. Arjmandi, BH; Bellmer, DD; Devareddy, L; Hooshmand, S; Khalil, DA; Korlagunta, K, )	0.13
" A pharmacokinetic analysis of radiolabeled G was performed to determine its bioavailability and metabolism in both species."	( Disposition of genistein in rainbow trout (Oncorhynchus mykiss) and siberian sturgeon (Acipenser baeri). Bennetau-Pelissero, C; Cravedi, JP; Gontier-Latonnelle, K; Lamothe, V; Laurentie, M; Le Menn, F; Perdu, E, 2007)	0.34
" In this study, we examined the pharmacokinetic properties and bioavailability of GT in rats and compared with those of GT-glu."	( Comparison of oral bioavailability of genistein and genistin in rats. Choi, YW; Ha, KW; Han, IH; Huh, JS; Kang, MJ; Kwon, SH; Lee, BS; Lee, J; Lee, JR; Lee, MS; Lee, MW; Lee, SK, 2007)	0.34
" We have critically evaluated the literature that estrogenic compounds modulate vascular reactivity in vitro and in vivo, and conclude that isoflavones may protect against cardiovascular disease by virtue of their ability to activate intracellular signaling pathways, leading to increased NO bioavailability and an upregulation of antioxidant gene expression via the key transcription factors NFkappaB and Nrf2."	( Cardiovascular targets for estrogens and phytoestrogens: transcriptional regulation of nitric oxide synthase and antioxidant defense genes. de Winter, P; Li, FY; Mann, GE; Rowlands, DJ; Siow, RC, 2007)	0.61
" Marketed preparations show variability in bioavailability and there are variations in kinetics due to ethnicity and diet."	( Plasma levels of genistein following a single dose of soy extract capsule in Indian women. Agashe, S; Chandrasekharan, S; Joshi, JV; Menon, SK; Pandey, SN; Vaidya, AD; Vaidya, RA, 2007)	0.34
" Poor oral absorption and efficient conjugation explain the low bioavailability of free genistein."	( The bioavailability and disposition kinetics of genistein in cats. Backus, RC; Cave, NJ; Klasing, KC; Marks, SL, 2007)	0.34
" Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies."	( Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males. Asselineau, J; Bennetau-Pelissero, C; Chantre, P; Durand, M; Lamothe, V; Moore, N; Perez, P; Potier, M; Sauvant, P; Vergne, S, 2008)	0.35
" In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus "high" doses, in contrast to much of the previous literature."	( Genistein genotoxicity: critical considerations of in vitro exposure dose. King, AA; Klein, CB, 2007)	0.34
" Recent studies indicate that women with intestinal capacity to convert daidzein to equol also have the capacity to alter steroid metabolism and bioavailability of estrogens."	( Individual differences in equol production capability modulate blood pressure in tibolone-treated postmenopausal women: lack of effect of soy supplementation. Appt, S; Clarkson, TB; Mikkola, TS; Tikkanen, MJ; Törmälä, RM; Ylikorkala, O, 2007)	0.34
" With regard to this there should be taken a reference to the bioavailability and metabolism of the isoflavones and the fact that there are remarkable interindividual differences which could be influenced to a great extent by the composition of intestinal flora."	( [Isoflavones--an update on scientific data]. Döll, M, 2008)	0.35
" Differences in the bioactivities of individual phytoestrogens, differences in phytoestrogen metabolism and bioavailability within different study populations, and imprecise reporting of the dose of phytoestrogens administered in intervention studies may have contributed to the disparity in study findings."	( Soy phytoestrogens: impact on postmenopausal bone loss and mechanisms of action. Kruger, MC; Poulsen, RC, 2008)	1.16
"Daidzein is a very good candidate for treating cardio-cerebrovascular diseases, but its poor oral absorption and bioavailability limit its curative efficacy."	( The role of daidzein-loaded sterically stabilized solid lipid nanoparticles in therapy for cardio-cerebrovascular diseases. Chen, L; Gao, Y; Gu, W; Li, Y; Xu, Z, 2008)	0.35
" The absolute bioavailability of taxifolin after oral administration of lipid solution was 36%."	( Determination and pharmacokinetic study of taxifolin in rabbit plasma by high-performance liquid chromatography. Karlina, MV; Kosman, VM; Makarov, VG; Makarova, MN; Pozharitskaya, ON; Shikov, AN, 2009)	0.35
"There are limited reports on the bioavailability and pharmacokinetics of isoflavones in elderly humans and aged animals."	( Effect of glycosidation of isoflavones on their bioavailability and pharmacokinetics in aged male rats. Cooke, GM; Gilani, GS; Robertson, P; Sepehr, E, 2009)	0.35
"Inclusion complexes of cyclodextrins with nonpolar drugs are a topic of current interest in pharmaceutical science, because they increase the aqueous solubility, chemical stability and bioavailability of poorly water-soluble drugs."	( Influence of the "host-guest" interactions on the mobility of genistein/beta-cyclodextrin inclusion complex. Crupi, V; Majolino, D; Paciaroni, A; Stancanelli, R; Venuti, V, 2009)	0.35
" The systemic bioavailability and fractional absorption of R-(+)[2-13C]equol were higher than those of S-(-)[2-13C]equol or the racemate."	( The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Brown, NM; Heubi, JE; Jha, P; Setchell, KD; Zhao, X, 2009)	0.35
"The high bioavailability of both diastereoisomers contrasts with previous findings for the soy isoflavones daidzein and genistein, both of which have relatively poor bioavailability, and suggests that low doses of equol taken twice daily may be sufficient to achieve biological effects."	( The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Brown, NM; Heubi, JE; Jha, P; Setchell, KD; Zhao, X, 2009)	0.35
" Therefore, the present study aims to investigate the effects of genistein, a potent phyto-antioxidant, and exercise training on age-induced endothelial dysfunction in relation to NO bioavailability using in situ NO-sensitive fluorescent dye detection."	( Increased NO bioavailability in aging male rats by genistein and exercise training: using 4, 5-diaminofluorescein diacetate. Eksakulkla, S; Patumraj, S; Siriviriyakul, P; Suksom, D, 2009)	0.35
" In conclusion, the bioavailability of phytoestrogens, especially when given in mixtures, is subject to high interindividual variation."	( Cosupplementation of isoflavones, prenylflavonoids, and lignans alters human exposure to phytoestrogen-derived 17beta-estradiol equivalents. Bolca, S; Bracke, M; De Keukeleire, D; Depypere, H; Heyerick, A; Possemiers, S; Verstraete, W; Wyns, C, 2009)	0.62
" In the present paper, we will discuss the role of bioavailability and metabolism in the instability of individual response to PE."	( Controversies concerning the use of phytoestrogens in menopause management: bioavailability and metabolism. de Cremoux, P; Jacquot, Y; Leclercq, G; This, P, 2010)	0.64
" The intestinal microflora is important in rendering soy isoflavones bioavailability by facilitating their conversion to equol."	( Combination of genistin and fructooligosaccharides prevents bone loss in ovarian hormone deficiency. Arjmandi, BH; Hooshmand, S; Juma, S, 2010)	0.36
" Here we review quantitative data on phytoestrogens, their interaction with estrogen receptors, their bioavailability and pharmacokinetics, and their effects on breast cancer cells and animal models."	( Phytoestrogens: science, evidence, and advice for breast cancer patients. Cassileth, B; Davatgarzadeh, A; Deng, G; Yeung, S, 2010)	2.08
"The investigation into the potential usefulness of phytoestrogens in the treatment of menopausal symptoms requires large-scale clinical trials that involve rapid, validated assays for the characterization and quantification of the phytoestrogenic precursors and their metabolites in biological matrices, as large interindividual differences in metabolism and bioavailability have been reported."	( Development of a high-throughput LC/APCI-MS method for the determination of thirteen phytoestrogens including gut microbial metabolites in human urine and serum. Bolca, S; De Keukeleire, D; Heyerick, A; Wyns, C, 2010)	0.84
" In order to evaluate the function of IFLs, alone or when exposure happens through soy intake, pharmacokinetics and bioavailability are critical issues to be considered in epidemiologic and clinical research."	( Phytoestrogenic isoflavonoids in epidemiologic and clinical research. Custer, LJ; Franke, AA; Halm, BM; Kakazu, K; Li, X, 2009)	0.35
"The present study aimed to improve the bioavailability of biochanin A, a poorly soluble bioflavonoid, via the preparation of solid dispersion (SD) using Solutol HS15 and HPMC 2910."	( Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: in vitro and in vivo evaluation. Han, HK; Lee, BJ; Lee, HK, 2011)	0.37
"8 mgkg(-1)day(-1), sc) and Atorvastatin (30 mgkg(-1)day(-1), po Positive Control) for one week markedly improved vascular endothelial dysfunction due to increase in nitric oxide bioavailability perhaps by inhibiting caveolin-1 and activation of PI3K-AKT pathway."	( Ameliorative effect of daidzein: a caveolin-1 inhibitor in vascular endothelium dysfunction induced by ovariectomy. Sharma, PL; Sharma, S; Singh, M, 2012)	0.38
" The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity."	( Isoflavones: estrogenic activity, biological effect and bioavailability. Drago, F; Melilli, B; Piazza, C; Salomone, S; Vitale, DC, 2013)	0.39
" However, they exhibit poor oral bioavailability which limits their clinical utility in humans."	( Disposition of pharmacologically active dietary isoflavones in biological systems. Arora, S; Raju, KS; Siddiqui, N; Taneja, I, 2013)	0.39
"A novel drug delivery system, TPGS 1000 (TPGS) emulsified zein nanoparticles (TZN), were designed with an objective to improve the oral bioavailability of daidzin, an isoflavone glycoside with estrogenic activities."	( TPGS emulsified zein nanoparticles enhanced oral bioavailability of daidzin: in vitro characteristics and in vivo performance. Gu, L; Zou, T, 2013)	0.39
" In conclusion, the formulation in nanoemulsion forms obviously increased the intestinal absorption rate of diarylheptanoids."	( Increased in situ intestinal absorption of phytoestrogenic diarylheptanoids from Curcuma comosa in nanoemulsions. Chaiittianan, R; Hu, Y; Sripanidkulchai, B; Sripanidkulchai, K; Su, J, 2013)	0.39
" Further studies are needed to determine the bioavailability of these compounds and their possible beneficial health effects when taken by moderate beer consumption."	( Beer and beer compounds: physiological effects on skin health. Becker, T; Chen, W; Qian, F; Ring, J, 2014)	0.4
" S-(-)equol, a metabolite of the soy isoflavone daidzein, has a higher bioavailability and greater affinity for estrogen receptor β than daidzein."	( S-(-)equol producing status not associated with breast cancer risk among low isoflavone-consuming US postmenopausal women undergoing a physician-recommended breast biopsy. Barnes, S; Krontiras, H; Nagy, TR; Virk-Baker, MK, 2014)	0.4
" This study investigates the interactions between selected prenylflavonoids and breast cancer resistance protein (BCRP/ABCG2), an efflux transporter important for xenobiotic bioavailability and multidrug resistance (MDR)."	( Hop-derived prenylflavonoids are substrates and inhibitors of the efflux transporter breast cancer resistance protein (BCRP/ABCG2). Birch, NP; Cooney, J; Jensen, D; Li, Y; Paxton, JW; Scheepens, A; Tan, KW, 2014)	0.4
" The intestinal bioavailability of these compounds was investigated using Caco-2 cells."	( Isoflavones in food supplements: chemical profile, label accordance and permeability study in Caco-2 cells. Almeida, IM; Alves, RC; Oliveira, MB; Rodrigues, F; Sarmento, B, 2015)	0.42
"Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed."	( Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats. Alcorn, J; Krol, ES; Muir, AD; Mukker, JK; Singh, RS, 2015)	0.42
" Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites."	( Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators. Bandelow, S; Hogervorst, E; Kridawati, A; Soni, M; White, LR, 2016)	0.63
" However, the diarylheptanoids isolated from the plant rhizome are shown to have low oral bioavailability and faster elimination characteristics."	( Effects of Vehicles and Enhancers on the Skin Permeation of Phytoestrogenic Diarylheptanoids from Curcuma comosa. Jaipakdee, N; Limpongsa, E; Sripanidkulchai, B; Tuntiyasawasdikul, S, 2017)	0.46
" However, poor bioavailability of resveratrol is a potential limitation for resveratrol treatment and cancer outcome in vivo."	( Resveratrol as MDR reversion molecule in breast cancer: An overview. Alamolhodaei, NS; Hayes, AW; Karimi, G; Ramezani, M; Tsatsakis, AM, 2017)	0.46
" Widely used soy is a source of poorly absorbed isoflavones glycosides."	( Evaluation of estrogenic activity of red clover (Trifolium pratense L.) sprouts cultivated under different conditions by content of isoflavones, calorimetric study and molecular modelling. Brzozowska, E; Budryn, G; Cerón-Carrasco, JP; Gałązka-Czarnecka, I; Grzelczyk, J; Mostowski, R; Pérez-Sánchez, H; Żyżelewicz, D, 2018)	0.48
" However, there is little information on the oral bioavailability and tissue distribution of puerarin with respect to its pharmacodynamic activities."	( Absolute oral bioavailability and disposition kinetics of puerarin in female rats. Anukunwithaya, T; Hunsakunachai, N; Khemawoot, P; Malaivijitnond, S; Poo, P; Rodsiri, R, 2018)	0.48
"Puerarin reached a maximum concentration in the blood of 140-230 μg/L within 1 h of oral dosing, and had an absolute oral bioavailability of approximately 7%."	( Absolute oral bioavailability and disposition kinetics of puerarin in female rats. Anukunwithaya, T; Hunsakunachai, N; Khemawoot, P; Malaivijitnond, S; Poo, P; Rodsiri, R, 2018)	0.48
"The absolute oral bioavailability of puerarin was approximately 7% at doses of 5 and 10 mg/kg."	( Absolute oral bioavailability and disposition kinetics of puerarin in female rats. Anukunwithaya, T; Hunsakunachai, N; Khemawoot, P; Malaivijitnond, S; Poo, P; Rodsiri, R, 2018)	0.48
" Recent developments such as clinical trials, precise bioassays for screening and selection of potential phytoestrogens, drug delivery systems to enhance bioavailability of therapeutically favorable phytoestrogens, regulatory guidelines on phytoestrogen-based supplements, and avenues that need further improvement are also discussed."	( Phytoestrogens: The current state of research emphasizing breast pathophysiology. Anandhi Senthilkumar, H; Fata, JE; Kennelly, EJ, 2018)	2.14
" Equol, a metabolite of a soy isoflavone converted from daidzein by specific gut bacteria, has a greater bioavailability compared with other soy isoflavones."	( Effectiveness of natural S-equol supplement for premenstrual symptoms: protocol of a randomised, double-blind, placebo-controlled trial. Chiba, Y; Shiina, M; Takeda, T, 2018)	0.48
" It may help to develop novel formulations with better solubility and bioavailability of genistein."	( An Overview on Genistein and its Various Formulations. Ahsan, F; Akhtar, J; Jaiswal, N; Singh, SP, 2019)	0.51
" Genistein has intrinsically low oral bioavailability that affects its dose-response activities."	( Increasing protective activity of genistein by loading into transfersomes: A new potential adjuvant in the oxidative stress-related neurodegenerative diseases? Cavalli, R; Cossu, M; Fancello, S; Galleri, G; Gavini, E; Giunchedi, P; Langasco, R; Migheli, R; Rassu, G, 2019)	0.51
" Isoflavone aglycones (IFAs) of soybeans in human diets have poor solubility in water, resulting in low bioavailability and bioactivity."	( Enrichment of Polyglucosylated Isoflavones from Soybean Isoflavone Aglycones Using Optimized Amylosucrase Transglycosylation. Jang, D; Jung, YS; Kim, AT; Kim, DO; Kim, MS; Kim, YJ; Nam, TG; Park, CS; Rha, CS; Seo, DH, 2020)	0.56
" MPS is considered as a highly porous biomaterial which typically possesses nanometer-sized porous microstructure and low density, providing a large effective specific surface area (SSA) and hydrophilic surface to improve solubility, stability and bioavailability of poorly water-soluble active agents."	( Fabrication of nanostructured mesoporous starch encapsulating soy-derived phytoestrogen (genistein) by well-tuned solvent exchange method. Abolmaali, SS; Kadivar, M; Shekarchizadeh, H; Soleimanpour, M; Tamaddon, AM, 2020)	0.56
" However, the complexities of biological effects after ingestion of phytoestrogens and the differences in their metabolism and bioavailability indicate that interpretation of either risk or benefits needs to be made with caution."	( The influence of phytoestrogens on different physiological and pathological processes: An overview. Del Bianco-Borges, B; Petrine, JCP, 2021)	1.2
" Depending on their concentration and bioavailability in various plant sources, phytoestrogens can act as estrogen agonist or antagonists."	( A review on phytoestrogens: Current status and future direction. Chakrabarti, S; Ghosh, K; Gorai, S; Pal, S; Patra, S; Pradhan, S, 2023)	1.52

Excerpt	Relevance	Reference
" Neonatal rats were dosed with 10 or 100 micrograms of coumestrol or equol on postnatal day (PND) 1-10."	( Methylation profile and amplification of proto-oncogenes in rat pancreas induced with phytoestrogens. Blann, E; Bo, J; Lyn-Cook, BD; Medlock, K; Payne, PW; Sheehan, D, 1995)	0.51
" A dose-response curve was always consistently obtained using estradiol-17 beta (E2), with a mid point at around 100 nM E2 and a maximum response at around 1000 nM."	( Vitellogenin synthesis in cultured hepatocytes; an in vitro test for the estrogenic potency of chemicals. Bennetau, B; Dunoguès, J; Flouriot, G; Foucher, JL; Le Gac, F; Pelissero, C; Sumpter, JP, 1993)	0.29
"This chapter reviews the reproductive actions of phytoestrogens, comparing mechanisms of action, dose-response relationships, and human exposures."	( Reproductive actions of phytoestrogens. Naftolin, F; Whitten, PL, 1998)	0.86
" Weaning female B6D2F1 mice were dosed with glycitein (3 mg/day), genistein (3 mg/day), and diethylstilbestrol (DES) (0."	( Estrogenic activity of glycitein, a soy isoflavone. Hendrich, S; Murphy, PA; Song, TT, 1999)	0.3
" The recognition (and further acceptance) of the role of the residual estrogens might have influence on the indication, choice and dosage of preparation and duration of hormone replacement therapy."	( [Menopause and hormone replacement therapy]. Tóth, KS, 2000)	0.31
" The powders, dosed on a per-kilogram body weight basis, provided mean isoflavone intakes of 8, 65, and 130 mg/day, for the control, low-isoflavone, and high-isoflavone diet periods, respectively."	( Lack of effect of isoflavonic phytoestrogen intake on leptin concentrations in premenopausal and postmenopausal women. Duncan, AM; Kurzer, MS; Merz-Demlow, BE; Phipps, WR; Wangen, KE; Xu, X, 2001)	0.31
" The molecular effects and control mechanisms of these substances, their pharmacokinetics, threshold levels and dose-response differences are issues that require further research before a full assessment of their effect on humans can be drawn."	( Possible health impact of phytoestrogens and xenoestrogens in food. Daxenberger, A; Ibarreta, D; Meyer, HH, 2001)	0.61
"This article documents and quantitatively assesses the capacity of estrogen, phytoestrogens, and antiestrogens to affect biphasic dose-response relationships in animal/human models and across a broad range of cell types, affecting multiple endpoints."	( Estrogen and related compounds: biphasic dose responses. Calabrese, EJ, 2001)	0.54
" (2) Exposure paradigms: extrapolating dosing in animals to exposures in humans becomes complex."	( Reproductive toxicology: current and future directions. Hoyer, PB, 2001)	0.31
" The knowledge gained at the cellular and molecular levels, and biological activities of PSMs including tannin-polyphenols, saponins, mimosine, flavonoids, terpenoids, and phytates, would be useful in planning for future epidemiological studies and human cancer prevention trials, especially when a large pure dosage is not the option to deliver the active compounds to many tissues."	( Potential therapeutic applications of some antinutritional plant secondary metabolites. Bhat, TK; Singh, B, 2003)	0.32
" To further speed up the analysis the rats were dosed using the 'n-in-one' (cassette) protocol."	( Determination of rat oral bioavailability of soy-derived phytoestrogens using an automated on-column extraction procedure and electrospray tandem mass spectrometry. Harris, HA; Mallis, LM; McConnell, OJ; Sarkahian, AB; Zhang, MY, 2003)	0.56
" Although the estrogenic effects of a phytoestrogen-enriched diet caused a decrease in testosterone and/or 11-ketotestosterone values in the CD-fed fish, there was no dose-response relationship between androgen and amount of NP to which the FD-fed fish were exposed."	( Effects of nonylphenol and phytoestrogen-enriched diet on plasma vitellogenin, steroid hormone, hepatic cytochrome P450 1A, and glutathione-S-transferase values in goldfish (Carassius auratus). Arizono, K; Ishibashi, H; Matsumura, N; Soyano, K; Tachibana, K; Tatarazako, N; Tominaga, N; Tomiyasu, Y; Tsuchimoto, M, 2004)	0.32
" New low-dose preparations and new dosage forms of hormone therapy are available."	( Treatment options for menopausal hot flashes. Sikon, A; Thacker, HL, 2004)	0.32
" Two recent studies showed excellent efficacy against classic menopausal complaints and osteoprotective properties, and extracts were deemed safe even when the dosage was increased threefold."	( Black cohosh: just another phytoestrogen? Emons, G; Viereck, V; Wuttke, W, 2005)	0.33
" Regarding a potential for use in osteoporosis-prevention therapy, the dosage of a phytoestrogen, which is taken, will play an important role concerning a desired in vivo profile."	( Regulation of osteoblastic phenotype and gene expression by hop-derived phytoestrogens. Effenberger, KE; Johnsen, SA; Monroe, DG; Spelsberg, TC; Westendorf, JJ, 2005)	0.56
" A trend to a greater percentage urinary recovery of daidzein and glycitein was observed among women consuming fermented soya milk at a dosage of 40 mg isoflavone (P=0."	( Bioavailability of isoflavone phytoestrogens in postmenopausal women consuming soya milk fermented with probiotic bifidobacteria. Shah, NP; Stojanovska, L; Tsangalis, D; Wilcox, G, 2005)	0.62
" Our data shows that supplementation of genistein at a dosage comparable to the isoflavone consumption in humans did not affect the reproductive system but resulted in enhancement of NMU-induced tumorigenesis in adult female rats."	( Genistein enhances N-nitrosomethylurea-induced rat mammary tumorigenesis. Kijkuokool, P; Malaivijitnond, S; Parhar, IS, 2006)	0.33
" However, there were significant increases in 7alpha- and 7beta-OOHs, 7alpha- and 7beta-OHs, and 7-keto after ethanol dosage compared to controls."	( Protective effect of daidzein against acute ethanol-induced lipid peroxidation in rat jejunum. Adachi, J; Nakagawa, K; Ueno, Y; Wong, MC, 2006)	0.33
" Initially, dose-response curves were characterized for each of the six SCs (methoxyclor, o,p-DDT, octylphenol, bisphenol A, beta-hexachlorocyclohexane, 2,3-bis(4-hydroxyphenyl)-propionitrile) in each of the assays."	( Analysis of the interaction of phytoestrogens and synthetic chemicals: an in vitro/in vivo comparison. Bhaskar Gollapudi, B; Carney, EW; Charles, GD; Gennings, C; Kan, HL; Tornesi, B; Zacharewski, TR, 2007)	0.63
" However, many important scientific problems have not been constrained, whether do the metabolites of lignans from foods have their potential genic toxicity? What are the anticancer mechanisms of lignans? What is the dosage of lignans to achieve the desired biological effect? In this paper, the references on lignans have systematically been reviewed in the following aspects: classification, distribution, metabolism, pharmacological activities and analytical methods, and a prospective of future studies on lignans is also elucidated."	( [Lignan: an important natural estrogen from plants]. Li, X; Liu, X; Wang, JH; Yuan, JP, 2006)	0.33
" Although a daily dosage of isoflavone was not sufficient to prevent tissue fibrosis under marked oxidative stress in the early stage of diabetes, isoflavones might promise significant clinical benefits by reducing oxidative stress in the heart during aging."	( Inhibitory effects of soy isoflavones on cardiovascular collagen accumulation in rats. Ebihara, K; Kishida, T; Miyatake, A; Mizushige, K; Mizushige, T, 2007)	0.34
" A five-fold increase in the dosage of IX without change in 8-PN concentration resulted in a significant lower IX recovery and a higher 8-PN recovery."	( Microbial and dietary factors associated with the 8-prenylnaringenin producer phenotype: a dietary intervention trial with fifty healthy post-menopausal Caucasian women. Bolca, S; Bracke, M; De Henauw, S; De Keukeleire, D; Depypere, H; Heyerick, A; Huybrechts, I; Maervoet, V; Possemiers, S; Van de Wiele, T; Verstraete, W; Vervarcke, S, 2007)	0.34
"Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index."	( [Efficacy of standardized isoflavones extract (Soyfem) (52-104 mg/24h) in moderate and medium-severe climacteric syndrome]. Drews, K; Kaluba-Skotarczak, A; Kazikowska, A; Malec, M; Puk, E; Seremak-Mrozikiewicz, A, 2007)	0.34
" In keeping with these in vivo outcomes, we observed that the level of cyclin D1 (and progesterone receptor) in MCF-7 xenografts was considerably reduced by ICI 182 780, an effect enhanced by concomitant treatment with 50 SSE, but reduced by the higher dosage (i."	( Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 in an experimental model of estrogen-dependent breast cancer. De Stefano, I; Fabrizi, M; Ferlini, C; Gallo, D; Mantuano, E; Mozzetti, S; Scambia, G, 2007)	0.34
" Almost all supplements contained measurable amounts of genistein and/or daidzein, known estrogenic agents, at up to 22 mg/day of isoflavone, per recommended daily dosage of supplement."	( Analysis of flavonoid phytoestrogens in botanical and ephedra-containing dietary supplements. Capps, K; Grippo, AA; Gurley, BJ; Rougeau, B, 2007)	0.65
" Relative estrogenic activities of the compounds were determined from their dose-response curves."	( Vitellogenin-inducing activities of natural, synthetic, and environmental estrogens in primary cultured Xenopus laevis hepatocytes. Kawahara, A; Mitsui, N; Tooi, O, 2007)	0.34
"Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index."	( [The safety and tolerance of isoflavones (Soyfem) administration in postmenopausal women]. Drews, K; Kaluba-Skotarczak, A; Kazikowska, A; Malec, M; Puk, E; Seremak-Mrozikiewicz, A, 2007)	0.34
" mirifica tuberous powder at a dosage of 0, 10, 100 and 1000 mg/kg BW/day for four consecutive weeks."	( Pretreatment with phytoestrogen-rich plant decreases breast tumor incidence and exhibits lower profile of mammary ERalpha and ERbeta. Cherdshewasart, W; Panriansaen, R; Picha, P, 2007)	0.34
" Well-designed trials are required to delineate the potential clinical usefulness of these agents through issues, such as determining the optimal period and route of administration, systemic bioavailability, optimal dosing and toxicity of the agent, and single or combinatorial approach."	( Chemoprevention of prostate cancer through dietary agents: progress and promise. Afaq, F; Khan, N; Mukhtar, H; Syed, DN, 2007)	0.34
" Optimal dosage of genistein, quercetin and in combination with chemicals for leukemia cells were determined by experiments."	( [Synergistic antileukemic effect of phytoestrogens and chemotherapeutic drugs on leukemic cell lines in vitro]. Chen, CS; Shen, J; Tai, YC; Wong, CH; Xie, Z; Zhang, WJ, 2008)	0.62
" As these products are commonly used in the management of menopause symptoms, any clinical benefits would be dependent on the exact dosage of isoflavones received."	( Determination of phytoestrogens in dietary supplements by LC-MS/MS. Bailey, V; Clarke, DB; Lloyd, AS, 2008)	0.69
" After dosing IX, 80% was converted into 8-PN in the Hop + model and highest 8-PN production, plasma concentrations, and urinary and fecal excretion occurred in the Hop + rats."	( Eubacterium limosum activates isoxanthohumol from hops (Humulus lupulus L.) into the potent phytoestrogen 8-prenylnaringenin in vitro and in rat intestine. Bruneau, A; De Keukeleire, D; Espín, JC; González-Sarrías, A; Heyerick, A; Philippe, C; Possemiers, S; Rabot, S; Tomás-Barberán, FA; Verstraete, W, 2008)	0.35
"5, 10, or 51 mg/kg per day for females during the time that the rats were directly consuming dosed feed."	( Multigenerational reproductive study of genistein (Cas No. 446-72-0) in Sprague-Dawley rats (feed study). , 2008)	0.35
" The results demonstrated a dose-response effect of estrogen and no effect of non-aromatizable androgens on food intake or growth performance."	( Sex steroid-induced inhibition of food intake in sea bass (Dicentrarchus labrax). Cerdá-Reverter, JM; Leal, E; Muriach, B; Sánchez, E, 2009)	0.35
" The discrepancies between the experimental findings and clinical data may be related to the vascular estrogen receptors (ER), the type, route of administration, or dosage of MHT, and subject's age."	( Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Khalil, RA; Serock, MR; Wells, AK, 2008)	0.35
" The luc-induction was determined either 8h after maternal dosing with a single intraperitoneal (IP) dose or 24h after the last of a series of 8 daily oral dosages."	( Estrogenicity of food-associated estrogenic compounds in the fetuses of female transgenic mice upon oral and IP maternal exposure. Murk, AJ; Rietjens, IM; Ter Veld, MG; Zawadzka, E, 2009)	0.35
" No significant differences in the bioavailability of daidzein were observed in aged rats dosed with aglycon, glucoside or Novasoy."	( Effect of glycosidation of isoflavones on their bioavailability and pharmacokinetics in aged male rats. Cooke, GM; Gilani, GS; Robertson, P; Sepehr, E, 2009)	0.35
" At a dosage of 250 microg/pellet the red clover extract showed excellent inhibition of angiogenesis."	( Inhibition of angiogenesis and inflammation by an extract of red clover (Trifolium pratense L.). Krenn, L; Paper, DH, 2009)	0.35
"Fifty female Sprague-Dawley rats were randomly divided into 5 groups: the control group (SHAM), the ovariectomized group (OVX), the ovariectomized rats receiving low genistein dosage (OVX+L), the moderate genistein dosage group (OVX+M) and the high genistein dosage group (OVX+H)."	( Effects of phytoestrogen genistein on genioglossus function and oestrogen receptors expression in ovariectomized rats. Li, W; Liu, YH, 2009)	0.35
" Mouse pups were dosed orally with genistein in a soy formula-corn oil emulsion from Postnatal Day (PND) 1 to PND 5, then effects on reproductive and non-reproductive organs were assessed after dosing and during subsequent development."	( Acute and chronic effects of oral genistein administration in neonatal mice. Andrews, RN; Cimafranca, MA; Cooke, PS; Davila, J; Doerge, DR; Ekman, GC; Flaws, JA; Helferich, WG; Neese, SL; Peretz, J; Sarkar, J; Schantz, SL; Woodling, KA, 2010)	0.36
" Women undergoing treatment for osteoporosis require long-term dosing therapeutic regimens, that offer no symptomatic relief, and may cause side effects."	( Genistein aglycone: a dual mode of action anti-osteoporotic soy isoflavone rebalancing bone turnover towards bone formation. Altavilla, D; Bitto, A; D'Anna, R; Granese, R; Irrera, N; Marini, H; Minutoli, L; Polito, F; Squadrito, F, 2010)	0.36
" In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test in animals dosed at levels up to the standard limit of 2000 mg/kg."	( Genotoxicity assessment of S-equol in bacterial mutation, chromosomal aberration, and rodent bone marrow micronucleus tests. Jackson, R; Proudlock, R; Schwen, R, 2010)	0.36
" These models have used various dosing strategies to mimic the phytoestrogen levels in human populations."	( Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes. Jefferson, WN; Williams, CJ, 2011)	0.37
" The coincubation of increasing concentration of E2 (10(-12)-10(-6) M) with 10 μM of tested compounds resulted in a downward shift of E2-ERE dose-response curves."	( Estrogenic activities of sesame lignans and their metabolites on human breast cancer cells. Mahidol, C; Pianjing, P; Rangkadilok, N; Satayavivad, J; Thiantanawat, A; Watcharasit, P, 2011)	0.37
"5 μg/rat) and progesterone (500 μg/rat) were acutely treated by oral gavage with Humulus lupulus extract dosed at 5, 10 and 25mg/kg and then tested for partner preference and sexual receptivity."	( Increased sexual motivation in female rats treated with Humulus lupulus L. extract. Benelli, A; Carnevale, G; Di Viesti, V; Zanoli, P; Zavatti, M, 2011)	0.37
"Consumption of dietary isoflavones or equol exposure in rats has body weight controlling effects and equol specifically may have antidepressant potential dependent upon diet initiation and/or dosage of treatments."	( Neuromodulation by soy diets or equol: anti-depressive & anti-obesity-like influences, age- & hormone-dependent effects. Blake, C; Fabick, KM; Lephart, ED; Lund, TD; Setchell, KD, 2011)	0.37
" These results indicate that equol at low dosage can prevent skeletal muscle cell damage induced by H(2)O(2), while pretreatment with high-dosage equol shows a synergistic effect with H(2)O(2) in inducing cell damage."	( Antioxidant effect of a phytoestrogen equol on cultured muscle cells of embryonic broilers. Lu, LZ; Ni, YD; Wei, XJ; Wu, J; Zhao, RQ, 2011)	0.37
" comosa extract which are required for clinical dose and dosage design."	( Pharmacokinetics and organ distribution of diarylheptanoid phytoestrogens from Curcuma comosa in rats. Hu, Y; Piyachuturawat, P; Sripanidkulchai, B; Sripanidkulchai, K; Su, J; Suksamrarn, A, 2012)	0.62
" Isoformo at the concentration reaching the bone marrow achieved out of its most effective oral dosing induced stromal cell mineralization and osteogenic gene expression in the calvaria of neonatal rats."	( Isoformononetin, a methoxydaidzein present in medicinal plants, reverses bone loss in osteopenic rats and exerts bone anabolic action by preventing osteoblast apoptosis. Changkija, B; Chattopadhyay, N; Dixit, M; Jain, GK; Khan, K; Khan, MP; Kumar, A; Lahiri, S; Maurya, R; Nagar, GK; Singh, D; Singh, SP; Srivastava, K; Trivedi, R; Tyagi, AM; Yadav, DK, 2013)	0.39
" Although the literature contains many facts concerning PEs and the breast, further prospective studies are needed to identify structural breast changes produced by PEs in order to identify the appropriate dosage and indications of use."	( Clinical and ultrasonographic changes of the breast after use of soy isoflavones. Afshar, S; Alipour, S; Bayani, L; Dastjerdi, MV; Eslami, B; Hosseini, L; Moini, A; Saberi, A, 2012)	0.38
" In an initial dose-response study, SIL in a dose of 50mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone."	( Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats. Abdel-Naim, AB; Atawia, RT; Khalifa, AE; Mosli, HA; Tadros, MG, 2013)	0.39
"The relatively modest benefit of vasomotor symptom relief in clinical trials of isoflavones may reflect once-daily dosing and low percentages of participants who are able to metabolize daidzein into equol, a potentially more biologically active isoflavone."	( Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial. Churchill, L; Crawford, SL; Jackson, EA; Lampe, JW; Leung, K; Ockene, JK, 2013)	0.39
"We randomized 130 perimenopausal (no menses in the past 3 mo) and postmenopausal (≥12 mo of amenorrhea) women with a mean of five or more moderate/severe hot flashes per day to treatment arms with varying total daily isoflavone doses and dosing frequency, separately for equol producers and nonproducers."	( Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial. Churchill, L; Crawford, SL; Jackson, EA; Lampe, JW; Leung, K; Ockene, JK, 2013)	0.39
"Hot flash intensity scores were lowest in women randomized to the highest total daily dose (100-200 mg) and in women randomized to the highest dosing frequency (twice daily to thrice daily), with greater benefits on nighttime scores than on daytime scores."	( Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial. Churchill, L; Crawford, SL; Jackson, EA; Lampe, JW; Leung, K; Ockene, JK, 2013)	0.39
"These results suggest that a twice-daily to thrice-daily dosing frequency may improve the benefit of isoflavones for vasomotor symptom relief, particularly in equol producers and for nighttime symptoms."	( Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial. Churchill, L; Crawford, SL; Jackson, EA; Lampe, JW; Leung, K; Ockene, JK, 2013)	0.39
" Further investigation in a mouse model of human menopause indicates that chronic exposure to the phyto-β-SERM formulation at a clinically relevant dosage prevents/alleviates menopause-related climacteric symptoms."	( Early intervention with an estrogen receptor β-selective phytoestrogenic formulation prolongs survival, improves spatial recognition memory, and slows progression of amyloid pathology in a female mouse model of Alzheimer's disease. Brinton, RD; Chen, S; Mao, Z; Schneider, LS; Zhao, L, 2013)	0.39
"Six-month consumption of whole soy and purified daidzein at provided dosage had no improvement on body weight and composition compared with isocaloric milk placebo among prehypertensive equol-producing postmenopausal women."	( A six-month randomized controlled trial of whole soy and isoflavones daidzein on body composition in equol-producing postmenopausal women with prehypertension. Chen, YM; Ho, SC; Liu, ZM; Woo, J, 2013)	0.39
" A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture."	( Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus. Li, J; Li, N; Li, X; Li, Z; Liu, J; Liu, T; Xiao, H; Zhao, H, 2014)	0.4
" From postnatal day (PND) 1 to 22, rat pups were daily orally dosed with 50mg/kg Gen to mimic blood Gen levels in human infants fed soy formula."	( Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats. Flaws, JA; Helferich, WG; Lezmi, S; Pan, YX; Schantz, SL; Strakovsky, RS, 2014)	0.4
" In summary, oral dosing of GEN reduced the incidence and increased the time to onset of T1D in female NOD mice but only when fed a soy- and alfalfa-free diet."	( Genistein protects female nonobese diabetic mice from developing type 1 diabetes when fed a soy- and alfalfa-free diet. Auttachoat, W; Elmore, SA; Germolec, DR; Guo, TL; Kooistra, L; Smith, MJ; White, KL; Zheng, JF, 2015)	0.42
" A hundred and seventy-five 30-day-old male Wistar rats were dosed orally by stomach tube every day for 35 days, with saline solution, low and high doses of genistein, daidzein and a mixture of both."	( The effects of isoflavones on androgens and glucocorticoids during puberty on male Wistar rats. Caceres, S; Illera, JC; Illera, MJ; Martinez-Fernandez, L; Millan, P; Monsalve, B; Peña, L; Silvan, G, 2014)	0.4
" Pregnant Sprague Dawley rats were gavaged from Gestational Day 14 to birth with corn oil, genistein, DEHP, or their mixture at 10 mg/kg/day, a dose selected from previous dose-response studies using single chemicals for its lack of long-term testicular effects."	( Disruption of rat testis development following combined in utero exposure to the phytoestrogen genistein and antiandrogenic plasticizer di-(2-ethylhexyl) phthalate. Boisvert, A; Culty, M; Duong, TB; Francois, S; Jones, S; Thrane, P, 2014)	0.4
" The dosing regimen for STZ consisted of three 100mg/kg doses (i."	( Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet. Guo, TL; Ling, X; Wang, Y; Xiong, T; Zheng, J, 2014)	0.4
" The notion that these EDs do not follow classical dose-response effects and involve different mechanisms of toxicity from perinatal ages to adulthood highlights the importance of assessing impacts across a range of doses and ages."	( In utero exposure to di-(2-ethylhexyl) phthalate induces testicular effects in neonatal rats that are antagonized by genistein cotreatment. Boisvert, A; Culty, M; Francois, S; Jones, S; Zhang, L, 2015)	0.42
" Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined."	( Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators. Bandelow, S; Hogervorst, E; Kridawati, A; Soni, M; White, LR, 2016)	0.43
" Study-specific relative risks (RR) were pooled in both categorical and dose-response meta-analyses."	( Phyto-oestrogens and colorectal cancer risk: a systematic review and dose-response meta-analysis of observational studies. Botma, A; Chang-Claude, J; Hüsing, A; Jiang, R; Rudolph, A, 2016)	0.43
" Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures."	( Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow. Bateman, ME; Boue, SM; Bratton, MR; Bunnell, BA; Burow, ME; Hayes, DJ; Hunter, RS; Komati, R; Riley, KE; Sridhar, J; Strong, AL; Wang, G, 2017)	0.46
" The model obtained was used to translate in vitro oestrogenic concentration-response curves of genistein to in vivo oestrogenic dose-response curves for intake of genistein and genistin."	( In vitro-in silico-based analysis of the dose-dependent in vivo oestrogenicity of the soy phytoestrogen genistein in humans. Boonpawa, R; Punt, A; Rietjens, IMCM; Spenkelink, A, 2017)	0.46
" To test this hypothesis, we dosed sexually mature female CD-1 mice (35days) with 0, 300, 500, or 1000ppm genistein for 30, 60, 150, and 240days."	( Preconception exposure to dietary levels of genistein affects female reproductive outcomes. Flaws, JA; Hartman, JA; Helferich, WG; Patel, S, 2017)	0.46
" Middle-aged (12-month old) Long-Evans female rats were ovariectomized and orally dosed with either 0 mg, 6 mg, 12 mg or 24 mg of ISL 60 min before testing on the DSA task."	( The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation. Bandara, S; Doerge, DR; Helferich, WG; Khan, IA; Kundu, P; Monaikul, S; Neese, SL; Schantz, SL, )	0.13
" Genistein has intrinsically low oral bioavailability that affects its dose-response activities."	( Increasing protective activity of genistein by loading into transfersomes: A new potential adjuvant in the oxidative stress-related neurodegenerative diseases? Cavalli, R; Cossu, M; Fancello, S; Galleri, G; Gavini, E; Giunchedi, P; Langasco, R; Migheli, R; Rassu, G, 2019)	0.51
"05, indicating a non-monotonic dose-response profile."	( Antineuroinflammation activity of n-butanol fraction of Marsilea crenata Presl. in microglia HMC3 cell line. Agil, M; Hasanah, M; Laswati, H; Ma'arif, B; Mirza, DM, 2020)	0.56
"Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634)."	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Prudêncio, M; Pulkki, K; Pupier, C; Qian, H; Qian, ZP; Qiu, Y; Qu, G; Rahimi, S; Rahman, AU; Ramadan, H; Ramanna, S; Ramirez, I; Randolph, GJ; Rasheed, A; Rault, J; Raviprakash, V; Reale, E; Redpath, C; Rema, V; Remucal, CK; Remy, D; Ren, T; Ribeiro, LB; Riboli, G; Richards, J; Rieger, V; Rieusset, J; Riva, A; Rivabella Maknis, T; Robbins, JL; Robinson, CV; Roche-Campo, F; Rodriguez, R; Rodríguez-de-Cía, J; Rollenhagen, JE; Rosen, EP; Rub, D; Rubin, N; Rubin, NT; Ruurda, JP; Saad, O; Sabell, T; Saber, SE; Sabet, M; Sadek, MM; Saejio, A; Salinas, RM; Saliu, IO; Sande, D; Sang, D; Sangenito, LS; Santos, ALSD; Sarmiento Caldas, MC; Sassaroli, S; Sassi, V; Sato, J; Sauaia, A; Saunders, K; Saunders, PR; Savarino, SJ; Scambia, G; Scanlon, N; Schetinger, MR; Schinkel, AFL; Schladweiler, MC; Schofield, CJ; Schuepbach, RA; Schulz, J; Schwartz, N; Scorcella, C; Seeley, J; Seemann, F; Seinige, D; Sengoku, T; Seravalli, J; Sgromo, B; Shaheen, MY; Shan, L; Shanmugam, S; Shao, H; Sharma, S; Shaw, KJ; Shen, BQ; Shen, CH; Shen, P; Shen, S; Shen, Y; Shen, Z; Shi, J; Shi-Li, L; Shimoda, K; Shoji, Y; Shun, C; Silva, MA; Silva-Cardoso, J; Simas, NK; Simirgiotis, MJ; Sincock, SA; Singh, MP; Sionis, A; Siu, J; Sivieri, EM; Sjerps, MJ; Skoczen, SL; Slabon, A; Slette, IJ; Smith, MD; Smith, S; Smith, TG; Snapp, KS; Snow, SJ; Soares, MCF; Soberman, D; Solares, MD; Soliman, I; Song, J; Sorooshian, A; Sorrell, TC; Spinar, J; Staudt, A; Steinhart, C; Stern, ST; Stevens, DM; Stiers, KM; Stimming, U; Su, YG; Subbian, V; Suga, H; Sukhija-Cohen, A; Suksamrarn, A; Suksen, K; Sun, J; Sun, M; Sun, P; Sun, W; Sun, XF; Sun, Y; Sundell, J; Susan, LF; Sutjarit, N; Swamy, KV; Swisher, EM; Sykes, C; Takahashi, JA; Talmor, DS; Tan, B; Tan, ZK; Tang, L; Tang, S; Tanner, JJ; Tanwar, M; Tarazi, Z; Tarvasmäki, T; Tay, FR; Teketel, A; Temitayo, GI; Thersleff, T; Thiessen Philbrook, H; Thompson, LC; Thongon, N; Tian, B; Tian, F; Tian, Q; Timothy, AT; Tingle, MD; Titze, IR; Tolppanen, H; Tong, W; Toyoda, H; Tronconi, L; Tseng, CH; Tu, H; Tu, YJ; Tung, SY; Turpault, S; Tuynman, JB; Uemoto, AT; Ugurlu, M; Ullah, S; Underwood, RS; Ungell, AL; Usandizaga-Elio, I; Vakonakis, I; van Boxel, GI; van den Beucken, JJJP; van der Boom, T; van Slegtenhorst, MA; Vanni, JR; Vaquera, A; Vasconcellos, RS; Velayos, M; Vena, R; Ventura, G; Verso, MG; Vincent, RP; Vitale, F; Vitali, S; Vlek, SL; Vleugels, MPH; Volkmann, N; Vukelic, M; Wagner Mackenzie, B; Wairagala, P; Waller, SB; Wan, J; Wan, MT; Wan, Y; Wang, CC; Wang, H; Wang, J; Wang, JF; Wang, K; Wang, L; Wang, M; Wang, S; Wang, WM; Wang, X; Wang, Y; Wang, YD; Wang, YF; Wang, Z; Wang, ZG; Warriner, K; Weberpals, JI; Weerachayaphorn, J; Wehrli, FW; Wei, J; Wei, KL; Weinheimer, CJ; Weisbord, SD; Wen, S; Wendel Garcia, PD; Williams, JW; Williams, R; Winkler, C; Wirman, AP; Wong, S; Woods, CM; Wu, B; Wu, C; Wu, F; Wu, P; Wu, S; Wu, Y; Wu, YN; Wu, ZH; Wurtzel, JGT; Xia, L; Xia, Z; Xia, ZZ; Xiao, H; Xie, C; Xin, ZM; Xing, Y; Xing, Z; Xu, S; Xu, SB; Xu, T; Xu, X; Xu, Y; Xue, L; Xun, J; Yaffe, MB; Yalew, A; Yamamoto, S; Yan, D; Yan, H; Yan, S; Yan, X; Yang, AD; Yang, E; Yang, H; Yang, J; Yang, JL; Yang, K; Yang, M; Yang, P; Yang, Q; Yang, S; Yang, W; Yang, X; Yang, Y; Yao, JC; Yao, WL; Yao, Y; Yaqub, TB; Ye, J; Ye, W; Yen, CW; Yeter, HH; Yin, C; Yip, V; Yong-Yi, J; Yu, HJ; Yu, MF; Yu, S; Yu, W; Yu, WW; Yu, X; Yuan, P; Yuan, Q; Yue, XY; Zaia, AA; Zakhary, SY; Zalwango, F; Zamalloa, A; Zamparo, P; Zampini, IC; Zani, JL; Zeitoun, R; Zeng, N; Zenteno, JC; Zepeda-Palacio, C; Zhai, C; Zhang, B; Zhang, G; Zhang, J; Zhang, K; Zhang, Q; Zhang, R; Zhang, T; Zhang, X; Zhang, Y; Zhang, YY; Zhao, B; Zhao, D; Zhao, G; Zhao, H; Zhao, Q; Zhao, R; Zhao, S; Zhao, T; Zhao, X; Zhao, XA; Zhao, Y; Zhao, Z; Zheng, Z; Zhi-Min, G; Zhou, CL; Zhou, HD; Zhou, J; Zhou, W; Zhou, XQ; Zhou, Z; Zhu, C; Zhu, H; Zhu, L; Zhu, Y; Zitzmann, N; Zou, L; Zou, Y, 2022)	0.72
" The effects on reproduction are not dose-response but are influenced by the type of isoflavone and period."	( Isoflavones alter male and female fertility in different development windows. de Oliveira, JM; Langoni de Freitas, GB; Sleiman, HK, 2021)	0.62
" Pregnant rats were grouped into control, 2 mg/kg and 4 mg/kg genistein groups, dosed accordingly till sacrificed at different gestation days (GD)."	( Modulatory role of genistein on placenta and maternal bone minerals composition: further insight into its influence on pregnancy and foetal development. Akinsanya, TH; Awobajo, FO; Egede, CB; Egege, IE; Oyediran, HS; Samuel, TA; Timothy, BO, 2020)	0.56
" Additionally, the dose-response relationships between urinary lignans or enterolactone and depressive symptoms showed a linear trend."	( The association between urinary phytoestrogens and depressive symptoms. Cui, K; Feng, Z; Luo, J; Zhang, D; Zhang, L; Zhang, T, 2022)	1

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	27 (0.75)	18.7374
1990's	259 (7.18)	18.2507
2000's	1649 (45.74)	29.6817
2010's	1371 (38.03)	24.3611
2020's	299 (8.29)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	258 (6.80%)	5.53%
Reviews	844 (22.25%)	6.00%
Case Studies	23 (0.61%)	4.05%
Observational	4 (0.11%)	0.25%
Other	2,665 (70.24%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (77)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
Iowa State Study on Flax Lignans and Heart Health [NCT01314586]		93 participants (Actual)	Interventional	2007-12-31	Completed
Community Alliance for Quality of Life in Long Term Care: Oxidative Stress and Nutritional Supplementation Intervention Study [NCT01234506]	Phase 2	21 participants (Actual)	Interventional	2010-10-31	Completed
Phase II Randomized Placebo-Controlled Clinical Trial of Genistein in Reducing the Toxicity and Improving the Efficacy of Intravesical Therapy [NCT01489813]	Phase 2	44 participants (Actual)	Interventional	2017-05-19	Active, not recruiting
Safety, Pharmacokinetics and Efficacy of AXP107-11 in Combination With Standard Gemcitabine (Gemzar®) Treatment in Patients With Locally Advanced or Metastatic, Unresectable, Adenocarcinoma of the Pancreas, Stage III-IV: A Prospective, Open Label, Multi-c [NCT01182246]	Phase 1/Phase 2	44 participants (Anticipated)	Interventional	2010-11-30	Recruiting
Can Dietary Phytoestrogens Slow Down Prostate Tumor Proliferation? A Randomized Study (PRODICA) [NCT02759380]		240 participants (Anticipated)	Interventional	2016-03-31	Recruiting
A Double-blind Randomized Controlled Trial on Whole Soy and Daidzein Supplementation on Reduction of Blood Pressure in Prehypertensive Postmenopausal Chinese Women [NCT01270737]		270 participants (Anticipated)	Interventional	2011-03-31	Not yet recruiting
Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer [NCT00118040]	Phase 2	60 participants (Actual)	Interventional	2005-06-24	Completed
Effect of Natural S-equol on Blood Pressure and Vascular funtion-a Six-month Randomized, Double-blind and Placebo-controlled Trial Among Equol Non-producers of Postmenopausal Women With Prehypertension or Untreated Stage 1 Hypertension [NCT02515682]		207 participants (Anticipated)	Interventional	2015-10-31	Not yet recruiting
Bioavailability of Isoflavones Delivered by Soy Almond Bread in Men With Recurring Prostate Cancer and Rising Prostate Specific Antigen [NCT01682941]		32 participants (Actual)	Interventional	2009-10-31	Completed
A Pilot Study of Soy Isoflavone, Genistein, in Combination With Radiation Therapy and Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT02075112]	Phase 1	24 participants (Actual)	Interventional	2013-11-30	Completed
A Phase II Study Of Genistein In Patients With Localized Prostate Cancer (Molecular Correlates of Soy In Humans) [NCT00058266]	Phase 2	36 participants (Actual)	Interventional	2002-12-31	Terminated(stopped due to Data Monitoring Committee cited poor accrual.)
S-Equol in Alzheimer's Disease (SEAD) Trial [NCT02142777]	Phase 1	15 participants (Actual)	Interventional	2014-07-31	Completed
Acute Equol Supplementation and Vascular Function in Postmenopausal Women With and Without CKD [NCT06128278]	Phase 2	38 participants (Anticipated)	Interventional	2023-03-07	Recruiting
Arterial Stiffness, Cognition and Equol [NCT05741060]	Phase 2	400 participants (Anticipated)	Interventional	2023-06-29	Recruiting
Randomized, Double Blind, Multicenter, Placebo Controlled, Proof of Concept Trial to Assess the Efficacy and Safety of 4 Weeks Treatment With AUS 131 (S Equol) on Benign Prostatic Hyperplasia [NCT00962390]	Phase 2	116 participants (Actual)	Interventional	2009-06-30	Completed
Randomized, Double Blind, Multicenter, Placebo Controlled, Proof of Concept Trial to Assess the Efficacy and Safety of 4 Weeks Treatment With AUS-131 (S-equol) on Vasomotor Symptoms in Menopausal Patients [NCT00962585]	Phase 2	169 participants (Actual)	Interventional	2010-06-30	Completed
A Phase I/IIa Study of Decitabine in Combination With Genistein in Pediatric Patients With Relapsed or Refractory Solid Tumors and Leukemia [NCT02499861]	Phase 1/Phase 2	6 participants (Actual)	Interventional	2015-07-31	Completed
Phytoestrogen, NO Donors, N-acetyl Cysteine Add Therapy to Clomiphene [NCT02493933]	Phase 1	240 participants (Anticipated)	Interventional	2015-07-31	Not yet recruiting
Soy Treatment for High-risk Women [NCT01219075]		110 participants (Actual)	Interventional	2010-07-01	Completed
Randomized, Double-Blind, Single Rising Dose Study of S-equol in Normal Volunteers [NCT00787007]	Phase 1	60 participants (Actual)	Interventional	2008-09-30	Completed
Phase I Single and Multiple-Dose Safety and Pharmacokinetic Clinical Study of Genistein in Normal Volunteers and in Prostate Neoplasia (Multiple Dose Safety and Pharmacokinetic Clinical Study of Genistein in Prostate Neoplasia) [NCT00005827]	Phase 1	0 participants (Actual)	Interventional	1999-12-31	Withdrawn
Effect of Enteral Genistein Supplementation on Inflammatory Cytokines, Morbidity and Mortality in Patients With Sepsis [NCT02796794]	Phase 4	30 participants (Anticipated)	Interventional	2015-06-30	Recruiting
A Clinical Study Assessing Efficacy of an Herbal Blend on Menopausal Symptoms and Quality of Life [NCT04228757]		130 participants (Actual)	Interventional	2019-06-28	Active, not recruiting
Phase IIB Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer [NCT00290758]	Phase 2	126 participants (Actual)	Interventional	2006-01-31	Completed
Genistein Supplementation to Mitigate Cardiometabolic Dysfunction in Patients Undergoing Androgen Deprivation Therapy for Prostate Cancer [NCT02766478]	Phase 2	10 participants (Actual)	Interventional	2017-10-16	Terminated(stopped due to Enrollment and study activities were suspended due to COVID-19.)
Genistein Stimulates Insulin Sensitivity Through Gut Microbiota Reshaping and Skeletal Muscle AMPK Activation in Obese Subjects [NCT04105023]		45 participants (Actual)	Interventional	2013-09-15	Completed
Phase I-II Trial of Genistein in Subjects Receiving Palliative External Beam Radiation Therapy for Osseous Metastases: A Study of Palliation of Symptoms and Quality of Life [NCT00769990]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2008-09-30	Withdrawn(stopped due to No patient accrual.)
A Pilot Trial of Phenylbutyrate/Genistein Duotherapy in Delta F508-Heterozygous Cystic Fibrosis Patients [NCT00590538]	Phase 1/Phase 2	9 participants (Actual)	Interventional	2003-02-28	Terminated(stopped due to 12/15/2008 Voluntarily placed on inactive status-requested by the PI)
Effects of a Genistein Concentrated Polysaccharide (GCP) on Patients With a Diagnosis of Prostate Cancer on Active Surveillance. [NCT00584532]	Phase 2/Phase 3	66 participants (Actual)	Interventional	2003-11-30	Completed
A Phase 1 Dose Escalation Trial Evaluating the Safety and Pharmacokinetic Profile of BIO 300 Oral Powder in Healthy Volunteers [NCT04650555]	Phase 1	34 participants (Actual)	Interventional	2020-12-08	Completed
A Pre-Surgical, Randomized Clinical Trial of Genistein in Resectable Pancreatic Adenocarcinoma [NCT00882765]	Phase 2	0 participants (Actual)	Interventional	2009-05-31	Withdrawn(stopped due to Study has been closed due to no accrual.)
Randomized, Double-Blind, Rising Multiple Dose Study of S-Equol in Normal Volunteers [NCT00998920]	Phase 1	41 participants (Actual)	Interventional	2008-12-31	Completed
A Pilot Trial of Phenylbutyrate/Genistein Duotherapy in Delta F508-Homozygous Cystic Fibrosis Patients [NCT00016744]	Phase 1/Phase 2	12 participants (Actual)	Interventional	2001-09-30	Completed
The Effect of Genistein (Supro®) on Coronary Artery Diameter and Blood Flow in Men and Women With Coronary Heart Disease [NCT00287690]	Phase 2/Phase 3	71 participants (Actual)	Interventional	1999-10-31	Completed
Effect of Activation of the Receptor PPARg/RXR as a Possible Treatment for Alzheimer's Disease. Role of Genistein. [NCT01982578]		27 participants (Actual)	Interventional	2017-09-01	Completed
A Phase I/II Clinical Study Evaluating the Safety and Effectiveness of BIO 300 Oral Suspension in Patients Receiving Chemoradiation Therapy for Non-Small Cell Lung Cancer (NSCLC) [NCT02567799]	Phase 1/Phase 2	21 participants (Actual)	Interventional	2015-11-30	Completed
A Pharmacokinetic Study of Genistein, a Tyrosine Kinase Inhibitor [NCT00001696]	Phase 1	15 participants	Interventional	1998-04-30	Completed
Phase 2 Trial of Genistein in Men With Circulating Prostate Cancer Cells [NCT01126879]	Phase 2	12 participants (Actual)	Interventional	2011-02-03	Terminated(stopped due to Closed due to low accrual)
Flaxseed Lignan as a Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer [NCT01276704]	Phase 2	180 participants (Actual)	Interventional	2011-01-31	Terminated(stopped due to accrual rate lower than anticipated; funding expired)
A Randomized, Placebo-Controlled Pilot Study of Genistein Supplementation in Pediatric Cancer Patients Receiving Myelosuppressive Chemotherapy [NCT02624388]	Phase 2	4 participants (Actual)	Interventional	2016-08-31	Terminated(stopped due to Poor enrollment)
The Effect of Increased Soy Protein Intake on Bone Metabolism [NCT00661856]		203 participants (Actual)	Interventional	2001-01-31	Completed
A Phase II Trial of a Combination Herbal Therapy for Men With Biochemical Recurrence of Prostate Cancer After Initial Local Therapy [NCT00669656]	Phase 2	43 participants (Actual)	Interventional	2008-07-06	Completed
Effects of Estradiol and Soy on Menopausal Symptoms [NCT00997893]	Phase 2	96 participants (Actual)	Interventional	2009-12-31	Completed
Safety Profile and Bone Efficacy of the Phytoestrogen Genistein in a Cohort of Osteopenic, Postmenopausal Women After Three Years of Treatment: a Follow-up Study [NCT00626769]		138 participants (Actual)	Observational	2005-07-31	Completed
The Study of the Effects of Soy Isoflavones on the Metabolism of Glucose and Lipids in Postmenopausal Chinese Women With Impaired Glucose Regulation [NCT00951912]		165 participants (Actual)	Interventional	2009-08-31	Completed
A Pilot Study of the Effect of Genistein in Combination With High-Dose Interleukin-2 on Cell Expansion and Gene Expression in Patients With Metastatic Melanoma or Renal Cell Carcinoma [NCT00276835]	Early Phase 1	15 participants (Actual)	Interventional	2005-11-30	Completed
Exercise and Phytoestrogens: a Synergistic Effect on Factors Predisposing to CVD in Postmenopausal Women [NCT01048606]	Phase 4	45 participants (Actual)	Interventional	2009-01-31	Completed
The Effects of Red Clover Treatment on Bone Tissue Regulation in Postmenopausal Osteopenia. [NCT02174666]		85 participants (Actual)	Interventional	2014-06-30	Completed
A Double-Blind, Randomized, Placebo-Controlled Study to Assess a Nutritional Supplement on Vasomotor Symptoms In Perimenopausal and Menopausal Women [NCT04516304]		118 participants (Actual)	Interventional	2019-03-27	Completed
Effects of Synthetic Genistein Supplementation on Blood and Tissue Biomarkers in Patients With Localized Prostate Cancer [NCT00546039]	Phase 2	47 participants (Actual)	Interventional	2007-04-30	Active, not recruiting
Genistein Use in Postmenopausal Women With Metabolic Syndrome [NCT00541710]	Phase 2/Phase 3	120 participants (Actual)	Interventional	2007-10-31	Completed
Phase I Multiple Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women [NCT00099008]	Phase 1	30 participants (Actual)	Interventional	2004-03-31	Completed
Community Alliance for Quality of Life in Long Term Care: Single Oral Dose of BeneFlax to Healthy Young and Older Adults [NCT01531569]	Phase 2	22 participants (Actual)	Interventional	2011-12-31	Completed
Clinical Trial on the Effectiveness of the Flavonoids Genistein and Quercetin in Men With Rising Prostate-specific Antigen [NCT01538316]		60 participants (Anticipated)	Interventional	2012-03-31	Recruiting
Dietary Phytoestrogens and Bone Metabolism [NCT00010686]	Phase 2	0 participants	Interventional		Completed
[NCT00061711]		355 participants	Interventional	2000-07-31	Completed
Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study [NCT01985763]	Phase 1/Phase 2	13 participants (Actual)	Interventional	2013-11-30	Completed
[NCT00355953]	Phase 2/Phase 3	400 participants	Interventional	2003-01-31	Completed
Metabolism and Bone Health [NCT00244907]	Phase 1	23 participants (Actual)	Interventional	2006-01-31	Completed
Effects of a Genistein Combined Polysaccharide (GCP) on Patients With a Diagnosis of Prostate Cancer on Active Surveillance. [NCT00269555]		62 participants	Interventional	2004-05-31	Completed
Impact of Phytoestrogens on Serum Lipids in Postmenopausal Women [NCT01497977]	Phase 4	74 participants (Actual)	Interventional	2008-09-30	Completed
A Phase I/IIa Dose-Escalation Study of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer (NSCLC) Subjects [NCT01628471]	Phase 1/Phase 2	20 participants (Actual)	Interventional	2012-11-30	Completed
Role of Genistein on Metabolic Syndrome in Post-menopausal Women [NCT01664650]	Phase 2/Phase 3	120 participants (Actual)	Interventional	2008-09-30	Completed
Once-Daily Oral Dose of BeneFlax to Healthy Older Adults [NCT01846117]	Phase 1/Phase 2	32 participants (Actual)	Interventional	2013-04-30	Completed
Phytoestrogens as an Alternative to Estradiol in Reversing the Antiestrogenic Effect of Clomid on Endometrium in Ovulation Induction in Cases of Polycystic Ovarian Syndrome [NCT02352597]	Phase 4	150 participants (Actual)	Interventional	2013-01-31	Completed
Examination of the Bioavailability and Bioactivity of the Two Natural Food Ingredients 6-Prenylnaringenin and 8-Prenylnaringenin. [NCT03140397]	Early Phase 1	16 participants (Actual)	Interventional	2016-01-31	Completed
A Phase I Study of B43-Genistein Immunoconjugate in Recurrent B-Lineage Acute Lymphoblastic Leukemia and Non Hodgkin's Lymphoma [NCT00004858]	Phase 1	0 participants	Interventional	2000-03-31	Active, not recruiting
Phase IIA, Randomized Placebo-Controlled Trial of Single High Dose Cholecalciferol and Daily Genistein (G-2535) Versus Placebo in Men With Early Stage Prostate Cancer Undergoing Prostatectomy [NCT01325311]	Phase 2	15 participants (Actual)	Interventional	2011-12-31	Completed
Metabolic, Endocrine, and Central Effects of Genistein Aglycone in Glucocorticoid Induced Osteoporosis [NCT03040531]	Phase 2/Phase 3	200 participants (Anticipated)	Interventional	2017-01-19	Recruiting
Effect of Two Different Isoflavone Supplement Preparations on Gene-expression in Postmenopausal Women [NCT01556737]		72 participants (Actual)	Interventional	2011-11-30	Completed
[NCT00000613]	Phase 2	0 participants	Interventional	1997-04-30	Completed
A Pre-surgical Clinical Trial of Therapy With S-equol in Women With Triple Negative Breast Cancer. [NCT02352025]	Early Phase 1	39 participants (Actual)	Interventional	2015-04-15	Completed
Phase II Trial of Gemcitabine and Genistein in Metastatic Breast Cancer Patients With Biomarker Assays [NCT00244933]	Phase 2	19 participants (Actual)	Interventional	2004-02-29	Completed
Phase II Trial of Novasoy®, Gemcitabine, and Erlotinib in Locally Advanced or Metastatic Pancreatic Cancer [NCT00376948]	Phase 2	20 participants (Actual)	Interventional	2005-05-31	Completed
Combined Natural Molecules Improve Markers of Metabolic Syndrome and Climacteric in Menopausal Women [NCT06057896]		200 participants (Actual)	Observational	2022-09-30	Completed
Effect of Soy Phytoestrogens and Acupuncture on Bone Mineral Density in Female Athlete Triad at Adolescence Age [NCT04748250]		60 participants (Actual)	Interventional	2020-07-20	Completed
S-Equol in Alzheimer's Disease 2 (SEAD2) Trial [NCT03101085]	Phase 1/Phase 2	40 participants (Actual)	Interventional	2017-05-05	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT00118040 (14) [back to overview]	Activated Caspase 3 in Tumor Tissue
NCT00118040 (14) [back to overview]	AKT in Tumor Tissue
NCT00118040 (14) [back to overview]	BLCA-4 in Urine by Visit
NCT00118040 (14) [back to overview]	COX2 in Tumor Tissue
NCT00118040 (14) [back to overview]	EGFR in Benign Tissue
NCT00118040 (14) [back to overview]	EGFR Mutations in Tumor Tissue
NCT00118040 (14) [back to overview]	Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment
NCT00118040 (14) [back to overview]	Ki-67 in Tumor Tissue
NCT00118040 (14) [back to overview]	MAP Kinase in Tumor Tissue
NCT00118040 (14) [back to overview]	pAKT in Tumor Tissue
NCT00118040 (14) [back to overview]	pEGFR in Benign Tissue
NCT00118040 (14) [back to overview]	pMAP Kinase in Tumor Tissue
NCT00118040 (14) [back to overview]	Survivin in Tumor Tissue
NCT00118040 (14) [back to overview]	Survivin in Urine by Visit (pg/ml)
NCT00244933 (1) [back to overview]	Objective Response Rate by RECIST Criteria Following
NCT00287690 (3) [back to overview]	Coronary Blood Flow
NCT00287690 (3) [back to overview]	Serum Genistein Concentrations
NCT00287690 (3) [back to overview]	Coronary Artery Diameter
NCT00290758 (12) [back to overview]	Monitor Drug Delivery by Measuring Plasma Genistein by HPLC
NCT00290758 (12) [back to overview]	Plasma Concentration of Sex Hormone Binding Globulin (SHBG)
NCT00290758 (12) [back to overview]	Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol
NCT00290758 (12) [back to overview]	Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2
NCT00290758 (12) [back to overview]	Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2
NCT00290758 (12) [back to overview]	Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling
NCT00290758 (12) [back to overview]	Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells.
NCT00290758 (12) [back to overview]	Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)
NCT00290758 (12) [back to overview]	Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)
NCT00290758 (12) [back to overview]	Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol
NCT00290758 (12) [back to overview]	Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D
NCT00290758 (12) [back to overview]	Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D
NCT00376948 (7) [back to overview]	Time to Progression
NCT00376948 (7) [back to overview]	Median Overall Survival Estimate
NCT00376948 (7) [back to overview]	Time to Treatment Failure
NCT00376948 (7) [back to overview]	Response Duration
NCT00376948 (7) [back to overview]	Patients Alive
NCT00376948 (7) [back to overview]	Overall Objective Response Rate (Complete and Partial Response)
NCT00376948 (7) [back to overview]	Grade 3 or Higher Toxicity Evaluation
NCT00951912 (15) [back to overview]	Percentage Change in Triglyceride
NCT00951912 (15) [back to overview]	Urinary Daidzein
NCT00951912 (15) [back to overview]	Percentage Change in Total Cholesterol
NCT00951912 (15) [back to overview]	Percentage Change in QUICKI
NCT00951912 (15) [back to overview]	Percentage Change in HOMA-IR
NCT00951912 (15) [back to overview]	Percentage Change in High Density Lipoprotein Cholesterol
NCT00951912 (15) [back to overview]	Urinary Genistein
NCT00951912 (15) [back to overview]	Percentage Change in Fasting Plasma Insulin
NCT00951912 (15) [back to overview]	Total Urinary Isoflavones
NCT00951912 (15) [back to overview]	Total Energy Intake at Follow-up
NCT00951912 (15) [back to overview]	Percentage Change in Fasting Plasma Glucose
NCT00951912 (15) [back to overview]	Percentage Change in AUC of Glucose
NCT00951912 (15) [back to overview]	Percentage Change in 120-minutes Postload Plasma Glucose
NCT00951912 (15) [back to overview]	Percentage Change in Low Density Lipoprotein Cholesterol
NCT00951912 (15) [back to overview]	Percentage Change in HbA1C
NCT00962390 (14) [back to overview]	Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.
NCT00962390 (14) [back to overview]	Investigators Assessment of Nocturia at Week 4
NCT00962390 (14) [back to overview]	Participants Assessment of Nocturia at Week 4
NCT00962390 (14) [back to overview]	Change in DAN Prostate Symptom Scale From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in I-PSS Total Score From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in in Dihydrotestosterone Concentration From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in Luteinizing Hormone Concentration From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in Post-Void Residual Volume From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in Prostate Volume From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in Qmax From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in Total Testosterone Concentration From Baseline at Week 4
NCT00962390 (14) [back to overview]	Change in Void Volume From Baseline at Week 4
NCT00962390 (14) [back to overview]	Percent Change in Qmax From Baseline at Week 4
NCT00962390 (14) [back to overview]	Categorical Change in Qmax From Baseline at Week 4
NCT00962585 (14) [back to overview]	Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4
NCT00962585 (14) [back to overview]	Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort)
NCT00962585 (14) [back to overview]	Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2
NCT00962585 (14) [back to overview]	Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4
NCT00962585 (14) [back to overview]	Change From Baseline in Estradiol Concentration at Weeks 2 and 4
NCT00962585 (14) [back to overview]	Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined
NCT00962585 (14) [back to overview]	Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort)
NCT00962585 (14) [back to overview]	Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period)
NCT00962585 (14) [back to overview]	Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined
NCT00962585 (14) [back to overview]	Change From Baseline in Progesterone Concentration at Week 2 and Week 4
NCT00962585 (14) [back to overview]	Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4
NCT00962585 (14) [back to overview]	Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period)
NCT00962585 (14) [back to overview]	Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4
NCT00962585 (14) [back to overview]	Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4
NCT00997893 (5) [back to overview]	Memory for Emotionally Valent Words and Neutral Words
NCT00997893 (5) [back to overview]	Change in Verbal Memory, Immediate Recall
NCT00997893 (5) [back to overview]	Change in Verbal Memory, Delayed Recall
NCT00997893 (5) [back to overview]	Change in STAI-6 Score
NCT00997893 (5) [back to overview]	Changes in STAI-6 Scores Before and After Psychosocial Stressor Over Time
NCT01048606 (1) [back to overview]	Body Composition: Dual-energy X-ray Absorptiometry Method
NCT01276704 (2) [back to overview]	Breast Cancer Prevention Trial (BCPT) Symptom Checklist
NCT01276704 (2) [back to overview]	Change in Percent of Breast Epithelial Cells With Ki-67 Immunocytochemical Expression
NCT01325311 (15) [back to overview]	PBMC CYP mRNA Expression of CYP27B1
NCT01325311 (15) [back to overview]	Tissue Levels of Calcitriol Between the Placebo and Cholecalciferol/Genistein Arms
NCT01325311 (15) [back to overview]	Detectability of Calcitriol Levels in Tissue Between the Placebo and Cholecalciferol/Genistein Arms
NCT01325311 (15) [back to overview]	Immunohistochemistry Measurements in Benign Prostate Tissue (BPT)
NCT01325311 (15) [back to overview]	Levels of Calcidiol in the Participants Serum
NCT01325311 (15) [back to overview]	Levels of Calcitriol in Participants Serum
NCT01325311 (15) [back to overview]	Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene)
NCT01325311 (15) [back to overview]	Serum Calcium Levels at Baseline and Pre-Surgery
NCT01325311 (15) [back to overview]	Total IGF-1 in Serum at Baseline and Pre-Surgery
NCT01325311 (15) [back to overview]	Total IGF-2 in Serum at Baseline and Pre-Surgery
NCT01325311 (15) [back to overview]	Total IGFBP-3 in Serum at Baseline and Pre-Surgery
NCT01325311 (15) [back to overview]	Total PSA in Serum
NCT01325311 (15) [back to overview]	Immunohistochemistry Measurements in Prostate Cancer Tissue (PCA)
NCT01325311 (15) [back to overview]	Total PTH in Serum at Baseline and Pre-Surgery
NCT01325311 (15) [back to overview]	PBMC CYP mRNA Expression of CYP24
NCT01985763 (9) [back to overview]	Overall Survival (OS)
NCT01985763 (9) [back to overview]	Best Overall Response Rate RECIST Criteria
NCT01985763 (9) [back to overview]	Number of Participants With an Overall Response Rate (ORR)
NCT01985763 (9) [back to overview]	Number of Participants With Best Overall Response Rate (ORR)
NCT01985763 (9) [back to overview]	Percent Change in Tumor Size
NCT01985763 (9) [back to overview]	Number of Adverse Events
NCT01985763 (9) [back to overview]	Percent of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months
NCT01985763 (9) [back to overview]	Response Rate RECIST Criteria
NCT01985763 (9) [back to overview]	Progression Free Survival (PFS)
NCT02567799 (21) [back to overview]	FVC as Measured by Pulmonary Function Test (PFT)
NCT02567799 (21) [back to overview]	Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300
NCT02567799 (21) [back to overview]	Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300
NCT02567799 (21) [back to overview]	Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1)
NCT02567799 (21) [back to overview]	Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) Patient Reported Outcome Questionnaire.
NCT02567799 (21) [back to overview]	Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire.
NCT02567799 (21) [back to overview]	Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin
NCT02567799 (21) [back to overview]	FEV1 as Measured by Pulmonary Function Test (PFT)
NCT02567799 (21) [back to overview]	Number of Participants With Adverse Events Throughout the Study
NCT02567799 (21) [back to overview]	Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]	Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT)
NCT02567799 (21) [back to overview]	Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan
NCT02567799 (21) [back to overview]	DLCO as Measured by Pulmonary Function Test (PFT)
NCT02567799 (21) [back to overview]	Extent of Esophagitis by Patient Reported Swallowing Diary
NCT02567799 (21) [back to overview]	Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy
NCT02567799 (21) [back to overview]	Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin
NCT02567799 (21) [back to overview]	Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]	Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy
NCT02567799 (21) [back to overview]	Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin
NCT02567799 (21) [back to overview]	Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]	Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300
NCT02766478 (4) [back to overview]	Arterial Stiffness
NCT02766478 (4) [back to overview]	Vascular Endothelial Function at Baseline and Week 8 Post-baseline
NCT02766478 (4) [back to overview]	β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline
NCT02766478 (4) [back to overview]	Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline

Activated Caspase 3 in Tumor Tissue

"Detecting the signal of the biomarker, Activated Caspase 3, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.~Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms." (NCT00118040)
Timeframe: up to 21 days on Study Drug

,,,

Intervention	percentage of Caspase 3 strength signal (Number)
	Strong	Moderate	Weak	Negative
Arm I (300mg Genistein)	10.53	0.00	26.32	63.16
Arm II (600mg Genistein)	11.11	5.56	27.78	55.56
Arm III (Placebo)	0.00	6.67	26.67	66.67
Arm IV (300mg Genistein + 600mg Genistein)	10.81	2.70	27.03	59.46

Intervention	pg/ml (Mean)
	Baseline	Day 8	Pre-Surgery
Arm I (300mg Genistein)	0.52	0.54	0.59
Arm II (600mg Genistein)	0.55	0.50	0.44
Arm III (Placebo)	0.46	0.53	0.49
Arm IV (300mg Genistein + 600mg Genistein)	0.54	0.52	0.52

Intervention	ng/ml (Median)
	Postmenopausal with ER- Cancer	Postmenopausal with ER+ Cancer	Postmenopausal Without Cancer	Premenopausal with ER- Cancer	Premenopausal with ER+ Cancer	Premenopausal without cancer
Arm A (Genistein)	368.62	65.20	190.42	472.09	423.12	269.88
Arm B (Placebo)	0	0	0.65	4.56	3.80	3.57

Intervention	ng/ml (Mean)
	Post menopausal with ER- cancer	Post menopausal without cancer	Pre menopausal with ER- cancer	Pre menopausal without Cancer
Arm I (Genistein)	-28.00	-14.17	-16.68	-20.49

Intervention	ng/ml (Mean)
	Post menopasual with ER+ caner	Post menopausal without cancer	Pre menopausal with ER- cancer	Pre menopausal with ER+ cancer	Pre menopausal without Cancer
Arm II (Placebo)	-61.06	-6.10	4.69	-31.46	12.17

Intervention	Participants (Count of Participants)
	diarrhea	fatigue	infection	nausea	neutrophil	pain	platelet	stomach mucostis	vomiting	wbc	other toxicity
Novasoy®, Gemcitabine & Erlotinib	3	5	1	7	4	5	1	1	4	2	4

Intervention	ng/mL (Least Squares Mean)
S-equol 10 mg BID	-0.1
S-equol 50 mg BID	-0.1
S-equol 150 mg BID	-0.3
Placebo BID	-0.4

Intervention	units on a scale (Mean)
	Total Score, Week 4 Values	Total Score, Change from Baseline	Sexual Function Score, Week 4 Values	Sexual Function Score, Change from Baseline
Placebo BID	20.3	-10.0	4.7	0.3
S-equol 10 mg BID	17.7	-8.2	2.2	-0.3
S-equol 150 mg BID	22.7	-4.7	5.6	-1.2
S-equol 50 mg BID	22.1	-11.5	4.2	0.2

Intervention	units on a scale (Mean)
	Week 4 Values	Change from Baseline
Placebo BID	15.07	-5.96
S-equol 10 mg BID	15.56	-5.81
S-equol 150 mg BID	17.54	-4.15
S-equol 50 mg BID	17.46	-6.18

Intervention	Participants (Count of Participants)
	Week 4 Values, <=30%	Week 4 Values, >30%
Placebo BID	19	9
S-equol 10 mg BID	18	7
S-equol 150 mg BID	13	9
S-equol 50 mg BID	22	4

Intervention	Participants (Count of Participants)
	Week 4 Values, <=2 mL/sec	Week 4 Values, >2 mL/sec
Placebo BID	17	11
S-equol 10 mg BID	17	8
S-equol 150 mg BID	13	10
S-equol 50 mg BID	19	7

Intervention	Percentage Change (Mean)
S-equol 10 mg BID	-36.7
S-equol 50 mg BID	-37.4
S-equol 150 mg BID	-30.6
Placebo	-27.4

Intervention	Percentage Change (Mean)
S-equol 10 mg BID	-29.1
S-equol 50 mg BID	-32.7
S-equol 150 mg BID	-30.2
Placebo	-0.6

Intervention	Number of MSVS/week (Mean)
	Week 1	Change from Baseline at Week 1	Week 1, LSMean	Week 2	Change from Baseline at Week 2	Week 2, LSMean
Placebo	54.1	-13.8	54.72	50.0	-17.9	50.66
S-equol 10 mg BID	53.6	-19.9	50.95	47.3	-23.3	43.96
S-equol 150 mg BID	54.4	-15.9	56.03	51.0	-19.4	51.56
S-equol 50 mg BID	63.1	-6.7	64.41	54.3	-14.8	54.22

Intervention	units on a scale (Mean)
	Baseline (Day 0)	Week 2	Change from Baseline at Week 2	Week 2, LSMean	Week 4	Change from Baseline at Week 4	Week 4, LSMean
Placebo	5.7	5.8	0.0	5.72	5.8	0.0	5.74
S-equol 10 mg BID	5.5	5.4	-0.1	5.51	5.4	-0.2	5.48
S-equol 150 mg BID	5.8	5.8	-0.0	5.75	5.6	-0.3	5.50
S-equol 50 mg BID	5.5	5.4	-0.1	5.49	5.5	-0.0	5.61

Intervention	Proportion Correct (Mean)
	Baseline (Week 0)- Control	Baseline (Week 0)- TSST	Post-Treatment (Week 12)- Control	Post-Treatment (Week 12)-TSST
Estradiol/Medroxyprogesterone Acetate	0.45	0.48	0.47	0.51
Phytoestrogen	0.45	0.40	0.42	0.46
Placebo	0.38	0.47	0.37	0.44

Intervention	test scores on the Logical Memory test (Mean)
Estradiol/Medroxyprogesterone Acetate	-.02
Phytoestrogen	2.31
Placebo	2.08

Intervention	Test scores on the Logical Memory test (Mean)
Estradiol/Medroxyprogesterone Acetate	.87
Phytoestrogen	1.61
Placebo	1.08

Intervention	score on STAI scale (Mean)
	Baseline (Week 0)	Early-Treatment(Week 10)	Late-Treatment(Week 12)	Post-Treatment (Week 16-18)
Estradiol/Medroxyprogesterone Acetate	12.31	11.69	12.88	11.84
Phytoestrogen	11.85	11.38	10.99	11.19
Placebo	10.76	11.24	10.55	11.15

Intervention	score on STAI scale (Mean)
	Baseline (Week 0), Before Stressor	Baseline (Week 0), After Stressor	Post-Treatment (Week 12), Before Stressor	Post-Treatment (Week 12), After Stressor
Estradiol/Medroxyprogesterone Acetate	8.73	12.61	8.25	13.70
Phytoestrogen	8.69	12.92	10.87	15.37
Placebo	9.77	12.23	9.61	12.69

Intervention	percent of total fat mass (Mean)
Placeco + Exercise	44.5
Phytoestrogens Without Exercise	48.8
Phytoestrogens + Exercise	43.8
Placebo Without Exercise	46.6

phytoestrogens

Description

Cross-References

Synonyms (2)

Research Excerpts

Overview

Effects

Actions

Treatment

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Research

Studies (3,605)

Market Indicators

Research Demand Index: 97.22

Study Types

Clinical Trials (77)

Trial Overview

Trial Outcomes

Activated Caspase 3 in Tumor Tissue

AKT in Tumor Tissue

BLCA-4 in Urine by Visit

COX2 in Tumor Tissue

EGFR in Benign Tissue

EGFR Mutations in Tumor Tissue

Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment

Ki-67 in Tumor Tissue

MAP Kinase in Tumor Tissue

pAKT in Tumor Tissue

pEGFR in Benign Tissue

pMAP Kinase in Tumor Tissue

Survivin in Tumor Tissue

Survivin in Urine by Visit (pg/ml)

Objective Response Rate by RECIST Criteria Following

Coronary Blood Flow

Serum Genistein Concentrations

Coronary Artery Diameter

Monitor Drug Delivery by Measuring Plasma Genistein by HPLC

Plasma Concentration of Sex Hormone Binding Globulin (SHBG)

Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol

Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2

Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2

Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling

Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells.

Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)

Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)

Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol

Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D

Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D

Time to Progression

Median Overall Survival Estimate

Time to Treatment Failure

Response Duration

Patients Alive

Overall Objective Response Rate (Complete and Partial Response)

Grade 3 or Higher Toxicity Evaluation

Percentage Change in Triglyceride

Urinary Daidzein

Percentage Change in Total Cholesterol

Percentage Change in QUICKI

Percentage Change in HOMA-IR

Percentage Change in High Density Lipoprotein Cholesterol

Urinary Genistein

Percentage Change in Fasting Plasma Insulin

Total Urinary Isoflavones

Total Energy Intake at Follow-up

Percentage Change in Fasting Plasma Glucose

Percentage Change in AUC of Glucose

Percentage Change in 120-minutes Postload Plasma Glucose

Percentage Change in Low Density Lipoprotein Cholesterol

Percentage Change in HbA1C

Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.

Investigators Assessment of Nocturia at Week 4

Participants Assessment of Nocturia at Week 4

Change in DAN Prostate Symptom Scale From Baseline at Week 4

Change in I-PSS Total Score From Baseline at Week 4

Change in in Dihydrotestosterone Concentration From Baseline at Week 4

Intervention	Ratio to Baseline (Geometric Mean)
Arm II (Placebo)	1.656
Arm I (Cholecalciferol, Genistein)	2.389

Intervention	ng/mL (Mean)
Arm II (Placebo)	0.045
Arm I (Cholecalciferol, Genistein)	0.057

Intervention	participants (Number)
	Undetectable	Detectable
Arm I (Cholecalciferol, Genistein)	6	1
Arm II (Placebo)	7	1

Intervention	Normalized Optical Density (Mean)
	AR (Nucleus)	VDR (Cytoplasm)	p21 (Nucleus)	PGE2 (Cytoplasm)	TUNEL Pos (Nucleus)	Caspase 3 (Cytoplasm)	PSMA (Cytoplasm)	IGF-1 (Cytoplasm)	IGF-2 (Cytoplasm)	Akt (Nucleus)	pAkt (Nucleus)	Akt (Cytoplasm)	pAkt (Cytoplasm)
Arm I (Cholecalciferol, Genistein)	0.414	0.515	0.097	0.184	0.192	0.352	-0.029	0.337	0.383	0.361	0.131	0.284	0.061
Arm II (Placebo)	-0.362	-0.451	-0.085	-0.161	-0.168	-0.308	0.025	-0.295	-0.335	-0.316	-0.114	-0.249	-0.053

Intervention	percentage of participants (Number)
	rs2209314- T/C	rs2209314- T/T	rs2248359- C/C	rs2248359- C/T	rs2248359- T/T	rs2296241- A/A	rs2296241- A/G	rs2296241- G/G	rs2762939- C/G	rs2762939- G/G	rs927650- C/C	rs927650- C/T	rs927650- T/T	rs703842- A/A	rs703842- A/G	rs703842- G/G
Arm I (Cholecalciferol, Genistein)	42.86	57.14	42.86	57.14	0	14.29	71.43	14.29	28.57	71.43	71.43	14.29	14.29	14.29	71.43	14.29
Arm II (Placebo)	37.5	62.5	37.5	37.5	25	37.5	35.5	25	37.5	62.5	0	50	50	50	37.5	12.5

Intervention	ng/mL (absolute change) (Mean)
	Baseline	Day 35
Arm I (Cholecalciferol, Genistein)	11.3	10.9
Arm II (Placebo)	10.5	10.8

Intervention	Ratio to Baseline (Geometric Mean)
Arm II (Placebo)	3.054
Arm I (Cholecalciferol, Genistein)	2.202

Intervention	Liters (Mean)
	Baseline	6 months post-RT	13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)	2.79	2.1	2.19
BIO 300 Oral Suspension (1500 mg/Day)	3.51	2.93	3.28
BIO 300 Oral Suspension (500 mg/Day)	2.46	2.32	2.32

Intervention	ng/mL (Mean)
	Week 2	Week 3	Week 4	Week 5	Week 6
BIO 300 Oral Suspension (1000 mg/Day)	5.84	5.56	3.82	6.71	24.0

Intervention	FACT-TOI Total Score (Mean)
	Screening	3 months post-RT	6 months post-RT	13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)	46.4	53.0	42.3	52.0
BIO 300 Oral Suspension (1500 mg/Day)	47.1	47.6	44.4	47.0
BIO 300 Oral Suspension (500 mg/Day)	66.6	54.5	55.4	50.8