Herbal Science Research - phytoestrogen

[...] effects of Cimicifuga racemosa [...] on the estrogen receptor positive human breast cancer cell line MCF-7.

Site Editor — Sat, 22 Sep 2007 18:18:28 -0700

Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.: BMC Pharmacol. 2007 Sep 20; 7(1): 11 Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M

ABSTRACT: BACKGROUND: Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract and cycloartane-type triterpenoids on the estrogen receptor positive human breast cancer cell line MCF-7. RESULTS: Both extract and purified compounds clearly inhibited cellular proliferation. Gene expression profiling with the extract allowed us to identify 431 regulated genes with high significance. The extract induced expression pattern differed from those of 17beta-estradiol or the estrogen receptor antagonist tamoxifen. We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. These functional groups were highly overrepresented among all regulated genes. Also several transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Real-Time RT-PCR analysis of 13 selected genes was conducted after treatment with purified compounds - the cycloartane-type triterpene glycoside actein and triterpene aglycons - showing similar expression levels compared to the extract. CONCLUSION: No estrogenic but antiproliferative and proapoptotic gene expression was shown for black cohosh in MCF-7 cells at the transcriptional level. The effects may be results of the activation of different pathways. The cycloartane glycosides and - for the first time - their aglycons could be identified as an active principle in black cohosh.

Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica [...]

Site Editor — Sat, 22 Sep 2007 18:02:00 -0700

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.: J Med Assoc Thai. 2007 Jul; 90(7): 1274-80 Chandeying V, Lamlertkittikul S

OBJECTIVE: To evaluate the preliminary efficacy and safety of Pueraria mirifica (Kwao Keur Kao), phytoestrogen, for the alleviation of climacteric symptoms. MATERIAL AND METHOD: Perimenopausal women attending with climacteric symptoms, such as hot flushes and night sweats, were invited to join the present study, conducted at the Menopausal Clinic, Hat Yai Regional Hospital. The patients were voluntarily enrolled and randomly received the raw material of Pueraria mirifica, oral 50 and 100 mg capsule, once daily for six months, as an open-label study. RESULTS: Of the 10 enrolled patients, 8 cases were completely evaluated. The modified Greene climacteric scale (MGCS) was satisfactorily decreased in both groups. The average scale declined from 44.1 at baseline, to be 26, 17, and 11.1 at 1-, 3-, and 6- month follow-up respectively. No other laboratory abnormalities, except one case had transiently increased the creatinine level, and one case of increased blood urea nitrogen. The mean serum estradiol was slightly increased, while the mean serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were nearly stable. CONCLUSION: Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal. women, but the data is insufficient to draw definite conclusions regarding the estrogenic effect.

[Effects of phytoestrogens on prostate cancer and benign prostatic hyperplasia]

Site Editor — Fri, 13 Jul 2007 17:50:17 -0700

[Effects of phytoestrogens on prostate cancer and benign prostatic hyperplasia]: Zhonghua Nan Ke Xue. 2007 May;13(5):457-61 Authors: Feng Y, Xia XY, Huang YF

Phytoestrogens are non-steroidal estrogens widely distributed in many kinds of plants. They are natural compounds structurally similar to estrogen and with estrogenic or anti-androgenic activities. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent and associated with age. Recently, in many epidemiological and experimental researches, it has been reported that phytoestrogens play a role in the prevention and treatment of PCa and BPH. Regulation of sexual hormones, inhibition of cell proliferation, induction of cell apoptosis and anti-oxidation of such plant estrogens may be involved in the mechanisms.

PMID: 17569267 [PubMed - in process]

[...] the growth stimulatory effect of soy and its isoflavones on established breast cancer

Site Editor — Sat, 23 Jun 2007 05:30:16 -0700

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?:

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?

Mol Nutr Food Res. 2007 Jun 20;

Authors: Power KA, Thompson LU

Consumption of phytoestrogen (PE)-rich foods (i. e., soy and flaxseed (FS)) is increasing because of their suggested health benefits. However, recent studies raise concern over the safety of soy and its isoflavones, particularly genistein (GEN), for postmenopausal breast cancer (BC), due to their potential stimulatory effects on human breast tissue and on the growth of existing tumors in rodents. FS, rich in PE lignans, which is metabolized to the mammalian lignans enterolactone (ENL) and enterodiol (END), has consistently been shown to have tumor inhibitory effects in a human clinical trial as well as rodent BC models. Using the preclinical athymic mouse postmenopausal BC model, combining FS with soy protein or GEN with END and ENL, was found to negate the tumor stimulatory effects of soy protein or GEN alone. The mechanism may be related to the modulation of estrogen receptor and MAPK signaling pathways. If these studies can be confirmed in clinical trials, then consumption of combined soy and FS, or their PEs, may reduce the tumor growth stimulatory effect of soy or GEN. This may indicate that if soy is consumed with lignan-rich foods, it may continue to induce its other beneficial health effects, without inducing adverse effect on postmenopausal BC.

PMID: 17579892 [PubMed - as supplied by publisher]

Phytoestrogens: perpetrators or protectors?

Site Editor — Mon, 11 Jun 2007 05:37:00 -0700

Phytoestrogens: perpetrators or protectors?: Future Oncol. 2007 Jun;3(3):307-318 Authors: Martin JH, Crotty S, Nelson PN

Phytoestrogens are estrogen-like substances produced by plants that account for some of the constituents present in vegetation that may be responsible for the health benefits of a diet rich in fruit and vegetables. Phytoestrogens have a plethora of different actions that they are capable of exerting on cellular metabolism. This review will focus on some of the major nonestrogen receptor-mediated cellular effects used by phytoestrogens and will draw attention to the fact that while they may have a number of beneficial effects, particularly in offering a protective effect against some hormone-dependent cancers, such as breast and prostate cancer, they may also have possible unfavorable effects by interfering with the functioning of normal cellular activities such as receptor-mediated signal transduction and DNA replication, as well as being genotoxic, mutagenic and promoting the proliferation of some cancer cells.

Mitochondrial oxidant signalling in Alzheimer's disease.

Site Editor — Wed, 30 May 2007 01:08:33 -0700

Mitochondrial oxidant signalling in Alzheimer's disease.: J Alzheimers Dis. 2007 May;11(2):175-81 Authors: Viña J, Lloret A, Vallés SL, Borrás C, Badía MC, Pallardó FV, Sastre J, Alonso MD

The role of free radicals in Alzheimer disease pathophysiology has been appreciated for a long time. Originally, radicals were considered as causative of oxidative damage. More recently their role as signalling molecules in this, as well as in other fields of free radical biology, has been underscored. Mitochondria are both generators and targets of radical damage in aging. In this paper we review evidence that radicals generated in mitochondria in the presence of Abeta are signals that trigger both the mitochondrial and the extra-mitochondrial pathways of apoptosis. There are gender specific differences in mitochondrial Abeta toxicity: mitochondria from young (but not from old) females appear to be protected. 17-beta Estradiol or phytoestrogens like genistein prevent the formation of oxidants by mitochondria and protect against mitochondrial Abeta toxicity. Experiments reported here indicate that phytoestrogens might have a role in the prevention of Alzheimer's disease.

Dietary phytoestrogen intake and cognitive function in older women.

Site Editor — Wed, 30 May 2007 01:05:28 -0700

Dietary phytoestrogen intake and cognitive function in older women.: J Gerontol A Biol Sci Med Sci. 2007 May;62(5):556-62 Authors: Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, van der Schouw YT

BACKGROUND: Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. METHODS: We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. RESULTS: No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). CONCLUSIONS: This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

Phytoestrogens and Coronary Microvascular Function in Women with Suspected Myocardial Ischemia: A Report from [...] (WISE) Study

Site Editor — Wed, 30 May 2007 01:03:14 -0700

Phytoestrogens and Coronary Microvascular Function in Women with Suspected Myocardial Ischemia: A Report from the Women's Ischemia Syndrome Evaluation (WISE) Study.: J Womens Health (Larchmt). 2007 May;16(4):481-8 Authors: Pepine CJ, Von Mering GO, Kerensky RA, Johnson BD, McGorray SP, Kelsey SF, Pohost G, Rogers WJ, Reis SE, Sopko G, Bairey Merz CN

Aims: Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography. Methods: Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures. Results: Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/- 0.6, and both were significantly (p= 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVR(NTG) and VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen. Conclusions: In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function.

Phytoestrogens in clinical practice: a review of the literature.

Site Editor — Fri, 25 May 2007 02:31:47 -0700

Phytoestrogens in clinical practice: a review of the literature.: Fertil Steril. 2007 May 8; Authors: Tempfer CB, Bentz EK, Leodolter S, Tscherne G, Reuss F, Cross HS, Huber JC

OBJECTIVE: To review clinical studies assessing the effect of phytoestrogen supplementation on the signs and symptoms of the climacteric syndrome and on the incidence of breast cancer, cardiovascular disease, and skeletal fractures. DESIGN: Literature research using PubMed and the Cochrane controlled trials register. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Six systematic reviews and meta-analyses of 25 randomized, controlled trials (RCTs) assessing the use of phytoestrogens for the treatment of the climacteric syndrome were identified. Systematic reviews of RCTs show contradictory results, and meta-analyses demonstrate no statistically significant reduction of vasomotor symptoms for phytoestrogens. Individual RCTs report significant reductions in vasomotor symptoms for red clover and soy phytoestrogens. In selected patient populations, such as in women with early natural postmenopause and mild to moderate vasomotor symptoms, a systematic review of five RCTs found a significant reduction of hot flashes in five out of five RCTs. Twenty-two case-control and cohort studies examined the incidence of breast cancer among women with and without a diet high in phytoestrogens. A meta-analysis of 21 studies found a significantly reduced incidence of breast cancer among past phytoestrogen users. RCTs document beneficial effects of phytoestrogens on surrogate parameters such as bone mineral density, vasodilation, platelet aggregation, insulin resistance, and serum concentrations of triglycerides, high-density lipoprotein, and low-density lipoprotein. None of the available RCTs documents a protective effect of phytoestrogens for the clinical end points of breast cancer, bone fracture, or cardiovascular events. CONCLUSION(S): Based on the available evidence, phytoestrogens should only be used in selected women, i.e., those presenting with mild to moderate vasomotor symptoms in early natural postmenopause. None of the compounds investigated so far have been proven to protect against breast cancer, bone fracture, or cardiovascular disease.

Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls.

Site Editor — Fri, 11 May 2007 16:18:53 -0700

Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls.: Environ Health Perspect. 2007 Jan;115(1):116-21 Authors: Wolff MS, Teitelbaum SL, Windham G, Pinney SM, Britton JA, Chelimo C, Godbold J, Biro F, Kushi LH, Pfeiffer CM, Calafat AM

BACKGROUND: Hormonally active environmental agents have been measured among U.S. children using exposure biomarkers in urine. However, little is known about their variation by race, age, sex, and geography, and no data exist for newly developed biomarkers. OBJECTIVE: Our goal was to characterize relevant, prevalent exposures for a study of female pubertal development. METHODS: In a pilot study among 90 girls from New York City, New York, Cincinnati, Ohio, and northern California, we measured 25 urinary analytes representing 22 separate agents from three chemical families: phytoestrogens, phthalates, and phenols. Exposures occur chiefly from the diet and from household or personal care products. RESULTS: Participants represented four racial/ethnic groups (Asian, black, Hispanic, white), with mean age of 7.77 years. Most analytes were detectable in > 94% of samples. The highest median concentrations for individual analytes in each family were for enterolactone (298 microg/L), monoethylphthalate (MEP; 83.2 microg/L), and benzophenone-3 (BP3; 14.7 microg/L). Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.8-53.2 microg/L. After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile. Three phthalate metabolites differed by race/ethnicity [MEP, mono(2-ethylhexyl) phthalate, and mono-3-carboxypropylphthalate]. CONCLUSIONS: A wide spectrum of hormonally active exposure biomarkers were detectable and variable among young girls, with high maximal concentrations (> 1,000 microg/L) found for several analytes. They varied by characteristics that may be relevant to development.

Pharmacokinetics and systemic endocrine effects of [...] 8-prenylnaringenin after single oral doses postmenopausal women

Site Editor — Fri, 11 May 2007 15:41:22 -0700

Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women.: Br J Clin Pharmacol. 2006 Sep;62(3):288-96 Authors: Rad M, Hümpel M, Schaefer O, Schoemaker RC, Schleuning WD, Cohen AF, Burggraaf J

AIMS: Pre-clinical data suggest that the racemic phyto-oestrogen 8-prenylnaringenin (8-PN) may have beneficial effects in postmenopausal women and may become an alternative to classical hormone replacement therapy (HRT) treatment regimes. The aim of this study was to investigate the pharmacokinetics, endocrine effects and tolerability of chemically synthesized 8-PN in postmenopausal women. METHODS: The study was performed using a randomized, double-blind, placebo-controlled, dose-escalation design with three groups of eight healthy postmenopausal women. In each group six subjects received 8-PN and two subjects placebo. 8-PN was given orally in doses of 50, 250 or 750 mg. Drug concentrations in serum, urine and faeces were measured up to 48 h and follicle-stimulating hormone/luteinizing hormone (LH) concentrations up to 24 h. RESULTS: All treatments were well tolerated and associated with a low incidence of (drug unrelated) adverse events. Serum concentrations of free 8-PN showed rapid drug absorption and secondary peaks suggestive of marked enterohepatic recirculation. Independent of the treatment group, approximately 30% of the dose was recovered in excreta as free compound or conjugates over the 48-h observation period. The first C(max) and AUC(0-48 h) showed dose linearity with ratios of 1 : 4.5 : 13.6 (C(max)) and 1 : 5.2 : 17.1 (AUC). The750- mg dose decreased LH concentrations by 16.7% (95% confidence interval 0.5, 30.2). CONCLUSION: Single oral doses of up to 750 mg 8-PN were well tolerated by postmenopausal women. 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. The decrease in LH serum concentrations found after the highest dose demonstrates the ability of 8-PN to exert systemic endocrine effects in postmenopausal women.

Genistein inhibits glutamate-induced apoptotic processes in primary neuronal cell cultures...

Site Editor — Wed, 31 Jan 2007 19:14:25 -0800

Genistein inhibits glutamate-induced apoptotic processes in primary neuronal cell cultures: an involvement of aryl hydrocarbon receptor and estrogen receptor/glycogen synthase kinase-3beta intracellular signaling pathway.: Neuroscience. 2007 Jan 26;

Authors: Kajta M, Domin H, Grynkiewicz G, Lason W

Phytoestrogens prevent neuronal damage, however, mechanism of their neuroprotective action has not been fully elucidated. This study aimed to evaluate the effects of genistein on glutamate-induced apoptosis in mouse primary neuronal cell cultures. Glutamate (1 mM) enhanced caspase-3 activity and lactate dehydrogenase (LDH) release in the hippocampal, neocortical and cerebellar neurons in time-dependent manner, and these data were confirmed at the cellular level with Hoechst 33342 and calcein AM staining. Genistein (10-10,000 nM) significantly inhibited glutamate-induced apoptosis, and the effect of this isoflavone was most prominent in the hippocampal cells. Next, we studied an involvement of estrogen and aryl hydrocarbon receptors in anti-apoptotic effects of genistein. A high-affinity estrogen receptor antagonist, ICI 182, 780 (1 muM), reversed, whereas less specific antagonist/partial agonist, tamoxifen (1 muM), either intensified or partially inhibited genistein effects. Aryl hydrocarbon receptor antagonist, alpha-naphthoflavone (1 muM), exhibited a biphasic action: it enhanced genistein action toward a short-term exposure (3 h) to glutamate, but antagonized genistein action toward prolonged exposure (24 h) to that insult. SB 216763 (1 muM), which preferentially inhibits glycogen synthase kinase-3beta (GSK-3beta), potentiated genistein effects. These data point to strong effects of genistein at low micromolar concentrations in various brain tissues against glutamate-evoked apoptosis. Moreover, this study provided evidence for involvement of aryl hydrocarbon receptor and estrogen receptor/GSK-3beta intracellular signaling pathway in anti-apoptotic action of genistein.

Garlic phytoestrogen compounds can protect bone loss in patients with prostate cancer under androgen deprivation.

Site Editor — Wed, 31 Jan 2007 19:12:32 -0800

Garlic phytoestrogen compounds can protect bone loss in patients with prostate cancer under androgen deprivation.: Med Sci Monit. 2007 Jan 18;13(2):BR25-31 Authors: Kream RM, Liu NJ, Zhuang M, Esposito PL, Esposito TR, Stefano GB, Witmeyer Iii JJ

Background: We have previously explored the functional role of the tachykinin substance P (SP) in the mediation of opioid-dependent antinociception and now describe the formulation, synthesis, and initial pharmacological characterization of a hybrid chimeric molecule, designated MSP9, containing the mu opioid receptor (MOR) agonist morphine covalently attached through a succinic acid linker to the SP receptor (SPR) agonist domain SP3-11. Material/Methods: Pharmacological characterization of MSP9, administered by the intramuscular route, was achieved in naive and morphine-tolerant male rats utilizing the tail-flick test. Results: MSP9 produced significant antinociceptive responses across a wide concentration range and displayed an atypical bell-shaped analgesic dose response relationship with peak effect of 40+/-10% reached at 0.2 mg/kg. The antinociceptive responses achieved by very low concentrations of MSP9 were not obtained by administration of equivalent low doses of morphine, suggesting that kinetic and dynamic parameters may contribute to its unusual analgesic properties. Importantly, MSP9 produces a strong antinociceptive response when administered to morphine-tolerant rats, suggesting a significant activation of kappa and/or delta receptors (KORs and DORs, respectively) in the presence of functionally down regulated MORs. Conclusions: Analyses employing selective, blood brain barrier (BBB) permeable, opioid and SP antagonists administered alone or in combination, indicate an obligate requirement for coincident activation of populations of CNS opioid and SP receptors. These combined data suggest that MSP9 activates multiple opioid- and SPR-expressing systems functionally linked to CNS analgesic responses, designating this class of hybrid chimeric molecules as prime candidates for therapeutic development for a wide range of clinical indications.

Ginkgo biloba-an appraisal.

Site Editor — Fri, 19 Jan 2007 18:34:50 -0800

Ginkgo biloba-an appraisal.: Kathmandu Univ Med J (KUMJ). 2004 Jul-Sep;2(3):225-9 Authors: Dubey AK, Shankar PR, Upadhyaya D, Deshpande VY

Ginkgo biloba has been used in traditional Chinese medicine for about 5000 years. A standardized preparation, EGb 761 has been recently prepared. The pharmacologically active constituents, flavonol glycosides and the terpene lactones are standardized. The terpene lactones comprise of ginkgolides A, B, C and bilobalides. The extract scavenges excess free radicals and pretreatment with EGb 761 reduces damage by free radicals in patients undergoing coronary bypass surgery. The action of platelet activating factor is antagonized and platelet aggregation is reduced. Blood flow is increased. Release of prostacyclines and nitric oxide was shown to be stimulated. Ginkgo biloba has been found to be useful in the treatment of Alzheimers disease and cognitive impairment. EGB 761 has shown beneficial effect in aging and mild cognitive impairment. Bilobalide has been shown to be protective against glutamate-induced excitotoxic neuronal death. Early studies indicate a potential role in age-related macular degeneration and some types of glaucoma. Anticancer action is related to antioxidant, anti-angiogenic and gene regulatory actions. Ginkgo biloba has shown overall improvement in about 65% of patients with cerebral impairment and a similar percentage suffering from peripheral vascular diseases. A recent study suggested that phytoestrogens in Ginkgo biloba may have a role as alternative hormone replacement therapy. Recent trials have not shown a beneficial effect of Ginkgo biloba in tinnitus and acute mountain sickness. Ginkgo biloba increased the bioavailability of diltiazem. The extract has been shown to protect against doxorubicin-induced cardiotoxicity and gentamicin-induced nephrotoxicity in animals. Ginkgo biloba inhibits microsomal enzymes and has a potential for drug interactions. Further studies to establish the efficacy of Ginkgo biloba are required.

Analysis of the interaction of phytoestrogens and synthetic chemicals: An in vitro/in vivo comparison.

Site Editor — Wed, 17 Jan 2007 06:32:55 -0800

Analysis of the interaction of phytoestrogens and synthetic chemicals: An in vitro/in vivo comparison.: Toxicol Appl Pharmacol. 2006 Dec 5; Authors: Charles GD, Gennings C, Tornesi B, Kan HL, Zacharewski TR, Bhaskar Gollapudi B, Carney EW

In the evaluation of chemical mixture toxicity, it is desirable to develop an evaluation paradigm which incorporates some critical attributes of real world exposures, particularly low dose levels, larger numbers of chemicals, and chemicals from synthetic and natural sources. This study evaluated the impact of low level exposure to a mixture of six synthetic chemicals (SC) under conditions of co-exposure to various levels of plant-derived phytoestrogen (PE) compounds. Estrogenic activity was evaluated using an in vitro human estrogen receptor (ER) transcriptional activation assay and an in vivo immature rat uterotrophic assay. 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. The six SCs were then combined at equipotent ratios and tested at 5-6 dose levels spanning from very low, sub-threshold levels, to a dose in which every chemical in the mixture was at its individual estrogenic response threshold. The SC mixtures also were tested in the absence or presence of 5-6 different levels of PEs, for a total of 36 (in vitro) or 25 (in vivo) treatment groups. Both in vitro and in vivo, low concentrations of the SC mixture failed to increase estrogenic responses relative to those induced by PEs alone. However, significant increases in response occurred when each chemical in the SC mixture was near or above its individual response threshold. In vitro, interactions between high-doses of SCs and PEs were greater than additive, whereas mixtures of SCs in the absence of PEs interacted in a less than additive fashion. In vivo, the SC and PE mixture responses were consistent with additivity. These data illustrate a novel approach for incorporating key attributes of real world exposures in chemical mixture toxicity assessments, and suggest that chemical mixture toxicity is likely to be of concern only when the mixture components are near or above their individual response thresholds. However, these data suggest that extrapolation from in vitro assays to in vivo mixture effects should be approached with caution.

[Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga racemosa dry extract]

Site Editor — Wed, 17 Jan 2007 06:30:11 -0800

[Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga racemosa dry extract]: Ginekol Pol. 2006 Sep;77(9):678-83 Authors: Radowicki S, Skórzewska K, Rudnicka E, Szlendak-Sauer K, Wierzba W

OBJECTIVES: Phytoestrogens could be an alternative method of the treatment of menopausal syndrome in women with contraindications to hormonal replacement therapy. Design: The aim of the study was to evaluate efficacy and safety of the therapy with Cimicifuga racemosa dry extract. MATERIAL AND METHODS: Twenty women aged mean 52.4 +/- 4.9 years with climacteric syndrome were treated with Cimicifuga racemosa dry extract in a dose of 40 mg a day during 6 months. Kupperman's Index, biochemical parameters and hormonal profile were estimated before and after 3 and 6 months of the therapy. RESULTS: Mean values of Kuppermen's Index were decreased from 30.2 +/- 5.7 points before the therapy to 8.5 +/- 6.3 points after 3 months and to 2.6 +/- 2.1 points after 6 months of the therapy (p < 0.05). No statistical differences in biochemical parameters' concentrations and hormonal profile were observed. CONCLUSIONS: Cimicifuga racemosa dry extract was an effective and safe therapy of climacteric women with contraindications to hormonal replacement therapy.

Plasma Phytoestrogens and Subsequent Breast Cancer Risk.

Site Editor — Thu, 04 Jan 2007 18:06:21 -0800

Plasma Phytoestrogens and Subsequent Breast Cancer Risk.: J Clin Oncol. 2007 Jan 2; Authors: Verheus M, van Gils CH, Keinan-Boker L, Grace PB, Bingham SA, Peeters PH

PURPOSE: Phytoestrogens are plant compounds that are structurally and functionally similar to mammalian estrogens. By competing for estrogen receptors, phytoestrogens possibly inhibit binding of the more potent endogenous estrogens and decrease their potential effects on breast cancer risk. We investigated the association between plasma phytoestrogen levels and breast cancer risk in a prospective manner. PATIENTS AND METHODS: We performed a nested case-control study within the Prospect cohort, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition. A total of 383 women (87 pre- or perimenopausal women [mean age, 52 years] and 296 postmenopausal women [mean age, 59 years]) who developed breast cancer were selected as case subjects and were matched to 383 controls, on date of blood sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and lignans (enterodiol and enterolactone) were measured. The isotope dilution liquid chromatography/tandem mass-spectrometry method incorporating triply (13)C-labeled standards was used for all analyses. Breast cancer odds ratios were calculated for tertiles of phytoestrogen plasma levels using conditional logistic regression analysis. RESULTS: For genistein, the risk estimate for the highest versus the lowest tertile was 0.68 (95% CI, 0.47 to 0.98). Similar protective effects, although not statistically significant, were seen for the other isoflavones. Lignan levels did not appear to be related to breast cancer risk. Results were the same in pre- or perimenopausal women, and in postmenopausal women. CONCLUSION: High genistein circulation levels are associated with reduced breast cancer risk in the Dutch population. No effects of lignans on breast cancer risk were observed.

Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo...

Site Editor — Wed, 03 Jan 2007 19:07:14 -0800

Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.: Ann Intern Med. 2006 Dec 19;145(12):869-79 Authors: Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J

BACKGROUND: Herbal supplements are widely used for vasomotor symptoms. OBJECTIVE: To test the efficacy of 3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo. DESIGN: 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004. SETTING: Group Health, Washington State. PARTICIPANTS: 351 women age 45 to 55 years with 2 or more vasomotor symptoms per day; 52% of the women were in menopausal transition and 48% were postmenopausal. MEASUREMENTS: Rate and intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor Symptom Subscale. INTERVENTIONS: 1) Black cohosh, 160 mg daily; 2) multibotanical with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo. RESULTS: Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale score did not differ between the herbal interventions and placebo at 3, 6, or 12 months or for the average over all the follow-up time points (P > 0.05 for all comparisons) with 1 exception: At 12 months, symptom intensity was significantly worse with the multibotanical plus soy intervention than with placebo (P = 0.016). The difference in vasomotor symptoms per day between placebo and any of the herbal treatments at any time point was less than 1 symptom per day; for the average over all the follow-up time points, the difference was less than 0.55 symptom per day. The difference for hormone therapy versus placebo was -4.06 vasomotor symptoms per day for the average over all the follow-up time points (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001). LIMITATIONS: The trial did not simulate the whole-person approach used by naturopathic physicians. Differences between treatment groups smaller than 1.5 Vasomotor symptoms per day cannot be ruled out. CONCLUSION: Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms. Clinical Trials Registration number: NCT00169299.

Phytoestrogens and indicators of breast cancer prognosis.

Site Editor — Wed, 03 Jan 2007 19:05:31 -0800

Phytoestrogens and indicators of breast cancer prognosis.: Nutr Cancer. 2006;56(1):3-10 Authors: Ha TC, Lyons-Wall PM, Moore DE, Tattam BN, Boyages J, Ung OA, Taylor RJ

Abstract: Breast cancer incidence is lower and survival is longer in Asian women residing in Japan, China, or the Philippines than Caucasian women residing in the United States. Phytoestrogen intake has been examined as a possible reason for the disparity in breast cancer incidence and survival. This study examined the association between phytoestrogen intake prior to diagnosis of breast cancer and indicators of breast cancer prognosis (tumor size, estrogen and progesterone receptor status, histological grade, lymphovascular invasion, nodal spread, and stage) in 128 women, aged 40-79 yr, newly diagnosed with invasive breast cancer. After controlling for significant confounding factors, higher intakes of phytoestrogens were associated with favorable indicators of breast cancer. In women with higher intakes of phytoestrogens, there was a 32% reduction in the odds of being diagnosed with any stage of cancer other than stage 1 (95% confidence interval, CI = 0.49-0.93; P = 0.02), a 38% reduction in odds of being diagnosed with positive lymphovascular invasion (95% CI = 0.40-0.95; P = 0.03), and a 66% increase in the odds of being diagnosed with a positive progesterone receptor (95% CI = 1.06-2.58; P = 0.03). We conclude that phytoestrogen intake prior to diagnosis may improve prognosis of breast cancer.

Phytoestrogen Exposure, Polymorphisms in COMT, CYP19, ESR1, and SHBG Genes, and Their Associations With Prostate Cancer Risk.

Site Editor — Wed, 03 Jan 2007 19:04:33 -0800

Phytoestrogen Exposure, Polymorphisms in COMT, CYP19, ESR1, and SHBG Genes, and Their Associations With Prostate Cancer Risk.: Nutr Cancer. 2006;56(1):31-9 Authors: Low YL, Taylor JI, Grace PB, Mulligan AA, Welch AA, Scollen S, Dunning AM, Luben RN, Khaw KT, Day NE, Wareham NJ, Bingham SA

Abstract: Prospective phytoestrogen exposure was assessed using both biomarkers and estimates of intake in 89 British men recruited into the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition study, men who subsequently developed prostate cancer. Results were compared with those from 178 healthy men matched by age and date of recruitment. Levels of seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in spot urine and serum samples. Five single-nucleotide polymorphisms in COMT, CYP19, ESR1, and SHBG genes were genotyped. Urinary levels of all phytoestrogens correlated strongly with serum levels. Correlation coefficients ranged from 0.63 (glycitein) to 0.88 (daidzein) (P < 0.001). Urinary and serum levels correlated significantly with isoflavone intake assessed from food diaries (R = 0.15-0.20; P < 0.05) but not with that from a food-frequency questionnaire. Odds ratios for phytoestrogen exposure, as assessed using the four methods, were not significantly associated with prostate cancer risk (P = 0.15-0.94). Men with the CC genotype for the ESRI PvuII polymorphism had significantly higher risk for prostate cancer compared with men with the TT genotype [adjusted odds ratio = 4.65 (1.60-13.49); P = 0.005]. Our results utilizing a combined prospective exposure provide no evidence that phytoestrogens alter prostate cancer risk in British men, whereas the C allele for the PvuII polymorphism may be associated with increased risk.

Circulating enterolactone and risk of endometrial cancer.

Site Editor — Wed, 04 Oct 2006 18:40:01 -0700

Circulating enterolactone and risk of endometrial cancer.: Int J Cancer. 2006 Aug 23; Zeleniuch-Jacquotte A, Lundin E, Micheli A, Koenig KL, Lenner P, Muti P, Shore RE, Johansson I, Krogh V, Lukanova A, Stattin P, Afanasyeva Y, Rinaldi S, Arslan AA, Kaaks R, Berrino F, Hallmans G, Toniolo P, Adlercreutz H

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer. (c) 2006 Wiley-Liss, Inc.

Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer.

Site Editor — Wed, 04 Oct 2006 18:28:46 -0700

Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer.: Prostate. 2006 Aug 18; Hedelin M, Bälter KA, Chang ET, Bellocco R, Klint A, Johansson JE, Wiklund F, Thellenberg-Karlsson C, Adami HO, Grönberg H

BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene. (c) 2006 Wiley-Liss, Inc.

Prenylflavonoids as Nonsteroidal Phytoestrogens and Related Structure-Activity Relationships.

Site Editor — Wed, 04 Oct 2006 18:24:37 -0700

Prenylflavonoids as Nonsteroidal Phytoestrogens and Related Structure-Activity Relationships.: ChemMedChem. 2006 Apr 10; 1(4): 482-488 Wang ZQ, Weber N, Lou YJ, Proksch P

In the search for estrogen receptor (ER) modulators, a series of prenylflavonoids were found to be widely distributed amongst tonic herbal medicines and to possess estrogen-like activity in MCF-7/BOS cells, as evaluated by an estrogen-screening assay. Cell-cycle analysis revealed that the stimulatory effects of these compounds toward cell proliferation were elicited at the G1-S checkpoint and could significantly increase the S-phase population of MCF-7 cells under hormone-free conditions. ER-responsive gene (PS2, PgR) and protein (PgR) expression was also detected; mRNA and protein-expression levels for PS2 and PgR were up-regulated by the compounds in a dose-dependent manner. These effects could be inhibited by the pure ER antagonist ICI 182,780 ((7alpha-[9-{4,4,5,5,5-pentafluoropentyl}sulfinyl]nonyl)estra-1,3,5(10)-triene-3,17beta-diol). It was therefore concluded that the estrogen-like effects of these prenylflavonoids were mediated primarily through ERs. Furthermore, to explore the structure-activity relationship based on the estrogen receptor and detailed molecular mechanisms among the prenylflavonoids, protein-ligand docking simulations were carried out by using the DS-MODELING software package. The binding affinity of each prenylflavonoid toward ERalpha was scored, and the receptor-ligand interaction was also analyzed to provide the simulation characteristics of virtual molecular recognition mechanisms.

Effect of pure genistein on bone markers and hot flushes.

Site Editor — Fri, 09 Jun 2006 04:26:55 -0700

Effect of pure genistein on bone markers and hot flushes.: Climacteric. 2005 Dec;8(4):371-9 Authors: Albertazzi P, Steel SA, Bottazzi M

OBJECTIVE: To evaluate the effect of 90 mg of daily genistein on markers of bone turnover and menopausal symptoms. DESIGN: This was a cross-over, placebo-controlled study involving 100 postmenopausal women. Subjects were randomly assigned to daily genistein or placebo for 6 weeks and crossed over to the alternative preparation for the following 6 weeks. Pure genistein was processed and encapsulated in accordance with British Pharmacopoeia standards. Each capsule contained 90 mg of pure genistein while the placebo contained just the recipients. RESULTS: In women with significant hot flushes (score (intensity x number) > or = 9), genistein reduced symptoms by 30% compared to baseline and the difference compared to placebo was statistically significant. No effect was observed on biochemical markers of bone turnover, possibly due to the short duration of each arm of the study. Genistein reduced osteocalcin, a marker of bone formation, by 3.6% compared to baseline and 0.31% compared to placebo (p = 0.81 and 0.40, respectively). Genistein increased cross-link telopeptide, a marker of bone resorption, by 1.8% compared to baseline and 0.29% compared to placebo; both differences were not statistically significant (p = 0.078 and 0.88, respectively). CONCLUSION: Pure genistein at a dose of 90 mg per day appears to reduce the number of hot flushes in postmenopausal women but the effect is mild.

Estrogenic properties of isoflavones derived from Millettia griffoniana.

Site Editor — Fri, 09 Jun 2006 04:23:43 -0700

Estrogenic properties of isoflavones derived from Millettia griffoniana.: Phytomedicine. 2006 Feb;13(3):139-45 Authors: Ketcha Wanda GJ, Njamen D, Yankep E, Tagatsing Fotsing M, Tanee Fomum Z, Wober J, Starcke S, Zierau O, Vollmer G

In most developing countries, 70-80% of the population still resort to traditional medicine for their primary health care. This medicine utilises medicinal plants which are traditionally taken as concoction and infusion. The root and stem bark of Millettia griffoniana (Leguminosae), has been reported to contain isoflavonoids, alkaloids, and diterpenoids. The possible benefit of some bioactive isoflavones derived from M. griffoniana prompted us to screen them for estrogenic activity. Six isoflavones and coumarin derived from M. griffoniana (bail) namely, compound nos. 1-6 (Fig. 1) were tested for their potential estrogenic activities in three different estrogen receptor alpha (ERalpha)-dependent assays. In a yeast-based ERalpha assay, all test substances and 17beta-estradiol as endogenous agonist, showed a significant induction of beta-galactosidase activity. The test compounds at the concentration of 5x10(-6)M could achieve 59-121% of the beta-galactosidase induction obtained with 10(-8)M 17beta-estradiol (100%). In the reporter gene assay based on stably transfected MCF-7 cells (MVLN cells), the estrogen responsive induction of luciferase was also stimulated by the M. griffoniana isoflavones. In Ishikawa cells, all substances exhibited estrogenic activity revealed by the induction of alkaline phosphatase (AlkP) activity. The estrogenic activities of isoflavones from M. griffoniana could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ERalpha. Although all substances showed estrogenic effects, 4'-methoxy-7-O-[(E)-3-methyl-7-hydroxymethyl-2,6-octadienyl]isoflavone (7-O-DHF), Griffonianone C (GRIF-C), and 3',4'-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone (7-O-GISO) were found to be the most potent of tested substances. In summary, estrogenic activities of the isoflavones derived from M. griffoniana were described for the first time using reporter gene assays and the estrogen-inducible AlkP Ishikawa model.

Alternative therapies for postmenopausal women.

Site Editor — Fri, 09 Jun 2006 04:12:39 -0700

Alternative therapies for postmenopausal women.: Int J Fertil Womens Med. 2005 May-Jun;50(3):101-14 Authors: Speroff L

Alternative therapies are being used by postmenopausal women in attempts to treat all of the complaints and medical conditions of the menopause. One-fifth of those who take prescription drugs for these indications also take herbal remedies and/or high-dose vitamins, most often without disclosing the fact to the physician. Although studies of alternative therapies are short-term and rarely focused on safety--let alone efficacy--in the long-term, there are many studies spread over the large number of substances involved. More than 130 studies, including meta-analyses, are reviewed in this article under the headings of phytoestrogens, especially from soy; therapies for hot flushes; and preventives for cardiovascular disease, osteoporosis, and breast cancer. Special attention is given to the recently recognized daidzein metabolite equol, and for the sake of completeness there are reviews of the unconventional, but not botanical, treatments estriol, transdermal progesterone, and dehydroepiandrosterone. The total picture produced by conscientious review of the studies is bleak overall, but there seems to be good reason to pursue the possibilities inherent in soy protein with phytoestrogens in populations of women who endogenously produce equol.

Ginkgo biloba-an appraisal.

Site Editor — Fri, 09 Jun 2006 04:07:46 -0700

Ginkgo biloba-an appraisal.: Kathmandu Univ Med J (KUMJ). 2004 Jul-Sep;2(3):225-9 Authors: Dubey AK, Shankar PR, Upadhyaya D, Deshpande VY

Metabolism of phytoestrogen conjugates.

Site Editor — Fri, 09 Jun 2006 04:07:36 -0700

Metabolism of phytoestrogen conjugates.: Methods Enzymol. 2005;400:316-42 Authors: D'Alessandro TL, Boersma-Maland BJ, Greg Peterson T, Sfakianos J, K Prasain J, Patel RP, Darley-Usmar VM, Botting NP, Barnes S

Phytoestrogens are plant-derived compounds with physiologic estrogenic effects. They are present in the plant as glycosidic conjugates, some of which contain further chemical modifications (acetate, malonate, and 3-hydroxy-3-methylglutarate esters and 2,3-dihydroxysuccinate ether). In the gastrointestinal tract, the conjugates undergo hydrolysis catalyzed by enzymes in the intestinal wall and by gut bacteria. On entering the systemic circulation, the phytoestrogens may undergo extensive metabolism to other compounds through reactions involving demethylation, methylation, hydroxylation, chlorination, iodination, and nitration. In addition, all these compounds can undergo conjugation to form beta-glucuronides and sulfate esters. This chapter describes the methods of analysis of all these compounds, the sources of or methods to manufacture suitable standards, and the procedures for examining the enzymes that catalyze these reactions.

The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties.

Site Editor — Fri, 09 Jun 2006 03:45:41 -0700

The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties.: Phytomedicine. 2006 Jan;13(1-2):119-31 Authors: Chadwick LR, Pauli GF, Farnsworth NR

As the population ages, there is an ever-increasing need for therapeutic agents that can be used safely and efficaciously to manage symptoms related to postmenopausal estrogen deficiency. Endogenous estrogens, e.g., 17beta-estradiol, of exogenous mammalian origin, e.g., horses, have long been used to manage such symptoms. There are more than 20 different classes of phytochemicals that have demonstrated affinity for human estrogen receptors in vitro. Some studies on exogenous estrogenic substances of botanical origin (phytoestrogens), such as standardized formulations of plant extracts with in vitro and in vivo estrogenic activity from soy (Glycine max Merill.) and red clover (Trifolium pratense L.), suggest clinical efficacy. Few clinical data for phytoestrogens other than isoflavonoids are available. In an exhaustive review of the literature through 2003, only two clinical trials were identified that were designed to evaluate the effect of hops (Humulus lupulus L.) on symptoms related to menopause. Folkloric, chemical, and biological literature relating primarily to the use of hops for their estrogenic activity, and two human clinical trials, are reviewed.

Sex hormones as potential modulators of vascular function in hypertension.

Site Editor — Fri, 09 Jun 2006 03:43:28 -0700

Sex hormones as potential modulators of vascular function in hypertension.: Hypertension. 2005 Aug;46(2):249-54 Authors: Khalil RA

The greater incidence of hypertension in men and postmenopausal women compared with premenopausal women has suggested gender differences in vascular function. Vascular effects of the female sex hormones estrogen and progesterone and the male hormone testosterone have been described. Sex steroid receptors have been identified in vascular endothelium and smooth muscle. Interaction of sex hormones with cytosolic/nuclear receptors initiates long-term genomic effects that stimulate endothelial cell growth but inhibit smooth muscle proliferation. Activation of sex hormone receptors on the plasma membrane triggers nongenomic effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause endothelium-independent inhibition of vascular smooth muscle contraction, [Ca2+]i, and protein kinase C. These vasorelaxant/vasodilator effects suggested vascular benefits of hormone replacement therapy (HRT) during natural and surgically induced deficiencies of gonadal hormones. Although some clinical trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of effect should not be generalized because it could be related to the type/dose of sex hormone, subjects' age, and other cardiovascular conditions. The prospect of HRT relies on continued investigation of the molecular mechanisms underlying the vascular effects of sex hormones and identification of compounds that specifically target the vascular sex hormone receptors. Naturally occurring hormones and phytoestrogens may be more beneficial HRT than synthesized compounds. Also, the type/dose, time of initiation, and duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby enhance the outlook of sex hormones as potential modulators of vascular function in hypertension.