title: Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants.
abstract: In this large cross-sectional study, we investigated the relationship between phytoestrogen exposure and circulating sex hormones and sex hormone-binding globulin (SHBG) levels in 1988 healthy postmenopausal women and their interactions with polymorphisms in genes involved in estrogen signaling. Plasma estradiol, testosterone, androstenedione, estrone, and SHBG were measured. Urinary levels of five isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and two lignans (enterodiol and enterolactone) were measured and used as biomarkers for dietary intakes. Eighteen polymorphisms in ESR1, ESR2, and NR1I2 genes were genotyped. Results showed that lignans were positively associated with plasma SHBG levels (eta(p)(2) = 1.2%; P < 0.001) and negatively associated with plasma testosterone (eta(p)(2) = 0.2%; P = 0.042). Equol was negatively associated with plasma estradiol levels (eta(p)(2) = 0.3%; P = 0.028), whereas O-desmethylangolensin was positively associated with plasma estradiol level (eta(p)(2) = 0.3%; P = 0.010). There were significant phytoestrogen interactions with polymorphisms in ESR1 and NR1I2 genes in affecting estrone levels. We conclude that phytoestrogens modulate sex hormone and SHBG levels in postmenopausal women and interact with gene variants involved in estrogen signaling. Such phytoestrogen-gene interactions may explain the conflicting literature on the hormonal effects of phytoestrogens.
authors.affiliation: Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Dunn Human Nutrition Unit Building, Hills Road, Cambridge CB2 2XY, United Kingdom.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Low
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Folkerd
authors.forename: Deborah
authors.initials: D
authors.lastname: Doody
authors.forename: James
authors.initials: J
authors.lastname: Taylor
authors.forename: Amit
authors.initials: A
authors.lastname: Bhaniani
authors.forename: Robert
authors.initials: R
authors.lastname: Luben
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D048789:Phytoestrogens / Q000008:administration & dosage* / Q000378:metabolism / Q000652:urine; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000097:blood / Q000378:metabolism; D000077297:Pregnane X Receptor; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis* / Q000378:metabolism; D013025:Glycine max
chemical_list: D014408:Biomarkers, Tumor; D012739:Gonadal Steroid Hormones; C000625852:NR1I2 protein, human; D048789:Phytoestrogens; D000077297:Pregnane X Receptor; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D012738:Sex Hormone-Binding Globulin