Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants.
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.
Low
Yen-Ling
YL
Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Dunn Human Nutrition Unit Building, Hills Road, Cambridge CB2 2XY, United Kingdom.
Dunning
Alison M
AM
Dowsett
Mitch
M
Folkerd
Elizabeth
E
Doody
Deborah
D
Taylor
James
J
Bhaniani
Amit
A
Luben
Robert
R
Khaw
Kay-Tee
KT
Wareham
Nick J
NJ
Bingham
Sheila A
SA
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
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