title: Soy Isoflavones for Reducing Bone Loss Study: effects of a 3-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women.
abstract: OBJECTIVE
  This study aims to assess the overall safety and potential endometrium-stimulating effects of soy isoflavone tablets consumed (3 y) by postmenopausal women and to determine endometrial thickness response to treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors.
  
  
  METHODS
  We randomized healthy postmenopausal women (aged 45.8-65.0 y) to placebo control or two doses (80 or 120 mg/d) of soy isoflavones at two sites. We used intent-to-treat analysis (N = 224) and compliant analysis (>95%; N = 208) to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound).
  
  
  RESULTS
  Median values for endometrial thickness (mm) declined from baseline through 36 months. Nonparametric analysis of variance for treatment differences among groups showed no differences in absolute (or percentage of change) endometrial thickness (χ(2) P ranged from 0.12 to 0.69) or in circulating hormones at any time point. A greater number of adverse events in the genitourinary system (P = 0.005) were noted in the 80 mg/day group compared with the 120 mg/day group, whereas other systems showed no treatment effects. The model predicting endometrial thickness response (using natural logarithm) to treatment among compliant women across time points was significant (P ≤ 0.0001), indicating that estrogen exposure (P = 0.0013), plasma 17β-estradiol (P = 0.0086), and alcohol intake (P = 0.023) contributed significantly to the response. Neither the 80 mg/day dose (P = 0.57) nor the 120 mg/day dose (P = 0.43) exerted an effect on endometrial thickness across time.
  
  
  CONCLUSIONS
  Our randomized controlled trial verifies the long-term overall safety of soy isoflavone tablet intake by postmenopausal women who display excellent compliance. We find no evidence of treatment effects on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, across a 3-year period.
authors.affiliation: From the 1National Institutes of Health, Bethesda, MD; 2Department of Statistics, Iowa State University, Ames, IA; 3US Department of Agriculture-Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis, Davis, CA; 4McFarland Clinic, Ames, IA; 5Mayo Validation Support Services, Rochester, MN; 6Center for Devices and Radiological Health, Food and Drug Administration, White Oak, MD; and 7Department of Food Science and Nutrition, University of Minnesota, St Paul, MN.
authors.forename: D Lee
authors.initials: DL
authors.lastname: Alekel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Genschel
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Koehler
authors.forename: Heike
authors.initials: H
authors.lastname: Hofmann
authors.forename: Marta D
authors.initials: MD
authors.lastname: Van Loan
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Beer
authors.forename: Laura N
authors.initials: LN
authors.lastname: Hanson
authors.forename: Charles T
authors.initials: CT
authors.lastname: Peterson
authors.forename: Mindy S
authors.initials: MS
authors.lastname: Kurzer
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004717:Endometrium / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D007529:Isoflavones / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000517:prevention & control*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D030262:Soybean Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D013972:Thyrotropin / Q000097:blood; D014463:Ultrasonography
chemical_list: D004967:Estrogens; D007529:Isoflavones; D012738:Sex Hormone-Binding Globulin; D030262:Soybean Proteins; D004970:Estrone; D004958:Estradiol; D013972:Thyrotropin; C017296:estrone sulfate