title: Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women.
abstract: BACKGROUND
  Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety.
  
  
  OBJECTIVE
  Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health.
  
  
  METHODS
  A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids.
  
  
  RESULTS
  The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor-negative endometrial cancer), which was less than the expected population rate for these cancers.
  
  
  CONCLUSIONS
  Daily supplementation for 2 y with 80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA. fmsteinberg@ucdavis.edu
authors.forename: Francene M
authors.initials: FM
authors.lastname: Steinberg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Murray
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lewis
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Cramer
authors.forename: Paula
authors.initials: P
authors.lastname: Amato
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Young
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnes
authors.forename: Karen L
authors.initials: KL
authors.lastname: Konzelmann
authors.forename: Joan G
authors.initials: JG
authors.lastname: Fischer
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Ellis
authors.forename: Roman J
authors.initials: RJ
authors.lastname: Shypailo
authors.forename: J Kennard
authors.initials: JK
authors.lastname: Fraley
authors.forename: E O'Brian
authors.initials: EO
authors.lastname: Smith
authors.forename: William W
authors.initials: WW
authors.lastname: Wong
mesh_terms: D001806:Blood Urea Nitrogen; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018546:Hypocotyl; D007529:Isoflavones / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D048789:Phytoestrogens / Q000009:adverse effects / Q000494:pharmacology*; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*; D017698:Postmenopause / Q000187:drug effects*; D013025:Glycine max / Q000737:chemistry*; D047071:beta-Glucans / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D047071:beta-Glucans; C508230:soy isoflavone aglycone