title: Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.
abstract: Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium.
  
  
  BACKGROUND
  We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women.
  
  
  METHODS
  One hundred healthy late postmenopausal women, with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention.
  
  
  RESULTS
  Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: -1.4%, p = 0.104; lumbar spine: -1.7%, p = 0.019) and 24 mo (femoral neck: -1.8%, p = 0.048; lumbar spine: -2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (-43%, p = 0.000) and 24 mo (-39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial.
  
  
  CONCLUSIONS
  EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Yinyu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects; D004311:Double-Blind Method; D004717:Endometrium / Q000187:drug effects; D034181:Epimedium / Q000737:chemistry*; D004958:Estradiol / Q000097:blood; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010349:Patient Compliance; D010352:Patient Dropouts; D048789:Phytoestrogens / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010919:Placebos; D017698:Postmenopause / Q000502:physiology*; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005419:Flavonoids; D048789:Phytoestrogens; D010919:Placebos; D004958:Estradiol