title: Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study.
abstract: BACKGROUND
  Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.
  
  
  OBJECTIVE
  We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.
  
  
  METHODS
  The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year.
  
  
  METHODS
  Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses.
  
  
  RESULTS
  Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers.
  
  
  RESULTS
  After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups.
  
  
  CONCLUSIONS
  After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, 98125 Messina, Italy.
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Burnett
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Stefano
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Marco
authors.initials: M
authors.lastname: Atteritano
authors.forename: Robert M
authors.initials: RM
authors.lastname: Levy
authors.forename: Rosario
authors.initials: R
authors.lastname: D'Anna
authors.forename: Nicola
authors.initials: N
authors.lastname: Frisina
authors.forename: Susanna
authors.initials: S
authors.lastname: Mazzaferro
authors.forename: Francesco
authors.initials: F
authors.lastname: Cancellieri
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Cannata
authors.forename: Francesco
authors.initials: F
authors.lastname: Corrado
authors.forename: Alessia
authors.initials: A
authors.lastname: Frisina
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Adamo
authors.forename: Carla
authors.initials: C
authors.lastname: Lubrano
authors.forename: Carlo
authors.initials: C
authors.lastname: Sansotta
authors.forename: Rolando
authors.initials: R
authors.lastname: Marini
authors.forename: Elena Bianca
authors.initials: EB
authors.lastname: Adamo
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D000368:Aged; D019313:BRCA1 Protein / Q000097:blood; D024682:BRCA2 Protein / Q000097:blood; D015415:Biomarkers; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000517:prevention & control; D001943:Breast Neoplasms / Q000453:epidemiology*; D004311:Double-Blind Method; D004717:Endometrium / Q000473:pathology; D005260:Female; D019833:Genistein / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D048789:Phytoestrogens / Q000009:adverse effects* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012854:Sister Chromatid Exchange
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D015415:Biomarkers; D048789:Phytoestrogens; D012333:RNA, Messenger; D019833:Genistein