Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study.
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.
Marini
Herbert
H
Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, 98125 Messina, Italy.
Bitto
Alessandra
A
Altavilla
Domenica
D
Burnett
Bruce P
BP
Polito
Francesca
F
Di Stefano
Vincenzo
V
Minutoli
Letteria
L
Atteritano
Marco
M
Levy
Robert M
RM
D'Anna
Rosario
R
Frisina
Nicola
N
Mazzaferro
Susanna
S
Cancellieri
Francesco
F
Cannata
Maria Letizia
ML
Corrado
Francesco
F
Frisina
Alessia
A
Adamo
Vincenzo
V
Lubrano
Carla
C
Sansotta
Carlo
C
Marini
Rolando
R
Adamo
Elena Bianca
EB
Squadrito
Francesco
F
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
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D015415:Biomarkers; D048789:Phytoestrogens; D012333:RNA, Messenger; D019833:Genistein