Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C143
The phytoestrogen genistein physiologically improves bone and cardiovascular functionality in postmenopausal women
H. Marini1, R. Marini1, R. D'Anna2, F. Squadrito3, E. Adamo1
1. Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Messina, Italy. 2. Department of Obstetrical and Gynecological Sciences, University of Messina, Messina, Italy. 3. Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy.
The phytoestrogen genistein aglycone has received wide attention over the last few years because of its potential preventive role for bone and cardiovascular diseases. We assessed the continued safety profile of genistein aglycone on breast and endometrium, and its physiological effects on bone metabolism and cardiovascular functionality after 3 years of treatment. The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. Participants gave written informed consent in accord with the Declaration of Helsinki. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54 mg of genistein aglycone daily (n=71) or placebo (n=67). Both arms received calcium and vitamin D3 in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our study, all patients received dietary instructions in an isocaloric fat-restricted diet. FRAX index and lumbar spine and femoral neck BMD were assessed. Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchanges and endometrial thickness were also evaluated. Secondary outcomes were biochemical levels of bone markers, fasting glucose and insulin, HOMA-IR, fibrinogen, and homocysteine. Standard clinical evaluations and laboratory analyses, including hematologic, kidney, and liver function tests, were done every 6 months. FRAX index calculated at the beginning and at the end of the treatment period showed a significant decrease in the genistein group compared with placebo after 3 years. After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved while sister chromatid exchanges were reduced compared with placebo. BMD increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein significantly reduced PYR, as well as serum CTX and sRANKL while increasing B-ALP and OPG levels. Moreover, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine. Results on routine testing did not change over time in placebo or genistein recipients. After 3 years of treatment, genistein exhibited a promising safety profile with positive physiological effects on bone and cardiovascular system in a cohort of osteopenic, postmenopausal women.
Where applicable, experiments conform with Society ethical requirements