Genistein Aglycone Does Not Affect Thyroid Function: Results from a Three-Year, Randomized, Double-Blind, Placebo-Controlled Trial

Context and Objective: Genistein aglycone positively affects postmenopausal symptoms. However, questions about its long-term safety on the thyroid gland still remain. Design: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. A subcohort (138 patients) continued therapy for an additional year. Setting: Patients received ambulatory care. Patients and Interventions: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67), plus calcium and vitamin D-3 at therapeutic doses. Circulating thyroid hormones (TSH, free T-3, free T-4) and autoantibodies (thyroid peroxidase, thyroglobulin, and thyroid microsomal antigen) were assessed in 40 genistein and 37 placebo subjects who completed 3 yr. Thyroid hormonereceptor (THR alpha and THR beta) and retinoid receptor (RAR alpha, RAR gamma, and RXR alpha) expression from peripheral blood monocytes was also evaluated at baseline, 12, 24, and 36 months in all 3-yr completers. Results: Genistein administration over 3 yr did not affect serum thyroid hormones or autoantibodies. In addition, there were no differences in THR alpha, THR beta, RAR alpha, RAR gamma, or RXR alpha mRNA expression between groups. Conclusion: These data suggest that genistein aglycone intake does not significantly increase the risk of clinical or subclinical hypothyroidism at the dose of 54 mg/d. (J Clin Endocrinol Metab 95: 3067-3072, 2010)