Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis)

Abstract

Objectives Soy isoflavones are commonly used to alleviate menopause-related symptoms. Menopausal women are at an increased risk for hypothyroidism and there are concerns that isoflavones may be detrimental to thyroid health. The aim of this study was to examine the effects of soy protein and isoflavones on thyroid function and the relationship between thyroid and ovarian function. Methods Adult female cynomolgus monkeys (Macaca fascicularis) were randomized to consume two diets differing only in protein source: casein-lactalbumin (n = 44) or soy protein with isoflavones (n = 41). After 34 months all animals were ovariectomized via laparotomy. Half of the monkeys from each diet treatment group continued to consume their Pre-Ovariectomy treatment phase diet (either SOY [n = 19] or CL [n = 21]) for an additional 34 months. The remaining animals did not continue their diets, and thus were not considered further. Circulating progesterone, triiodothyronine, thyroxine, and thyroid stimulating hormone were measured at baseline. Thyroid hormones were remeasured during each treatment phase. Results Dietary soy increased triiodothyronine in pre-ovariectomized monkeys and prevented a decline in thyroxine following surgical menopause (both p’s < 0.05). Mean progesterone concentrations were positively correlated with triiodothyronine at baseline in pre-ovariectomized monkeys (p < 0.01). Conclusions Progesterone levels and triiodothyronine are positively correlated in macaques. Dietary soy increases triiodothyronine in pre-ovariectomized monkeys and prevents a decline in thyroxine following surgical menopause. The outcomes observed in this study suggest soy protein and isoflavone consumption does not adversely affect and may even preserve thyroid function in postmenopausal women.

Lifelong exposure to dietary isoflavones reduces risk of obesity in ovariectomized Wistar rats

“…In line with our data Silverstein et al. reported that in ovariectomized monkeys long time ISO exposure increased T4 levels and thereby prevented the decline of T4 levels due to OVX .…”

Effects of isoflavones on breast tissue and the thyroid hormone system in humans: a comprehensive safety evaluation

“…The potential of isoflavones to influence the thyroid system in vivo was supported by results obtained in different animal studies (Chang and Doerge 2000 ; Divi et al 1997 ; Doerge and Sheehan 2002 ; Silverstein et al 2014 ; Sosic-Jurjevic et al 2014 ; White et al 2004 ). Chang and Doerge ( 2000 ) reported that the consumption of a standard soy-based rodent diet reduced TPO activity in rats by approximately 50% if compared to a soy-free diet.…”

Risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones

“…The Panel acknowledged that the potential effects of isoflavones on thyroid endpoints may have been investigated in other animal models, such as juvenile or non-OVX animals. However, the differences in thyroid physiology between the rat and the human make extrapolation from rodents to humans problematic (see, for example, explanation reported in the publication by Silverstein et al (2014): 'Studies using animal models can control for many of the environmental variables thought to influence thyroid function. Controlled experiments with rodents demonstrate that isoflavones induce increases in serum T4 concentration.…”

“…There were no statistically significant changes in the levels of T 3 or TSH in the treated animals compared with OVX controls. However, treatment with isoflavones preceded ovariectomy in the animals, so that these animals were intact when the treatment started (Silverstein et al, 2014).…”