![]() Isoflavone metabolism also differs markedly between rodents and humans. 25 The main thyroid hormone carrier protein in primates, thyroid binding globulin (TBG), is not present in rodents. Controlled experiments with rodents demonstrate that isoflavones induce increases in serum T4 concentration 23, 24 However, rodent thyroid function and regulation differs from that of primates. Studies using animal models can control for many of the environmental variables thought to influence thyroid function. Neither study controlled for the effects of caloric intake, circadian rhythm, and seasonality all of which may affect thyroid function. However, Duncan et al 20 studied a far more select and homogeneous sample and also found no thyroidal effects in post-menopausal women after 3 months of ISP treatment. ![]() This did not control for individual differences in age, ethnicity, 15 BMI, 16 smoking status, 17 diet, 18 and underlying disease 19 which may have confounded the results. ![]() Persky et al 14 found no significant effect of ISP on thyroid hormone concentrations after 3 and 6 months in women aged 49-83 years. 6 These studies were all short-term, cross-sectional, and used variable doses of isolated soy protein (ISP) supplementation. The majority of human studies, including both men and women’s studies, have found no significant effect of soy isoflavones on adult thyroid function. While mechanisms have been identified through which soy or soy isoflavones could interfere with thyroid function, reported effects are inconsistent. 8- 11 In post-menopausal women hypothyroidism prevalence reaches 10% 12 and may exacerbate disorders associated with menopause such as osteoporosis, cardiovascular disease, and neuropsychiatric disease. 7 In humans, rats, and monkeys hypothyroidism has been associated with menstrual irregularities and infertility. Soy was originally thought to be goitrogenic and cause hypothyroidism. 7 The thyroid predominantly releases T4 which is then converted to the more active T3 by peripheral deiodinases (type 1 and 2). In vitro, soy isoflavones inhibit TPO, but this inhibition can be prevented by iodine supplementation. TPO couples iodine to thyroglobulin in order to yield T3 or T4. TSH regulates thyroid peroxidase (TPO) activity and iodine uptake by the thyroid. 6 Thyroid function relies on the release of thyroid stimulating hormone (TSH) from anterior pituitary in response to circulating triiodothyronine (T3) and thyroxine (T4) levels. However soy isoflavones may negatively affect thyroid function. The popularity of soy isoflavones in menopausal women results from an apparent absence of adverse effects. Supplements commonly contain soy protein which is a rich source of isoflavones specifically genistein, daidzein, and glycitein. They have a greater affinity of ERβ than ERα and can exert both estrogen-agonist and estrogen-antagonist properties. In humans and animals isoflavones bind to estrogen receptors (ER). These observations have stimulated the use of alternatives to HT, including soy isoflavones, a plant-derived compound with estrogen-like activity. While estrogen replacement through hormone therapy (HT) is the most effective method for treating menopausal symptoms, 1 results of the Women’s Health Initiative 2 and Heart and Estrogen/Progestin Replacement Study 3, 4 suggest that the health risks associated with HT may outweigh the benefits. The menopausal transition is often accompanied by life-disrupting symptoms such as hot flashes and vaginal dryness, as well as increased risk of osteoporosis, cardiovascular disease, and cognitive decline.
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