This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The most common consumers of soy products are women of peri- and post-menopausal age who do so in an attempt to avoid the ill-effects of estrogen-based hormone replacement therapy. Thyroid diseases are also prevalent in this group (about 1 in 8). The health benefits of soy products on the cardiovascular system have been ascribed to constituent isoflavones, which share significant structural similarities with estradiol. The primary objective of this pilot project is to assess the effect of soy isoflavones on thyroid function tests in non-diabetic euthyroid, hypothyroid, and hyperthyroid individuals under medication. RESEARCH PLAN: Written, informed, voluntary consent was obtained from all subjects. Body weights for all individuals had been stable for at least 3 months prior to study. None of the participants was on a dietary or exercise program for weight reduction. Potential subjects with significant medical problems (major cardiovascular, hepatic and other endocrine disease) other than elevated total cholesterol, as determined by routine medical history, physical examination, blood and urine tests were excluded. A pregnancy test was performed in all women of reproductive potential, and pregnant or nursing women were excluded. Subjects with anemia [Hb12 g/dL (female) or 13 g/dL (male) or those taking estrogen-based oral contraceptive pills or drugs known to affect the blood coagulation system or platelets (e.g. Plavix and aspirin), or cholesterol-lowering medications such as Zocor and Lescol, and hypertensive subjects taking blood pressure medications such as Zestril and Lotrel were also excluded. Breast cancer survivors are also excluded from the study. Non-diabetic euthyroid, hypothyroid and hyperthyroid individuals (18-75 years, both males and females) are undergoing a randomized double-blind placebo-control crossover study in which the subjects ingest a soy isoflavone-rich or an isoflavone-poor protein product for 2 months (each arm). The absence of diabetes was confirmed by performing the oral glucose tolerance test. METHODS: Tests of the comprehensive metabolic panel, lipid profile and thyroid function (TSH, TT4, FT4, T3 Uptake) and platelet functions are being performed at the start and at the end of each arm (2 months) of the study. In addition to these tests, serum estradiol, FSH and DHEA levels are being measured in the female participants, and every attempt is being made to collect the blood samples about the same period in their menstrual cycles (follicular phase, in pre-menopausal women). In men, blood is being collected for the measurement of testosterone and LH levels. All participants are keeping food diaries, which are collected during their monthly follow-up visits. The study design calls for 10 subjects per group to complete the studies. CLINICAL
Women are more likely to develop thyroid problems and because of the increasing reports of adverse reactions with hormone replacement therapy involving ethinylestradiol, postmenopausal women are increasingly taking to phytoestrogens for the control of postmenopausal symptoms. Clearly, phytoestrogens are potent pharmacologically, albeit less potent than estradiol and ethinylestradiol. It is also becoming clear that ingested estrogens in birth control pills produce more problems than dermal estrogen patches. The central hypothesis is that the isoflavones in soy will stimulate the synthesis of hepatic thyroxine binding globulin (TBG). At the completion of this study, the results will show that ingestion of isoflavone-rich soy, with high levels of phytoestrogens, and even under decreased plasma estradiol levels, will have increased TBG production that will be reflected in decreased FT4, normal to high TT4 and increased pituitary thyrotopin (TSH). Using the 'first-strategy' TSH algorithm, this could lead to improper interpretation of test results - the euthyroid individual may be improperly classified as having subclinical/clinical hypothyroidism. For those with disease, this may cause physicians to adjust medications. The results of this study should alert physicians of the possibility of 'abnormal' thyroid function tests for euthyroid people ingesting soy, especially in postmenopausal women, when there is no direct thyroid dysfunction. We anticipant the greatest effect of the isoflavones on the hepatic TBG synthesis in the postmenopausals because of higher estradiol-masking effect in the pre-menopausal woman.
Showing the most recent 10 out of 600 publications
