Effect of estrogens on thyroid function. II. Alterations in plasma thyroid hormone levels and their metabolism.

The circulating levels of total triiodothyronine (TT₃), thyroxine (TT₄, and T₄-bbinding globulin (TBG) and the kinetics of T₃ and T₄ were studied in five menstruating rhesus monkeys before, during, and after prolonged treatment with estradiol monobenzoate (E₂B, 50 μg/kg body weight/day subcutaneously). A significant increase over pretreatment (p < 0.01) plasma TT₃, TT₄, and TBG was recorded on day 6 of E₂B therapy. A further significant stepwise increase in these parameters was noted up to day 19 of E₂B, when the levels plateaued for the rest of the period of E₂B treatment. Two weeks after discontinuation of E₂B, plasma TT₃, TT₄, and TBG had returned to the pretreatment range and remained so up to 40 days of observation. Although the percent free T₃ and percent free T₄ were significantly decreased (p < 0.01) during E₂B therapy, the absolute concentrations of free T₃ and free T₄ were not altered. After prolonged E₂B treatment the metabolic clearance rate, distribution space, and production rate (PR) of both T₃ and T₄ were decreased (p < 0.01). The extrathyroidal T₄ pool (ETT₄P) was significantly increased (p < 0.01), whereas ETT₃P did not show any significant alterations (p > 0.05). The decreased PR of T₄ might have been due to a direct inhibitory effect of E₂B on the thyroid, whereas the decrease in PR of T₃ might have been due to either decreased conversion of T₄ to T₃, to decreased secretion by the thyroid, or both.