Increased need for thyroxine in women with hypothyroidism during estrogen therapy

Background Women with hypothyroidism that is being treated with thyroxine often need higher doses when they are pregnant. Whether this need can be attributed solely to estrogen-induced increases in serum thyroxine-binding globulin or whether other factors are involved is not known. Methods In 11 postmenopausal women with normal thyroid function and 25 postmenopausal women with hypothyroidism treated with thyroxine, I assessed thyroid function before they started estrogen therapy and every 6 weeks for 48 weeks thereafter. The women with hypothyroidism included 18 women receiving thyroxine-replacement therapy and 7 women receiving thyrotropin-suppressive thyroxine therapy. On each occasion, serum thyroxine, free thyroxine, thyrotropin, and thyroxine-binding globulin were measured. Results In the women with normal thyroid function, the serum free thyroxine and thyrotropin concentrations did not change, whereas at 12 weeks the mean (+/- SD) serum thyroxine concentration had increased from 8.0 +/-0.9 mug per deciliter (103 +/- 12 nmol per liter) to 10.4 +/-1.5 mug per deciliter (134 +/- 19 nmol per liter, P< 0.001) and the serum thyroxine-binding globulin concentration had increased from 20.33.5 mg per liter to 31.3 +/-3.2 mg per liter (P<0.001). The women with hypothyroidism had similar increases in serum thyroxine and thyroxine-binding globulin concentrations during estrogen therapy, but their serum free thyroxine concentration decreased from 1.70.4 ng per deciliter (22 +/-5 pmol per liter) to 1.4 +/-0.3 ng per deciliter (18 +/-4 pmol per liter, P<0.001) and their serum thyrotropin concentration increased from 0.91.1 to 3.2 +/-3.1 muU per milliliter (P<0.001). The serum thyrotropin concentrations increased to more than 7 U per milliliter in 7 of the 18 women in the thyroxine-replacement group and to more than 1 muU per milliliter in 3 of the 7 women in the thyrotropin-suppression group. Conclusions In women with hypothyroidism treated with thyroxine, estrogen therapy may increase the need for thyroxine. (N Engl J Med 2001;344:1743-9.) Copyright (C) 2001 Massachusetts Medical Society.