Increased need for thyroxine in women with hypothyroidism during estrogen therapy

N Engl J Med. 2001 Jun 7;344(23):1743-9. doi: 10.1056/NEJM200106073442302.


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 microg per deciliter (103+/-12 nmol per liter) to 10.4+/-1.5 microg per deciliter (134+/-19 nmol per liter, P<0.001) and the serum thyroxine-binding globulin concentration had increased from 20.3+/-3.5 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 1.7+/-0.4 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 0.9+/-1.1 to 3.2+/-3.1 microU per milliliter (P<0.001). The serum thyrotropin concentrations increased to more than 7 microU per milliliter in 7 of the 18 women in the thyroxine-replacement group and to more than 1 microU 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Estrogens, Conjugated (USP) / pharmacology
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Medroxyprogesterone / therapeutic use
  • Middle Aged
  • Postmenopause / blood
  • Reference Values
  • Thyroid Function Tests
  • Thyroid Gland / drug effects
  • Thyroid Gland / physiology
  • Thyroid Neoplasms / drug therapy
  • Thyrotropin / blood
  • Thyroxine / administration & dosage*
  • Thyroxine / blood
  • Thyroxine / therapeutic use
  • Thyroxine-Binding Proteins / metabolism*


  • Estrogens, Conjugated (USP)
  • Thyroxine-Binding Proteins
  • Thyrotropin
  • Medroxyprogesterone
  • Thyroxine