Sex differences in thyroid axis function: Relevance to affective disorder and its treatment


  • Peter C. Whybrow M.D.

    Corresponding author
    1. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
    • Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
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Throughout life the thyroid economy differs for men and women. The “set point” for TSH is higher in women, they experience more goiter and nodule formation, and autoimmune thyroid disease is greater throughout life. Excluding cancer, the lifetime prevalence of thyroid disease for women is variously estimated between 2.25-4.0%, some 4 to 10 times the estimates for men.

Contrary to earlier interpretation, maternal thyroid hormones are now thought to be important in the early life of the fetus and the development of the CNS; however, after the first trimester maternal free thyroid hormone falls to reach a nadir post partum, a fact not to be discounted in postpartum psychosis.

Major depression is more common in women and approximately 5-10% have some metabolic evidence of a diminished thyroid economy. Adjunctive tri-iodothyronine has been shown to speed recovery from depression in women but not in men.

Manic-Depressive Illness in its classic form (Bipolar I) is approximately equal in prevalence between men and women. However, the malignant variant of treatment resistant rapid cycling (RC) is predominant in women and is significantly associated with Grade I hypothyroidism. Furthermore, the use of high dose thyroxine as an adjunct to anticycling medications such as lithium and the anticonvulsants with frequently mitigate the cycling and induce clinical remission.

Studies in premenopausal women (the common sufferers of RC) suggest that this pharmacologic use of thyroxine has few side effects and is without detectable increased risk of osteoporosis.

Particularly lithium, but also other clinically employed psychotropic agents, are antithyroid as well as thymoleptic injunction. The study of the interaction of lithium and thyroid metabolism at the cellular and molecular level will help inform these clinical observations. That the c-erb-A family of gene products share considerable homology at the DNA binding region across nuclear T3, glucocorticoid, and estrogen receptors may be of significance in this regard.

Thyroid screening of women with affective disorder is recommended for those who are aged 45 years or older, have a history of postpartum thyroiditis, or a family history of thyroid disease. Depression 3:33-42 (1995). © 1995 Wiley-Liss, Inc.