The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition

J Clin Endocrinol Metab. 2014 Mar;99(3):843-51. doi: 10.1210/jc.2013-3686. Epub 2014 Jan 13.


Context: TSH-suppressive doses of levothyroxine (L-T4) have adverse effects on bone and cardiac function, but it is unclear whether central nervous system function is also affected.

Objective: The aim of the study was to determine whether women receiving TSH-suppressive L-T4 doses have decrements in health status, mood, or cognitive function.

Design and setting: A cross-sectional comparison was made among three groups of women in an academic medical center research clinic.

Patients: Twenty-four women receiving chronic TSH-suppressive L-T4 doses, 35 women receiving chronic replacement L-T4 doses, and 20 untreated control women participated in the study.

Interventions: Subjects underwent testing at a single outpatient visit.

Main outcome measures: We measured health status (SF-36), mood (Profile of Mood States, Symptom Checklist 90-R, Affective Lability Scale), and cognitive function (declarative memory [Paragraph Recall], working memory [N-back, Subject Ordered Pointing], motor learning [Pursuit Rotor, Motor Sequence Learning Test], and executive function [Letter Cancellation Test, Trail Making Test, Iowa Gambling Test]).

Results: Women receiving TSH-suppressive or replacement L-T4 doses had decrements in health status and mood compared to healthy controls. These decrements were more pronounced in women receiving replacement, rather than suppressive, L-T4 doses. Memory and executive function were not affected in either treated group, compared to healthy controls.

Conclusions: Women receiving TSH-suppressive doses of L-T4 do not have central nervous system dysfunction due to exogenous subclinical thyrotoxicosis, but TSH-suppressed and L-T4-replaced women have slight decrements in health status and mood that may be related to self-knowledge of the presence of a thyroid condition or other uncharacterized factors. These mood alterations do not impair cognitive function.

Trial registration: NCT00565864.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Affect / drug effects*
  • Case-Control Studies
  • Cognition / drug effects*
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Female
  • Health Status*
  • Hormone Replacement Therapy / adverse effects*
  • Humans
  • Middle Aged
  • Thyroid Function Tests
  • Thyrotropin / antagonists & inhibitors*
  • Thyroxine / administration & dosage
  • Thyroxine / adverse effects*
  • Young Adult


  • Thyrotropin
  • Thyroxine

Associated data