Combined T3–T4 therapy against dementia?

A recent study found that combined hypothyroidism therapy (T3 and T4) reduces the risk of dementia and mortality!

In research published in the Journal of Clinical Endocrinology & Metabolism, a surprising but promising result was reported: thyroid treatment including liothyronine (T₃) was associated with lower rates of dementia and mortality compared to patients treated with levothyroxine (T₄) alone—even when their lab results indicated they were “well controlled” (i.e., had normal TSH levels).

What does this mean in practice?

• It may be worth considering T₃–T₄ combination therapy in patients with cognitive complaints.

• An individualized approach could be considered, particularly in cases of persistent cognitive symptoms.

• Combined therapy requires professional consultation and close laboratory monitoring—it is not recommended to adjust therapy independently.

Important: Further randomized trials are needed to confirm these findings and to evaluate long-term safety.

Why?

• International guidelines recommend T4 monotherapy first, as it is considered safe and effective for the majority of patients.

• Most patients respond well to T4 monotherapy (e.g., Letrox, Euthyrox), since the body can convert T4 into T3, the active hormone.

• There is no clear scientific consensus on the effectiveness of combination therapy—most large, randomized clinical trials have not shown a clear advantage over T4 monotherapy.

• T3 has a short half-life and acts more quickly, making it harder to maintain stable blood levels—this may increase the risk of arrhythmia or anxiety in sensitive patients.

• International professional guidelines (e.g., ATA, ETA) recommend combination therapy only in exceptional cases, under strict medical supervision, when symptoms persist despite normal TSH levels.

Combination therapy may be considered in patients who:

• have normal TSH levels but significant cognitive complaints,

• have thoroughly discussed treatment options with their physician,

• agree to strict clinical and laboratory monitoring, and careful dose adjustment.

  
  

Authors: Beltrão et al.

Method: Retrospective cohort study with a large sample size

Findings:

• Patients treated with T₃–T₄ combination therapy had a lower incidence of dementia.

• Mortality was also lower during the study period.