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12-04-2025 | Hypothyroidism | Review

Effects of timing and scheduling in levothyroxine adherence to hypothyroidism control: Meta-analysis with trial sequential analysis of Randomized Clinical Trials

Authors: Bruno Simas da Rocha, Vitor Bock Silveira, Dimitris Varvaki Rados, André Borsato Zanella, Rafael Selbach Scheffel, Ana Luiza Maia, Jose Miguel Dora

Published in: Endocrine

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Abstract

Purpose

Treatment adherence for chronic conditions is a common clinical challenge. This systematic review aimed to assess the impact of scheduling and timing on levothyroxine adherence in patients with hypothyroidism.

Methods

We searched multiple databases (PubMed, EMBASE, SCOPUS, Web Of Science, and CINAHL) using relevant terms related to hypothyroidism and medication adherence. Two independent reviewers conducted study selection, evaluation, and data extraction. The primary outcome was thyrotropin (TSH) levels, analyzed using inverse-variance meta-analysis. Trial sequential analysis (TSA) was conducted to assess the statistical reliability of the meta-analyses results.

Results

Of the 706 articles initially found, 11 met the inclusion criteria: eight assessed evening administration and three evaluated weekly administration of levothyroxine. Comparison between evening and morning administration showed no significant difference in changes of TSH levels (dTSH 0.18; 95% confidence interval [95%CI] −0.29–0.65, P = 0.46). However, considering weekly administration of levothyroxine, TSH levels were higher in the experimental group (dTSH 1.14; 95%CI 0.80–1.14, P < 0.01), although the mean final TSH remained within the reference range in both groups. TSA indicated that the required information size was achieved for scheduling interventions.

Conclusion

Both daily timing and weekly administration of levothyroxine were effective in maintaining TSH levels within reference values. Individualized dosing regimens may be considered based on patient convenience and preference.
Appendix
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Metadata
Title
Effects of timing and scheduling in levothyroxine adherence to hypothyroidism control: Meta-analysis with trial sequential analysis of Randomized Clinical Trials
Authors
Bruno Simas da Rocha
Vitor Bock Silveira
Dimitris Varvaki Rados
André Borsato Zanella
Rafael Selbach Scheffel
Ana Luiza Maia
Jose Miguel Dora
Publication date
12-04-2025
Publisher
Springer US
Published in
Endocrine
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-025-04229-4

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