Thyroid Hormone Treatment and Breast Cancer Risk in Women: A Systematic Review and Meta-Analysis of Observational Studies

Objective: Thyroid hormone treatment is the standard therapy for hypothyroidism, particularly in women. Concerns have been raised that exogenous thyroid hormone use may increase breast cancer risk, but evidence remains inconclusive. This study aimed to systematically review and synthesize observational evidence on the association between thyroid hormone treatment and breast cancer risk in women. Design: We conducted a systematic review and meta-analysis of observational studies. Methods: MEDLINE, EMBASE, and Web of Science were searched from January 1976 to February 2025. Eligible studies assessed breast cancer incidence in adult women receiving thyroid hormone treatment versus non-users. Pooled ORs were calculated. Findings from cohort studies reporting hazard ratios were synthesized qualitatively. Heterogeneity, publication bias, and certainty of evidence were assessed. PROSPERO ID: CRD42022348966. Results: Four case–control studies including 221,254 women receiving thyroid hormone treatment and 4,385,666 controls were included in the prespecified primary OR-based meta-analysis. In the primary random-effects meta-analysis, thyroid hormone treatment showed a possible epidemiological signal with breast cancer risk (OR 1.43, 95% CI: 0.90–2.28; I2 = 94.3%), although the confidence interval crossed unity and heterogeneity was substantial. Formal assessment of publication bias was performed but should be interpreted cautiously given the small number of included studies. The certainty of evidence was rated as low due to heterogeneity, serious inconsistency and imprecision. Conclusions: Thyroid hormone treatment was associated with a possible epidemiological signal for breast cancer in observational studies; however, the primary pooled estimate was not statistically significant and should be interpreted as hypothesis-generating because of substantial heterogeneity and residual confounding. Further well-designed prospective studies are required before causal or clinical inferences can be made.