Systematic review and meta-analysis links infertility to higher thyroid cancer risk
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Key Takeaway
Consider that infertility is associated with a modestly increased thyroid cancer risk, but causation is not established.
This is a systematic review and meta-analysis of observational studies evaluating the association between infertility and thyroid cancer risk. The authors synthesized data from studies including a total of 4,563,090 participants.
The primary finding was that infertility was associated with a significantly higher risk of thyroid cancer, with a pooled relative risk (RR) of 1.37 (95% CI, 1.15–1.63). Sex-stratified analyses showed a stronger association in men (RR, 1.53; 95% CI, 1.43–1.65) than in women (RR, 1.31; 95% CI, 1.04–1.66).
The authors acknowledged substantial heterogeneity across the included studies (I² = 81.9%) and evidence of small-study effects as key limitations. They did not report on specific study settings, follow-up durations, or safety outcomes.
The review concludes that infertility is associated with an increased thyroid cancer risk, but the substantial heterogeneity and observational nature of the evidence preclude causal inference. The authors note that the findings should be interpreted with caution and do not establish underlying mechanisms.
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View Original Abstract ↓
BackgroundEpidemiologic evidence on the association between infertility and thyroid cancer risk remains inconsistent. We conducted a systematic review and meta-analysis to synthesize available observational evidence and quantify this association.MethodsWe systematically searched PubMed, Web of Science, and Scopus from inception to February 10, 2026, to identify observational studies evaluating the association between infertility and thyroid cancer risk. Eligible cohort and case–control studies reporting relative effect estimates with 95% confidence intervals (CIs) were included. Summary risk estimates were pooled using random-effects models. Between-study heterogeneity was assessed using the I² statistic. Prespecified subgroup analyses were conducted by sex and study design. Sensitivity analyses and assessments of publication bias were also performed.ResultsNine studies met the inclusion criteria, including seven cohort studies and two case–control studies, comprising a total of 4,563,090 participants. In the pooled analysis, infertility was associated with a significantly higher risk of thyroid cancer (relative risk [RR], 1.37; 95% CI, 1.15–1.63), with substantial heterogeneity across studies (I² = 81.9%). Sex-stratified analyses suggested a stronger association among men (RR, 1.53; 95% CI, 1.43–1.65) than among women (RR, 1.31; 95% CI, 1.04–1.66), although the test for interaction was not statistically significant. The findings were robust across sensitivity analyses. Evidence of small-study effects was observed; however, the association remained statistically significant after adjustment using the trim-and-fill method.ConclusionsThis study suggests that infertility is associated with an increased risk of thyroid cancer. Although substantial heterogeneity was observed, the association remained consistent across multiple sensitivity analyses. However, further well-designed research is needed to verify and clarify this association and its underlying mechanisms.
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