Impact of hypothyroidism and hyperthyroidism on endometrial cancer incidence: Results from a large population-based cohort study

The limited number of studies examining the association between thyroid diseases and endometrial cancer have yielded inconsistent findings. The study aimed to examine the association between hypothyroidism and hyperthyroidism and the risk of endometrial cancer using comprehensive nationwide register data from Denmark. We conducted a population-based cohort study including 1,057,937 women born in Denmark between 1960 and 1997. Information on thyroid disease diagnoses, cancer diagnoses, covariates, migration, and vital status was obtained from nationwide Danish health and administrative registers. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for endometrial cancer overall and for type I tumors. A landmark analysis examined risks associated with exposures before age 40, and pseudo-observation methods estimated absolute risk differences. During a median follow-up of 17.5 years, 1,159 women were diagnosed with endometrial cancer. Women with hypothyroidism had a higher rate of overall endometrial cancer (HR: 1.54, 95% CI: 1.22–1.94) and type I tumors (HR: 1.65, 95% CI: 1.29–2.11). These associations were consistent across subgroups defined by menopausal status and time since diagnosis. No association was observed for hyperthyroidism (HR: 1.13, 95% CI: 0.80–1.61). In the landmark analysis, hypothyroidism remained associated with an increased endometrial cancer rate, but the absolute risk difference by age 60 was modest and not statistically significant. In conclusion, hypothyroidism was associated with a modestly increased rate of endometrial cancer, while no association was observed for hyperthyroidism. These findings support further investigation into thyroid function and endometrial carcinogenesis.