Contrary to previous findings, reduced thyroid gland function (hypothyroidism) appears to be a protective factor against endometrial cancer (EC), meaning patients with this condition may have a lower risk of diagnosis, according to a study recently published in Biomedicines.
About thyroid hormones and EC
The thyroid gland produces two main hormones, T3 (triiodothyronine) and T4 (thyroxine), also known as tetraiodothyronine, which are responsible for regulating key bodily functions, including metabolic rate, growth and development. Additionally, thyroid hormones bind to specific receptors in endometrial cells, modulating their function. Both hypo- and hyperthyroidism are associated with irregular menstruation, infertility and adverse pregnancy outcomes.
Some studies have found that elevated TSH levels—a hallmark of hypothyroidism—are associated with increased endometrial cancer risk. However, the authors noted that obesity, a common feature of hypothyroidism and a well-documented risk factor for EC, could be a confounding factor influencing study results.
Genome-wide association study to clarify doubts
To further investigate the subject, the authors conducted a Genome-Wide Association Study (GWAS), which involves comparing the genomes of large groups of people with a particular trait to identify genetic markers that are more common in one group than in another.
They used European-ancestry GWAS summary statistics for EC and endometrioid EC and correlated these with hypothyroidism and obesity datasets, as well as datasets from individuals with obesity and thyroid disease.
Subsequently, the authors applied a Mendelian randomization (MR) approach to determine the association between EC, hypothyroidism and obesity. This method uses genetic variants as “proxies” for traits. Because genes are randomly assigned at conception, MR reduces the likelihood that results are skewed by lifestyle or environmental factors, and it helps determine whether a link is likely causal rather than coincidental.
Hypothyroidism linked to lower risk of EC
The results showed a causal relationship between hypothyroidism and a decreased risk of EC. Patients with Hashimoto’s thyroiditis, a common autoimmune cause of hypothyroidism, appeared to have a particularly lower risk. Further analyses revealed that overweight and obesity were associated with an increased EC risk.
“Our study establishes a robust causal association between hypothyroidism and a decreased risk of endometrial cancer,” the authors wrote. “However, the underlying mechanism for the potential protective effect of hypothyroidism remains unclear and warrants further investigation, with a potential role for autoimmune responses.”
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