Elevated Risk of Thyroid Malignancy in Biological Males Taking Estrogen Hormone Therapy

Objective: The role of estrogen in developing thyroid malignancy is poorly understood. Epidemiological studies have shown exogenous estrogen is associated with increased risk in females. Still, no studies to date have investigated this association among biological males undergoing estrogen hormone therapy. Study Design: Retrospective cohort study. Setting: TriNetX Research Network. Methods: Biologically male patients prescribed estrogen with at least 5 years of follow-up were queried from the database. Rates of diagnosis of malignant neoplasm of the thyroid gland within 5 years of estrogen hormone therapy prescription were determined, and statistics were conducted within the TriNetX platform. Results: We identified 6394 biologically male patients from 65 health care organizations prescribed estrogen hormone treatment. The average age was 44.4 years. When balanced for demographic factors as well as known risk factors for thyroid malignancy, the estrogen treatment cohort had a 0.64% risk for diagnosis of thyroid malignancy within 5 years, compared to a 0.27% risk among patients not taking estrogen (relative risk: 2.35, 95% confidence interval: 1.34-4.15, P =.002). Conclusion: We found a higher risk of developing thyroid cancer in biologically male patients prescribed estrogen hormone therapy. This is the first association found between estrogen and thyroid malignancy in this group.