Elevated Risk of Thyroid Malignancy With Estrogen Hormone Treatment in Biological Male Patients

Introduction: The role of estrogen in the development of thyroid malignancy is poorly understood. Many epidemiological studies have shown exogenous estrogen is associated with an increased risk in female patients, but no studies to date have investigated this association among biologically male patients undergoing estrogen hormone therapy.

Methods: A retrospective cohort study was conducted using the TriNetX Research Network to query biologically male patients prescribed estrogen with at least five years of follow-up. Rates of diagnosis of malignant neoplasm of the thyroid gland within five years of estrogen hormone therapy prescription were determined and statistics were conducted within the TriNetX platform.

Results: We identified 5,354 biologically male patients from 58 healthcare organizations who were prescribed estrogen hormone treatment. The average age was 44 years, with 22% having a formal diagnosis of gender identity disorder. 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 five years, compared to a 0.36% risk among patients not taking estrogen (relative risk 2.62, 95% CI 1.38 – 4.95, p = 0.002).

Conclusions: This is the first association found between estrogen and thyroid malignancy in biologically male patients. Further investigation into this association should focus on patient safety when undergoing estrogen-based hormone treatment.