Gender differences in thyroid cancer: a critical review

It has long been known that the incidence of thyroid cancer in women is significantly higher than that in men. The objective of this article is to review gender differences in thyroid cancer, as well as epidemiological, clinical and experimental research on the role of sex hormones, their receptors and other molecular factors in this well-established thyroid cancer gender discrepancy. Although more common in women, thyroid cancer typically presents at a more advanced stage and with a worse disease prognosis in men. Clinical evidence on the impact of estrogen and other sex hormones on thyroid cancer has remained inconclusive, although numerous experimental studies have suggested that these hormones and their receptors may play a role in tumorigenesis and tumor progression. Studies of thyroid cancer cell lines suggest that an imbalance between the two estrogen receptor (ER) isoforms, α and β, may be responsible for the cell proliferation seen with estrogen treatment. Expression studies on thyroid tumors indicate that they express ER and possibly progesterone receptors and androgen receptors, but there is conflicting evidence as to whether or not there is a difference in receptor status between thyroid cancers, benign thyroid lesions and normal thyroid tissue. There have been few studies evaluating the ERα/ERβ profiles in thyroid tumors and normal thyroid tissue. Our understanding of the underlying basis for sex differences in thyroid cancer has improved over the last few decades, but the relationship between gender and thyroid cancer risk has remained elusive. Areas for future research include ERα/ERβ profiling of normal and neoplastic thyroid tissue, association between ER status and tumor dedifferentiation, and evaluation of the signaling pathways by which estrogen and other sex steroids exert their effects on thyroid cancer cells. Sex steroid receptors, and then downstream signaling pathways, represent promising future therapeutic targets for thyroid cancer treatment, and further study is required.