Differentiated thyroid cancer: Why does it affect predominantly women during the reproductive period and have higher incidence of mutual association with breast cancer?

Differentiated thyroid cancer (DTC) is markedly more common in women than men, and its occurrence and risk for poorer prognosis are associated with pregnancy. Further, it is known that there is a high frequency of co-occurrence of DTC and breast cancer. Although the underlying mechanisms that contribute to these phenomena are not entirely clear, 2 hypotheses are proposed here. First, human chorionic gonadotropin (hCG) produced by the placenta may be involved, since hCG has a similar function to stimulate the thyroid as thyroid-stimulating hormone (TSH), the latter of which is known to play a role in causing DTC and may promote breast cancer through the secretion of thyroid hormones (THs). Second, thyrotropin-releasing hormone (TRH), which is stimulated by suckling in the puerperal period, induces the secretion of not only TSH and thus indirectly THs, but also prolactin (PRL), which can accelerate the development of breast cancer. These hypotheses also explain the pregnancy-associated transient increase in breast cancer risk, while inhibition of estrogen by PRL may have a long-term preventive effect on breast cancer. Pregnancy-associated hyperthyroidism may also account for female preponderance of thyroid disease in general as well as tumors in organs that the thyroid hormone targets such as cardiac myxoma and diffuse-type gastric carcinoma.