Abstract
Differentiated thyroid cancer (DTC) is markedly more common in women than men, the highest female-to-male ratio being recorded during the reproductive period. This evidence has led to the suggestion that female hormonal and reproductive factors may account for the observed DTC gender disparity. This review focuses on current evidence on the risk of DTC in conjunction with major female reproductive factors, including the impact of pregnancy on DTC occurrence and progression/recurrence. Overall, studies exploring the link between the risk of DTC and menstrual and menopausal factors, oral contraceptives and/or hormone replacement therapy, showed these associations, if any, to be generally weak. Nonetheless, there is some evidence that higher levels of exposure to estrogens during reproductive years may confer an increased risk of DTC. As far as pregnancy is concerned, it is unclear whether a potential association between parity and risk of DTC actually exists, and whether it is enhanced in the short-term following delivery. A possible role for pregnancy-related factors in DTC progression has been recently suggested by some reports, the results of which are consistent with a worse outcome in the short-term of women diagnosed with DTC during gestation compared to non-pregnant control patients. Also, some progression of disease has been described in women with structural evidence of disease prior to pregnancy. However, there seems to be no impact from pregnancy in DTC-related death or overall survival. Several in vitro and animal studies have evaluated the influence of estrogens (E) and estrogen receptors (ERs) on thyroid cell proliferation. Presently available data are indicative of a role of E and ERs in thyroid cancer growth, although considerable discrepancies in respect to ER expression patterns in thyroid cancer tissues actually exist. Further studies providing more direct evidence on the possible role of E and of placental hormones and growth factors on thyroid growth may expand our knowledge on the mechanisms beyond the gender disparity of proliferative thyroid diseases.
Highlights
Thyroid cancer is the most common endocrine malignancy and the eighth most common cancer in the USA [1]
A further meta-analysis focusing on papillary thyroid cancer (PTC) only, found late age at menopause to be associated with increased PTC risk (RR = 1.39, 95% CI 1.03–1.89) [34]
Since rearranged during transfection/ papillary thyroid carcinoma (RET/PTC) rearrangements are found in approximately 20% of spontaneous PTCs [94], a shared mechanism mediated by estrogen receptors (ERs)/ progesterone receptor (PR) signaling and involving the RET/PTC-dependent tyrosine kinase pathways might underlie the observed association of breast cancer and thyroid cancer
Summary
Thyroid cancer is the most common endocrine malignancy and the eighth most common cancer in the USA [1]. Reports analyzing gender distribution according to the histotypes collectively reveal a twofold to almost fourfold F/M IR ratios for differentiated thyroid cancer (DTC), but a lack of gender disparity for the medullary and the anaplastic types [5, 9,10,11]. Both the preponderance of DTC incidence in females and the incidence peak in women of childbearing age suggest that hormonal and reproductive factors may account for the observed DTC gender disparity. We briefly review current evidence on the role of the major female reproductive factors associated with DTC risk and the impact of pregnancy on thyroid cancer occurrence, progression, or recurrence
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