Female Reproductive Factors and Differentiated Thyroid Cancer

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.

Hormone Replacement Therapy in Cancer Survivors – Review of the Literature

“…Thyroid malignancy is more common in women than in men. Several epidemiologic studies have been carried out, but no strong evidence of relation between MHT and differentiated thyroid cancer could be found [162][163][164][165][166][167][168]. This is not changed even by the fact that in the past years, both positive and negative associations have been reported between the expression of estrogen and progesteron receptors and the outcome of thyroid cancer [169,170].…”

The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence

“…Some studies have shown an excess risk of thyroid cancer in the first 5 years after pregnancy but not subsequently , suggesting a transient effect of certain pregnancy‐related hormones or other exposures. Increasing levels of endogenous oestrogen throughout gestation may promote thyroid carcinogenesis via indirect stimulation of the pituitary‐thyroid axis or direct stimulation of normal and malignant thyroid cell growth and proliferation; these effects may be more pronounced in the context of iodine deficiency . Hyperemesis gravidarum, an early pregnancy complication related to altered pregnancy hormone levels, including hCG and oestrogen, has been associated with increased risk of thyroid cancer in both the mothers and their offspring .…”

Gender in Endocrine Diseases: Role of Sex Gonadal Hormones

“…Furthermore, females have a better survival rate than age-matched males. Therefore, thyroid cancer is more common in females but is more aggressive in males [ 41 , 42 ]. Pathophysiological reasons explaining this difference are unknown, but it has been proposed that estrogens may play a fundamental role.…”