Hormonal Factors and the Risk of Papillary Thyroid Cancer in the California Teachers Study Cohort

Background: Despite the increasing incidence of thyroid cancer, there is limited information on its etiology. The strikingly higher rates in young women, compared with men, suggest that sex steroid hormones may be involved in the development of this disease.

Methods: We investigated the effects of menstrual, reproductive, and other hormonal factors on papillary thyroid cancer risk in the prospective California Teachers Study cohort. Among 117,646 women, 233 were diagnosed with invasive histologically confirmed papillary thyroid cancer after cohort enrollment and before January 1, 2008. Relative risks (RR) and 95% CIs were estimated by using Cox proportional hazards regression models.

Results: Among younger women (age <45 years at baseline; approximately one-third of the cohort), but not older women, later age at menarche (age ≥14 years) was associated with increased risk (RR = 1.88, 95% CI: 1.13-3.13; p(interaction) by age = 0.06). Risk was also increased among young women who had longer (>30 days) adolescent menstrual cycles (RR = 1.78, 95% CI: 1.01-3.14) and whose last pregnancy had ended within five years of cohort enrollment (RR = 2.21, 95% CI: 1.13-4.34). Among older women (age ≥45 years at baseline), ever use of estrogen-only therapy was associated with a statistically nonsignificant increase in risk (RR = 1.69, 95% CI: 0.95-2.98).

Conclusions: The findings from this prospective analysis suggest that several factors related to delayed pubertal development and the transient effects of pregnancy may be particularly important in influencing risk in young women.

Impact: These results suggest the importance of future research into the role of progesterone and the estrogen-to-progesterone ratio.