Benign Breast and Gynecologic Conditions, Reproductive and Hormonal Factors, and Risk of Thyroid Cancer

Abstract

The higher incidence of thyroid cancer in women compared to men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50–78 years old, we prospectively examined associations of self-reported history of benign breast and gynecological conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in models using age as the time metric. During follow-up (median=11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (≥55 vs. <50 years: HR=2.24, 95% CI:1.20–4.18), greater estimated lifetime number of ovulatory cycles (≥490 vs. <415 cycles: HR= 2.40, 95% CI:1.33–4.30), greater number of live births (≥5 vs. 1–2: HR=1.72, 95% CI:1.05–2.82), and history of uterine fibroids (HR=1.72, 95% CI:1.18–2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were non-significantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer.

Are pregnancy, parity, menstruation and breastfeeding risk factors for thyroid cancer? Results from the Korea National Health and Nutrition Examination Survey, 2010‐2015

“…Therefore, we defined the number of reproductive years in this study to assess the exposure of thyroid tissue to endogenous sex hormone more clearly. After adjusting for other variables, the number of reproductive years significantly increased the risk of thyroid cancer, consistent with results of a previous study of Melissa et al . Previous studies have shown that oestrogen can promote proliferation and metastasis of thyroid cancer cells .…”

“…Third, pregnancy and parity showed the strongest associations with thyroid cancer. Several studies have shown that pregnancy and parity could increase the risk for thyroid cancer . In our study, pregnancy and parity significantly increased the risk thyroid cancer (Table ).…”

Tubal Ligation and Incidence of 26 Site-Specific Cancers in the Million Women Study

“…The strongest association was with a history of cervical intraepithelial neoplasia grade 3 (RR ¼ 4.03, 95% CI: 2.59-6.28), reflecting the importance of high-risk strains of human papilloma virus as causative agents of both cervical (Walboomers et al, 1999) example, as tubal ligation is usually performed for permanent contraception, it is likely to be more common among women who are sexually active, and who thus may be more likely to be exposed to sexually-transmitted infections, such as human papilloma virus, and the consequent increased risk of anal cancer. There have been reports on possible relationships between tubal ligation and other cancers, including possible reductions in risk of colorectal (Cape and Kreiger, 1999;Rosenblatt et al, 2004) and stomach cancer (Dorjgochoo et al, 2009), and increased risks of thyroid cancer (Braganza et al, 2014) and lymphatic and haematopoietic malignancies (Kjaer et al, 2004). We did not replicate any of these findings.…”

Relation between hysterectomy, oophorectomy and the risk of incident differentiated thyroid cancer: The E3N cohort

“…Hysterectomy is one of the most common surgical procedures in gynaecology worldwide and is mainly performed in case of a benign disease such as fibroma and endometriosis, conditions which are associated with lifetime sex steroid hormone exposure …”