Relation Between Hysterectomy, Oophorectomy and the Risk of Incident Differentiated Thyroid Cancer

The E3N Cohort

Agathe Guenego; Sylvie Mesrine; Laureen Dartois; Laurence Leenhardt; Françoise Clavel-Chapelon; Marina Kvaskoff; Marie-Christine Boutron-Ruault; Fabrice Bonnet

Disclosures

Clin Endocrinol. 2019;90(2):360-368. 

In This Article

Results

Among 89 340 women considered in the present analysis, 412 cases of first primary differentiated thyroid cancer (381 papillary and 31 follicular) were diagnosed during 1 603 264 person-years of observation (median follow-up duration of 9.9 years for cases and 21.4 years for non-cases). Of the 412 cases of thyroid cancer, the information on the micro- or macro-carcinoma status was missing for 9. A total of 166 (41%) were considered as micro-carcinoma (size <10 mm) and 237 were micro-carcinoma (size ≥10 mm).

As shown in Table 1, the frequency of goitre/thyroid nodules was similar between women with an history of hysterectomy and those who did not have hysterectomy. The prevalence of excessive weight or obesity was higher among the women with an history of hysterectomy as compared to those without hysterectomy.

Hysterectomy/Oophorectomy and Risk of Thyroid Cancer

Women with a history of hysterectomy had an increased risk of differentiated thyroid cancer (HR=2.05, 95%CI 1.65–2.55; model 2), as compared to women without hysterectomy (Figure 1, Table 2). When considering types of hysterectomy/oophorectomy, the highest risk was observed for women with hysterectomy and uni- or bilateral oophorectomy (HR=2.21, 95%CI 1.67–2.91). There was no association between oophorectomy alone and thyroid cancer risk. Risks were similar whatever the age at the hysterectomy or the time since hysterectomy. Associations were similar although slightly stronger after adjustment for reproductive factors (model 3) (Table 2). Results were similar for papillary and follicular cancers (HR=2.02, 95%CI 1.61–2.53 for papillary, HR=2.52, 95%CI 1.17–5.44 for follicular, P homogeneity =0.59, model 2). Both micro- and macro-carcinomas ((HR=1.81, 95%CI 1.28–2.57 and HR=2.16, 95%CI 1.62–2.88 respectively, P homogeneity =0.45, model 2) were associated with a history of hysterectomy.

Figure 1.

Risk of thyroid cancer according to the mode of diagnosis of fibroids and the absence of a history of hysterectomy. Hazard ratio and 95% CI are displayed from the multivariate model 2

The association between a history of hysterectomy and thyroid cancer risk was not modified by smoking status nor dysthyroidism history (P interaction =0.09 and 0.23, respectively) and was observed in all corresponding strata.

Fibroids

Overall, a history of benign gynaecological disease confirmed by surgery or laparoscopy was associated with increased thyroid cancer risk (HR 1.67, 95%CI 1.32–2.11; model 2; Table 3). The increase was driven by the association with uterine fibroids history (HR 1.91; 95% CI 1.50–2.44, model 2; Table 3). This association was observed whatever the mode of diagnosis of fibroids and irrespective of a history of hysterectomy (Table 3). Women with a confirmed history of fibroids had an increased risk of both micro- (HR=1.54, 95%CI 1.03–2.30, model 2) and macro-carcinomas (HR=2.16, 95%CI 1.57–2.97, model 2). If we consider simultaneously history of hysterectomy and of fibroids in the same multivariate statistical model (model 2), each variable remains statistically associated with the risk of thyroid cancer [hysterectomy (yes/no): HR=1.70, 95% CI :1.27–2.28; history of fibroids (yes/no): HR=1.33, 95% CI :1.01–1.75].

Neither self-reported nor confirmed history of endometriosis, uterine polyps or ovarian cysts were associated with thyroid cancer risk (Table 3). Results were similar for papillary and follicular thyroid cancers (data not shown).

Finally, we performed sensitivity analyses by excluding women who had an early diagnosis of thyroid cancer (first 2 years of follow-up) and the results were unchanged: women with a history of hysterectomy had an increased risk of differentiated thyroid cancer (HR=2.01, 95%CI 1.60–2.52; model 2), as compared to women without hysterectomy. Similarly, those who had a history of uterine fibroma were at higher risk of thyroid cancer as well (HR 1.84; 95% CI 1.47–2.30, model 2).

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