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

Abstract and Introduction

Abstract

Background: Thyroid cancers are threefold more frequent in women than in men. A role of reproductive or hormonal factors has been suggested but with contradictory results. We investigated potential associations between history of hysterectomy, with or without oophorectomy, and history of benign gynaecological disease (uterine fibroids, endometriosis) and the incidence of differentiated thyroid cancer, in a large French prospective cohort.

Methods: A total of 89 340 women from the E3N cohort were followed up between 1990 and 2012. Gynaecological diseases treated by surgery were self-reported. Thyroid cancers were validated by histological reports. Time-dependent covariates included smoking status, BMI and history of benign thyroid disease. Cox proportional hazard models with age as timescale were used to estimate Hazard Ratios (HR) and 95% confidence intervals (CI).

Results: A total of 412 cases of thyroid cancer were diagnosed during follow-up. A history of hysterectomy was associated with an increased risk of differentiated thyroid cancer (adjusted HR=2.05; 95%CI: 1.65-2.55). The association was not altered after further adjustment for reproductive factors. Endometriosis, uterine polyps, ovarian cysts and oophorectomy without hysterectomy were not associated with the risk of thyroid cancer. A history of fibroids was also significantly related to the risk of thyroid cancer over the follow-up period (adjusted HR=1.91; 95%CI: 1.50–2.44) and the increased risk persisted after adjustment for history of hysterectomy.

Conclusions: Women who had either a history of fibroids or hysterectomy had an increased risk of differentiated thyroid cancer. These findings suggest shared biological mechanisms between fibroids and thyroid cancer, which deserve to be further dissected.

Introduction

Incidence of thyroid cancer has increased worldwide over the recent decades.[1,2] Some established risk factors for thyroid cancer are known, such as ionizing radiation, benign thyroid disease, genetic predisposal and high body mass index (BMI).[1,3,4] Based on epidemiological data, it has long been proposed that hormonal factors may determine or modulate the risk of thyroid cancer. Indeed, thyroid cancers are threefold more frequent in women than in men after puberty and incidence decreases after menopause.[5,6] A role of female hormones in the aetiology of thyroid cancer has been suggested with a direct action of oestrogens, via its receptors (ER), on proliferative and neoplastic disorders.[6] However, the relationship between thyroid cancer risk and reproductive or hormonal factors is still debated, with contradictory and often inconclusive findings on the association between thyroid cancer and age at puberty, menopause, parity, breast-feeding or menopausal hormone therapy.[5,7–9]

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.[10–12]

Several studies have attempted to determine hormonal and reproductive factors involved in the development of thyroid cancer in women, with conflicting results.[5,9,13] A potential association between hysterectomy and thyroid cancer risk has already been described, but in studies with methodological heterogeneities and potential bias.[7,14–17] Moreover, links between thyroid cancer risk and hysterectomy, oophorectomy or benign gynaecological disease histories have not been investigated simultaneously, despite common aetiological factors and frequent morbid associations. Thus, we aimed to prospectively explore the link between differentiated thyroid cancer (micro- or macro-carcinomas) and a history of hysterectomy, with or without oophorectomy, in a large cohort, according to age and time since gynaecological surgery. In addition, we investigated the relation between a history of benign gynaecological disease (uterine fibroids, endometriosis, ovarian cyst and uterine polyp) and the risk of incident thyroid cancer.

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