Thyroid cancer treatment among adolescents and young adult women and reproductive outcomes: a population-based cohort study.
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STUDY QUESTION: Are different types of thyroid cancer treatment among young women associated with adverse reproductive outcomes? SUMMARY ANSWER: All types of thyroid cancer treatment were associated with infertility diagnosis and early menopause, but not associated with premature ovarian insufficiency (POI) or lower childbirth rates. WHAT IS KNOWN ALREADY: Thyroid cancer and/or its treatment may affect thyroid function, and thyroid hormone imbalances may affect reproduction. STUDY DESIGN SIZE DURATION: Population-based matched cohort study included adolescent and young adult women (AYAs, 15-39 years) treated for thyroid cancer in Ontario, Canada between 1992 and 2019, after they had lived at least 3 years free of recurrence. PARTICIPANTS/MATERIALS SETTING METHODS: Each participant was matched to five cancer-free women based on age, census subdivision, parity, and year of cancer diagnosis. The study cohort consisted of 6474 women undergoing thyroid cancer treatment and 31 922 women without cancer. Exposure status was determined by thyroid cancer treatment, namely: (i) cancer-free (unexposed; referent), (ii) less than total thyroidectomy (LTT), (iii) total thyroidectomy (TOT), or (iv) total thyroidectomy in combination with radioactive iodine therapy (TOT+RAI). Among the exposed, 3396 (52.5%) received TOT, 1520 had (23.5%) LTT, and 1558 (24.1%) had TOT+RAI. Our main outcomes of interest were infertility diagnosis, POI (i.e. cessation of ovarian function before age 40 years), early menopause (menopause before age 45 years), and childbirth rates. Poisson regression models generated weighted relative risks (wRR) using inverse probability of treatment weighting to adjust for imbalances in baseline characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Mean (SD) age at thyroid cancer diagnosis was 30.6 (6.1) years. The rate of infertility was 3186/31 922 (10.0%) among unexposed, 177/1520 (11.6%) after LTT, 414/3396 (12.2%) after TOT, and 213/1558 (13.7%) following TOT+RAI. The weighted relative risk (wRR) was 1.26 (1.12-1.39) for LTT, 1.22 (1.13-1.32) for TOT, and 1.34 (1.19-1.48) following TOT+RAI. The rate of early menopause was 713/31 922 (2.2%) among unexposed, 46/1520 (3.0%) after LTT, 78/3396 (2.3%) after TOT, and 54/1558 (3.5%) following TOT+RAI. The wRR was 1.42 (1.09-1.72) for LTT, 1.02 (0.83-1.20) for TOT, and 1.54 (1.21-1.89) following TOT+RAI. The rates of POI and childbirth were similar between the unexposed and treatment groups. LIMITATIONS REASONS FOR CAUTION: Misclassification is a possibility when using linkage of administrative databases. Absence of information about thyroid hormone supplementation and TSH levels in the study databases is another limitation. Since the unexposed group consisted of cancer-free women, we cannot distinguish whether the observed associations reflect the effects of thyroid cancer itself or its treatment. WIDER IMPLICATIONS OF THE FINDINGS: In this study, thyroid cancer and/or all types of its treatment were associated with a higher rate of infertility diagnosis and early menopause, but not associated with POI or lower childbirth rates. These findings highlight the need for counselling and surveillance about reproductive outcomes among AYA women with thyroid cancer. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Research Institute McGill University Health Centre and a Fonds de recherche du Québec-Santé (FRQ-S) Chercheur Boursier Clinicien award. All of the authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.