Background. Thyroid status may influence tumorigenesis of gynecologic cancers, yet epidemiologic studies of this relationship are limited and inconsistent. Methods. We evaluated the association of self-reported history of physician-diagnosed hypothyroidism and hyperthyroidism with medical-record confirmed endometrial (EC; all invasive adenocarcinomas) and ovarian cancer (OC; epithelial ovarian or peritoneal cancers) in Nurses' Health Study (NHS) from 1976 to 2010 and NHSII from 1989 to 2011. Cox proportional hazard models were used to estimate multivariable rate ratios (RRs) and 95% confidence intervals based on pooled cohort data. Results. We confirmed 1314 incident cases of EC and 1150 cases of OC. Neither a history of hypothyroidism nor hyperthyroidism was significantly associated with risk of EC or OC. However, having a history of hypothyroidism for 8+ years (median) was nonsignificantly inversely associated with EC (RR？=？0.81; 95% CI？=？0.63–1.04; P-trend with history duration？=？0.11) and OC (RR？=？0.87, 95% CI？=？0.66–1.15; P-trend？= 0.13). Having a history of hyperthyroidism for 6+ years (median) was non-significantly positively associated with EC (RR？=？1.69; 95% CI？=？0.86–3.30; P-trend？=？0.12) but not OC (RR？=？1.12; 95% CI？=？0.46–2.72; P-trend？=？0.95). Conclusions. A history of hypothyroidism or hyperthyroidism was not significantly associated with risk of EC or OC. 1. Introduction Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and the fourth most common cancer overall in women [1]. Most cases are diagnosed in postmenopausal women at an early stage and have an excellent prognosis; however, those presenting with advanced or recurrent disease have limited treatment options and survival of less than 3 years [2, 3]. The number of deaths from EC has doubled over the last 20 years, and the reason for this is not well understood [4]. Well established risk factors for EC are hormonally linked and include a greater lifetime exposure to estrogen, obesity, and diabetes and display a progression from atypical hyperplasia to cancer [5, 6]. Similarly, ovarian cancer (OC) risk is estrogen-linked but very little is known about the etiology or its precursors and it remains the most lethal gynecologic cancer [7]. The hypothalamic-pituitary axis (HPA) regulates the female reproductive tract not only through the regulation of estrogen and other sex hormones but also through interactions with related pathways including thyroid hormones [8]. Thyroid hormones (T3 and T4) are important regulators of differentiation, growth, and
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