A Large Cohort Study of Hypothyroidism and Hyperthyroidism in Relation to Gynecologic Cancers

Table 3

Hazard ratios (95% confidence intervals) of ovarian cancer by self-reported history of hypothyroidism and hyperthyroidism status in the combined Nurses’ Health Study (NHS, 1976–2010) and Nurses’ Health Study II (NHSII, 1989–2011).

Ovarian cancer	History of hypothyroidism				History of hyperthyroidism
	No	Yes			No	Yes
All epithelial /peritoneal cancer
Number of cases	1052	92			1052	6
Person-years	4,427,881	329,761			4,427,881	28,582
Age-adjusted	1 (ref.)	0.94 (0.75, 1.16)			1 (ref)	0.69 (0.31, 1.55)
Multivariable-adjusted*	1 (ref.)	0.84 (0.68, 1.04)			1 (ref)	0.67 (0.30, 1.49)
Multivariable-adjusted^†	1 (ref.)	0.87 (0.70, 1.08)			1 (ref)	0.68 (0.30, 1.53)
Multivariable-adjusted^‡	1 (ref.)	0.76 (0.58, 0.99)			—	—
Serous histology only
No. of cases	615	56			615	3
Multivariable-adjusted^∣∣	1 (ref.)	0.84 (0.64, 1.11)			1 (ref)	0.56 (0.18, 1.76)
	No	Yes <8 years^¶	Yes 8+ years^¶	𝑃-trend	No	Yes <6 years^¶	Yes 6+ years^¶	𝑃-trend
All epithelial /peritoneal cancer
Number of cases	1052	36	56		1052	1	5
Person-years	4,427,881	151,040	178,721		4,427,881	14,452	14,130
Age-adjusted	1 (ref.)	0.88 (0.63–1.22)	0.98 (0.75–1.29)	0.55	1 (ref)	0.23 (0.03–1.63)	1.17 (0.48–2.82)	0.98
Multivariable-adjusted*	1 (ref.)	0.80 (0.57–1.11)	0.87 (0.66–1.15)	0.13	1 (ref)	0.22 (0.03–1.57)	1.12 (0.46–2.72)	0.95
Multivariable-adjusted^†	1 (ref.)	0.83 (0.59–1.16)	0.90 (0.68–1.18)	0.21	1 (ref)	0.23 (0.03–1.62)	1.14 (0.47–2.76)	0.98
Multivariable-adjusted^‡	1 (ref.)	0.63 (0.38–1.06)	0.81 (0.60–1.10)	0.06	—	—	—	—
Serous histology only
No. of cases	615	23	33		615	1	2
Multivariable-adjusted^∣∣	1 (ref.)	0.85 (0.56–1.19)	0.84 (0.59–1.20)	0.17	1 (ref)	0.36 (0.05–2.53)	0.79 (0.20–3.20)	0.59

∗Multivariable core model is stratified by age (in months), and two-year cycle at risk and cohort (NHS/NHSII) and is adjusted for body mass index (kg/m²; continuous linear variable and missing data indicator), family history of breast or ovarian cancer (yes/no), parity (continuous linear variable of number of children), oral contraceptive use history (never, <1, 1–4, 5–9, 10+ years of use, missing data indicator), age at menarche (continuous linear variable and missing data indicator), age at menopause (continuous linear variable and missing data indicator), use of estrogen only postmenopausal hormone therapy (never user, past user with <5 years duration, past user with ≥5 years duration, current user with <5 years duration, current user with ≥5 years duration), use of estrogen plus progestin only postmenopausal hormone therapies (never user, past user with <5 years duration, past user with ≥5 years duration, current user with <5 years duration, current user with ≥5 years duration), use of other postmenopausal hormone therapy (never user, past user with <5 years duration, past user with ≥5 years duration, current user with <5 years duration, current user with ≥5 years duration), hysterectomy (yes/no), tubal ligation (yes/no), and infertility (none, self is infertile, spouse is infertile, missing).
†To core model, additionally adjusted for greater health surveillance that may be associated with thyroid screening (report of physical exam and high cholesterol).
‡Hypothyroidism and hyperthyroidism defined only for those who reported the same diagnosis at least twice during followup; adjusted for the same variables as in core model.
∣∣Ovarian cancer with serous invasive histology (including papillary) or poorly differentiated histology; adjusted for the same variables as in core model.
¶Duration of having a history of hypothyroidism (median = 8 years) or hyperthyroidism (median = 6 years).