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).