Table 4.
Multivariable-adjusteda hazard ratios (HR) and 95% confidence intervals for endometrial cancer in relation to OC use by estrogen and progestin type in the Nurses’ Health Study II (1989–2017)
| Person-years | Cases | HR | 95% CI | |
|---|---|---|---|---|
| Estrogen type | ||||
| Mestranol (ME) | ||||
| Never OC use | 344,113 | 175 | 1.00 | (ref.) |
| Ever ME use | 805,651 | 317 | 0.74 | (0.61–0.90) |
| Exclusive ME use | 374,797 | 167 | 0.76 | (0.61–0.94) |
| Duration of ME use | ||||
| ≤ 1 year | 207,686 | 83 | 0.79 | (0.60–1.03) |
| > 1–5 years | 383,169 | 155 | 0.77 | (0.62–0.96) |
| > 5 years | 183,683 | 69 | 0.66 | (0.50–0.88) |
| Continuous, in yearsb | 0.96 | (0.92–1.00) | ||
| Continuous, in years, adjusted for continuous duration of EEb | 0.96 | (0.92–1.00) | ||
| p-trendc | 0.01 | |||
| p-trendb | 0.22 | |||
| Ethinyl estradiol (EE) | ||||
| Never OC use | 344,113 | 175 | 1.00 | (ref.) |
| Ever EE use | 1,353,870 | 424 | 0.76 | (0.63–0.91) |
| Exclusive EE use | 855,881 | 256 | 0.77 | (0.63–0.94) |
| Duration of EE use | ||||
| ≤ 1 year | 251,449 | 120 | 1.08 | (0.85–1.37) |
| > 1–5 years | 538,573 | 177 | 0.79 | (0.64–0.98) |
| > 5 years | 465,600 | 99 | 0.52 | (0.41–0.67) |
| Continuous, in yearsb | 0.92 | (0.90–0.95) | ||
| Continuous, in years, adjusted for continuous duration of MEb | 0.92 | (0.90–0.95) | ||
| p-trendc | < 0.0001 | |||
| p-trendb | < 0.0001 | |||
| p-het ME versus EEd | 0.01 | |||
| Progestin type | ||||
| First-generation progestin (P1) | ||||
| Never OC use | 344,113 | 175 | 1.00 | (ref.) |
| Ever P1 use | 1,409,364 | 479 | 0.76 | (0.64–0.91) |
| Exclusive P1 use | 905,756 | 331 | 0.78 | (0.65–0.94) |
| Duration of P1 use | ||||
| ≤ 1 year | 288,175 | 126 | 0.95 | (0.75–1.20) |
| > 1–5 years | 589,882 | 205 | 0.78 | (0.63–0.96) |
| > 5 years | 444,438 | 124 | 0.62 | (0.49–0.78) |
| Continuous, in yearsb | 0.95 | (0.93–0.97) | ||
| Continuous, in years, adjusted for continuous duration of P2b | 0.95 | (0.92–0.97) | ||
| p-trendc | < 0.0001 | |||
| p-trendb | 0.0006 | |||
| Second-generation progestin (P2) | ||||
| Never OC use | 344,113 | 175 | 1.00 | (ref.) |
| Ever P2 use | 771,415 | 246 | 0.73 | (0.60–0.89) |
| Exclusive P2 use | 305,419 | 108 | 0.75 | (0.59–0.96) |
| Duration of P2 use | ||||
| ≤ 1 year | 189,539 | 84 | 1.06 | (0.81–1.38) |
| > 1–5 years | 343,216 | 111 | 0.73 | (0.57–0.93) |
| > 5 years | 189,403 | 37 | 0.43 | (0.30–0.61) |
| Continuous, in yearsb | 0.90 | (0.86–0.95) | ||
| Continuous, in years, adjusted for continuous duration of P1b | 0.90 | (0.86–0.94) | ||
| p-trendc | < 0.0001 | |||
| p-trendb | < 0.0001 | |||
| p-het P1 versus P2d | 0.03 | |||
aAdjusted for age (months), calendar period, BMI (kg/m2, continuous), number of full-term pregnancies (continuous), smoking status (never/past/current), menopausal status (premenopausal/postmenopausal/perimenopausal or unknown), use of HT (never/ever), diagnosis of PCOS (yes/no), laparoscopically confirmed endometriosis (yes/no), age of menarche (years), and use of IUD/diaphragm (yes/no)
bCalculation including ever OC users only
cCalculation including never OC users
dCalculation using duration trends for ever OC users only