Abstract
Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses’ Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65–0.91]; >10 years of use, 0.43 [0.32–0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 [0.41–0.67]) and second-generation progestins (0.43 [0.30–0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50–0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49–0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.
Highlights
Oral contraceptives (OCs) are among the birth control methods most commonly used by women of reproductive age [1,2,3]
While this study provided data on newer OC formulations, it was restricted to women younger than age 50, a population that typically has relatively low incidence of the disease [20], which may limit the generalizability of these findings
Reported OC use for 2 months or more but less than 10 months in a year was counted as 6 months of use in that year, 10 or more months of use in a year was counted as 12 months, and less than 2 months of use in a year was counted as no use
Summary
Oral contraceptives (OCs) are among the birth control methods most commonly used by women of reproductive age [1,2,3]. An estimated 79% of women ages 15–44 years were ever OC users in the United States in 2011–2013 (~ 42.5 million women) [1]. OCs are generally constituted of an estrogen and a progestin; progestin-only OCs are available, but less frequently prescribed (~ 2% of current OC users in the U.S in 2006–2010) [4]. Four generations of progestins have been utilized, with differing androgenic and metabolic effects [2, 7,8,9,10]. Sex steroids have established effects on the endometrium, with estrogen promoting, and progesterone inhibiting, proliferation [11,12,13]. As described in a meta-analysis and other prospective studies with long-term follow-up [14,15,16,17,18], OC
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