Association of oral contraceptive use with mortality: Findings from NHANES

The formulations and usage patterns of oral contraceptives have evolved, necessitating updated evidence on their long-term safety.

To assess the associations between duration of oral contraceptive use and all-cause, cardiovascular, and cancer mortality.

We analyzed 19,275 women from the National Health and Nutrition Examination Survey with mortality follow-up through 2019. Use of oral contraceptives was classified by duration (≤1, 1-5, >5 years). Weighted Cox models estimated hazard ratios with 95% CIs; restricted cubic splines examined dose-response relationships.

Among 19,725 women (mean age 47.4 years), the median duration of oral contraceptive use was 3 years. Over a median follow-up of 12.2 years, compared with never-users, those using for >5 years had adjusted hazard ratios of 0.53 (95% CI, 0.37-0.76) for all-cause, 0.50 (95% CI, 0.26-0.96) for cardiovascular, and 0.38 (95% CI, 0.17-0.86) for cancer mortality, with a trend toward lower risks for all three outcomes (all P for trend <0.05). Restricted cubic splines revealed inverse linear associations with all-cause and cancer mortality, and a nonlinear association with cardiovascular mortality. Results remained consistent after propensity score matching.

The duration of oral contraceptive use was not associated with excess mortality risk and showed inverse linear or nonlinear associations with all-cause, cardiovascular, and cancer mortality, supporting their long-term safety.