Impact of progestin type on the risk of drug interactions between combined oral contraceptives and psychotropic drugs: A pooled analysis of real-world data.

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To assess the risk of contraceptive failure and adverse events (AEs) associated with the type of progestin when coadministered with psychotropic drugs within a routine clinical practice setting. A pooled analysis of four large, prospective, multinational cohort studies including women with a new prescription of combined oral contraceptives (COCs) and concomitant psychotropic drug use from 13 European countries and the United States. We determined the frequency of contraceptive failures and AEs within 6months after COC initiation by progestin type. Furthermore, we calculated crude and propensity score weighted incidence rate ratioswith corresponding 95% confidence intervalsvia Poisson regression. Covariates used for propensity score estimation included age, body mass index, smoking, medical history, history of hormonal contraceptive use, and education level. Our analysis comprised 7679 COC users reporting psychotropic drug use at baseline. The most common progestin type was drospirenone (30.0%) followed by norethisterone acetate/norethindrone acetate (20.5%), levonorgestrel (17.3%), norgestimate (11.6%), norethindrone (5.7%), nomegestrol/nomegestrol acetate (5.6%), desogestrel (4.9%), and dienogest (4.4%). Overall, 39 (0.5%) contraceptive failures and 156 (2.0%) AEs occurred within the first 6months of follow-up. Head-to-head comparison of different progestins against levonorgestrel regarding AEs showed a significantly lower risk for drospirenone (weighted incidence rate ratio 0.5, 95% confidence interval [0.3-0.9]), while no difference was observed for other progestins. Among women using psychotropic drugs, drospirenone was associated with a lower risk of AEs compared to levonorgestrel, while other progestins showed no significant differences. The number of contraceptive failures was low across progestins. Compared to levonorgestrel, drospirenone has shown a reduced risk of adverse events when coadministered with psychotropic drugs, whereas other common progestins showed no significant differences. Contraceptive failures were rare across progestins. This analysis provides valuable real-world data on potential drug interactions and may be used for future updates of evidence-based guidelines on contraception.