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

Abstract

Objectives: 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.

Study design: 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 6 months after COC initiation by progestin type. Furthermore, we calculated crude and propensity score weighted incidence rate ratios with corresponding 95% confidence intervals via Poisson regression. Covariates used for propensity score estimation included age, body mass index, smoking, medical history, history of hormonal contraceptive use, and education level.

Results: 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 6 months 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.

Conclusions: 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.

Implications: 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.

Keywords: Adverse events; Combined oral contraceptives; Drug interactions; Progestins; Psychotropic drugs; Routine clinical practice.