Comparative adverse event reporting patterns of desogestrel versus norethisterone in third-generation combined oral contraceptives: A disproportionality analysis of the FAERS satabase

The aim was to investigate the adverse event reporting patterns of 2 commonly used combined contraceptives (desogestrel/ethinyl estradiol (DES) and norethisterone/ethinyl estradiol (NOR)) using the Food and Drug Administration Adverse Event Reporting System database. We selected data from the first quarter of 2004 to the second quarter of 2024 from the Food and Drug Administration Adverse Event Reporting System database for disproportionate analysis. We performed signal detection and comparative analysis using the reporting odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean for adverse events (AEs) related to DES, and NOR. From January 1, 2004 to June 30, 2024, a total of 35,83,091 reports related to drug AEs were extracted. Among these, 1177 reports were associated with DES, involving 4057 AEs; 1677 reports were associated with NOR, involving 4353 AEs. In the category of reproductive system and breast disorders, the reporting association for abnormal withdrawal bleeding was stronger for DES, while withdrawal bleeding and hypomenorrhoea were more frequently reported with NOR. In pregnancy, puerperium, and perinatal conditions, signals for complications of delivery and labor were more prominent in patients using DES. Conversely, NOR showed stronger associations with reports of contraceptive failure (pregnancy during oral contraceptive use and pregnancy while using contraceptives). In vascular disorders, vena cava thrombosis and splenic infarction were reported more frequently in patients using NOR, while arterial thrombosis and embolism were more commonly reported in those using DES. Subgroup analyses showed that women aged 18 to 40 years had a greater number of preferred terms and signal strength in the aforementioned 3 major systems. In this analysis, DES showed stronger reporting signals for arterial thrombosis, perinatal complications, and abnormal withdrawal bleeding, while NOR was more associated with vena cava thrombosis, contraceptive failure, withdrawal bleeding, and breast enlargement. Clinicians may pay particular attention to women of reproductive age, specifically those aged 18 to 40 years.