Objective  To analyze the clinical characteristics of cerebrovascular embolism and thrombosis adverse events associated with levonorgestrel intrauterine system (LNG-IUS), thereby provide reference for clinical safe drug use.

Methods The cerebrovascular embolism and thrombosis adverse events associated with levonorgestrel were searched from the World Health Organization (WHO) global database of reported potential side effects of medicinal products (VigiBase). The clini-cal characteristics of the individual cases with well-documented reports (VigiGrade completeness score≥0.80 or with detailed original reports) were analyzed. The causality between drug and adverse events were assessed by Bradford Hill Criteria.

Results  Up to 2 February, 2020, a total of 53 reports of levonorgestrel-related cerebrovascular embolism and thrombosis were reported in VigiBase, which were from 14 countries, and all patients were female. Of them, 37 reports (69.8%) were related to LNG-IUS. The 37 cases were from 11 countries, 28 cases were reported by healthcare professionals (22 cases by physicians, 1 case by pharmacist, 5 cases by other healthcare professionals), 7 cases were reported by patients, and 2 cases with unknown reporter. Of the 37 reports, 9 were fully in-formative, the median age of patients was 35 years old (16-53 years old), 2 patients were overweight, 1 patient had coagulation-related abnormalities, and the time to onset of cerebrovascular embolism and thrombosis after administration of LNG-IUS ranged from 8 days to 4 years.

Conclusion  The use of LNG-IUS may increase the risk of intracranial thrombosis. The combination of other thrombotic risk factors (eg, overweight, abnormal coagulation) may further increase the risk of intracranial throm-bosis.

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