Cohort Study of Psychiatric Adverse Events Following Exposure to Levonorgestrel-Containing Intrauterine Devices in UK General Practice

Introduction: Intrauterine devices are implantable contraceptives of which some brands steadily release levonorgestrel over an extended time period. Exposure to a levonorgestrel-releasing intrauterine device has been associated with depression and, more recently, a connection to anxiety, panic attacks, sleep problems and restlessness has been suggested. This study uses data from the THIN database of UK general practice to investigate these suggestions.Methods: A cohort study was performed to compare the incidence of psychiatric adverse events between groups of women who were new users of levonorgestrel-releasing and non-hormonal intrauterine devices. Hazard ratios for the first occurrence of psychiatric symptoms or prescriptions of disease-specific treatments were calculated on an intention-to-treat basis using a proportional hazards model.Results: Significant associations were found between levonorgestrel exposure and records of anxiety (hazard ratio = 1.18; 95% confidence interval 1.08-1.29) and sleep problems (hazard ratio = 1.22; 95% confidence interval 1.08-1.38) in women without a prior record of these events. No significant associations were found for panic attacks or restlessness. Clear baseline differences in clinical characteristics and age between the groups were present. These were included in the model as potential confounding factors.Conclusion: Statistically significant associations of levonorgestrel exposure with anxiety and sleep problems were observed. Substantive differences in baseline characteristics of the treated groups make robust conclusions difficult but the results strongly suggest that additional studies are warranted.