COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study

Abstract

Objective: To assess the association between COVID-19 vaccination and the risk of the abnormal uterine bleeding (AUB) specifically focusing on vaginal or uterine bleeding that requires hospital care in women. Methods: We used a nationwide database in the Republic of Korea that combined COVID-19 registry data, which contains information on COVID-19 vaccination, with the claims database of the National Health Insurance Service. We included women aged 16-64 who received their first vaccine dose and were newly diagnosed with AUB in inpatient or outpatient settings within 180 days after receiving the first dose. A population-based selfcontrolled case series analysis was used to estimate the incidence rate ratio (IRR) during the risk periods, including 1-14, 1-21, and 1-28 days after each vaccine dose, compared to the baseline period. The baseline period was defined as the period of 1-180 days following the first vaccine dose, excluding the periods that corresponds to the risk periods. To address the SCCS assumption violation from recurrent nature, only the first event during the observation period was considered. Results: Among 83,422 eligible patients, the risk of AUB requiring hospital care within 14 days following COVID19 vaccination was slightly elevated compared to the baseline period (IRR 1.04, 95 % CI 1.02-1.06). The risk was notably higher after the first dose, regardless of the risk interval (14-day risk period: IRR 1.12, 95 % CI 1.09-1.15; 21-day risk period: IRR 1.08, 95 % CI 1.06-1.10; 28-day risk period: IRR 1.07, 95 % CI 1.05-1.09). No significant increase was observed after the second and third doses. Conclusion: This study found a modest increase in healthcare utilization for AUB after the first dose of COVID-19 vaccination. However, this trend diminished with subsequent doses, showing no significantly increased risk. These findings should be interpreted while considering factors that influence healthcare-seeking behavior for unexpected vaginal or uterine bleeding.