Association between COVID-19 vaccination and healthcare contacts for menstrual disturbance and pre- and post-menopausal bleeding – a nationwide cohort study of 3 million Swedish women

Background: Several studies using self-reported data have indicated menstrual disturbances after Covid-19 vaccination. Large individual-level observational studies using healthcare contact data are warranted to better characterize and quantify such suspected adverse effects of vaccination.

Objectives: To evaluate the risks of clinically diagnosed menstrual disturbance, pre-menopausal and post-menopausal bleeding after Covid-19 vaccination, using data from Swedish national patient registers.

Methods: This nationwide register-based cohort study included 2 946 448 Swedish women aged 12-74. The study period was from 27 December 2020 to 28 February 2022. Data on Covid-19 vaccinations, all inpatient and specialized outpatient care, as well as sociodemographic characteristics, were obtained from national registers. Exposure was Covid-19 vaccination, by vaccine product (BNT162b2, mRNA-1273 and AZD1222) and dose (1, 2 and 3). Outcomes were menstrual disturbance and pre-menopausal bleeding (in ages 12-49 years), and post-menopausal bleeding (in ages 45-74). Cox regression was used to estimate hazard ratios (HR) for each outcome in two risk windows (i.e., 1-7 days and 8-90 days) after each dose of each vaccine product. We assessed a crude model without any adjustment and a full model adjusted for personal characteristics and prior comorbidities; results are reported for the latter.

Results: In total, 88% of women received at least one Covid-19 vaccination and more than 50% of vaccinated individuals received three doses before the end of follow-up. The highest risks for post-menopausal bleeding were observed after the third dose, both in the 1-7 days risk window (HR 1.28, 95% CI 1.01 to 1.62) and the 8-90 days risk window (HR 1.25, 95% CI 1.04 to 1.50). The impact of adjustment for covariates was modest. Analyses of associations with individual vaccine products and risk of post-menopausal bleeding suggested a 23-33% increased risk with BNT162b2 and mRNA-1273 after the third dose, but a less clear association with AZD1222. For menstrual disturbance and pre-menopausal bleeding, adjustment for covariates almost completely removed the weak associations seen in the crude analyses.

Conclusions: We observed weak and inconsistent associations between Covid-19 vaccination and healthcare contacts for post-menopausal bleeding, and even less evidence of associations for menstrual disturbance and pre-menstrual bleeding. These findings do not provide substantial support for a causal association between Covid-19 vaccination and healthcare contacts related to menstrual/bleeding disorders.