Covid-19 vaccination and menstrual bleeding disturbances among women of fertile age: a Norwegian registry study

This study evaluated the relationship between Covid-19 vaccination and menstrual bleeding disturbances using a large national registry linkage including 666,467 women between 20 and 40 years of age residing in Norway on January 1st, 2019. Information on vaccination-BNT162b2 and mRNA-1273 - was obtained from the Norwegian vaccination registry. Diagnoses of menstrual disturbances (absent/scanty, excessive, irregular/frequent menstruation, and intermenstrual bleeding) was obtained from the general practitioner database. We examined new-onset menstrual bleeding disturbances using a Cox regression comparing vaccinated to unvaccinated women, where women contributed follow-up time as unvaccinated until the day of vaccination. In addition, we conducted a self-controlled case-series analysis, and a sensitivity analysis excluding all those who remained unvaccinated throughout the pandemic, to evaluate the role of unmeasured confounding. We observed an increased risk of several menstrual bleeding disturbances after vaccination against Covid-19, ranging from an adjusted HR (aHR) of 1.18 (95% CI: 1.04, 1.33) for intermenstrual bleeding to 1.29 (95% CI: 1.23, 1.36) for irregular/frequent menstrual periods. However, estimates were fully attenuated when excluding women who remained unvaccinated at the end of follow-up (aHRs between 0.97 and 1.08). No differences were identified according to vaccine dose or type. Our self-controlled case series analysis confirmed no increased risk after a first dose of vaccination, though there was a slightly increased risk of menstrual bleeding disturbances from 61 days after vaccination with dose 2. In conclusion, the modestly increased risk of menstrual bleeding disturbances after Covid-19 vaccination appeared to reflect a role of unmeasured confounding by women who never received Covid-19 vaccinations, as associations did not remain when risk after vaccination were compared to risk before vaccination among ever vaccinated women.