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.

本研究使用大型国家登记联系评估了 Covid-19 疫苗接种与月经出血障碍之间的关系，其中包括 2019 年 1 月 1 日居住在挪威的 666,467 名 20 至 40 岁的女性。有关疫苗接种 BNT162b2 和 mRNA-1273 的信息来自挪威疫苗接种登记处。月经紊乱的诊断 （缺经/稀少、月经过多、月经不规律/频繁和月经间期出血） 来自全科医生数据库。我们使用 Cox 回归检查了新发月经出血障碍，将接种疫苗的女性与未接种疫苗的女性进行比较，其中女性在接种疫苗当天之前未接种疫苗的随访时间占主导地位。此外，我们进行了一项自我对照的病例系列分析，以及一项排除了整个大流行期间未接种疫苗的所有人群的敏感性分析，以评估未测量混杂因素的作用。我们观察到接种 Covid-19 疫苗后多次月经出血障碍的风险增加，从月经间期出血的调整 HR （aHR） 为 1.18 （95% CI： 1.04， 1.33） 到月经不规律/频繁的 1.29 （95% CI： 1.23， 1.36）。然而，当排除随访结束时仍未接种疫苗的女性时（aHR 在 0.97 和 1.08 之间），估计值完全减弱。未发现疫苗剂量或类型的差异。我们的自我对照病例系列分析证实，接种第一剂疫苗后风险没有增加，尽管从接种第 2 剂疫苗后 61 天开始，月经出血紊乱的风险略有增加。 总之，接种 Covid-19 疫苗后月经出血障碍的风险略有增加，这似乎反映了从未接种过 Covid-19 疫苗的女性无法测量的混杂作用，因为在接种疫苗的女性中，接种疫苗后的风险与接种疫苗前的风险进行比较时，关联并不存在。