Centre for Fertility and Health, Norwegian Institute of Public Health, P.O. Box 222, Skøyen, Oslo, 0213, Norway.
Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway.
Eur J Epidemiol. 2024 Oct;39(10):1127-1138. doi: 10.1007/s10654-024-01170-0. Epub 2024 Nov 6.
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.
这项研究使用一个包括 666467 名年龄在 20 至 40 岁之间的挪威女性的大型全国登记处进行了联系，评估了 COVID-19 疫苗接种与月经出血紊乱之间的关系。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（无/稀少、过多、不规则/频繁的月经和月经间期出血）是从全科医生数据库获得的。我们使用 Cox 回归比较了接种疫苗和未接种疫苗的女性，在接种疫苗之前，女性作为未接种疫苗的人贡献随访时间。此外，我们进行了自身对照病例系列分析，并进行了一项敏感性分析，排除了整个大流行期间一直未接种疫苗的所有人群，以评估未测量混杂因素的作用。我们观察到接种 COVID-19 疫苗后出现几种月经出血紊乱的风险增加，范围从月经间期出血的调整后的 HR（aHR）为 1.18（95%CI：1.04，1.33）到不规则/频繁的月经为 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，这些估计值完全减弱（aHR 在 0.97 和 1.08 之间）。疫苗剂量或类型没有差异。我们的自身对照病例系列分析证实，第一剂疫苗接种后没有增加风险，但在接种第二剂疫苗后 61 天，月经出血紊乱的风险略有增加。总之，COVID-19 疫苗接种后月经出血紊乱的风险适度增加似乎反映了从未接种过 COVID-19 疫苗的女性未测量混杂因素的作用，因为在比较接种疫苗后的风险与接种疫苗的女性之前的风险时，关联并不存在。
