ABSTRACT
Objective: To prospectively determine whether COVID-19 vaccination is associated with change in menstrual cycle length following vaccination. Material(s) and Method(s): We conducted a longitudinal analysis within a subgroup of 13,018 participants in the Apple Women's Health Study (AWHS) who enrolled between November 2019 and December 2021, having met the following eligibility criteria: were living in the U.S., met minimum age requirements for consent, were English speaking, actively tracked their menstrual cycles, and responded to the COVID-19 vaccination update survey. Cycles tracked when participants were not pregnant, lactating, or using hormonal contraceptives were included. We used conditional linear regression and multivariable linear mixed-effects models with random intercepts to estimate the covariate-adjusted difference in mean cycle length, measured in days, between pre-vaccination cycles and post-vaccination cycles within vaccinated participants, and between vaccinated and unvaccinated participants. We present Bonferroni-adjusted confidence intervals to account for multiple comparisons. Result(s): A total of 120,815 cycles (median = 10 cycles per participant;interquartile range: 4-21) from 9,295 women (8,129 vaccinated;1,160 unvaccinated) were included. Forty-eight percent of participants received the Pfizer-BioNTech vaccine, 32% received Moderna, and 7% received Johnson & Johnson/Janssen. We found no evidence of a difference between mean menstrual cycle length in the unvaccinated and vaccinated participants prior to vaccination (0.16 days, 95% CI: -0.44, 0.75). Among vaccinated women, COVID-19 vaccination was associated with a small increase in cycle length for cycles containing the first dose (0.47, 95% CI: 0.17, 0.76) and cycles containing the second dose (0.36, 95% CI: 0.06, 0.65) of Pfizer-BioNTech or Moderna vaccines compared with pre-vaccination cycles. Cycles containing the single dose of Johnson & Johnson/Janssen were, on average, 1.22 days longer (95% CI: 0.41, 2.03) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length, with a 0.11 (95% CI: -0.17, 0.38) day increase in mean cycle length in the first cycle following vaccination, 0.12 (95% CI: -0.15, 0.40) in the second, -0.22 (95% CI: -0.50, 0.05) in the third, and -0.25 (95% CI: -0.52, 0.02) in the fourth cycle post-vaccination. Conclusion(s): COVID-19 vaccination was associated with an immediate short-term increase in menstrual cycle length. However, the magnitude of this increase diminished in cycles following vaccination, and no association with cycle length persisted over time. Impact Statement: Menstrual cycle change following COVID-19 vaccination appears temporary and should not discourage women from becoming vaccinated. Copyright © 2022