Timing of Coronavirus Disease 2019 (COVID-19) Vaccination and Effects on Menstrual Cycle Changes

Abstract

Objective: To assess whether menstrual cycle timing (follicular or luteal phase) of coronavirus disease 2019 (COVID-19) vaccine administration is associated with cycle length changes.

Methods: We used prospectively collected (2021-2022) menstrual cycle tracking data from 19,497 reproductive-aged users of the application "Natural Cycles." We identified whether vaccine was delivered in the follicular or luteal phase and also included an unvaccinated control group. Our primary outcome was the adjusted within-individual change in cycle length (in days) from the average of the three menstrual cycles before the first vaccination cycle (individuals in the unvaccinated control group were assigned a notional vaccine date). We also assessed cycle length changes in the second vaccination cycle and whether a clinically significant change in cycle length (8 days or more) occurred in either cycle.

Results: Most individuals were younger than age 35 years (80.1%) and from North America (28.6%), continental Europe (33.5%), or the United Kingdom (31.7%). In the vaccinated group, the majority received an mRNA vaccine (63.8% of the full sample). Individuals vaccinated in the follicular phase experienced an average 1-day longer adjusted cycle length with a first or second dose of COVID-19 vaccine compared with their prevaccination average (first dose: 1.00 day [98.75% CI, 0.88-1.13], second dose: 1.11 days [98.75% CI, 0.93-1.29]); those vaccinated in the luteal phase and those in the unvaccinated control group experienced no change in cycle length (respectively, first dose: -0.09 days [98.75% CI, -0.26 to 0.07], second dose: 0.06 days [98.75% CI, -0.16 to 0.29], unvaccinated notional first dose: 0.08 days [98.75% CI, -0.10 to 0.27], second dose: 0.17 days [98.75% CI, -0.04 to 0.38]). Those vaccinated during the follicular phase were also more likely to experience a clinically significant change in cycle length (8 days or more; first dose: 6.8%) than those vaccinated in the luteal phase or unvaccinated (3.3% and 5.0%, respectively; P <.001).

Conclusion: COVID-19 vaccine-related cycle length increases are associated with receipt of vaccination in the first half of the menstrual cycle (follicular phase).

Fig. 1.. STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) flow diagram. Sample sizes for first and second dose refer to the number of included individuals with cycle data from each dose of the initial coronavirus disease 2019 (COVID-19) dosing regimen. Unvaccinated individuals were assigned a notional vaccination date.

Fig. 2.. Adjusted within-individual change in menstrual cycle length (in days) from the three-prevaccination cycle average to vaccination cycle, by timing of vaccination, for first (A) and second (B) coronavirus disease 2019 (COVID-19) vaccine doses. Estimates are adjusted for age group, body mass index category, race and ethnicity, parity, education, relationship status, and geographic region after multiple imputation of missing data. Error bars represent 98.75% CIs.

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