Prolongation of the Menstrual Cycle After Receipt of the Primary Series and Booster Doses of mRNA Coronavirus Disease 2019 (COVID-19) Vaccination

Abstract

OBJECTIVE: To quantitatively evaluate the effect of a booster vaccination dose against coronavirus disease 2019 (COVID-19) on menstrual cycle in a large-scale retrospective cohort study using a menstrual cycle tracking smartphone application (app). METHODS: Prospectively or retrospectively recorded data, including the start and finish dates of menstrual cycles, were collected with the app. Detailed data on vaccinations, side effects, and participants' characteristics were retrospectively collected from a questionnaire on the app. For each COVID-19 vaccination shot (first, second, and third), within-individual changes in menstrual cycle length up to the fourth postvaccination cycle were evaluated. RESULTS: Among the 7,376 and 6,873 participants who had the first and second COVID-19 vaccine doses in different menstrual cycles, respectively, menstrual cycles immediately after the vaccination (first postvaccination cycles) were an average of 0.22 days (95% CI, 0.06–0.39) and 0.37 days (95% CI, 0.20–0.54) longer than the prevaccination cycle. In contrast, among the 1,672 participants who received the first and second doses in the same cycle, the first postvaccination cycle was an average of 4.21 days (95% CI, 3.69–4.72) longer. The second to fourth postvaccination cycles returned to the level of the prevaccination cycle. However, among the 4,768 participants who had the third COVID-19 vaccine dose, the menstrual cycle immediately after the vaccination was an average of 1.20 days (95% CI, 1.00–1.40) longer, with prolongation of cycles of 0.27 days (95% CI, 0.10–0.44) to 0.41 days (95% CI, 0.22–0.59) persisting from the second to the fourth postvaccination cycle. CONCLUSION: The booster shot against COVID-19 may have a greater and longer-lasting effect on menstrual cycles than the primary-series shots. Although the effect size was small, evidence on the side effects of immunization on menstruation should be accumulated.

In Reply:

“…Here we provide the additional data requested by Hosoya et al detailing the change in lengths of follicular and luteal phases (Table 1) after coronavirus disease 2019 (COVID-19) vaccination, by timing of vaccination. We did not find similar changes in the follicular or luteal phase for people vaccinated in the follicular phase as published in Hosoya et al 1 The increase in follicular phase length that we observed 2 is smaller (approximately 1 day compared to 2–3 days in Hosoya et al), and we did not observe a decrease in luteal phase length. However, we did see a slightly shorter follicular phase for individuals vaccinated in the luteal phase, but these individuals received their vaccination after the completion of their follicular phase, so this finding is not due to vaccine exposure.…”

“…Likely this difference in findings between the two studies is due not only to our larger sample size but, more importantly, the data source. The data from the menstrual cycle tracking application used in Hosoya et al 1 do not include an ovulation date. Luteal phase was defined as the last 14 days of the cycle.…”

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

“…The peak plasma concentration of betamethasone is reached by 12 hours, whereas betamethasone acetate acts as a reservoir for sustained action. 3 The time of maximum plasma concentration is the same for both, which is 3 hours, although the combination has a multiphasic concentration that lasts for up to 2 weeks or more. 4 In women in whom preterm labor is inevitable, the preferred drug of choice is one with quick onset of action, and prolonged steroid exposure is undesirable.…”

“…We show results from data used in our study, “Prolongation of the Menstrual Cycle After Receipt of the Primary Series and Booster Doses of mRNA Coronavirus Disease 2019 (COVID-19) Vaccination,” 3 which limited cycles to those with ovulation date estimable from logged basal body temperature with the Sensiplan method. 4 We found that the prolongation of menstrual cycle length after vaccination during the follicular phase is a combination of a 2–3-day prolongation in the follicular phase and a 1–2-day shortening of luteal length (Table 1).…”