Effect of COVID-19 vaccination on the timing and flow of menstrual periods in two cohorts

Abstract

COVID-19 vaccination protects against the potentially serious consequences of SARS-CoV-2 infection, but some people have been hesitant to receive the vaccine because of reports that it could affect menstrual bleeding. To determine whether this occurs we prospectively recruited a cohort of 79 individuals, each of whom recorded details of at least three consecutive menstrual cycles, during which time they each received at least one dose of COVID-19 vaccine. In spontaneously cycling participants, COVID-19 vaccination was associated with a delay to the next period, but this change reversed in subsequent unvaccinated cycles. No delay was detected in those taking hormonal contraception. To explore hypotheses about the mechanism by which these menstrual changes occur, we retrospectively recruited a larger cohort, of 1,273 people who had kept a record of their menstrual cycle and vaccination dates. In this cohort, we found a trend toward use of combined hormonal contraception being protective against reporting a delayed period, suggesting that menstrual changes following vaccination may be mediated by perturbations to ovarian hormones. However, we were unable to detect a clear association between the timing of vaccination within the menstrual cycle and reports of menstrual changes. Our findings suggest that COVID-19 vaccination can lengthen the menstrual cycle and that this effect may be mediated by ovarian hormones. Importantly, we find that the menstrual cycle returns to its pre-vaccination length in unvaccinated cycles.

Keywords: COVID-19; SARS-CoV-2; menstrual cycle; menstruation; vaccination; withdrawal bleed.

Figure 1

STROBE flowcharts for the prospective (A) and retrospective (B) cohorts.

Figure 2

Effect of COVID-19 vaccination on menstrual timing and flow in a prospectively-recruited cohort. (A,B) Violin plots showing the distribution by which periods or withdrawal bleeds began in pre-vaccine cycles, the cycle following dose 1 of the COVID-19 vaccine, interdose cycles, the cycle following dose 2 of the COVID-19 vaccine, and subsequent cycles, where “0” denotes the period or withdrawal bleed beginning on the expected day, negative numbers denote days early and positive numbers days late. Data for spontaneously cycling (A) and participants on hormonal contraception (B) are shown. (C,D) Violin plots showing the distribution of flow scores for periods or withdrawal bleeds in pre-vaccine cycles, the cycle following dose 1 of the COVID-19 vaccine, interdose cycles, the cycle following dose 2 of the COVID-19 vaccine, and subsequent cycles. Data for spontaneously cycling (C) and participants on hormonal contraception (D) are shown. The post-vaccine cycles are shaded as a visual aid. Statistical testing with a mixed effects model, with Tukey's test for multiple comparisons. * adjusted p < 0.05, ** adjusted p < 0.01.

Figure 3

Associations between menstrual changes and brand of vaccine, or use of hormonal contraception. (A,B) Proportional area charts depicting the proportion of participants who reported a change to the timing (A) or flow (B) of the period following vaccination, stratified by brand of vaccine. (C,D) Proportional area charts depicting the proportion of participants who reported a change to the timing (C) or flow (D) of the period following vaccination, stratified by type of hormonal contraception. Statistical testing with a Chi squared test with Holm-Bonferroni sequential correction for multiple hypothesis testing. Adjusted p-values are shown; * denotes categories in which the standardized residual is greater than the critical value (1.96).

Figure 4

Associations between menstrual changes and timing of vaccination within the menstrual cycle. The proportional area charts depict the proportion of respondents who reported a change to the timing (A) or flow (B) of the period following vaccination, stratified by day of the menstrual cycle on which the vaccine was given, relative to the predicted day of ovulation. Statistical testing with a Chi squared test with Holm-Bonferroni sequential correction for multiple hypothesis testing. Adjusted p-values are shown; * denotes categories in which the standardized residual is greater than the critical value (1.96).

Figure 5

Ordinal logistic regression analyses on the effects of pre-existing gynecological condition and other factors on the risk of reporting menstrual changes. The forest plots depict the odds ratio (OR) of an earlier than usual (compared to on time) or on time (compared to later than usual) period following dose 1 (A) or dose 2 (B) of COVID-19 vaccine, depending on respondent age, receipt of the AstraZeneca (AZ) or Moderna vaccine, respondent cycle length, respondent having endometriosis, heavy menstrual bleeding (“heavy bleeding”) or PCOS, timing of vaccination as a continuous variable (“timing (num)”) or timing of vaccination between 3 days before and 4 days after ovulation (“timing (round ov.)”) or timing of vaccination more than 4 days after ovulation (“timing (after ov.)”). The OR of a lighter than usual (compared to same as usual) or a same as usual (compared to heavier than usual) period following dose 1 or dose 2 of COVID-19 vaccine is shown in (C,D), respectively, for the same explanatory variables.