Women receiving one dose of a COVID-19 vaccine during a single menstrual cycle had an increase in cycle length of nearly one day, compared to unvaccinated women, according to a study funded by the National Institutes of Health.
The authors, led by Alison Edelman, M.D., M.P.H., of Oregon Health & Science University, Portland, noted that menstrual cycles typically vary a small amount from month to month, and the increase they saw was well within the range of normal variability. They added that additional research is needed to determine how COVID-19 vaccination could potentially influence other menstrual characteristics, such as associated symptoms (pain, mood changes, etc.) and characteristics of bleeding (including heaviness of flow).
“It is reassuring that the study found only a small, temporary menstrual change in women,” said Diana W. Bianchi, M.D., director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “These results provide, for the first time, an opportunity to counsel women about what to expect from COVID-19 vaccination so they can plan accordingly.”
NICHD and NIH’s Office of Research on Women’s Health funded the study, which was part of $1.67 million awarded to five institutions to explore potential links between COVID-19 vaccination and menstrual changes.
The study authors analyzed de-identified data from a fertility tracking app, Natural Cycles. Users input data on their temperature and their menstrual cycles and can consent to the use of their de-identified data for research.
For unvaccinated individuals, data was collected for six consecutive cycles. Of the 3,959 individuals in the study, 2,403 were vaccinated and 1,556 were unvaccinated.
Most vaccinated users received the Pfizer and Moderna vaccines. On average, the first vaccination dose was associated with a .71-day cycle increase in cycle length and the second dose with a .91-day increase. Therefore, users vaccinated over two cycles had an increase of less than one day in each of the vaccination cycles.
A subgroup of app users who received two vaccine doses in the same menstrual cycle (358 users) had a larger average increase in cycle length of two days. However, this change appears to decrease in subsequent cycles, indicating that the menstrual changes likely are temporary. The authors added that the International Federation of Gynecology and
We evaluated 23,754 menstrual cycles prospectively reported by 3,959 U.S. individuals to evaluate whether COVID-19 vaccination is associated with menstrual cycle disturbances during cycles when vaccination occurs. After adjusting for confounders, we found that normally cycling individuals experienced small variations in cycle length regardless of vaccination status.
Statistically significant differences existed between vaccination status groups, but the change in cycle length was less than 1 day, which is below the reportable difference in the menstrual cycle tracking application and is not clinically significant. A subset of individuals who received both vaccine doses in a single cycle had, on average, an adjusted 2-day increase in their vaccination cycle length compared with unvaccinated individuals.
Although approximately 10% of these individuals experienced a clinically notable change in cycle length of 8 days or more, this change attenuated quickly within two postvaccine cycles. We found no change in menses length between or within vaccination cohorts.
Menstrual cycle timing is regulated by the hypothalamic-pituitary-ovarian axis, which can be affected by life, environment, and health stressors.11–13,16 Our results cannot be explained by generalized pandemic stress because our unvaccinated control group saw no changes over a similar time period. Our findings are consistent with a recent analysis of 18,076 Natural Cycles application users before and during the pandemic that also demonstrated no population-level cycle timing disruptions due to pandemic stress.17
mRNA vaccines create a robust immune response or stressor, which could temporarily affect the hypothalamic-pituitary-ovarian axis if timed correctly.18–20 Our findings for individuals who received two doses in a single cycle supports this hypothesis. Given the dosing schedule of the mRNA COVID-19 vaccines in the United States (21 days for Pfizer and 28 days for Moderna), an individual receiving two doses in a single cycle would have received the first dose in the early follicular phase.
Cycle length variability results from events leading to the recruitment and maturation of the dominant follicle during the follicular phase, processes known to be affected by stress.12,21 In contrast, an acute severe illness with or without septicemia, such as COVID-19, could be catastrophic to hypothalamic-pituitary-ovarian axis function, sometimes permanently.18,22–24
This research directly addresses concerns raised by self-reports through VAERS and public discourse.5–7,25 The types of concerns raised range from cycle and menses length changes to differences in menstrual-associated symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.6
Self-reports are useful for rapidly identifying potential signals or rare adverse events, but they are limited by significant confounding and reporting biases. Our study strengths include prospectively collected menstrual cycle data, which limits recall bias, a control group of unvaccinated individuals, and adjustment for sociodemographic factors associated with vaccination status and menstrual cycle changes (eg, age, BMI).
Our sample size is also sufficiently large to identify small differences, even 1 day, in cycle and menses length that may be of interest to individuals but might not rise to the level of clinical concern (8 days or more) or trigger a medical evaluation for secondary amenorrhea (no menses for 3 months).8,26 However, for an individual, small cycle changes can cause concern or raise hopes, especially if avoiding or planning for pregnancy, and this level of detail will likely be valuable.
Our study also has limitations. First, it may not be generalizable to the U.S. population given the selection of Natural Cycles users (more likely to be White, college educated, and have lower BMIs than national distributions and not using hormonal contraception). Second, we also chose to analyze a cohort with consistent normal cycle lengths to clearly identify any associations between cycle and menses length and COVID-19 vaccination.
We recognize that many individuals who menstruate do not fit into this normal category.8,10 Other subpopulations are known to have greater baseline variations in menstrual cyclicity, such as individuals with BMIs higher than 35. We do not yet know whether these populations experience greater changes in cycle and menses length in association with COVID-19 vaccination.
Third, although our results suggest that individuals receiving two doses in a single cycle return to baseline cycle length quickly, our data do not yet include enough subsequent cycles without vaccine to investigate this fully for the entire vaccinated cohort. Finally, we do not have data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in either our vaccinated or unvaccinated groups.
Our findings are reassuring; we find no population-level clinically meaningful change in menstrual cycle length associated with COVID19 vaccination. Our findings support and help explain the self-reports of changes in cycle length. Individuals receiving two COVID-19 vaccine doses in a single cycle do appear to experience a longer but temporary cycle length change. Coronavirus disease 2019 (COVID-19) vaccination is not associated with changes in menses length. Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.
Edelman, A. et al. Determining the impact of COVID-19 vaccination on the menstrual cycle: a U.S. cohort. Obstetrics & Gynecology. DOI:10.1097/AOG.0000000000004695 (2022)