Vaccine / menstruation study

January 7, 2022 Followup! The results of the survey above were published in October 2021:

Characterizing menstrual bleeding changes occurring after SARS-CoV-2 vaccination
Menstrual bleeding after SARS-CoV-2 vaccination
Authors: Katharine MN Lee, Eleanor J Junkins, Urooba A Fatima, Maria L Cox, Kathryn BH Clancy
October 12, 2021

Abstract:
Many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. This emerging phenomenon was undeniable yet understudied. We investigated menstrual bleeding patterns among currently and formerly menstruating people, with a research design based off our expectations that these bleeding changes related to changes in clotting or inflammation, affecting normal menstrual repair. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual, while 44% reported no change, after being
vaccinated. Among people who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of post menopausal people reported breakthrough bleeding. We found increased/breakthrough bleeding was significantly associated with age, other vaccine side effects (fever, fatigue), history of pregnancy or birth, and ethnicity. Changes to menstrual bleeding are not uncommon nor dangerous, yet attention to these experiences is necessary to build trust in medicine.

Results:
After data cleaning and aggregation of the first three months of data collection, participants in our sample (N=39,129) were between 18 to 80 years old (median=33 years; median age=34.22 years, SD=9.18). All participants were fully vaccinated (at least fourteen days after all required doses) and had not contracted COVID-19 (diagnosed or suspected). This sample was (90.9%) woman-only identifying and 3,557 (9.1%) gender diverse; 32,983 (84.3%) white only identifying and 6,146 (15.7%) racially diverse; and 31,134 (79.6%) non-Hispanic or Latinx and 7,995 (20.4%) Hispanic, Latinx, or other.
Respondents in this sample were vaccinated with Pfizer (N=21,620), Moderna, (N=13,001), AstraZeneca (N=751), Johnson & Johnson (N=3,469), Novavax (N=61), or other (N=204) vaccines, with 23 not reporting vaccine type. Self-report of localized vaccine side effects (soreness at injection site) after the first dose and second dose were 87.6% and 77.4%, respectively, across all vaccine types. Systemic vaccine side effects (headache, nausea, fever,
and/or fatigue) were experienced by 54.3% and 74.6% of participants after the first and second dose, respectively. Of those that reported systemic vaccine side effects, 40.6% experienced systemic effects after both doses.
Vaccine symptoms, period changes (flow and length), period symptoms, and timing of period symptoms reported by study respondents are presented by age categories. The Johnson & Johnson vaccine, being the only single
dose vaccine at the time of survey, was excluded from later analyses.

Of Note:
“In spontaneously cycling subgroups, a higher proportion of respondents with endometriosis (52.4%), menorrhagia (44.6%), and/or fibroids (46.3%) reported experiencing a heavier menstrual flow post-vaccine than the non-diagnosed respondents (40.8%)” and “premenopausal, spontaneously cycling respondents who were diagnosed with endometriosis, menorrhagia, and/or fibroids were more likely to report experiencing heavier bleeding post-vaccine compared to those without any diagnosed reproductive condition. We also find that many respondents who had post-vaccine changes did not have them until fourteen days or longer post-inoculation, which extends beyond the typical seven days of adverse symptom reporting in vaccine trials.”

You can read the full article as a PDF here.

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There have been concurrent studies on this topic, and so far I have found two more:

Effect of COVID-19 vaccination on menstrual periods in a retrospectively recruited cohort
Victoria Male
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
November 15, 2021

Introduction:
As the UK COVID-19 vaccination programme is rolled out to younger participants, the MHRA’s surveillance scheme, Yellow Card, is increasingly receiving reports from people who have noticed a change in their menstrual cycle following vaccination: at 10 November 2021, 37571 such reports had been made. It is important to note that most people who report such a change following vaccination find that their period returns to normal the following cycle and that there is no evidence that COVID-19 vaccination adversely affects female fertility. Nonetheless, people are concerned by these reports. Investigating the potential link between COVID-19 vaccination and menstrual changes is important for maintaining public trust in the vaccination programme and, if a link is found, to allow people to plan for potential changes to their cycles.

Results:

• Brand of vaccine is not associated with differences in timing or flow of next period.
• People on hormonal contraception were more likely to report a change to menstrual flow.
• Timing of vaccination does not have a clear effect on timing or flow of next period.
• Menstrual changes following dose 2 are closely associated with those following dose 1.
• People who have a diagnosis of endometriosis or PCOS may be more likely to experience a change in the timing of their cycle following vaccination.

Of Note:
“We found that respondents who had a diagnosis of a menstrual or gynaecological condition were not more likely to report a change in flow than those who did not have such a diagnosis, and that those with a diagnosis of heavy or abnormal menstrual bleeding or uterine fibroids were not more likely to report a change in timing. We hope that our findings will be reassuring to people with these conditions. However, we did find a slight increase in the frequency of people with endometriosis who reported an earlier than usual period, and in people with polycystic ovaries who reported a later than usual period. It will be important to follow up this finding to determine whether these groups really are more likely to experience a change to the timing of their cycle. In the interim, we emphasise that these findings should not be used to counsel people who have these diagnoses against vaccination. Indeed, it is important for those who are particularly concerned about changes to their menstrual cycles to be reminded that COVID infection itself may cause this.”

You can read the full article as a PDF here.

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Association Between Menstrual Cycle Length and Coronavirus Disease 2019
(COVID-19) Vaccination
A U.S. Cohort
Alison Edelman, MD, MPH, Emily R. Boniface, MPH, Eleonora Benhar, PhD, Leo Han, MD, MPH, Kristen A. Matteson, MD, MPH, Carlotta Favaro, PhD, Jack T. Pearson, PhD, and Blair G. Darney, PhD, MPH
January 5, 2022

OBJECTIVE:
To assess whether coronavirus disease 2019 (COVID-19) vaccination is associated with changes in cycle or menses length in those receiving vaccination as compared with an unvaccinated cohort.

METHODS:
We analyzed prospectively tracked menstrual cycle data using the application “Natural Cycles.” We included U.S. residents aged 18–45 years with normal cycle lengths (24–38 days) for three consecutive cycles before the first vaccine dose followed by vaccine-dose cycles (cycles 4–6) or, if unvaccinated, six cycles over a similar time period. We calculated the mean within-individual change in cycle and menses length (three prevaccine cycles vs first- and seconddose cycles in the vaccinated cohort, and the first three cycles vs cycles four and five in the unvaccinated cohort). We used mixed-effects models to estimate the adjusted difference in change in cycle and menses length between the vaccinated and unvaccinated cohorts.

RESULTS:
We included 3,959 individuals (vaccinated 2,403; unvaccinated 1,556). Most of the vaccinated cohort received the Pfizer-BioNTech vaccine (55%) (Moderna 35%, Johnson & Johnson/Janssen 7%). Overall, COVID-19 vaccine was associated with a less than 1-day change in cycle length for both vaccine-dose cycles compared with prevaccine cycles (first dose 0.71 dayincrease, 98.75% CI 0.47–0.94; second dose 0.91, 98.75% CI 0.63–1.19); unvaccinated individuals saw no significant change compared with three baseline cycles (cycle four 0.07, 98.75% CI 20.22 to 0.35; cycle five 0.12, 98.75% CI 20.15 to 0.39). In adjusted models, the difference in change in cycle length between the vaccinated and unvaccinated cohorts was less than 1 day for both doses (difference in change: first dose 0.64 days, 98.75% CI 0.27–1.01; second dose 0.79 days, 98.75% CI 0.40–1.18). Change in menses length was not associated with vaccination.

CONCLUSION:
Coronavirus disease 2019 (COVID-19) vaccination is associated with a small change in cycle length but not menses length.

Of note:
We conducted multiple sensitivity analyses to confirm the robustness of our results.

• First, we compared changes in cycle and menses length by vaccine brand.
• Second, we excluded individuals with any prevaccination cycle whose absolute cycle length was outside of the 24–38-day range (579 individuals).
• Third, we excluded any individuals who reported polycystic ovarian syndrome, thyroid disorder, or endometriosis (226 individuals).
• Fourth, we excluded any individuals who reported use of emergency contraception during at least one study cycle (157 individuals).
• Finally, although the data did not meet the missing at random assumption required for imputation techniques, we used imputation followed by weighting with covariate balancing propensity scores and bootstrapped SEs to confirm that our results were not biased by missing data.

You can read the rest as PDF here.