Table 1

Prospective cohort studies of premenopausal individuals

First author (reference)Publication yearStudy designLocationSample
size
Age of participantsStudy periodVaccine typesOutcome(s)Control variablesMain resultsOverall risk of bias rating
Alvergne19 2022Two cohorts: retrospective+prospectiveUKProspective: 79 Retrospective: 1273≥18 yearsRetrospective: 7/2021–10/2021 Prospective: not providedPfizer, Moderna, AstraZeneca, JanssenTiming and flow of mensesNone
  • Post-vaccine menses: 2.3 days late on average (prospective cohort)

  • No meaningful change in flow

  • No association by brand - those on progestogen-only contraception: more likely to report heavy flow

High
Bouchard58 2022Prospective cohortNorth America7618–42 yearsNot providedPfizer or Moderna mRNA vaccinesProspectively collected daily diary data on: cycle length, days of flow, volume, luteal phase length, signs of ovulation. Secondary outcomes: perceived menstrual changes attributed to vaccinationNone (time-invariant variables controlled as part of pre–post design)75 women provided 588 cycles for analysis (227 pre-vaccine cycles, 145 vaccine cycles, 216 post-vaccine cycles). 22% perceived changes in their menstrual cycle post-vaccination but there were no significant differences in menstrual cycle length or days of flow comparing pre-vaccine, vaccine and post-vaccine cyclesModerate
Chiang20 2023Prospective cohort studyTaiwan20≥20 yearsNot providedModerna, Pfizer, AstraZenecaCycle length, bleed lengthNone
(pre–post design)
Bleed length: 6.08 (pre) vs 6.45 (first dose) vs 6.00 days (second dose). Cycle length: 29.42 (pre) vs 30.84 (first dose) vs 30.30 days (second dose)High
Duijster59 2023Prospective cohort event monitoring study+spontaneous reportsThe Netherlands13 56716–55 years1/2/2021–29/3/2022AstraZeneca, Janssen, Moderna or Pfizer vaccineAmenorrhoea/oligomenorrhoea, dysmenorrhoea, heavy menstrual bleeding, intermenstrual bleeding, irregular bleeding, reduced blood loss, and withdrawal blood loss abnormalAgeIncreased odds of any menstrual abnormality for Janssen (OR 1.83; 95% CI 1.33 to 2.49), Moderna (OR 2.44; 95% CI 1.86 to 3.20) and Pfizer (OR 3.04; 95% CI 2.36 to 3.93) vs AstraZeneca. Most menstrual abnormalities (63.8%, n=352) occurred after second dose of vaccination vs first dose (36.2%). Overall, median time to resolution of abnormalities was 7 days (IQR 4–14 days)Moderate
Edelman15 2022Prospective cohort studyGlobal19 62218–45 years10/2020–11/2021Pfizer, Moderna, AstraZeneca, JanssenCycle length, menses lengthAge, BMI, education, parity, relationship status, global regionAdjusted difference (β) in change in cycle length between vaccinated and unvaccinated: first dose: 0.71 (95% CI 0.47 to 0.96); second dose: 0.56 (95% CI 0.28 to 0.84). After second dose: −0.11 (95% CI −0.33 to 0.10). Adjusted difference in change in menses length for vaccinated vs unvaccinated:first dose: 0.07 (95% CI 0.00 to 0.13); second dose: 0.13 (95% CI 0.06 to 0.20)Low
Edelman14 2022Prospective cohort studyUS395918–45 years10/2020-9/2021Pfizer, Moderna, JanssenCycle length, menses lengthAge, race/ ethnicity, BMI, parity, relationship status, educationCycle length: first dose: β=0.64 (0.27 to 1.01); second dose: β=0.79 (0.40 to 1.18); Days of flow: first dose: β=0.08 (–0.04 to 0.19); second dose: β=0.08 (–0.04 to 0.20)Low
Gibson16 2022Prospective cohort studyUS9652≥18 years11/2019–1/2022Moderna, Pfizer, JanssenCycle lengthAge, BMI, seasonalityAll vaccinations: first dose of mRNA vaccine (0.50 days, 95% CI 0.22 to 0.78); second dose of mRNA vaccine (0.39 days, 95% CI 0.11 to 0.67); Janssen vaccine: 1.26 days longer (95% CI 0.45 to 2.07) than pre-vaccination cycles. Follicular phase vaccination: first dose of mRNA vaccine (0.97 days, 95% CI 0.53 to 1.42); second dose of mRNA vaccine (1.43 days, 95% CI 1.06 to 1.80); Janssen dose (2.27 days, 95% CI 1.04 to 3.50)Low
Mohr-Sasson17 2023Prospective cohortIsrael3512–16 years6/2021–7/2021PfizerChange in: cycle regularity, cycle length, cycle intensity, AMH during 3-month periodAge, BMI, side effects31.8% of regularly menstruating girls had irregular periods after vaccination; 50% of pre-menarcheal girls reported menarche on 3- month follow-up; AMH levels not appreciably different pre- and post-vaccinationHigh
Rogers23 2022Prospective cohortUK11 47518–59 years2/2021–10/2021AstraZeneca, Pfizer, SpikeVaxCycle changesNoneReported HR for first dose of AstraZeneca (reference) with second dose of AstraZeneca, first dose of Pfizer, and second dose of Pfizer. All nullModerate
Wang21 2022Prospective cohort studyUS and Canada385821–56 years
(all premenopausal)
4/2020–11/2021mRNA and adenovirus-vectorCycle lengthSociodemographic and behavioural factors±pandemic stressorsVaccination was associated with longer cycles after vaccination (0–6 months: OR 1.67 (95% CI 1.05 to 2.64); 7–9 months: OR 1.43 (95% CI 0.96 to 2.14); >9 months: OR 1.41 (95% CI 0.91 to 2.18)) and among those whose cycles were short, long or irregular before vaccination (OR 2.82 (95% CI 1.51 to 5.27); OR 1.10 (95% CI 0.68 to 1.77) for those with normal length, regular cycles before vaccination). mRNA and adenovirus-vectored vaccines were both associated with this changeLow
Wesselink22 2023Prospective cohort studyUS and Canada113721–45 years6/2021–8/2022Moderna, Pfizer, JanssenCycle regularity, cycle length, bleed length, heaviness of bleed and menstrual painSociodemographic, lifestyle, medical and reproductive factorsParticipants had 1.1-day longer cycles after the first dose of vaccine (95 % CI 0.4 to 1.9) and 1.3-day longer cycles after the second dose (95 % CI 0.2 to 2.5). Associations were attenuated at the second cycle post-vaccination. There was little association with cycle regularity, days of flow, menstrual volume or painLow
  • AMH, anti-Müllerian hormone; BMI, body mass index; CI, confidence interval; HR, hazard ratio; IQR, interquartile range; mRNA, messenger RNA; OR, odds ratio; UK, United Kingdom; US, United States; β, mean difference.