Table 2

Retrospective cohort studies or registry-based cohort studies of premenopausal individuals

First author (reference)Publication yearStudy designLocation of studySample
size
Age of participantsStudy periodVaccine typesOutcome(s)Control variablesMain resultsOverall risk of bias rating
Alahmadi41 2022Retrospective cohort studySaudi Arabia67318–45 years1/2021–1/2022Moderna, AstraZeneca, Pfizer-BiotechMenstrual length, days of flow, volume, pain regarding pre- and post-COVID-19 vaccinationNone
(pre–post comparison)
Changes in menstruation after both vaccine doses were observed for 47%: 23% more pain after first dose and 21% after second dose. Moderna vaccine was associated with greatest changes (65.4%), AstraZeneca was associated with fewest changes (44.9%). Duration of changes in cycles after vaccination (one dose or both) was <1 month for 42% and ≥3 months for 27.1%. Vaccination was associated with minor and transient increase in menstrual painHigh
Barabás51 2022Retrospective cohort studyHungary156318–65 yearsRecruited: 9/2021–12/2021 Data collected: 2019–2022Pfizer, Moderna, AstraZeneca, Sputnik, Janssen, SinopharmCycle length, menses length, cycle regularityNone40.4% reported menstrual changes: 29.9% shorter cycles; 22.2% longer cycles; 13.9% missed period; 7.8% prolonged bleeding; 12.2% irregular bleeding; 4.3% heavier bleeding; 2.8% strong menstrual cramps; 2.0% period reappearanceHigh
Bisgaard Jensen49 2023Registry-based cohort studyDenmark13 64816–65 years5/2021–12/2021Pfizer-BioNTech, Moderna, other or mixedLonger menstrual cycle, shorter menstrual cycle, heavier menstrual bleeding, lighter menstrual bleeding, more regular menstrual cycle, more irregular menstrual cycle, menstrual absence, prolonged bleeding, shortened bleeding, menstrual pain, intermenstrual bleeding, 2-monthly menstrual bleedings, duration of any menstrual changesVaccine symptoms, prior COVID-19 infection, concerned about vaccine, stress, age, smoking, health, use of hormonal contraception; alcohol use, physical activity, weight, pre-vaccination menstrual regularity, vaccine type30% women reported any menstrual change (95% CI 29.31 to 30.86). Less than 10% of women reported either longer or shorter cycles, heavier or lighter bleeding, more regular or irregular cycles, or other menstrual changesHigh
Caspersen18 2023Population-based cohort studyNorway756512–15 years8/2021–10/2021Comirnaty vaccineMother’s report of daughter’s periods before vs after vaccination: (1) heavier bleeding than usual, (2) prolonged menses, (3) shorter interval between menses than usual, (4) longer interval between menses than usual, (5) spotting between menses and (6) greater menstrual painNone (self-matched case series study)RR for heavier bleeding 1.60 (95% CI 1.43 to 1.80); RR for prolonged bleeding 1.39 (95% CI 1.22 to 1.59); RR for shorter interval 1.19 (95% CI 1.07 to 1.32); RR for longer interval 1.15 (95% CI 1.05 to 1.27); RR for spot bleeding 1.06 (95% CI 0.92 to 1.23); RR for stronger period pain 1.14 (95% CI 1.04 to 1.26); RR for period pains without bleeding 1.00 (95% CI 0.90 to 1.11); RR for other pelvic symptoms 0.97 (95% CI 0.76 to 1.25)High
Darney33 2023Retrospective cohort studyFive global regions955518–44 years10/2020–5/2022Pfizer, Moderna, AstraZeneca, Janssen, Covishield and Sputnik, Covaxin, Sinopharm and SinovacMean number of heavy bleeding days and changes in bleeding quantity at three time points (first dose, second dose and post-exposure menses)Age, race, ethnicity, parity, BMI, education, relationship status, region.About 66% reported no change in heavy bleeding days, regardless of vaccination status. Little difference in heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced increases in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; β=4.0%, 99.2% CI 0.7 to 7.2)Low
Dellino60 2022Retrospective cohort studyItaly10018–45 years4/2021–4/2022Pfizer, Moderna, AstraZenecaLate period, abnormal uterine bleedingNone23% had menstrual delay, 77% had AUBHigh
Hallberg61 2022Registry-based cohort studySweden1.6 million15–49 years12/2020–1/2022Pfizer, Moderna, AstraZenecaICD-10 codes: N91 (absent, scanty, rare menstruation), N92 (excessive, frequent, irregular menstruation), N93 (other abnormal uterine/vaginal bleeding)NoneStandardised incidence ratios (comparing with unvaccinated patients in 2019): N91: 0.93 (0.86 to 1.00); N92: 1.04 (1.01 to 1.07); N93: 1.23 (1.17 to 1.28)High
Hasdemir62 2023Retrospective cohort studyTurkey258“Reproductive-aged women”Not providedCoronaVac, Pfizer“Menstrual dysregulation”NonePrevalence of new-onset menstrual dysregulation following vaccination was 20.6% and it differed compared with baseline. Menstrual pattern returned to normal in 59.6% of vaccinated womenHigh
Ljung24 2023Registry-based cohort studySweden2 946 44812–74 years12/2020–2/2022BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, AZD1222Healthcare contact (admission to hospital or visit) for menstrual disturbance or bleeding before or after menopause (ICD-10 codes N91, N92, N93, N95)Age, country of birth, employed in healthcare, marital status, education, health-seeking behaviours, comorbidity, and treatmentsPostmenopausal: highest risks observed after third dose, in 1–7-day risk window (HR 1.28, 95% CI 1.01 to 1.62) and 8–90-day risk window (HR 1.25, 95% CI 1.04 to 1.50). There was a 23–33% increased risk after 8–90 days with BNT162b2 and mRNA-1273 after the third dose, but association with ChAdOx1 nCoV-19 was unclear. Premenopausal: no association with menstrual disturbances or bleedingModerate
Trogstad63 2023Retrospective cohort study (Norwegian Young Adult Cohort)Norway39 77218–30 years5/2021–10/2021Data from National Immunisation Registry (SYSVAK). Pfizer, Moderna, AstraZeneca (through 3/2021 only)Menstrual disturbances (heavier bleeding than usual, prolonged bleeding, shorter interval between menstruations, longer interval between menstruations, spot bleedings, stronger pain during menstruation, period pain without bleeding) before and after the first and second dose of COVID-19 vaccine.Self-controlled case series designIn the first cycle after vaccination: increased occurrence of unusually heavy and prolonged bleeding, spot bleeding, interval changes, and increased pain during periods vs last cycle prior to vaccination. The association was strongest for heavy menstrual bleeding increasing from 8% before vaccination to 14–15% after vaccination, corresponding to RR of 1.90 (95% CI 1.69 to 2.13 after first vaccine dose; RR 1.84, 95% CI 1.66 to 2.03 after second dose). The association between vaccination and menstrual disturbances did not differ by vaccine brand, use of hormones, or history of gynaecological conditionsModerate
Wong48 2022Retrospective cohort study (vaccine surveillance)US62 679≥18 years12/2020–1/2022Pfizer, Moderna, JanssenMenstrual irregularities or vaginal bleedingNone63 815 respondents reported on menstrual irregularities or vaginal bleeding, which included 62 679 female respondents (1.0% of 5 975 363 female respondents aged ≥18 years). Common themes identified included timing of menstruation (70 981 (83.6%) responses) and severity of menstrual symptoms (56 890 (67.0%) responses). Other themes included menopausal bleeding (3439 (4.0%) responses) and resumption of menses (2378 (2.8%) responses)Moderate
  • AUB, abnormal uterine bleeding; CI, confidence interval; HR, hazard ratio; ICD-10, International Classification of Diseases, 10th Revision; OR, odds ratio; RR, relative risk; US, United States; β, mean difference.