First author (reference) | Publication year | Study design | Location of study | Sample size | Age of participants | Study period | Vaccine types | Outcome(s) | Control variables | Main results | Overall risk of bias rating |
Alahmadi41 | 2022 | Retrospective cohort study | Saudi Arabia | 673 | 18–45 years | 1/2021–1/2022 | Moderna, AstraZeneca, Pfizer-Biotech | Menstrual length, days of flow, volume, pain regarding pre- and post-COVID-19 vaccination | None (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 pain | High |
Barabás51 | 2022 | Retrospective cohort study | Hungary | 1563 | 18–65 years | Recruited: 9/2021–12/2021 Data collected: 2019–2022 | Pfizer, Moderna, AstraZeneca, Sputnik, Janssen, Sinopharm | Cycle length, menses length, cycle regularity | None | 40.4% 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 reappearance | High |
Bisgaard Jensen49 | 2023 | Registry-based cohort study | Denmark | 13 648 | 16–65 years | 5/2021–12/2021 | Pfizer-BioNTech, Moderna, other or mixed | Longer 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 changes | Vaccine 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 type | 30% 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 changes | High |
Caspersen18 | 2023 | Population-based cohort study | Norway | 7565 | 12–15 years | 8/2021–10/2021 | Comirnaty vaccine | Mother’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 pain | None (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 | 2023 | Retrospective cohort study | Five global regions | 9555 | 18–44 years | 10/2020–5/2022 | Pfizer, Moderna, AstraZeneca, Janssen, Covishield and Sputnik, Covaxin, Sinopharm and Sinovac | Mean 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 | 2022 | Retrospective cohort study | Italy | 100 | 18–45 years | 4/2021–4/2022 | Pfizer, Moderna, AstraZeneca | Late period, abnormal uterine bleeding | None | 23% had menstrual delay, 77% had AUB | High |
Hallberg61 | 2022 | Registry-based cohort study | Sweden | 1.6 million | 15–49 years | 12/2020–1/2022 | Pfizer, Moderna, AstraZeneca | ICD-10 codes: N91 (absent, scanty, rare menstruation), N92 (excessive, frequent, irregular menstruation), N93 (other abnormal uterine/vaginal bleeding) | None | Standardised 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 | 2023 | Retrospective cohort study | Turkey | 258 | “Reproductive-aged women” | Not provided | CoronaVac, Pfizer | “Menstrual dysregulation” | None | Prevalence 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 women | High |
Ljung24 | 2023 | Registry-based cohort study | Sweden | 2 946 448 | 12–74 years | 12/2020–2/2022 | BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, AZD1222 | Healthcare 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 treatments | Postmenopausal: 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 bleeding | Moderate |
Trogstad63 | 2023 | Retrospective cohort study (Norwegian Young Adult Cohort) | Norway | 39 772 | 18–30 years | 5/2021–10/2021 | Data 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 design | In 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 conditions | Moderate |
Wong48 | 2022 | Retrospective cohort study (vaccine surveillance) | US | 62 679 | ≥18 years | 12/2020–1/2022 | Pfizer, Moderna, Janssen | Menstrual irregularities or vaginal bleeding | None | 63 815 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.