
==== Front
BMC Womens Health
BMC Womens Health
BMC Women's Health
1472-6874
BioMed Central London

3349
10.1186/s12905-024-03349-9
Systematic Review
Prevalence of menstrual alterations following COVID-19 vaccination: systematic review & meta-analysis
Al Shahrani Abeer asalshahran@pnu.edu.sa
drabeer_fm@yahoo.com

1
Alhumaidan Norah 2
Alzelfawi Lama 2
AlDosari Lena 2
Alhindawi Zeena 2
Alotaibi Nahlah 3
Aljohani Renad 3
1 https://ror.org/05b0cyh02 grid.449346.8 0000 0004 0501 7602 Department of Family and Community Medicine, College of Medicine, Princess Nourah bint Abdulrahman University, P.O.Box 84428, Riyadh, 11671 Saudi Arabia
2 https://ror.org/05b0cyh02 grid.449346.8 0000 0004 0501 7602 College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
3 https://ror.org/0149jvn88 grid.412149.b 0000 0004 0608 0662 College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
19 9 2024
19 9 2024
2024
24 5239 6 2024
2 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

COVID-19 vaccines can lead to diverse local and systemic side effects, but there is limited evidence concerning their association with menstrual cycle changes. This study aimed to assess the prevalence of menstrual cycle alterations after COVID-19 vaccination among adult women.

Methods

We systematically searched the PubMed, Web of Science and Science Direct databases for observational studies that included adult women and investigated the range of menstrual alterations. The quality of the studies was evaluated via the Newcastle–Ottawa scale. All the data were analyzed via Comprehensive Meta-Analysis Software Version 4.0. Forest plots were created to calculate the individual and pooled prevalence rates of different types of menstrual changes and 95% confidence intervals (CI) via fixed-effects and random-effects models, as appropriate. Heterogeneity was assessed with Q statistics and the I2 test.

Results

Eleven studies, encompassing 26,283 adult women, met our eligibility criteria. Among the selected studies, five were cohort studies, five were cross-sectional studies, and one employed a case‒control design. The menstrual changes included abnormal cycle duration, dysmenorrhea, irregular cycles, and abnormal cycle flow (heavy and light flow), with pooled percentages of 27.3% (CI: 7.2–64.6%), 22% (CI: 5.2–59.4%), 16% (CI: 5.8–37.2%), 11.7% (CI: 5.8–22%), and 5.5% (CI: 2.3–12.5%), respectively.

Conclusions

This review highlights the prevalence of menstrual changes after COVID-19 vaccination and emphasizes the importance of considering menstrual health as an integral part of postvaccination monitoring and health care interventions. However, longitudinal studies are essential for establishing a definitive causal relationship between COVID-19 vaccination and menstrual alterations.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12905-024-03349-9.

Keywords

COVID-19
Vaccine
Menstrual cycle
http://dx.doi.org/10.13039/501100004242 Princess Nourah Bint Abdulrahman University PNURSP2024R289 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcBackground

The COVID-19 pandemic, which emerged in Wuhan, China, in December 2019, created a global health crisis. In response, researchers and public health officials have made substantial efforts to develop vaccines aimed at mitigating the impact of the virus [1]. By late 2020, several vaccines had been successfully developed and authorized for emergency use, resulting in their widespread distribution in early 2021 [2]. Vaccines have become the most effective method to curb the pandemic, leading to notable reductions in both the incidence of COVID-19 and associated mortality rates [3, 4]. Despite their effectiveness, vaccine uptake has been impeded by concerns regarding their efficacy, potential adverse effects, and safety, and the expedited nature of their development [5, 6].

Many studies have been conducted to assess the safety, efficacy, and potential adverse effects of COVID-19 vaccines [7, 8]. Among the observed adverse effects, menstrual cycle changes have emerged as a significant concern [9, 10]. This issue has been substantiated by reports from numerous women who experienced unexpected alterations in their menstrual cycles through the Vaccine Adverse Event Reporting System (VAERS) and social media [11, 12]. Furthermore, observational studies commonly reported longer or shorter menstrual cycles, increased irregularity, and heavier bleeding after COVID-19 vaccination [13, 14]. However, these changes were typically short-term and resolved spontaneously in approximately half of the cases [15, 16].

The National Institutes of Health (NIH) agreed to fund five institutes to explore a potential link between COVID-19 vaccination and menstrual cycle changes, including the underlying mechanisms [17]. This could have lead to greater interest from researchers in investigating the prevalence of menstrual changes following COVID-19 vaccination, but few studies have investigated the underlying mechanisms [18]. Thus, it is important to consolidate these diverse findings for a more comprehensive understanding of the impact of COVID-19 vaccination on the menstrual cycle [19]. Therefore, we performed this systematic review and meta-analysis to summarize the available qualitative and quantitative data from observational studies that investigated menstrual cycle changes associated with COVID-19 vaccination in adult women.

Objective

This systematic review was carried out to answer the following research question:

In adult women, is the use of the COVID-19 vaccine associated with menstrual cycle changes compared with no vaccination?

Methods

This review adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement [20].

Eligibility criteria

The criteria for considering relevant studies for this review were as follows:

Types of studies

We included observational studies on humans that investigated the association of the COVID-19 vaccine with menstrual changes, including cross-sectional, prospective or retrospective case‒control, or cohort studies. We excluded experimental in vitro studies, case reports, review articles, editorials, expert opinions, and preprinted articles. Randomized controlled trials (RCTs) were excluded because our study aimed to determine the pooled prevalence of menstrual changes caused by the COVID-19 vaccine. Additionally, vaccine trials did not prospectively collect data on menstrual health outcomes [21].

2. Types of participants

We included human studies in which participants were adult women aged 18–55 years who were otherwise healthy. We excluded studies with the following participant criteria: aged less than 18 years or more than 55 years; pregnant or lactating participants; participants with hormonal or other pathologies that might cause menstrual changes other than the potential effect of the COVID-19 vaccine.

3. Types of interventions

We sought studies in which participants received at least two doses of COVID-19 vaccines of any type.

4. Outcomes

We included studies examining a range of menstrual abnormalities, which included flow (heavy, light, normal), regularity (regular or irregular), duration of cycle (normal or abnormal), and presence of painful menstruation (dysmenorrhea), regardless of whether these changes were self-reported or clinically measured. We excluded studies that investigated the side effects of the COVID-19 vaccine in general and surveillance reports.

Information sources and search strategy

We systematically searched the PubMed, Science Direct, and Web of Science databases for articles published until July 2023. Moreover, we examined the references of the selected articles to find additional relevant articles. Three authors conducted an independent search via the following search terms: (“COVID-19 vaccine” AND “menstrual cycle” OR, “menstrual irregularities”); we also searched for the most widely used vaccine trade names (“Pfizer” OR “Janssen” OR “AstraZeneca” OR “Moderna”, AND “menstrual cycle” OR, “menstrual irregularities”). We also used the truncation (*) with the same root word (vaccine) to find additional research articles. We used truncation to ensure that all potential variants of the search term were found. No limits were applied to the search results except for studies in humans, publication type, or duration filters (2020–July 2023); however, no language restriction was used.

Selection and data collection process

The citations were retrieved via reference management software (Mendeley). Duplicate citations were removed. All the remaining studies underwent a thorough review process. Two authors independently assessed each study, and a third author reviewed all discrepancies to resolve any disagreements during the initial screening. The initial screening involved scrutinizing titles and abstracts against the predefined eligibility criteria. A structured data collection approach was adopted via a Google Excel spreadsheet (Supplementary Tables 1–4). This sheet included essential study information such as the author’s name, year of publication, country of origin, study design, sample size, participant age, inclusion criteria, exclusion criteria, administered vaccine, reported outcomes and results. This methodical process ensured the systematic compilation of relevant data from the selected studies.

Data items

All outcomes for which data were obtained were self-reported menstrual changes in terms of flow (heavy, normal, light), which was normal between 20 and 90 mL, approximately 1 and 5 tablespoons; regularity (interval variations between cycles, where the average is to have periods every 28 days); duration of menstruation (number of bleeding days, where normal is between 2 and 7 days); and duration of cycle (first day of period to the day before the next one, where normal is from 23 to 35 days). Studies have reported menstrual changes via different measurements, such as frequency and the risk ratio. Therefore, we have entered data on positive events to calculate individual and pooled event rates to ensure consistency.

Study risk of bias assessment

In this review, the methodological quality of various types of studies, including cohort and case‒control studies, was evaluated via the Newcastle–Ottawa scale [22]. For cross-sectional studies, a modified version of the Newcastle–Ottawa scale was used as suggested in a previous systematic review [23]. Two independent reviewers conducted the assessments, and a third reviewer resolved any disagreements through mutual consensus. Notably, the overall quality of the studies was not used as a basis for exclusion in this review. Instead, the primary focus was on conducting a comprehensive assessment of postvaccination menstrual changes across the selected studies.

Synthesis methods

All the data were analyzed via Comprehensive Meta-Analysis Software Version 4.0. Forest plots were created to calculate the individual and pooled prevalence of different types of menstrual disorders, 95% confidence intervals (CIs) were calculated for both fixed effects and random effects, and heterogeneity was assessed with Q statistics and the I2 test. The cutoff values for the I2 statistic were used to classify heterogeneity as very low (0–25%), low (25–50%), moderate (50–75%), or high (> 75%). Publication bias was assessed via funnel plots and Begg’s adjusted rank correlation test. A P value < 0.10 was considered to indicate publication bias.

Results

Study selection

The PubMed search produced 65 articles, the Web of Science search yielded 54 articles, and ScienceDirect provided 330 articles. A manual search for relevant articles resulted in the identification of 14 articles. After excluding articles that did not meet the inclusion criteria and removing duplicate citations, 83 articles were identified for thorough retrieval and examination. At this stage, three articles were excluded because they were preprints [24–26]. Among the remaining 80 articles, 69 were excluded for several reasons related to participants, interventions, study design, and scope of the studies. These included studies that involved adolescents, peri/postmenopausal, breastfeeding, and pregnant women; studies with unclear pregnancy and/or lactation status; studies that involved women with known hormonal or pathological conditions that affect menstruation; studies with unspecified menstrual changes; studies with unstated COVID-19 vaccine types; studies that reported COVID-19-related adverse events, including menstrual changes, without specifying the type of change; and other reasons, such as study design (experimental, quasiexperimental, mixed-method) or studies of menstrual changes with different scopes, such as fertility and endometriosis. Thus, 11 studies were included for the final review, synthesis of evidence, and assessment of the risk of bias [27–37]. The process of selection and exclusion is shown in the PRISMA flow chart (Fig. 1).

Fig. 1 PRISMA flowchart

Study characteristics

The 11 studies that were selected included 26,283 participants. Among the selected studies, diverse research designs were used. Specifically, five studies adopted a cohort design; one study employed a case‒control approach. Additionally, five studies utilized a cross-sectional design. For details of the study design, participant demographics, type of vaccine administered, and specific outcomes, please refer to Table 1 for a comprehensive overview.

Table 1 Study characteristics

Author
(year)
[ref]	Country	Study design	Age	Inclusion criteria	Exclusion criteria	Vaccine(s) administered (n)	Results (%)/Vaccine	
Farland (2022) [27]	United States	Cohort	18–45 years	Women 18–45 years old

Menstruating

With and without a history of SARS-CoV-2 infection

Living in Arizona, USA

	Pregnant

Peri or postmenopausal

Hysterectomy or oophorectomy

Did not receive two doses of Pfizer-BioNTech or Moderna vaccines or one dose of Janssen vaccine.

	mRNA

Pfizer-BioNTech (Moderna), vector (Janssen)

	24.8% of patients reported alterations in their menstrual cycles following vaccination. The majority (56.3%) noticed these changes after their second dose of the vaccine, compared to the first dose (18%) and the third dose (14%).

The most frequently reported changes were irregular menstruation (43.0%), increased premenstrual symptoms (34.1%), increased menstrual pain/cramps (30.4%), and abnormally heavy bleeding (31.1%).Participants previously had an average cycle length of 27 days (SD = 6.1; median = 28) before receiving the COVID-19 vaccine. While their cycles averaged 29 days (SD = 14; median = 31) after vaccination, for those who reported a change in menstrual flow before vaccination, 11% reported spotting, 37% light bleeding, 41% moderate bleeding, and 11% heavy bleeding. After vaccination, these averages changed to 15% spotting, 26% light bleeding, 48% moderate bleeding, and 11% heavy bleeding.

	
Matar (2022) [28]	Jordan, Palestine, Syria, Egypt, Sudan, and Libya	Cross-sectional	Above 18 years	Women over 18 years old

Menstruating

	Pregnant /Breastfeeding women

Taking OCPs

Using IUD

Had endometriosis

Had PCOS

	mRNA (Moderna), Viral vector (Johnson & Johnson/Janssen, AstraZeneca)	Women who received one or more doses of COVID-19 vaccine had significantly higher frequencies of tiredness (89.7%), pelvic pain (85.6%), back pain (82.9%), and thigh pain (63.9%) compared to unvaccinated individuals.

Participants who were fully vaccinated had higher frequencies of all of the following: back pain (82.3%), nausea (44.2%), tiredness (90.5%), pelvic pain with periods (85.3%).

Menstrual irregularity was statistically significantly observed after Johnson & Johnson vaccine, followed by Sinopharm, Moderna, and AstraZeneca.

	
Namiki (2022) [29]	Japan	Cross-sectional	Above 18 years	Females over 18 years old

Medical experts

Received Pfizer–BioNTech vaccine

	No consent

Males

Postmenopausal females

Contradictory answers

Pregnant women

Breastfeeding

	mRNA (Pfizer-BioNTech)	The frequency of abnormal bleeding following the first dose was 0.6% and increased following the second (1.0%) and third dose (3.0%).

The frequency of irregular menstrual cycles also increased from 1.9% following the first dose to 4.9% and 6.6% following the second and the third doses, respectively.

	
Quejada (2022) [30]	Colombia	Cross-sectional	18–41 years	18–41 years old

Vaccinated against COVID-19

Normal cycles according to FIGO before vaccination

Normal cycles and bleeding despite the use of hormonal contraceptives (combined or progestin-only)

	Pregnant or lactating (in the last 6 months)

History of diseases that produce menstrual irregularities or early menopause such as anorexia, bulimia, polycystic ovary syndrome, hypothyroidism, obesity (Body Mass Index (BMI) > 30), or low weight (BMI < 18)

Hysterectomy or oophorectomy

High performance athletes

Women who had COVID-19 in the last year

	mRNA (Pfizer-BioNTech, Moderna), Viral vector (Johnson & Johnson/Janssen, Oxford-AstraZeneca), inactivated virus (Sinovac), Others (Clover, Sputnik, CanSino, Sinopharm)	Overall, 25% reported that the cycle became infrequent (> 38 days), while 22.28% indicated that it was frequent (< 24 days), and 9.23% reported amenorrhea.

These menstrual changes were observed more with Pfizer and Sinovac vaccines.

In relation to the duration of the menstrual cycle, (65.2%) had normal ranges (< 8 days), 26.08% had prolonged cycle (> 9 days), and only (8.69%) reported amenorrhea.

The menstrual flow was reported as abnormal by 69% of participants, being heavy (41.8%), light (20.65%), and absent in 6.52%. 30.97% of participants described the menstrual volume as normal after vaccination.

When discriminating by the type of vaccine: 9.23% vaccinated with Pfizer reported light volume, while the others reported predominantly heavy cycles (with J&J/Janssen Sinovac, Moderna, and AstraZeneca).

	
Edelman (2022) [31]	United States	Cohort	18–45 years	18–45 years old

At least three cycles post pregnancy or post use of hormonal contraception

Normal prevaccination menstrual cycle lengths

Contributed six consecutive cycles of data

	Menopausal

Received the Oxford/AstraZeneca vaccine

	mRNA (Pfizer-BioNTech, Moderna), Viral vector (Janssen), unspecified	In the first vaccine cycle, the percentage of participants who experienced a clinically significant change in cycle length did not differ by vaccination status (4.3% for unvaccinated vs. 5.2% for vaccinated).

During the second vaccine cycle, a slightly higher percentage of participants had a change in cycle length (4.6% unvaccinated vs. 6.5% vaccinated).

The increases in cycle length for both the first and second vaccine cycles were reported more among individuals who received both vaccine doses within a single cycle (cycle four). 10.6% had an increase in cycle length of 8 days or more compared with 4.3% in the unvaccinated cohort.

	
Trogstad (2023) [32]	Norway	Cohort	18–30 years	Received two COVID-19 vaccine doses at least 6 weeks prior to completing the questionnaire	Received three vaccine doses

Inconsistency between self-reported vaccination and registry information

Reported not to menstruate

Unvaccinated

Received the first vaccine dose less than 6 weeks prior to completing the questionnaire

	mRNA (Pfizer-BioNTech, Moderna), Viral vector (Janssen, Oxford-AstraZeneca)	Overall, The prevalence of any reported menstrual disturbance was 38.8% after the first vaccine dose.

The prevalence of heavy bleeding was 13.6% in the cycle after the first dose, and 15.3% after the second vaccine dose. The prevalence of prolonged menstrual bleeding was 12.5% after the first dose, and 14.3% after the second dose.

Increased risk of heavier menstrual bleeding than usual after both first and second doses, RR = 1.90 (95% CI 1.69–2.13) and RR = 1.84 (95% CI 1.66–2.03), respectively.

Increased risks after both the first and second dose for prolonged bleeding (RR = 1.46 (95% CI 1.31–1.61) for dose 1 and 1.71 (95% CI 1.55–1.89) for dose 2).

Increased risks after both the first and second dose for shorter interval (RR = 1.32 (95% CI 1.19–1.46) for dose 1 and 1.57 (95% CI 1.42–1.73) for dose 2).

Increased risks after both the first and second dose for stronger period pain (RR = 1.35 (95% CI 1.24–1.47) for dose 1 and 1.62 (95% CI 1.49–1.77) for dose 2).

For spot bleeding, only a slight increase was observed after the first dose.

N.B. These changes were further analyzed by vaccine type, with the following results:

Heavier menstrual bleeding dose 1

Any vaccine: RR of 1.90 (95% CI 1.69–2.13)

Comirnaty: RR of 1.89 (95% CI 1.63–2.18)

Spikevax: RR of 1.86 (95% CI 1.54–2.26)

Vaxzevria: RR of 2.40 (95% CI 1.29–4.46)

Heavier menstrual bleeding dose 2

Any vaccine: RR of 1.84 (95% CI 1.66–2.03)

Comirnaty: RR of 1.75 (95% CI 1.52–2.02)

Spikevax: RR of 1.92 (95% CI 1.67–2.21)

Prolonged menstrual bleeding dose 1

Any vaccine: RR of 1.46 (95% CI 1.31–1.61)

Comirnaty: RR of 1.51 (95% CI 1.32–1.73)

Spikevax: RR of 1.44 (95% CI 1.22–1.70)

Vaxzevria: RR of 1.06 (95% CI 0.62–1.79)

Prolonged menstrual bleeding dose 2

Any vaccine: RR of 1.71 (95% CI 1.55–1.89)

Comirnaty: RR of 1.65 (95% CI 1.44–1.89)

Spikevax: RR of 1.78 (95% CI 1.53–2.06)

Shorter interval dose 1

Any vaccine: RR of 1.32 (95% CI 1.19–1.46)

Comirnaty: RR of 1.31 (95% CI 1.15–1.48)

Spikevax: RR of 1.32 (95% CI 1.12–1.56)

Vaxzevria: RR of 1.53 (95% CI 0.91–2.57)

Shorter interval dose 2

Any vaccine: RR of 1.57 (95% CI 1.42–1.73)

Comirnaty: RR of 1.46 (95% CI 1.26–1.69)

Spikevax: RR of 1.67 (95% CI 1.46–1.90)

Longer interval dose 1

Any vaccine: RR of 1.07 (95% CI 0.97–1.17)

Comirnaty: RR of 1.10 (95% CI 0.98–1.23)

Spikevax: RR of 1.01 (95% CI 0.85–1.19)

Vaxzevria: RR of 1.08 (95% CI 0.57–2.03)

Longer interval dose 2

Any vaccine:, RR of 1.24 (95% CI 1.13–1.37)

Comirnaty: RR of 1.22 (95% CI 1.06–1.42)

Spikevax: RR of 1.26 (95% CI 1.11–1.44)

Vaginal spotting dose 1

Any vaccine:, RR of 1.09 (95% CI 1.01–1.17)

Comirnaty: RR of 1.13 (95% CI 1.02–1.25)

Spikevax: RR of 1.01 (95% CI 0.89–1.13)

Vaxzevria: RR of 1.32 (95% CI 0.89–1.94)

Vaginal spotting dose 2

Any vaccine: RR of 1.49 (95% CI 1.37–1.62)

Comirnaty: RR of 1.47 (95% CI 1.30–1.65)

Spikevax: RR of 1.51 (95% CI 1.35–1.70)

Stronger period pains dose 1

Any vaccine: RR of 1.35 (95% CI 1.24–1.47)

Comirnaty: RR of 1.32 (95% CI 1.18–1.46)

Spikevax: RR of 1.45 (95% CI 1.25–1.68)

Vaxzevria: RR of 1.14 (95% CI 0.78–1.67)

Stronger period pains dose 2

Any vaccine: RR of 1.62 (95% CI 1.49–1.77)

Comirnaty: RR of 1.50 (95% CI 1.33–1.69)

Spikevax: RR of 1.75 (95% CI 1.55–1.98)

	
Wesselink (2023) [33]	United States	Cohort	21–45 years	21–45 years old

Resided in the United States or Canada

Trying to conceive without the use of fertility treatment

	Received first dose before enrollment	mRNA (Pfizer-BioNTech, Moderna), Viral vector (Janssen, Oxford-AstraZeneca)	Overall, 15% reported irregular menstrual cycles at baseline.

On first and second follow-up after first dose, the prevalence of irregular cycles was 22.7% and 20.4%, respectively.

Mean typical menstrual cycle length reported at baseline was 28.6 days among those with regular cycles.

Mean cycle length in unvaccinated menstrual cycles was 29.6 days compared with mean cycle length in the first (30.9 days) and second (30.3 days) cycles after the first vaccine dose.

The prevalence of short menstrual cycles (less than 24 days) did not show significant variation based on vaccination status.

The prevalence of long menstrual cycles (more than 38 days) increased from 5.9% in unvaccinated individuals to 11.1% in the first cycle following the first dose, then decreased to 7.3% in the second cycle following the first dose.

The prevalence of bleeding lasting 7 days or more and the need for 20 or more tampons/pads was similar regardless of vaccination status.

The prevalence of menstrual pain requiring medication was 29.8% in unvaccinated follow-up questionnaires and increased to 34.8% and 31.9% in the first and second follow-up questionnaires after the first dose, respectively.

	
Kumar (2023) [34]	India	Cross-sectional	18–45 years	18–45 years old

Received two doses of either COVISHIELD or COVAXIN vaccine with or without a booster dose

Had previous three regular cycles before vaccination

	Unvaccinated or not fully vaccinated

Had previously irregular cycles

Pregnant

Immediate postpartum or postaborted pregnancy, lactating, on hormonal or IUCD contraceptives

On anticoagulants/antipsychotic drugs

Currently suffering from COVID-19 infection

With comorbidities like diabetes, thyroid disorders, hyperprolactinemia, tuberculosis, autoimmune diseases, morbidly obese

Acutely ill patient

Not willing to be a part of the study

	Recombinant (COVISHIELD), inactivated virus (COVAXIN)	Regularity of menstrual cycle:

COVAXIN: Regular (92.8%), irregular (7.2%)

COVISHIELD: Regular (94.7%), irregular (5.3%)

Duration of menstrual bleeding (days):

COVAXIN: ≤5 days (78.1%), > 5-≤7 days (20.6%), > 7-≤10 days (0.9%), > 10-≤15 days (0.3%), > 15 days (0.16%)

COVISHIELD: ≤5 days (77.8%), > 5-≤7 days (21.4%), > 7-≤10 days (0.4%), > 10-≤15 days (0.3%), > 15 days (0.02%)

Change in menstrual bleeding flow

COVAXIN: Yes (6.1%), No (93.9%)

COVISHIELD: Yes (5.0%), No (95.0%)

If yes, then

COVAXIN: excessive (55.3%), scanty (44.7%), amenorrhea (3–5 months) (0%)

COVISHIELD: excessive (48.4%), scanty (50.2%), amenorrhea (3–5 months) (1.3%)

Number of Pads/Days

COVAXIN: 0–2 (30.2%), 3–4 (44.6%), 5–6 (23.8%), 7–8 (1.4%)

COVISHIELD: 0–2 (14.3%), 3–4 (65.2%), 5–6 (19.8%), 7–8 (0.58%)

New Onset Passage of Clots

COVAXIN: Yes (9.2%), No (90.8%)

COVISHIELD: Yes (7.5%), No (92.5%)

Menstrual cycle Length:

COVAXIN: 28–30 days (92.5%), < 20 days (3.2%), > 38 days (4.3%)

COVISHIELD: 28–30 days (94.9%), < 20 days (1.5%), > 38 days (3.6%)

New onset/worsening of menstrual symptoms before, during, or after the menstrual cycle:

COVAXIN: Yes (10.8%), No (89.2%)

COVISHIELD: Yes (13.1%), No (86.0%)

If yes, then the symptoms were as follows

COVAXIN: Severe dysmenorrhea (58.5%), dysmenorrhea + diarrhea (0%), severe lower backache (13.3%), lower abdominal pain (19.3%), weakness and body aches (1.5%), vaginal pain (1.5%), excessive white discharge (0.7%), others (5.2%)

COVISHIELD: Severe dysmenorrhea (54.3%), dysmenorrhea + diarrhea (0.3%), severe lower backache (8.5%), lower abdominal pain (17.7%), weakness and body aches (10.6%), vaginal pain (1.7%), excessive white discharge (0.7%), others (6.1%)

	
Alvergne (2023) [35]	United Kingdom	Case control	28–43 years	Over 18 years

Had ever menstruated

Currently lived in the UK

Gave informed consent for the use of their data

	Did not have a period in the 12 months preceding survey

Postmenopausal or transitioning

Breastfeeding or pregnant

Those who selected ‘‘Other changes’’, those who contributed text to the effect of ‘‘too early to say’’ when describing menstrual disturbances following COVID-19 vaccination

Who lived outside the UK

	Viral vector (Oxford-AstraZeneca)	82% reported no changes to their menstrual cycles

6.2% reported more disruption

1.6% reported less disruption

Current smokers were 1.3 times as likely to report any changes

Those with positive COVID-19 disease history were 37–46% as likely to report menstrual changes

	
Hasdemir (2023) [36]	Turkey	Cohort	19–49 years	19–49 years old

Health care providers who were a member of Celal Bayar University Medical School and Hospital

Vaccinated with inactivated (CoronaVac) and mRNA-based (Pfizer-BioNTechVR) vaccine

	Being pregnant

Postpartum or breastfeeding

Having systemic illnesses (chronic renal failure, cancer, or major psychiatric diseases) that could affect the menstrual pattern

Having hematological disorders

Thyroid disease

Hyperprolactinaemia

History of hysterectomy and/or oophorectomy

Current and/or prior SARSCoV-2 infection

	Combined (Pfizer-BioNTech),

inactivated virus (CoronaVac)

	The prevalence of menstrual dysregulation following vaccination was 20.6%, varying by age group: 19–29 (12.9%), 30–39 (21.5%), and 40–49 (27.7%).

Regarding menstrual pattern changes after vaccination, 22.2% reported dysregulation, while 77.8% did not.

The prevalence of menstrual dysregulation by dose was first dose (3.5%), second dose (6.6%), third dose (5.0%), and 4th dose (20.0%).

Types of menstrual dysregulation included hypermenorrhea (33.3%), oligomenorrhea (35.2%), menorrhagia (22.2%), and hypomenorrhea (9.3%).

	
Kajiwara (2023) [37]	Japan	Cross-sectional	18–22 years	18–22 years old

Enrolled at a medical university

	Participants with an irregular menstrual cycle

Participants with a menstrual cycle length not in the range of 20–40 daysParticipants with insufficient data on their normal menstrual cycle before or after vaccine uptake

	mRNA (Pfizer-BioNTech, Moderna)	Increase in menstrual cycle length:

After the first vaccination 1.6 ± 2.8 days

After the second vaccination: 2.5 ± 3.8 days

Women who received two doses of the vaccines within a single menstrual cycle: increase length after vaccination: 3.9 ± 3.3 days

The severity and proportion of side effects following the second dose of the vaccine were highest during the menstrual period and lowest during the ovulation period.

	

Risk of bias in studies

Assessment of quality for the five cohort studies revealed one study of good quality (7 points), whereas the remaining studies were of fair quality (3–4 points) owing to a lack of unexposed controls, ascertainment of exposure, and adequate follow-up. On the other hand, one cross-sectional study was of fair quality (5 points), whereas four studies were of poor methodological quality (2–4 points) owing to the lack of information on nonrespondents, ascertainment of exposure to the COVID-19 vaccine, and assessment of outcomes via self-reports. The details are shown in Tables 2, 3, and 4.

Table 2 Quality assessment of studies using the Newcastle‒Ottawa scale for assessing cohort studies

Study ID	Selection	Comparabilitya	Outcome	Total (9)	
Representativeness of exposed cohort
(+)	Selection of the nonexposed cohort (+)	Ascertainment of exposure
(+)	Absence of outcome of interest at start
(+)	(++)	Assessment of outcome (+)	Length of follow-up (+)	Adequacy of follow-up (+)	
Hasdemir (2023) [36]	-	-	-	+	-	+	+	-	3	
Trogstad (2023) [32]	+	-	+	-	-	-	+	-	3	
Edelman (2022) [31]	-	-	-	+	+	-	+	-	3	
Farland (2022) [27]	+	-	-	+	+	-	-	+	4	
Wesselink (2023) [33]	+	+	-	+	++	-	+	+	7	
aComparability of cohorts on the basis of the design or analysis

+ Represents the number of scores

Table 3 Quality assessment of studies using the Newcastle‒Ottawa scale for assessing case‒control studies

Study ID	Selection	Comparabilitya	Outcome	Total (9)	
Representativeness of the case (+)	Adequacy of case definition (+)	Selection of controls (+)	Definition of controls
(+)	(++)	Ascertainment of exposure
(+)	Same method of ascertainment for cases and controls (+)	Nonresponse rate (+)	
Alvergne

(2023) [35]

	+	-	+	 +	+	-	+	-	5	
aComparability of cases and controls on the basis of the design or analysis

+ Represents the number of scores

Table 4 Quality assessment of studies using a modified Newcastle‒Ottawa scale for assessing cross-sectional studies

Study ID	Selection	Comparabilitya	Outcome	Total (9)	
Representativeness of sample (+)	Sample size
(+)	Nonrespondents
(+)	Ascertainment of the exposure
(+)	(++)	Assessment of outcome
(++)	Statistical test
(+)	
Kajiwara (2023) [37]	+	-	-	-	-	-	+	2	
Quejada (2022) [30]	+	+	-	-	-	-	-	2	
Kumar (2023) [34]	+	+	-	-	-	+	+	4	
Namiki (2022) [29]	+	-	-	-	++	-	+	4	
Matar (2022) [28]	+	+	-	-	++	-	+	5	
aComparability of subjects in different outcome groups on the basis of design or analysis

+ Represents the number of scores

Key findings on menstrual cycle changes associated with COVID-19 vaccination

The studies included in our analysis did not provide data on the overall prevalence of menstrual cycle changes. Instead, they provide information specific to various types of menstrual alterations. Therefore, we generated multiple forest plots categorizing menstrual cycle changes into irregular cycles, abnormal cycle duration, abnormal menstrual flow, and dysmenorrhea.

Prevalence of irregular cycles after COVID-19 vaccination

Seven studies were included in the analysis of the incidence of irregular circulation cycles after COVID-19 vaccination. Overall, the pooled prevalence was 16% (95% CI: 5.8–37.2%). There was high heterogeneity among the included studies (I2 = 100%; Q = 2576; P value < 0.001), as shown in the forest plot (Fig. 2). However, no publication bias was found in any of the studies (p = 0.440) according to Begg’s adjusted rank correlation test.

Fig. 2 Forest plot of irregular cycles after COVID-19 vaccination

Prevalence of abnormal cycle duration after COVID-19 vaccination

Figure 3 shows the forest plot for the pooled prevalence of abnormal cycle duration after COVID-19 vaccination. Four studies were included in the analysis of the prevalence of abnormal cycle duration after COVID-19 vaccination. Overall, the pooled prevalence was 27.3% (95% CI: 7.2–64.6%). There was highly significant heterogeneity among the included studies (I2 = 100%; Q = 2658; P value < 0.001). No publication bias was found in any of the studies (p = 0.248) via Begg’s adjusted rank correlation test.

Fig. 3 Forest plot of abnormal cycle duration after COVID-19 vaccination

Prevalence of abnormal menstrual flow after COVID-19 vaccination

Figure 4 shows the forest plot for the pooled prevalence of heavy flow after COVID-19 vaccination, in which seven studies were included. Overall, the pooled incidence was 11.7% (95% CI: 5.8–22%), and there was highly significant heterogeneity among the included studies (I2 = 100%; Q = 1116; P value < 0.001). No publication bias was found in any of the studies (p = 0.326) via Begg’s adjusted rank correlation test. Furthermore, five studies were included in the analysis of the prevalence of light menstrual flow after COVID-19 vaccination. Overall, the pooled prevalence was 5.5% (95% CI: 2.3–12.5%). There was highly significant heterogeneity among the included studies (I2 = 99%; Q = 317; P value < 0.001). No publication bias was found in any of the studies (p = 0.312) via Begg’s adjusted rank correlation test.

Fig. 4 Forest plot of heavy menstrual flow after COVID-19 vaccination

Prevalence of dysmenorrhea after COVID-19 vaccination

Figure 5 shows the forest plot for the pooled prevalence of painful menstruation (dysmenorrhea) after COVID-19 vaccination, in which five studies were included for data analysis. Overall, the pooled prevalence was 22.1% (95% CI: 5.2–59.4%). There was highly significant heterogeneity among the included studies (I2 = 100%; Q = 3764; P value < 0.001). No publication bias was found in any of the studies (p = 0.164) via Begg’s adjusted rank correlation test.

Fig. 5 Forest plot of dysmenorrhea after COVID-19 vaccination

Discussion

The results of our systematic review and meta-analysis highlight the potential association of COVID-19 vaccination with menstrual cycle changes among adult women. We observed that more than one quarter of women experienced abnormal cycle duration, followed by dysmenorrhea in approximately 22% of women, while abnormal menstrual cycle length and flow were less common. When these findings are compared with the literature on menstrual alterations related to COVID-19 vaccination, our results align with and add context to previous observations [38]. One large prospective study indicated that women who received the COVID-19 vaccine experienced a slight increase in the menstrual cycle length of less than one day after both the first and second doses [21]. Individuals who received the vaccine during the follicular phase of their menstrual cycle were more likely to experience cycle length disturbances than those who received it during the luteal phase [39].

The current review revealed a lower prevalence of heavy menstrual flow than did another meta-analysis, which reported that menorrhagia was the most frequently observed menstrual change, with a pooled prevalence of 24.24% [40]. However, our findings might be explained by novel data suggesting that decreased menstrual volume and a prolonged cycle are consequences of SARS-CoV-2 infection independent of its severity [41], and four of our included studies involved patients with prior COVID-19 disease [27, 31, 34, 35]. In contrast, a recently published systematic review and meta-analysis did not find a significant difference in the risk of adverse menstrual events between women who received the COVID-19 vaccine and those who did not, but the evidence is limited by significant heterogeneity and a high risk of bias in the included studies [42].

Moreover, the reporting in this SR was limited to certain outcomes; for example, the duration of menstrual changes and linked vaccine type were reported in three prospective cohort studies that followed participants for sufficient periods. Overall, menstrual changes are temporary and typically last for one to two menstrual cycles postvaccination [31, 33, 36]. One recent study revealed that participants who received the booster vaccine dose had an average cycle duration of 1.20 days longer (95% CI: 1.00–1.40), which persisted from the second to the fourth cycle after receiving the mRNA vaccine [43]. When the vaccination types were compared, the group that received only CoronaVac reported a higher rate of menstrual irregularities than did the groups that received both CoronaVac and BioNTech, with 32.2% and 19.1%, respectively (p = 0.033) [36]. Sensitivity analyses comparing menstrual cycle changes by vaccine brand did not significantly vary among the vaccinated cohorts that received the Pfizer-BioNTech vaccine (55%), the Moderna vaccine (35%), or the Johnson & Johnson/Janssen vaccine (7%) [33].

Although the current review did not explore potential causal relationships, it is important to note that various pandemic-related factors can lead to temporary changes in the menstrual cycle [44]. Several intrinsic mechanisms have been proposed to clarify the link between significant immune challenges, such as vaccination, and the menstrual cycle [45, 46]. These mechanisms involve immune activation in response to diverse stimuli, including immunological influences on the hormones that regulate the menstrual cycle [47, 48]. Furthermore, immune cells in the uterine lining play crucial roles in the build-up and breakdown of this tissue during each menstrual process [49]. Other extrinsic factors that could contribute to menstrual changes include stress related to the pandemic, lifestyle changes due to the pandemic, and infection with SARS-CoV-2 [18, 50]. Reaching a definitive conclusion regarding the direct link between these changes and a specific type of COVID-19 vaccine presents a significant challenge. This challenge arises from various factors, including differences in study designs, research methods, and subjectivity in reporting these outcomes. Moreover, early assessments of adverse events in COVID-19 vaccine trials were focused primarily on systemic and major adverse events [51, 52].

This review was based on an extensive search, pooling data from studies with different populations, and applying strict eligibility criteria to eliminate studies with potential confounding factors. We calculated both individual event rates and combined event rates via appropriate statistical methods. These qualities can be considered strengths of the analysis. Thus, this study may provide valuable insights into menstrual alterations in adult women after COVID-19 vaccination. Nevertheless, it is essential to interpret the results cautiously due to certain limitations. First, there was a moderate to high risk of bias for some of the included studies, owing to the study design, reliance on self-reported outcomes, short follow-up periods, and lack of control groups. Second, we observed significant heterogeneity in our findings, likely stemming from several factors, including variations in sample size, differences in sampling methods, the diverse nature of the populations studied, and variations in settings and vaccine administration.

Currently, we have sufficient evidence from studies over the past three years indicating the association of the COVID-19 vaccine with temporary menstrual cycle alterations in adult women. However, the exact mechanisms remain unclear; therefore, experimental studies are warranted to determine the temporal link between the COVID-19 vaccine and menstrual cycle changes. The following criteria might optimize the study design and strengthen outcomes: (1) recruitment of unvaccinated controls; (2) inclusion of different age categories, e.g., adolescents and perimenopausal women; (3) the establishment of clinical measures for menstrual characteristics; (4) adequate follow-up of not less than one year after exposure to the COVID-19 vaccine series/booster dose; (4) adjustment for other factors that contribute to menstrual changes.

Finally, it is important to consider the menstrual cycle as a crucial indicator of women’s health and not merely fertility/pregnancy-related health. Thus, efforts should be made to increase the awareness of health care providers regarding the latest evidence of the impact of the COVID-19 pandemic on women’s health. Moreover, women’s concerns about vaccination should be addressed, and proper counseling based on the available evidence should be provided. With respect to public health considerations, although menstrual cycle changes are potential side effects of COVID-19 vaccination, they should not discourage vaccination. Additionally, mechanisms of reporting and monitoring of menstrual health outcomes for future COVID-19 vaccination programs should be strengthened.

Conclusions

This systematic review consolidates the growing body of evidence regarding the potential association of COVID-19 vaccination with menstrual cycle alterations, highlighting abnormal cycle duration and dysmenorrhea as more commonly reported than other menstrual cycle characteristics. However, the evidence is limited by a moderate risk of bias and heterogeneity among the included studies. Thus, further trials are needed to explore causal relationships. While these observed menstrual variations prompt significant considerations for women’s health and health care practices, vaccination continues to be advised for women of reproductive age.

Supplementary Information

Supplementary Material 1.

Author contributions

“Conceptualization, A.A.; methodology, N.A2, L.A, and Z.A.; data curation, N.A3, L. A, and R.A.; writing—original draft preparation, A.A, and L.A.; Statistical analysis and synthesis: Dr. Ahmed Hassan (Biostatistician). N.A2 , N.A3 and R.A. prepared all Tables, Z.A prepared Figs. 1, 2, 3, 4 and 5. All authors have read and agreed to the published version of the manuscript.”

Funding

This research was funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R289), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Chi WY Li YD Huang HC COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection J Biomed Sci 2022 29 1 82 10.1186/s12929-022-00853-8 36243868
Chi WY, Li YD, Huang HC, et al. COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection. J Biomed Sci. 2022;29(1):82.36243868
2. Rahman MA, Islam MS. Early approval of COVID-19 vaccines: pros and cons. Hum Vaccines Immunotherapeutics. 2021;17(10).
3. Han X, Xu P, Ye Q. Analysis of COVID-19 vaccines: types, thoughts, and application. J Clin Lab Anal. 2021;35(9).
4. Patel R, Kaki M, Potluri VS, Kahar P, Khanna D. A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson. Human Vaccines and Immunotherapeutics. 2022;18(1).
5. Roy DN Biswas M Islam E Azam MS Potential factors influencing COVID-19 vaccine acceptance and hesitancy: a systematic review PLoS ONE 2022 17 3 e0265496 10.1371/journal.pone.0265496 35320309
Roy DN, Biswas M, Islam E, Azam MS. Potential factors influencing COVID-19 vaccine acceptance and hesitancy: a systematic review. PLoS ONE. 2022;17(3):e0265496.35320309
6. Adu P Poopola T Medvedev ON Collings S Mbinta J Aspin C Implications for COVID-19 vaccine uptake: a systematic review J Infect Public Health 2023 16 3 441 66 10.1016/j.jiph.2023.01.020 36738689
Adu P, Poopola T, Medvedev ON, Collings S, Mbinta J, Aspin C, et al. Implications for COVID-19 vaccine uptake: a systematic review. J Infect Public Health. 2023;16(3):441–66.36738689
7. Toubasi AA, Al-Sayegh TN, Obaid YY, Al-Harasis SM, AlRyalat SAS. Efficacy and safety of COVID-19 vaccines: a network meta-analysis. J Evidence-Based Med. 2022;15(3).
8. Beladiya J Kumar A Vasava Y Parmar K Patel D Patel S Dholakia S Sheth D Boddu SHS Patel C Safety and efficacy of COVID-19 vaccines: a systematic review and meta-analysis of controlled and randomized clinical trials Rev Med Virol 2024 34 1 e2507 10.1002/rmv.2507 38282394
Beladiya J, Kumar A, Vasava Y, Parmar K, Patel D, Patel S, Dholakia S, Sheth D, Boddu SHS, Patel C. Safety and efficacy of COVID-19 vaccines: a systematic review and meta-analysis of controlled and randomized clinical trials. Rev Med Virol. 2024;34(1):e2507.38282394
9. Zhang B Yu X Liu J Liu J Liu P COVID-19 vaccine and menstrual conditions in female: data analysis of the vaccine adverse event reporting system (VAERS) BMC Women’s Health 2022 22 1 403 10.1186/s12905-022-01934-4 36195902
Zhang B, Yu X, Liu J, Liu J, Liu P. COVID-19 vaccine and menstrual conditions in female: data analysis of the vaccine adverse event reporting system (VAERS). BMC Women’s Health. 2022;22(1):403.36195902
10. Chao MJ Menon C Elgendi M Effect of COVID-19 vaccination on the menstrual cycle Front Med (Lausanne) 2022 9 1065421 10.3389/fmed.2022.1065421 36590952
Chao MJ, Menon C, Elgendi M. Effect of COVID-19 vaccination on the menstrual cycle. Front Med (Lausanne). 2022;9:1065421.36590952
11. Wong KK Heilig CM Hause A Myers TR Olson CK Gee J Marquez P Strid P Shay DK Menstrual irregularities and vaginal bleeding after COVID-19 vaccination reported to v-safe active surveillance, USA in December, 2020-January, 2022: an observational cohort study Lancet Digit Health 2022 4 9 e667 75 10.1016/S2589-7500(22)00125-X 35961858
Wong KK, Heilig CM, Hause A, Myers TR, Olson CK, Gee J, Marquez P, Strid P, Shay DK. Menstrual irregularities and vaginal bleeding after COVID-19 vaccination reported to v-safe active surveillance, USA in December, 2020-January, 2022: an observational cohort study. Lancet Digit Health. 2022;4(9):e667–75.35961858
12. Katz A Tepper Y Birk O Eran A Web and social media searches highlight menstrual irregularities as a global concern in COVID-19 vaccinations Sci Rep 2022 12 1 17657 10.1038/s41598-022-20844-x 36271079
Katz A, Tepper Y, Birk O, Eran A. Web and social media searches highlight menstrual irregularities as a global concern in COVID-19 vaccinations. Sci Rep. 2022;12(1):17657.36271079
13. Wang S Mortazavi J Hart JE Hankins JA Katuska LM Farland LV Gaskins AJ Wang YX Tamimi RM Terry KL Rich-Edwards JW Missmer SA Chavarro JE A prospective study of the association between SARS-CoV-2 infection and COVID-19 vaccination with changes in usual menstrual cycle characteristics Am J Obstet Gynecol. 2022 227 5 739.e1 739.e11 10.1016/j.ajog.2022.07.003 35841938
Wang S, Mortazavi J, Hart JE, Hankins JA, Katuska LM, Farland LV, Gaskins AJ, Wang YX, Tamimi RM, Terry KL, Rich-Edwards JW, Missmer SA, Chavarro JE. A prospective study of the association between SARS-CoV-2 infection and COVID-19 vaccination with changes in usual menstrual cycle characteristics. Am J Obstet Gynecol. 2022;227(5):739.e1-739.e11.35841938
14. Bisgaard Jensen C Bech BH Hansen SN Rask CU Fink P Nielsen H Meinertz Dantoft T Thysen SM Rytter D Prevalence of and risk factors for self-reported menstrual changes following COVID-19 vaccination: a Danish cohort study Hum Reprod 2023 38 9 1825 34 10.1093/humrep/dead144 37437904
Bisgaard Jensen C, Bech BH, Hansen SN, Rask CU, Fink P, Nielsen H, Meinertz Dantoft T, Thysen SM, Rytter D. Prevalence of and risk factors for self-reported menstrual changes following COVID-19 vaccination: a Danish cohort study. Hum Reprod. 2023;38(9):1825–34.37437904
15. Laganà AS Veronesi G Ghezzi F Ferrario MM Cromi A Bizzarri M Garzon S Cosentino M Evaluation of menstrual irregularities after COVID-19 vaccination: results of the MECOVAC survey Open Med (Wars) 2022 17 1 475 84 10.1515/med-2022-0452 35350834
Laganà AS, Veronesi G, Ghezzi F, Ferrario MM, Cromi A, Bizzarri M, Garzon S, Cosentino M. Evaluation of menstrual irregularities after COVID-19 vaccination: results of the MECOVAC survey. Open Med (Wars). 2022;17(1):475–84.35350834
16. Laganà AS Lukanovič D Noventa M Margioula-Siarkou C Terzic S Chiantera V Menstrual cycle changes after COVID-19 vaccination or infection: not two sides of the same coin Evid Based Nurs 2023 26 3 110 1 10.1136/ebnurs-2022-103613 36804196
Laganà AS, Lukanovič D, Noventa M, Margioula-Siarkou C, Terzic S, Chiantera V. Menstrual cycle changes after COVID-19 vaccination or infection: not two sides of the same coin. Evid Based Nurs. 2023;26(3):110–1.36804196
17. Shriver EK. (2021). Item of Interest: NIH funds studies to assess potential effects of COVID-19 vaccination on menstruation. https://www.nichd.nih.gov/newsroom/news/083021-COVID-19-vaccination-menstruation. Accessed 8 Aug 2024.
18. Dellino M Vimercati A D’Amato A Damiani GR Laganà AS Cicinelli E Pinto V Malvasi A Scacco S Ballini A Resta L Ingravallo G Maiorano E Cazzato G Cascardi E GONE WITH THE WIND: the transitory effects of COVID-19 on the Gynecological System J Pers Med 2023 13 2 312 10.3390/jpm13020312 36836546
Dellino M, Vimercati A, D’Amato A, Damiani GR, Laganà AS, Cicinelli E, Pinto V, Malvasi A, Scacco S, Ballini A, Resta L, Ingravallo G, Maiorano E, Cazzato G, Cascardi E. GONE WITH THE WIND: the transitory effects of COVID-19 on the Gynecological System. J Pers Med. 2023;13(2):312.36836546
19. Sharp GC Fraser A Sawyer G Kountourides G Easey KE Ford G Olszewska Z Howe LD Lawlor DA Alvergne A Maybin JA The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities Int J Epidemiol 2022 51 3 691 700 10.1093/ije/dyab239 34865021
Sharp GC, Fraser A, Sawyer G, Kountourides G, Easey KE, Ford G, Olszewska Z, Howe LD, Lawlor DA, Alvergne A, Maybin JA. The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities. Int J Epidemiol. 2022;51(3):691–700.34865021
20. Page MJ McKenzie JE Bossuyt PM Boutron I Hoffmann TC Mulrow CD The PRISMA 2020 statement: an updated guideline for reporting systematic reviews Syst Reviews 2021 10 1 89 10.1186/s13643-021-01626-4
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Reviews. 2021;10(1):89.
21. Edelman A Boniface ER Male V Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data BMJ Med 2022 1 e000297 10.1136/bmjmed-2022-000297 36381261
Edelman A, Boniface ER, Male V, et al. Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data. BMJ Med. 2022;1:e000297.36381261
22. The Ottawa Hospital Research Institute (no date) Ottawa Hospital Research Institute. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed: 6 Aug 2023.
23. Herzog R Is Healthcare Workers’ intention to vaccinate related to their knowledge, beliefs and attitudes? A systematic review BMC Public Health 2013 13 154 10.1186/1471-2458-13-154 23421987
Herzog R, et al. Is Healthcare Workers’ intention to vaccinate related to their knowledge, beliefs and attitudes? A systematic review. BMC Public Health. 2013;13:154.23421987
24. Alvergne A, Kountourides G, Argentieri MA, Agyen L, Rogers N, Knight D, Olszewska Z. COVID-19 vac-cination and menstrual cycle changes: a United Kingdom (UK) retrospective case–control study. MedRXiv, 2021–11.
25. Zhang B, Yu X, Liu J et al. COVID-19 vaccine and menstrual conditions in female: data analysis of the vaccine adverse event reporting system, 07 April 2022, PREPRINT (Version 2) available at Research Square [10.21203/rs.3.rs-1388159/v2]
26. Gibson EA, Li H, Fruh V, Gabra M, Asokan G, Jukic AMZ, Baird DD, Curry CL, Fischer-Colbrie T, Onnela JP, Williams MA, Hauser R, Coull BA, Mahalingaiah S. Covid-19 vaccination and menstrual cycle length in the Apple Women’s Health Study. medRxiv [Preprint]. 2022 Jul 10:2022.07.07.22277371.
27. Farland LV Khan SM Shilen A Heslin KM Ishimwe P Allen AM COVID-19 vaccination and changes in the menstrual cycle among vaccinated persons Fertil Steril 2023 119 3 392 400 10.1016/j.fertnstert.2022.12.023 36539055
Farland LV, Khan SM, Shilen A, Heslin KM, Ishimwe P, Allen AM, et al. COVID-19 vaccination and changes in the menstrual cycle among vaccinated persons. Fertil Steril. 2023;119(3):392–400.36539055
28. Matar SG Nourelden AZ Assar A Bahbah EI Alfryjat AM Hasabo EA Effect of COVID-19 vaccine on menstrual experience among females in six arab countries: a cross-sectional study Influenza Other Respir Viruses 2023 17 1 e13088 10.1111/irv.13088 36578138
Matar SG, Nourelden AZ, Assar A, Bahbah EI, Alfryjat AM, Hasabo EA, et al. Effect of COVID-19 vaccine on menstrual experience among females in six arab countries: a cross-sectional study. Influenza Other Respir Viruses. 2023;17(1):e13088.36578138
29. Namiki T Komine-Aizawa S Takada K Takano C Trinh QD Hayakawa S The association of three doses of the BNT162b2 mRNA vaccine with abnormal bleeding and an irregular menstrual cycle among premenopausal females: a single institute observation study J Obstet Gynecol Res 2022 48 11 2903 10 10.1111/jog.15400 36319205
Namiki T, Komine-Aizawa S, Takada K, Takano C, Trinh QD, Hayakawa S. The association of three doses of the BNT162b2 mRNA vaccine with abnormal bleeding and an irregular menstrual cycle among premenopausal females: a single institute observation study. J Obstet Gynecol Res. 2022;48(11):2903–10.36319205
30. Quejada L, Toro Wills MF, Martínez-Ávila MC, Patiño-Aldana AF. Menstrual cycle disturbances after COVID-19 vac-cination. Womens Health (Lond). 2022.
31. Edelman A Boniface ER Benhar E Han L Matteson KA Favaro C Association between Menstrual cycle length and coronavirus disease 2019 (COVID-19) vaccination: a U.S. Cohort Obstet Gynecol 2022 139 4 481 9 10.1097/AOG.0000000000004695 34991109
Edelman A, Boniface ER, Benhar E, Han L, Matteson KA, Favaro C, et al. Association between Menstrual cycle length and coronavirus disease 2019 (COVID-19) vaccination: a U.S. Cohort. Obstet Gynecol. 2022;139(4):481–9.34991109
32. Trogstad L Laake I Robertson AH Mjaaland S Caspersen IH Juvet LK Heavy bleeding and other menstrual disturbances in young women after COVID-19 vaccination Vaccine 2023 41 36 5271 82 10.1016/j.vaccine.2023.06.088 37451876
Trogstad L, Laake I, Robertson AH, Mjaaland S, Caspersen IH, Juvet LK, et al. Heavy bleeding and other menstrual disturbances in young women after COVID-19 vaccination. Vaccine. 2023;41(36):5271–82.37451876
33. Wesselink AK Lovett SM Weinberg J Geller RJ Wang TR Regan AK COVID-19 vaccination and menstrual cycle characteristics: a prospective cohort study Vaccine 2023 41 29 4327 34 10.1016/j.vaccine.2023.06.012 37301706
Wesselink AK, Lovett SM, Weinberg J, Geller RJ, Wang TR, Regan AK, et al. COVID-19 vaccination and menstrual cycle characteristics: a prospective cohort study. Vaccine. 2023;41(29):4327–34.37301706
34. Kumar N Gangane N Mohapatra I Rukadikar C Sharmila V Pushpalatha K Effect of COVID-19 vaccination on menstrual cycle patterns of Reproductive age women: a multicentric observational study Curr Drug Res Re-views 2023 16 1 101 12
Kumar N, Gangane N, Mohapatra I, Rukadikar C, Sharmila V, Pushpalatha K, et al. Effect of COVID-19 vaccination on menstrual cycle patterns of Reproductive age women: a multicentric observational study. Curr Drug Res Re-views. 2023;16(1):101–12.
35. Alvergne A Kountourides G Argentieri MA Agyen L Rogers N Knight D A retrospective case–control study on menstrual cycle changes following COVID-19 vaccination and disease iScience 2023 26 4 106401 10.1016/j.isci.2023.106401 36987520
Alvergne A, Kountourides G, Argentieri MA, Agyen L, Rogers N, Knight D, et al. A retrospective case–control study on menstrual cycle changes following COVID-19 vaccination and disease. iScience. 2023;26(4):106401.36987520
36. Hasdemir PS Senol Akar S Goker A Kosova F Ucar D Ozalp Ates FS The effect of COVID-19 vaccinations on menstrual cycle and serum anti-mullerian hormone levels in reproductive age women Hum Fertility 2023 26 1 153 61 10.1080/14647273.2023.2181710
Hasdemir PS, Senol Akar S, Goker A, Kosova F, Ucar D, Ozalp Ates FS, et al. The effect of COVID-19 vaccinations on menstrual cycle and serum anti-mullerian hormone levels in reproductive age women. Hum Fertility. 2023;26(1):153–61.
37. Kajiwara S Akiyama N Baba H Ohta M Association between COVID-19 vaccines and the menstrual cycle in young Japanese women J Infect Chemother 2023 29 5 513 8 10.1016/j.jiac.2023.01.003 36623727
Kajiwara S, Akiyama N, Baba H, Ohta M. Association between COVID-19 vaccines and the menstrual cycle in young Japanese women. J Infect Chemother. 2023;29(5):513–8.36623727
38. Nazir M Asghar S Rathore MA Shahzad A Shahid A Ashraf Khan A Malik A Fakhar T Kausar H Malik J Menstrual abnormalities after COVID-19 vaccines: A systematic review Vacunas 2022 23 S77 87 10.1016/j.vacun.2022.07.001 35873308
Nazir M, Asghar S, Rathore MA, Shahzad A, Shahid A, Ashraf Khan A, Malik A, Fakhar T, Kausar H, Malik J. Menstrual abnormalities after COVID-19 vaccines: a systematic review. Vacunas. 2022;23:S77–87.35873308
39. Payne LA Wise LA Wesselink AK Association between COVID-19 vaccination and menstruation: a state of the science review BMJ Sex Reproductive Health 2024 50 212 25 10.1136/bmjsrh-2024-202274
Payne LA, Wise LA, Wesselink AK, et al. Association between COVID-19 vaccination and menstruation: a state of the science review. BMJ Sex Reproductive Health. 2024;50:212–25.
40. Al Kadri HM Al Sudairy AA Alangari AS Al Khateeb BF El-Metwally AA COVID-19 vaccination and menstrual dis-orders among women: findings from a meta-analysis study J Infect Public Health 2023 16 5 697 704 10.1016/j.jiph.2023.02.019 36934644
Al Kadri HM, Al Sudairy AA, Alangari AS, Al Khateeb BF, El-Metwally AA. COVID-19 vaccination and menstrual dis-orders among women: findings from a meta-analysis study. J Infect Public Health. 2023;16(5):697–704.36934644
41. Lebar V Laganà AS Chiantera V Kunič T Lukanović D The Effect of COVID-19 on the Menstrual cycle: a systematic review J Clin Med 2022 11 13 3800 10.3390/jcm11133800 35807090
Lebar V, Laganà AS, Chiantera V, Kunič T, Lukanović D. The Effect of COVID-19 on the Menstrual cycle: a systematic review. J Clin Med. 2022;11(13):3800.35807090
42. Peinemann F Oberle D Drechsel-Bäuerle U Keller-Stanislawski B Adverse menstrual events reported after and before (or without) COVID-19 vaccination: a systematic review and Meta-analysis of comparative observational studies Pharmacoepidemiol Drug Saf 2024 33 8 e5877 10.1002/pds.5877 39090813
Peinemann F, Oberle D, Drechsel-Bäuerle U, Keller-Stanislawski B. Adverse menstrual events reported after and before (or without) COVID-19 vaccination: a systematic review and Meta-analysis of comparative observational studies. Pharmacoepidemiol Drug Saf. 2024;33(8):e5877.39090813
43. Hosoya S Piedvache A Nakamura A Nasu R Hine M Itoi S Yokomizo R Umezawa A Hiraike O Koga K Osuga Y Narumi S Morisaki N Prolongation of the menstrual cycle after receipt of the primary series and booster doses of mRNA coronavirus Disease 2019 (COVID-19) vaccination Obstet Gynecol 2024 143 2 284 93 10.1097/AOG.0000000000005476 38061045
Hosoya S, Piedvache A, Nakamura A, Nasu R, Hine M, Itoi S, Yokomizo R, Umezawa A, Hiraike O, Koga K, Osuga Y, Narumi S, Morisaki N. Prolongation of the menstrual cycle after receipt of the primary series and booster doses of mRNA coronavirus Disease 2019 (COVID-19) vaccination. Obstet Gynecol. 2024;143(2):284–93.38061045
44. Tayyaba Rehan S Imran L Mansoor H Sayyeda Q Hussain HU Cheema MS Tahir MJ Asghar MS Mahmmoud Fadelallah Eljack M Islam MS Effects of SARS-CoV-2 infection and COVID-19 pandemic on menstrual health of women: a systematic review Health Sci Rep 2022 5 6 e881 10.1002/hsr2.881 36248348
Tayyaba Rehan S, Imran L, Mansoor H, Sayyeda Q, Hussain HU, Cheema MS, Tahir MJ, Asghar MS, Mahmmoud Fadelallah Eljack M, Islam MS. Effects of SARS-CoV-2 infection and COVID-19 pandemic on menstrual health of women: a systematic review. Health Sci Rep. 2022;5(6):e881.36248348
45. Minakshi R Rahman S Ayaggari A Dutta D Shankar A Understanding the trauma of Menstrual Irregularity after COVID Vaccination: a bird’s-Eye View of Female Immunology Front Immunol 2022 13 906091 10.3389/fimmu.2022.906091 35769462
Minakshi R, Rahman S, Ayaggari A, Dutta D, Shankar A. Understanding the trauma of Menstrual Irregularity after COVID Vaccination: a bird’s-Eye View of Female Immunology. Front Immunol. 2022;13:906091.35769462
46. Li S Liu H Li D Chen F Female reproductive health during the COVID-19 pandemic: latest evidence and understanding Arch Gynecol Obstet 2023 308 6 1691 6 10.1007/s00404-023-06976-z 36856820
Li S, Liu H, Li D, Chen F. Female reproductive health during the COVID-19 pandemic: latest evidence and understanding. Arch Gynecol Obstet. 2023;308(6):1691–6.36856820
47. Skelly DT Harding AC Gilbert-Jaramillo J Knight ML Longet S Brown A Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern Nat Commun 2021 12 1 5061 10.1038/s41467-021-25167-5 34404775
Skelly DT, Harding AC, Gilbert-Jaramillo J, Knight ML, Longet S, Brown A, et al. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern. Nat Commun. 2021;12(1):5061.34404775
48. Hajjo R, Momani E, Sabbah DA, Baker N, Tropsha A. Identifying a causal link between prolactin signaling pathways and COVID-19 vaccine-induced menstrual changes. NPJ Vaccines. 2023;8. 10.1038/s41541-023-00719-6.
49. Monin L Whettlock EM Male V Immune responses in the human female reproductive tract Immunology 2020 160 2 106 15 10.1111/imm.13136 31630394
Monin L, Whettlock EM, Male V. Immune responses in the human female reproductive tract. Immunology. 2020;160(2):106–15.31630394
50. Mitra A Verbakel JY Kasaven LS Tzafetas M Grewal K Jones B Bennett PR Kyrgiou M Saso S The menstrual cycle and the COVID-19 pandemic PLoS ONE 2023 18 10 e0290413 10.1371/journal.pone.0290413 37819943
Mitra A, Verbakel JY, Kasaven LS, Tzafetas M, Grewal K, Jones B, Bennett PR, Kyrgiou M, Saso S. The menstrual cycle and the COVID-19 pandemic. PLoS ONE. 2023;18(10):e0290413.37819943
51. Beatty AL Peyser ND Butcher XE Cocohoba JM Lin F Olgin JE Pletcher MJ Marcus GM Analysis of COVID-19 vaccine type and adverse effects following vaccination JAMA Netw Open 2021 4 12 e2140364 10.1001/jamanetworkopen.2021.40364 34935921
Beatty AL, Peyser ND, Butcher XE, Cocohoba JM, Lin F, Olgin JE, Pletcher MJ, Marcus GM. Analysis of COVID-19 vaccine type and adverse effects following vaccination. JAMA Netw Open. 2021;4(12):e2140364.34935921
52. Graña C Ghosn L Evrenoglou T Jarde A Minozzi S Bergman H Buckley BS Probyn K Villanueva G Henschke N Bonnet H Assi R Menon S Marti M Devane D Mallon P Lelievre JD Askie LM Kredo T Ferrand G Davidson M Riveros C Tovey D Meerpohl JJ Grasselli G Rada G Hróbjartsson A Ravaud P Chaimani A Boutron I Efficacy and safety of COVID-19 vaccines Cochrane Database Syst Rev 2022 12 12 CD015477 36473651
Graña C, Ghosn L, Evrenoglou T, Jarde A, Minozzi S, Bergman H, Buckley BS, Probyn K, Villanueva G, Henschke N, Bonnet H, Assi R, Menon S, Marti M, Devane D, Mallon P, Lelievre JD, Askie LM, Kredo T, Ferrand G, Davidson M, Riveros C, Tovey D, Meerpohl JJ, Grasselli G, Rada G, Hróbjartsson A, Ravaud P, Chaimani A, Boutron I. Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev. 2022;12(12):CD015477.36473651
