British Journal of Research Open Access

Effect of Covid-19 Vaccination on Menstrual Pattern Changes: A Systematic Review

Nathalia Isabella Muskitta^1*, Natan Kevin Partogu Siagian¹ and Amanda Rumondang^{1,2 1}Department of Medicine, University of Indonesia, Indonesia
²Department of Obstetrics and Gynecology, Dr. Cipto Mangunkusumo National Central General Hospital, Indonesia
^*Correspondence: Nathalia Isabella Muskitta, Department of Medicine, University of Indonesia, Indonesia, Email:

Received: 20-Feb-2023, Manuscript No. IPJBR-23-15729; Editor assigned: 22-Feb-2023, Pre QC No. IPJBR-23-15729 (PQ); Reviewed: 08-Mar-2023, QC No. IPJBR-23-15729; Revised: 13-Mar-2023, Manuscript No. IPJBR-23-15729 (R); Published: 20-Mar-2023, DOI: 10.21767/2394-3718.23.10.06

Abbreviations

(PICO) Population Intervention Comparison Outcome; (PRISMA) Preferred Reporting Items for Systematic Reviews and Meta Analyses; (JBICAT) Joanna Briggs Institute Critical Appraisal Tool

Introduction

The Covid-19 vaccine prevents the spread of the SARS-CoV-2 virus and reduces the risk of morbidity or mortality [1]. As the scope of Covid-19 widens, some post-vaccination side effects have been reported; one of which is menstrual changes [2]. In the largest surveillance system in the United Kingdom, more than 36,000 menstrual changes post-vaccination have been reported. Meanwhile, around the world, there are various results on menstruation changes post-vaccination [3]. Menstruation is important in women’s health, especially during the reproductive period. In this pandemic era, public concern that circumvents this issue is the effect of Covid-19 vaccination on infertility regarding its effects on menstruation. Another concern comes from parents of female adolescents because they think about the child’s puberty after the Covid-19 vaccination [3]. A deeper understanding of possible menstrual changes post-vaccination is needed for better counselling before the administration of the Covid-19 vaccination. However, no systematic review has discussed the impact of post-covid-19 vaccination on menstruation. Therefore, the presentation of this systematic review aims to determine the impact of the Covid-19 vaccination on menstrual patterns.

Materials and Methods

The clinical question is specified using PICO (Population, Intervention, Comparison, and Outcome) format (Table 1). This clinical question is the basis of our systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) consensus [4]. We formulated a search strategy using keywords from the clinical question and its synonyms. This search strategy is then finely tuned using the WordFreq and Search Refinery functions from the Systematic Review Accelerator, Bond University, Australia [5]. Details of the search strategy are further explored in the appendices.

Table 1: Population intervention comparison and outcome (PICO).

The literature search was done on the 16^th and 17^th of June, 2022 on 4 online databases: PubMed, EMBASE, CENTRAL, and ProQuest. A manual search was also done based on the referThe literature search was done on the 16^th and 17^th of June, 2022 on 4 online databases: PubMed, EMBASE, CENTRAL, and ProQuest. A manual search was also done based on the references used in the articles. We independently screened all titles and abstracts found. Studies that are selected by at least 2 researchers are then reviewed entirely by the eligibility criteria (Table 2). All conflicts are resolved by discussion. The search process is reported in a PRISMA flowchart [4].

Table 2: Eligibility criteria.

Two researchers independently appraised each identified article using the Joanna Briggs Institute Critical Appraisal Tool (JBI CAT) [6]. Data extraction was also done by 2 independent researchers using an online questionnaire that include the study methods (year, location, and design), subjects (population size and eligibility criteria), intervention (vaccination status and type of vaccine), results, and other notable findings. Differing opinions are resolved by discussion. The conclusion is then graded according to the GRADE consensus [7].

Results

14 studies fulfill the eligibility criteria (Figure 1). All studies found are observational studies from the last 2 years (2021- 2022). 11 of those studies use a cross-sectional study design [8-18]. The other 3 studies are cohort studies [19-21].

Figure 1: The PRISMA flowchart.

The characteristics of the studies found can be explored in Table 3.

Table 3: Characteristics of included studies.

Results of the critical appraisal using JBI CAT are reported in Table 4 with 3 answer options (Yes (+), Uncertain (?), and No (-)) [6]. 6 studies use online-based self-reported questionnaires; thus we deemed the measurement tools to not be valid (Q3, Q7) [8,9,12-16]. 8 studies ignore possible menstruation-specific confounders due to being a general report of all post-vaccination side effects [8-16]. All 3 cohort studies lacked proper and adequate follow-up periods (Q9, Q10) [19-21].

Table 4: Critical appraisal of included articles using JBI CAT.

Discussion

Studies found in our search had inconsistent definitions of menstrual changes. Studies by Muhaidat et al., Lagana et al., and Rogers et al., use a set of conditions which is considered abnormal [16,17,20]. Lagana et al., defined abnormal menstruation as a menstrual cycle of <25 days or >36 days, menstruation duration of <3 days or >7 days, and an abnormal estimated blood loss in comparison to previous menstruations [16]. In comparison, Muhaidat et al., reported menstrual cramps, menstrual cessation, worsening of premenstrual symptoms and intermenstrual bleeding as its conditions [17]. Other studies either did not prespecify what counts as menstrual changes, or only choose a single condition [9,16,18,21]. These menstrual changes appear variably in different populations. 3 studies mentioned that menstrual disorders are one of the rarer post-vaccination side effects in Africa (0.5%), India (0.16%) and Spain (1^st dose: 0.7%, 2^nd dose: 0.25%) [10,13,14]. In contrast, menstrual disorders are the second most common side effect (4%, 8%) in female doctors and dentists in Jordan and Saudi Arabia [12]. But, it is consistent that the majority of menstrual changes happen mostly after the first dose (46.7%) in comparison to the second dose (32.4%) or after both doses (20.9%) [17]. One possible cause of the differences between populations is the preferred vaccine used in said population. Post-vaccination menstrual changes were more common after Pfizer-BioNTech than AstraZeneca [8,20]. However, there was no statistically significant difference found [20]. Another study by Sa et al., also found that Pfizer-BioNTech had unfavorable odds ratio for menstrual changes in comparison to Moderna (0.593%, 95% CI=0.561-0.628) and Johnson & Johnson (0.992, CI 0.909-1.083) [18] (Tables 5-8).

Table 5: PubMed Search Strategy (June 16 2022, 09:54:21 PubMed Time).

Table 6: CENTRAL Search Strategy (June 17 2022, 05:41:33 PubMed Time).

Table 7: ProQuest Strategy (June 17 2022, 09:14:02 PubMed Time).

Table 8: EMBASE Strategy (June 17 2022, 23:30:01 PubMed Time).

Changes in menstrual cycle duration were found after the 1^st dose of AstraZeneca (55.6%), Pfizer-BioNTech (41.4%), Moderna (52.6%), and Johnson & Johnson (66.7%) vaccines [16]. The average menstrual cycle duration significantly increased from 27+6 days (pre-vaccination) to 28.1+10 days (post-vaccination) [17]. This finding is supported by Edelman et al., who also reported significant menstrual cycle duration change in the vaccinated population in comparison to the unvaccinated cohort [19]. Increased menstrual cycle duration can be due to increased menstruation duration (6+0.03 days to 6+0.05 days) or delayed menstruation (0.4%) [9,17]. Menorrhagia is also reported in 78 cases (3.4%) [17]. Relative risk of increased menstrual bleeding was 1.90 (95% CI: 1.69-2.13) and 1.84 (95% CI=1.66-2.03) respectively after the 1^st and 2^nd dose of vaccination [21]. The risk of increased menstrual bleeding can be due to changes in estimated menstrual bleeding, menstruation frequency, or the aforementioned menstruation duration. Changes in the estimated amount of menstrual blood, which is the most common cause, were found after the first dose of AstraZeneca (66.7%), Pfizer-BioNTech (47.4%), Moderna (52.6%), and Johnson & Johnson (66.7%) [16]. Changes in menstruation frequency are also reported after the first dose of AstraZeneca (66.7%), Pfizer-BioNTech (57.1%), Moderna (47.4%), and Johnson & Johnson (33.3%) vaccines [16]. In Indonesia, Sinovac- CoronaVac vaccine is more extensively used during the earlier vaccination effort. Menstrual changes post-Sinovac-CoronaVac administration happens in 20.2% of patients during the first 3 months [15]. During the next 3 months, the percentage decreases to 14.1% [15]. Results of other vaccines in Indonesia show that irregular menstruation is more likely found patients given Moderna (15.4%) than AstraZeneca (8%) vaccines (p=<0,000) [11].

The mechanism of Covid-19 vaccination altered menstruation is still unknown. However, a hypothesis links this phenomenon to vaccine-induced thrombocytopenia and the immune system that also occurs in various other types of vaccines, such as Measles Mumps Rubella (MMR), hepatitis A, hepatitis B, and others [17]. Thrombocytopenia could explain frequent menstrual bleeding [18]. In addition, the increased menstrual disturbance after the Covid-19 vaccination was also associated with anxiety or stress because the Covid-19 vaccine was still newly discovered [13]. Another hypothesis is the ability of mRNA-based vaccines that were assessed to induce novel immune responses that could affect the hypothalamic-pituitary-ovarian axis [19].

Menstrual changes that occurred post-Covid-19 vaccination have negatively affected the quality of life of more than 50% of women [17]. A slight change in menstruation could be a problem, especially for someone who planning or avoiding pregnancy [19]. However, menstrual changes that occur are generally moderate (54%) and did not require hospitalization [20]. Data showed that 92.3% of women who experience menstrual disorders after the 1^st dose of vaccination still continue to get the 2^nd dose of vaccination [21]. It is because menstrual disorders that occur are generally temporary and do not affect fertility [12]. Therefore, giving Covid-19 vaccination is still considered to have greater benefits than not clinically significant menstrual changes [19,21]. This study describes various changes in menstruation after Covid-19 vaccination with various types of vaccines, either mRNA or vector-based. This broad discussion topic is supported by an article search strategy designed to be as sensitive as possible. The limitation of this study lies in the lack of articles specifically written to discuss the PICO carried. In addition, the majority of studies found are based on online self-reporting, so there is a risk of memory and representational bias. Based on these considerations, the researchers assess that the synthesis of evidence in this article meets the very low-GRADE criteria [7]. This shows that quality research is still very much needed in this area of science.

Conclusion

Based on the studies that have been described, there are variations in menstrual changes after the Covid-19 vaccination seen from the cycle, duration, frequency, quantity of bleeding, and other complaints related to menstruation. The mechanism behind this is still unclear, but it is associated with thrombocytopenia, stress, and effects on the hypothalamic-pituitary-ovarian axis. Menstrual changes after the Covid-19 vaccination can affect women’s quality of life, but only temporarily. Therefore, giving the Covid-19 vaccination is still beneficial for reproductive women.

Declaration

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and materials

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Funding

This research received no external funding.

Authors Contribution

Conceptualization: N.I.M., N.K.P.S and A.R

Methodology: N.K.P.S

Investigation: N.I.M., N.K.P.S and A.R

Data curation: N.I.M. and N.K.P.S

Writing-original draft preparation: N.I.M

Writing-review and editing: A.R

Visualization: N.I.M. and N.K.P.S

Supervision: A.R

Project administration: N.I.M

Funding acquisition: A.R

All authors read and approved the final manuscript.

Orcid Details

Nathalia Isabella Muskitta: https://orcid.org/0000-0003-0999- 4227

Natan Kevin Partogu Siagian: https://orcid.org/0000-0003- 3073-5027

Amanda Rumondang: https://orcid.org/0000-0002-7949-4415

Acknowledgement

Not applicable.

Conflict of Interest

The authors declare that they have no conflict of interests.

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