After menstrual disorders or changes were reported in temporal proximity of COVID-19 vaccination, there was public concern that COVID-19 vaccination could have an effect on menstruation. Experts from the Paul-Ehrlich-Institut are researching whether such reported changes differ in women that are unvaccinated (or not yet vaccinated) and those that are vaccinated (after vaccination).

The team's research included a literature search in relevant medical databases, carried out on 1 September 2023. The search yielded 21 comparative studies. These studies consisted generally of interviews with women before (or without) and after vaccination. Studies that reported exclusively on menstruation status after COVID-19 vaccination were not included as they lacked a comparison group.

The following menstrual events were included in the study: irregular menstruation, heavy flow, prolonged menstruation, prolonged cycle length, and pain. Each study compared the frequency of the total number of these events in the group of vaccinated women to the frequency in the group of unvaccinated (or not yet vaccinated) women.

The results were summarised in a meta-analysis and a pooled estimate was calculated. No significant difference was found between the two groups. This suggests that the reported changes may have been caused by factors other than COVID-19 vaccination. Some of the studies included reported that menstrual changes were more likely to occur in women who had experienced a COVID-19 infection, smoked, had concerns about the safety of COVID-19 vaccines, were depressed, were under stress, or had experienced abnormal cycles in the past. In general, the changes were mild and disappeared after one or two cycles.

Figure 1 shows the literature search and selection process.

Figure 1: Literature search and selection process Source: Paul-Ehrlich-Institut

Table 1 provides an overview of the most important characteristics of the 21 studies included in the analysis.

Table 1: Characteristics of the Analysed Studies

Study ID	Study type	Type of collection	Tracking	Adjustment	Region
Akarsu 2022	Survey	about the past	once	no	Turkey
Alvergne 2022	Survey	followed over time	once	no	United Kingdom
Alvergne 2023a	Survey	about the past	once	yes	United Kingdom
Alvergne 2023b	Cohort	about the past	twice	yes	Western countries 1(a)
Barabas 2022	Survey	about the past	thrice	no	Hungary
Bisgaard-Jensen 2023	Survey	about the past	thrice	yes	Denmark
Bouchard 2022	Survey	followed over time	twice	no	USA, Canada
Caspersen 2023	Survey	about the past	once	no	Norway
Chiang 2023	Survey	about the past	once	no	Taiwan
Dabbousi 2022	Survey	about the past	once	no	Lebanon
Darney 2023	Cohort	followed over time	continuous	yes	Western countries 2(b)
Edelman 2022b	Cohort	followed over time	continuous	yes	Western countries 2(b)
Gibson 2022	Survey	followed over time	monthly	yes	USA
Kajiwara 2023	Survey	about the past	twice	no	Japan
Ljung 2023	Cohort	about the past	continuous	yes	Sweden
Lucac 2023	Survey	about the past	once	yes	Germany
Matar 2022	Survey	about the past	once	no	Arabic countries(c)
Saleh-Alzahrani 2023	Survey	about the past	once	no	Saudi-Arabia
Trogstad 2023	Survey	about the past	once	no	Norway
Wang 2022	Cohort	followed over time	monthly	yes	USA, Canada
Wesselink 2023	Cohort	followed over time	every 8 weeks	yes	USA, Canada

Abbreviations:
ID = identification
^(a) Western countries: United States, United Kingdom, Germany, Canada, France, Australia, and others.
^(b) Western countries: United States, Canada, United Kingdom, Europe, Australia, and New Zealand.
^(c) Arabic countries: Jordania, Syria, Palestine, Egypt, Libya, and Sudan.

The data from nine studies were evaluated together in a meta-analysis. The pooled estimate for the comparison of pre- versus post-vaccination was 1.13 (95% confidence interval: 0.96–1.31). Thus no significant difference was found in this analysis in the frequency of menstrual events between the two groups (see Figure 2).

Figure 2: Forest plot post- versus pre-vaccination: any menstrual event Source: Paul-Ehrlich-Institut

Abbreviations:
95% CI = 95% confidence interval
I2 = Index of heterogeneity (the smaller the value, the lesser the heterogeneity)
M-H = Mantel-Haenszel statistical method
Random = random effects analysis model
P = probability
Risk ratio = risk ratio effect measure based on dichotomous data

Six studies investigated whether there might have been other causes for the reported menstrual disorders in addition to COVID-19 vaccination. The following factors had an influence on the questionnaire answers:

• previous COVID-19 infection,
• concerns about the safety of COVID-19 vaccines,
• poor subjective overall health,
• smoking,
• a history of cycle irregularities,
• high stress levels,
• depression, and
• subjective perception.

Most studies suggest that the changes observed were transient, minor, and non-serious (see Table 2).

Table 2: Quotes from the Conclusions of Included Studies

Study ID	Quotes
Akarsu 2022	20.3% had an irregular menstrual cycle after vaccination, 21.8% had menstrual cycle irregularity before vaccination.
Alvergne 2022	In spontaneously cycling participants, COVID-19 vaccination was associated with a delay to the next period, but this change reversed in subsequent unvaccinated cycles. No delay was detected in those taking hormonal contraception.
Alvergne 2023a	The prevalence of reporting any menstrual changes was higher for women who smoke, have a history of COVID-19 disease, or are not using oestradiol-containing contraceptives. COVID-19 vaccination alone was not associated with abnormal menstrual cycle parameters, while a history of COVID-19 disease was associated with an increased risk of reporting heavier bleeding, “missed” periods, and inter-menstrual bleeding.
Alvergne 2023b	Experiencing COVID-19 is associated with a small change in cycle length similar to COVID-19 vaccination. These changes resolve quickly within the next cycle.
Barabas 2022	We concluded that the reported menstrual cycle abnormalities during the peak of COVID-19 in Hungary might be the result of elevated depressive symptoms.
Bisgaard-Jensen 2023	Any menstrual change following COVID-19 vaccination was reported by 30% of menstruating women. Most of the potential risk factors were associated with reports of menstrual changes following COVID-19 vaccination.
Bouchard 2022	Although 22% of women subjectively identified changes in their menstrual cycle, there were no significant differences in menstrual cycle parameters (cycle length and menses duration) between the pre-vaccine, vaccine, and post-vaccine cycles. COVID-19 vaccines were not associated with significant changes in menstrual cycle parameters.
Caspersen 2023	Only 1.5% of the vaccinated girls had previously had a laboratory confirmed SARS-CoV-2 infection, compared to 28.0% of the unvaccinated girls. Notably, menstrual irregularities were relatively common in this sample of 12- to 15-year-old girls, independent of vaccination, and infection status.
Chiang 2023	The blood cell counts, inflammatory markers, and menstruation of female athletes were not affected by COVID-19 vaccines.
Dabbousi 2022	Moreover, 12.5% of participants experienced irregular cycles before the vaccine; this number increased to 20.4% after the vaccine. One possible explanation for this irregularity is the psychological stress perceived by the woman before, during, and/or after receiving the vaccine, as higher stress levels were associated with menstrual irregularity.
Darney 2023	A small increase in the probability of greater total bleeding quantity occurred following the first COVID-19 vaccine dose, which resolved in the cycle after the postvaccination cycle. The total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transient.
Edelman 2022b	Individuals who were vaccinated had a less than 1 day adjusted increase in the length of their first and second vaccine cycles, compared with individuals who were not vaccinated (0.71 day increase) for first dose. COVID-19 vaccination is associated with a small and likely to be temporary change in menstrual cycle length but no change in menses length.
Gibson 2022	COVID-19 vaccination was associated with a small increase in MCL for cycles in which participants received the first dose. Postvaccination cycles returned to average pre-vaccination length. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated.
Kajiwara 2023	Compared to the predicted menstrual cycle length, the actual menstrual cycle length increased by 1.9 ± 3.0 days before vaccination and 1.6 ± 2.8 days (p = 0.557) after the first vaccination. Although the second dose of the vaccine prolonged the menstrual cycle, it was not significant.
Ljung 2023	These findings do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.
Lukac 2023	The final analysis included 1726 participants. Cycle length and blood volume significantly changed after vaccination, but not menses duration. The risk factors for the variations in cycle length were previous cycle irregularities, and risk factors for the changes in bleeding volume were age and body mass index. The combination of vaccines (homogenous or heterogeneous) and different types of immunization (infection and vaccination) had no significant effect on cycle irregularities.
Matar 2022	Our findings indicate that COVID-19 vaccine may have an effect on menstruation in terms of menstrual pain and bleeding heaviness. The evidence needs to be further investigated in longitudinal studies.
Saleh-Alzahrani 2023	Abnormal menstruation after the COVID-19 vaccine was significantly associated with menstrual abnormality before receiving the COVID-19 vaccine, hypertension, polycystic ovary syndrome, and any gynecological condition.
Trogstad 2023	The prevalence of any menstrual disturbance was 36.7% in the last menstrual cycle prior the first vaccine dose. Menstrual disturbances were common regardless of vaccination. We found increased risk of menstrual disturbances after vaccination, particularly for heavier bleeding than usual, prolonged bleeding, shorter interval between menstruations, and stronger period pain.
Wang 2022	COVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long, or irregular before vaccination.
Wesselink 2023	We did not observe strong associations between COVID-19 vaccination and cycle regularity, bleed length, heaviness of bleed, or menstrual pain. In conclusion, COVID-19 vaccination was associated with a circa 1-day temporary increase in menstrual cycle length but was not appreciably associated with other menstrual cycle characteristics.

Abbreviations:
COVID-19 = Coronavirus disease 2019
MCL = menstrual cycle length

The study team did not find a meta-analysis in the literature that included only comparative studies. Some data could not be included in the meta-analyses because it was not suitable. This was partly compensated for by additional information provided by the study authors. Furthermore, 44 studies were found that reported exclusively on post-vaccination data. The frequency of menstrual events ranged from 0.3% to 77.8%, with an average of 1.52% of the total number of participants.

Phelan 2021 had conducted a survey on the impact of the pandemic on women's health in September 2020. Up to 50% of the participants reported menstrual changes pre-vaccination. According to Benedetti 2007, the term nocebo effect means "that expectation of a negative outcome may lead to the worsening of a symptom". Haas 2022 concluded in a systematic review that 76.0% of systemic adverse events after the first COVID-19 vaccination can be attributed to nocebo reactions. Hauser 2012 reported that negative expectations of a medical intervention can lead to various unwanted effects and Huang 2010 pointed out that the nocebo effects are spread via social media and public concern about topics such as the safety of vaccination programs.

The meta-analysis showed no significant difference in the frequency of menstrual events between the group of unvaccinated women (or pre-vaccination) compared to vaccinated women (post-vaccination). Most studies indicate that the changes reported are transient, minor, and non-serious. These reported changes should not be a barrier to vaccination.