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. Three studies mentioned that menstrual disorders are one of the rarer post-vaccination side effects in Africa (0.5%), India (0.16%) and Spain (1st dose: 0.7%, 2nd 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]
Changes in menstrual cycle duration were found after the first 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 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 first and second 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 three months.[15] During the next three 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 first dose of vaccination still continue to get the second 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.