Coronavirus disease 2019 (COVID-19) is as an emerging infectious disease (EID) that has caused the worst public health catastrophe of the 21st century thus far. In order to contain the spread of the epidemic, countries around the world have launched vaccination campaigns for COVID-19 vaccine and have taken various measures to monitor for adverse reactions after vaccination. VAERS as a vaccine adverse reaction self-reporting system, a total of 14,431 menstrual disorder-like events were reported by female in VAERS, and 13,118 (90.90%) were exposed to the COVID-19 vaccine, from the establishment of the database in 1990 to November 12, 2021. The general characteristics of the reports showed that female in the age group 30–49 years reported the highest number of incidents of menstrual disorders compared to other vaccines. There were 1065 reports mentioning serious adverse events, again with the highest percentage of reports for Pfizer-Biontech vaccination. The majority of reports of menstrual disorders occurred after the first dose of the COVID-19 vaccine, with only about 0.5% reported after the third dose of the vaccine. The time between vaccination and adverse reaction reporting was within 100 days in 82.92% of patients, but only 18.01% of patients reported that their adverse reactions had disappeared, and 62.88% of patients reported that they still had adverse reactions related to vaccination.
To my knowledge, this is the first time that a menstrual disorder-related event has been linked to the COVID-19 vaccine. Normal female menstruation is judged by the cycle of menstruation, the period, the volume, the color, the quality and the accompanying symptoms of menstruation. Among the events of menstrual disorders reported by the COVID-19 vaccine, Menstruation irregular was found to be the most frequently reported, followed by Menstruation prolonged, Intermenstrual bleeding and Menstrual disorder, with Menorrhagia being the least frequently reported. Dietary nutrition, environmental factors, lifestyle and mental health conditions are important factors affecting menstrual irregularities in female of reproductive age. During the covid-19 epidemic, female were more vulnerable to stress and were significantly more depressed and distressed than men, and middle-aged females are the major groups for the first vaccination. This may explain the climb in reports of menstrual disorders after vaccination with the COVID-19 vaccine. Our study found a potential association signal between COVID-19 vaccine and menstrual disorders events with ROR = 7.83 and met the lower limit of ROR 95% CI > 1 and number of cases > 3. However, adverse reactions were reported independent of region, with ROR < 1. In addition, studies have found a greater correlation between prolonged and irregular menstrual cycles and the risk of premature death (age < 70 years), so that menstrual disorders in female must be taken seriously enough.
Study shows age and gender differences in adults who report adverse reactions after vaccination with COVID-19 vaccine. However, after the launch of COVID-19 vaccine, attention to adverse reactions associated with vaccination has been focused on the elderly, adolescents, and even pregnant female and young children, while attention to young adult female has been lacking. However, female of reproductive age account for the majority of adverse reaction reports received by VAERS for menstrual disorders. Our study found that reports of adverse reactions to menstrual disorders in females aged 30–49 years increased nearly tenfold compared to the pre-marketing period of the vaccine. There was a danger signal between this age group of female compared to other age groups for menstrual disorders events after COVID-19 vaccination with a lower limit of the ROR 95% CI > 1. To address some limitations of the spontaneous data, such as missing data in the report, a sensitivity analysis was conducted to exclude age unknowns and produce similar results. Reports of menstrual disorder-like events after vaccination of female with the COVID-19 vaccine are age-related, and females of reproductive age between 30–49 years old need to pay particular attention to adverse reactions after vaccination.
Three COVID-19 vaccines are authorized or approved for use among adults in the United States, respectively: mRNA-1273 from Moderna 、BNT162b2 from Pfizer-BioNTech 、Ad26.COV2 from Janssen. Inoculation with Pfizer-BioNTech accounted for the majority of reports of menstrual disorders, with Moderna in second place and Janssen in third. As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥ 12 years in the United States. And as of November 12, 2021, VAERS has received reports of menstrual disorders representing approximately 1 in 100,000 of the total number of Pfizer vaccinations. Adverse reactions to vaccination appear to be insignificant compared to the serious life-threatening effects of infection with the virus, and there is a lack of much substantial evidence linking vaccination to adverse reactions[26, 27]. Eric Wan and colleagues in The Lancet Infectious Diseases had suggested that the overall increased risk of Bell's palsy after COVID-19 vaccination. However, to this date there is no clear evidence of a link between the COVID-19 vaccine and Bell's palsy. Based on various studies of real-world data[29, 30], all approved or licensed COVID-19 vaccines provide substantial protection, although the degree of protection varies among vaccines.
However, there are several limitations to our study. First, the main limitation of our study is that it is unclear whether these adverse reactions were caused by disease or exposure to the vaccine, and there is a lack of data related to specific medical history and menstrual histories. Second, based on the spontaneous reporting nature of VAERS, our results are susceptible to various biases, such as data omission, overreporting, and underreporting. Third, co-vaccination may suppress or enhance the immune response, and this study only refers to the report of vaccination alone and does not include the data of co-vaccination. All of the above may cause bias in our results.