Studies on vaccines rarely consider menstruation as a variable and focus on how vaccines affect fertility or pregnant women. A U.S. Vaccine Adverse Event Reporting System (VAERS) study found that vaccines and immune responses may affect menstruation, indicating the need for further study.
A recent study in Science Advances examined changes in menstrual bleeding following vaccination against severe acute respiratory disease coronavirus 2 (SARS-CoV-2) among ethnically and gender-diverse pre-and postmenopausal women. The results denoted heavier menstrual bleeding episodes in women who generally had regular menstruation and breakthrough bleeding among postmenopausal women, as well as in those on gender-affirming hormones and long-acting contraceptives. These changes were associated with age, ethnicity, history of pregnancy or birth, and coronavirus disease 2019 (COVID-19) vaccine side effects.
Background
Menstruation is the monthly shedding of the uterus lining. Previous reports, in the year 2021, stated unexpected menstrual bleeding post-COVID-19 vaccination. However, there is no standard protocol for monitoring vaccine-related adverse events beyond seven days; besides, follow-up correspondence does not address menstrual cycles or bleeding. Therefore, vaccine manufacturers have not been able to explain these menstruation-related changes as a chance event or an adverse reaction to vaccination.
Vaccines protect against diseases by activating the immune system; it involves a cascade of various localized or systemic inflammatory reactions. The menstrual cycle is an inflammatory and hemorrhagic process. A few trials have examined the direct effects of vaccination on the menstrual cycle. For instance, studies have shown that menstrual irregularities were associated with typhoid and hepatitis vaccines. Research in this area is in the pipeline due to the acute immunological challenge posed by the existing COVID-19 vaccinations.
An ongoing investigation is being conducted to collect responses from menstruating and formerly menstruating adults. This preliminary investigation has identified the parameters of the phenomena of postvaccination menstruation alterations based on the results of the first round of analysis. Using data collected in the first three months, researchers describe trends in menstrual bleeding or breakthrough bleeding. to the aim was to answer the following research questions:
- What type of menstrual bleeding alterations are experienced by women with regular menstruation following vaccination against SARS-CoV-2?
- How frequently is breakthrough bleeding reported by non-menstruating respondents reporting after they receive vaccination against SARS-CoV-2?
- Can these menstruation alterations be correlated to a modified pattern of menstrual bleeding – to provide clues as to the mechanisms at work within the uterus?
The study
The survey comprised the first three months’ data of respondents in the sample (N = 39,129) with women in the age range of 18-80 years. Non-menstruating individuals fell into two categories – premenopausal women (using long-acting reversible contraceptives (LARCs), continuous hormonal contraceptives, and/or gender-affirming treatment that halts menstruation) and postmenopausal women – who were 55 years of age and hadn't menstruated for at least a year before COVID-19 vaccination.
All subjects were completely immunized and did not suffer from COVID-19 (neither diagnosed nor suspected). Overall, 21,620 participants were vaccinated with Pfizer; 13,001 with Moderna; 751 with AstraZeneca; 3,469 with Johnson & Johnson; 61 with Novavax; and 204 with other vaccines; 23 respondents did not report the vaccine type.
Study findings
It was noted that increased bleeding was the most prevalent vaccination-related alteration in menstruation. Changes in the menstrual cycle were reported by women who menstruate frequently. Overall, 42.1% experienced heavier menstrual flow post-vaccination, whereas, 14.3% reported either no change or lighter menstrual flow and 43.6% did not notice any change in their menstrual flow post-vaccination.
However, there was a higher likelihood of heavy menstrual flow in women who were non-white, Hispanic/Latinx, older, had a diagnosed reproductive disorder, used hormonal contraception, had experienced pregnancy, and in those who had fever or exhaustion post-vaccination. Both, history of pregnancy and parity correlated to heavier menstrual flow. On the other hand, the vaccine type, ethnicity, and hormonal contraceptive use showed negligible effects on menstrual alterations post-vaccination.
Additionally, women with reproductive conditions like – endometriosis, menorrhagia, fibroids, polycystic ovary syndrome (PCOS), and adenomyosis reported a heavier menstrual flow following vaccination than those without identified reproductive disorders.
Further, non-menstruating, premenopausal respondents (N = 1,815) undergoing hormone therapy were significantly more likely to experience breakthrough bleeding post-vaccination than those undergoing gender-affirming care.
Participants who were Hispanic/Latinx had experienced pregnancy but had not given birth, with a diagnosed reproductive condition, who were taking LARC only, or those with fever post-vaccination showed a greater preponderance for breakthrough bleeding.
Meanwhile, non-Hispanic/Latinx participants had a lesser prevalence of breakthrough menstrual bleeding. The rate of breakthrough bleeding was not significantly affected by the type of vaccine administered, the side effects of the vaccine, or the reproductive history.
Of note, the post-vaccine menstrual changes did not manifest until a week after inoculation. Hence, these alterations could not be recorded in the monitored vaccine trials. The findings may have important implications in studying post-menopausal breakthrough bleeding from dormant ovaries. Vaccination-related menstrual alterations may also depict the vulnerability of women with hyperproliferative and vascular or hemostatic conditions.