As vaccination spread to younger age groups, some women noted menstrual changes after vaccination, and concern and need for robust data and research arose. But not only have menstrual changes been reported in association with Covid vaccines, but also against other pathogens, so a secondary objective of this work is to understand the mechanisms by which menstrual changes associated with vaccines can occur.
The article published by Science magazine entitled Vaccination against Covid-19 and menstruation begins.
Covid vaccination affected menstruation
Now, new research shows that many of the complaints were valid. A study of almost 20,000 people around the world shows that getting vaccinated against covid can change the timing of the menstrual cycle. Vaccinated people experienced, on average, about a day of delayed menstruation, compared to those who had not been vaccinated.
The study data, published Tuesday in the British Medical Journal, was taken from a popular period-tracking app called Natural Cycles and included people from around the world, but the majority were from North America, Britain and Europe.
The researchers used “de-identified” data from the app to compare menstrual cycles among 14,936 participants who were vaccinated and 4,686 who were not.
In this sense, according to a study by the Norwegian Institute of Public Health (NIPH), 37.8% of the patients analyzed described some aspect different from the usual in their cycle, even before vaccination.
Another US study using a menstrual cycle tracking app reported a standard deviation in cycle length of 4.2 days in unvaccinated women. All of this underlined the need for formal approaches, with unvaccinated comparison groups, to identify changes specifically associated with the vaccine.
The findings have been consistent. Thus, vaccination against Covid is associated with a small increase in the duration of the menstrual cycle, although this resolves quickly: according to different American studies, the duration of the cycle returns to normal after two cycles.
The NIPH study found that heavier-than-normal bleeding was more commonly associated with vaccination, with 13.6% of participants reporting this during the post-vaccination period compared with 7.6% during the pre-vaccination period to vaccination.
The UK study of 79 participants was unable to detect an increase in menstrual flow associated with vaccination, although this could be due to the smaller cohort size.
These conflicting results could also reflect the increased risk of recall bias in the NIPH study. To resolve this, approaches that combine large cohorts and real-time data collection are needed.
Two possible biological mechanisms
Two biologically plausible mechanisms have been proposed by which immune stimulation might cause menstrual changes: innate immune responses might transiently interfere with hormones that drive the menstrual cycle, or it might affect macrophages and natural killer cells in the lining of the uterus, which control the degradation and regeneration of this tissue throughout the cycle.
In support of the hypothesis that the effects are hormonally mediated, women in whom the ovarian hormones estrogen and progesterone are supplied exogenously by combined hormonal contraception (pill) are less likely to experience menstrual changes after vaccination. In addition, vaccination within the menstrual cycle affects whether the cycle length is increased.
The menstrual cycle is divided into two phases: the follicular phase, which occurs before ovulation and can be prolonged by hormonal changes, and the luteal phase, which occurs after the release of the ovum and lasts more constantly.
If the menstrual changes are mediated by immune effects on the control of ovarian hormones, vaccination would be expected to prolong the follicular phase, but this can only occur if the vaccines are administered during this phase.
Supporting the possibility that the Covid-19 vaccine affects immune cells in the lining of the uterus, a survey of more than 27,000 women found that increasing age was associated with an increased risk of heavier bleeding. This could suggest that poor tissue repair, which is mediated by immune cells in the womb and may be less effective in older people, is the mechanism by which the covid vaccine increases menstrual flow.
Therefore, the evidence for the underlying mechanism is mixed and could be consistent with effects mediated by ovarian hormones (affecting cycle length) and endometrial repair (affecting menstrual flow). More research is required to definitively identify the pathways involved.
Shortly after vaccines were introduced to protect people against COVID-19, women around the world began reporting changes in their periods after receiving the vaccine; some noted longer cycles and others heavier bleeding. Because the reports did not suggest problems serious enough to investigate, the vaccine manufacturers did not include menstrual impact tests during their trials.
Victoria Male, a Senior Lecturer in Reproductive Immunology at Imperial College London, suggests that the result was hesitancy on the part of some women to get vaccinated, fearing that doing so could lead to other unknown problems, such as fertility problems. And this, she adds, added fuel to the misinformation campaigns targeting COVID-19 vaccines.
In her article, Male notes that other researchers have since investigated the matter by conducting studies, and in doing so, have found evidence showing that some COVID-19 vaccines do have an impact on the menstrual cycle, although He notes, such impacts have been found to be small and temporary. She also points out that it is not yet known why this happens.
She suggests that it might have something to do with the cytokines that are produced after inoculation and their impact on the signalling that occurs between the pituitary gland, the hypothalamus, and the ovaries.
Another possibility, she suggests, is that the vaccines have an as-yet-unknown impact on immune cells that are involved in repairing the tissue of the lining of the uterus after it is shed during menstruation. She also notes that it is not yet known if being infected with COVID-19 has any impact on the menstrual cycle.
Does SARS-CoV-2 infection affect menstruation?
While studies can track before and after vaccination, it is more difficult in the case of infection because it is unpredictable, can last days or weeks, and many people are unaware they are infected (asymptomatic), making it difficult to define non-infectious control.
In studies in the early stages of the pandemic, between 15 and 25% of women reported changes in their periods after Covid infection, but one was done in hospitalized with Covid, another in women with persistent Covid and was not found to include an uninfected control group. in none, so they could be overestimated. Another study found no effect of infection but also had several limitations in detecting small or temporary effects.
As lessons, it can be pointed out that although more than half of the world’s population menstruates at some point in their lives, data on the effects of menses are rarely collected in vaccine trials, something that needs to change.
Menstrual cycle tracking apps have proven effective because they have large volumes of data available and real-time data collection mitigates recall bias. But these app users are not representative of the global population because they mostly live in high-income countries and young, white, highly educated women are overrepresented. They also know they are vaccinated and that can affect their perception of aspects of menstruation, so including a blinded control group, as in vaccine trials, avoids these problems.
These advances also open up several avenues of research. It is important to recruit people who are already planning to receive a vaccine dose, which avoids the ethical challenges of giving participants an immune boost solely for experimental reasons.
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