Authors: Romina Garcia de Leon, Neuroscience MSc student, Faculty of Medicine, UBC; Jennifer Richard, PhD, Department of Psychology, UBC; Liisa Galea, PhD, WHRC Lead | Editors: Alex Lukey and Arrthy Thayaparan (Blog Coordinators)
Published: June 18th, 2021
“Imagine if you didn’t know that fever could be a vaccine side effect? You might be concerned that something untoward was happening to your body when all you were experiencing was a typical post vaccine fever. That is exactly the same with menstrual irregularities.” (Gunter, 2021).
There is a growing concern that the COVID-19 vaccine is causing disruptions to menstrual cycles and questions as to why the vaccine may have this effect have been raised by women awaiting their vaccines. Valid, as these questions are, we have few answers as there has been very little to no research in this area. In fact, most of these concerns have been reported through social media and voluntary self-report on databases such as the United States’ Vaccine Adverse Event Reporting System (VAERS) and the Canada Vigilance Adverse Reaction Online Database.
Yet, to date, there have been no systemic studies to examine whether the COVID-19 vaccine – or other factors – are causing these irregularities. So, short of an actual study to show that there is any effect of the COVID-19 vaccine on menstrual cycles, what can we infer?
Unfortunately, given the dearth of research into women’s health, it is not altogether surprising that we do not have this information at the ready. Studies looking at females alone make up only about 6% of the literature. Male-only studies make up approximately 40% of the total studies, although the total number varies by discipline. Women’s health includes studies that would examine how hormonal contraceptives influence mood, or how menopause influences memory in middle age or – you guessed it – how vaccines affect the menstrual cycle or even whether there is a time during your menstrual cycle that the vaccine could cause the fewest side effects. The disparity in women’s health research is no exception in COVID-19 literature.
Thus far, studies examining the main receptor that SARS-CoV-2 binds to in order to enter cells, and infect the body, angiotensin-converting enzyme 2 (ACE2), have been predominantly conducted in males. In fact, a recent study showed the extent of the disparity with 70% of the research conducted involving male-only studies, and only 11% involving females. As a result, it is not surprising that we know so little about how COVID-19 or the COVID-19 vaccines may affect menstrual or menopausal symptoms.
Certainly, many people will already be aware that menstrual cycle variations occur naturally (with more regular cycling often achieved through taking steps to control the menstrual cycle – e.g. taking hormonal contraceptives) and that menopausal symptoms can vary dramatically. Generally, cycle lengths vary in the general population because of many factors including biological and environmental factors. So, with this in mind, what science is there to show what we might expect post-COVID-19 vaccination?
Plausible Theories
A recent study showed that COVID-19 infection itself influences menstruation. Specifically, a research group in China analyzed data from 177 menstruating people diagnosed with COVID-19, and found that a quarter of all participants had a change in menstrual pattern. In this study, researchers identified that nearly all participants returned to their normal menstrual pattern 1 to 2 months following their COVID-19 diagnosis. However, based on these findings, it is clear that further research is also needed to investigate whether the COVID-19 vaccine also affects menstruation.
In the meantime, there are theories that may provide insight into what may be happening to the menstrual cycle, and why, in response to COVID-19 vaccination. But before we begin it is important to acknowledge that the entire female reproductive tract (vagina, cervix, uterus, endometrium) is a system that responds to immune challenges (think yeast infections and pelvic inflammatory disease) but this system also needs to show immune tolerance (as is the case in pregnancy – the fetus is a foreign body that we don’t want the body to reject). It shouldn’t surprise us that some changes occur in the reproductive tract when the immune system is challenged…like with infections or vaccine stimulations.
Environmental: Stress
Stress itself can challenge our immune system. A stress response, much like a foreign body, can cause an immune response (and this makes perfect sense from an evolutionary perspective as stress and infection were often seen together!) In doing so, disruptions to our menstrual cycle and menopausal status may occur with stress. Throughout the COVID-19 pandemic, many of us have undoubtedly experienced higher levels of stress. Moreover, women around the world have reported a disproportionate amount of stress, compared to men, for example, due to the added challenges imposed by school closures and daycare closures. If women have been reporting high-stress levels – and a lot of stress can affect the menstrual cycle – is the stress of the pandemic resulting in abnormal periods?
In May 2020, a research group analyzed data from 263 participants and found that an increase in COVID-19 pandemic-related stress was correlated with an increase in menstrual irregularities. Similarly, preliminary data from Canada showed that 27.8% of women experienced menstrual irregularities after receiving the COVID-19 vaccine (unpublished data). This leads us to question whether the changes seen in menstruation are an indirect result of higher levels of stress due to the ongoing pandemic or a direct response to vaccination, or perhaps a combination of the two!?
Biological: A direct link
Vaccines (for example, against rubella) can trigger menstrual irregularities depending on what stage it is received during the menstrual cycle. The endometrium, which is the lining of the uterus, is part of the immune system. This complex reproductive organ is host to a multitude of immune cells and offers protection from infections. These immune cells also vary cyclically, according to the phase of the menstrual cycle. This makes sense: the lining of the uterus sheds tissue which results in menstrual bleeding (and builds tissue too). It may be that when an immune response is mounted post-vaccination, the endometrium reacts by adapting its immune environment to protect the uterus. This abrupt change may trigger abnormal menstrual changes such as an increase (or decrease) in menstrual length and blood volume.
Interestingly, the ACE2 receptors involved in COVID-19 infection are found on the reproductive tract – including the endometrium and ovaries. The presence of this receptor in the ovaries modulates the production of sex hormones, estradiol and progesterone, which in turn can increase or decrease cells on the endometrium. If this theory checks out, does the time the vaccine is administered during one’s cycle change the probability of having menstrual irregularities? A research group in Spain looked at just this. They found that ACE2 receptors increase in the endometrium during the luteal phase (the time between ovulation and the start of menstruation), suggesting a higher risk for viral infection during this time. Meaning that menstrual side effects may be dependent on cycle stage at the time of vaccine administration. But until this is examined and tested in a research setting, this will remain simply a theory.
The COVID-19 Vaccine and Post-menopausal symptoms
What about people reporting bleeding after menopause?
Just like there is a lack of research into the impact of COVID-19 infection/vaccination on menstruation, even less is known about how this may affect post-menopausal women. Could the vaccine or infection be directly impacting the reproductive system? Recently, post-menopausal women have taken to social media to report abnormal bleeding following a COVID-19 infection or vaccination. Although there are reductions in some immune cells in the endometrium post-menopause, immune cells are still reactive across the reproductive tract. There is, however, a scarcity of research on this subject.
Although we do not yet know if COVID-19 vaccines are the cause of the reported incidents of post-menopausal bleeding, there may be several other reasons for bleeding to occur, such as hormone therapy or medication-related changes in the endometrium. Regardless, risk of postmenopausal bleeding after vaccination seems to be low as it was not reported in initial trials, and few incidents have been reported so far (27 cases of postmenopausal hemorrhage have been reported in VAERS) with about 50% of women (almost 83 million!) in the USA already having received at least one vaccine against COVID-19. It should, however, be noted that this is a voluntary self-report system for recording adverse events and it is unclear whether all women would consider post-menopausal bleeding as a vaccine-related event.
Is there a direct link to the female reproductive system through ACE2 receptors in menopause as well?
Considering that knowledge on immune changes during pre-menopause is still growing, information about the levels of ACE2 receptors (reminder, these are the receptors that allow for COVID-19 infection) in the endometrium post-menopause is unknown. However ACE2 receptors are linked to levels of estrogens so it may not be surprising that menopausal status is related to COVID-19 outcomes, with postmenopausal people having more severe outcomes compared to pre-menopause. Intriguingly, women over 50 that receive hormone therapy are at reduced risk of mortality due to COVID-19. ACE2 receptors are found in numerous tissues and the distribution of these receptors does change with age in females in the heart and possibly lung, but there are few studies in this area. However, the potential connections between COVID-19 vaccination and effects on the endometrial immune system, and ACE2, will require further study. But it is important to recognize that the female reproductive tract is actively involved in immune challenges even post-menopause.
Let’s get vaccinated!
In sum, we know very little of the side effects of any vaccine, let alone the current vaccines available for COVID-19, on menstruating and post-menopausal women. Yet, we know for sure that these risks are far smaller than the risk of becoming severely ill from COVID-19 itself. Although the risk of mortality from COVID-19 is higher in males, the incidence of COVID-19 infection is actually higher in females and although it needs more study, long-haul COVID symptoms (those that last post infection) is more common in women than in men. That’s why more than ever it is important to be vaccinated.
The bottom line as we see it: There is no evidence that the COVID-19 vaccine alters menstruation or menopause long-term. Whether COVID-19 vaccination is behind the reported cases of postmenopausal bleeding, or menstrual changes, remains to be investigated. And this again highlights the need for additional research on women’s health, in general. For example, had there been more concerted research efforts examining menstruation and menopausal physiology, the current issue of possible vaccine side effects may have been avoided (or at least better understood!). As a whole, however, the take-home message is that although there may be potential side effects on menstruation and menopausal status as a result of the COVID-19 vaccine, these, like other vaccine side effects, appear to be temporary. It is therefore important to follow health guidelines and get vaccinated as soon as possible.
If you are interested in participating in a study, Dr. Kate Clancy at the University of Illinois has a survey open documenting any menstrual cycle abnormalities following the vaccine: https://redcap.healthinstitute.illinois.edu/surveys/index.php?s=LL8TKKC8DP
More reading? – Check out these blogs on the COVID-19 vaccine and menstrual irregularities or bleeding post menopause by Jen Gunter.
