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Non-Menstruating Women Reported Vaginal Bleeding After COVID-19 Vaccination

A woman receiving a vaccine.
Credit: CDC / Unsplash.
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A new study from the Norwegian Institute of Public Health (NIPH) found that women who do not menstruate, due to the use of hormonal contraception or menopause, reported unexpected vaginal bleeding after COVID-19 vaccination.

Unexpected bleeding in non-menstruating women

While the COVID-19 outbreak is no longer considered a Public Health Emergency of International Concern (PHEIC), the pandemic is not over. Vaccine development and distribution continues and, accordingly, research exploring vaccine efficacy and safety persists.

In 2021, anecdotal reports of menstrual cycle changes post-COVID-19 vaccination emerged, leading to the launch of several research projects probing the reported side effect with more scrutiny. Over two years later, it’s understood that vaccination for COVID-19 can be associated with some changes – often temporary – to the menstrual cycle in some people. In October 2022, heavy menstrual bleeding was listed as a possible side effect for mRNA vaccines.

A large portion of the female population does not menstruate regularly due to menopause or the use of hormonal contraception. Less research has explored whether similar effects of altered bleeding patterns occur in these populations. The new study, published in Science Advances, utilized questionnaire data from 22,000 women enrolled in two other NIPH research projects: the Senior Cohort and the Norwegian Mother, Father and Child (MoBa) studies. Participants were asked whether they had experienced any unexpected vaginal bleeding in 2021, the time period when the majority of the population received a COVID-19 vaccine dose.

Pre-, post- and menopausal women experience unexpected bleeding

The researchers categorized the participants’ and their responses into three groups: those that were post-menopausal (7725 women), perimenopausal (7148 women) and non-menstruating premenopausal (7052 women). Most of the women in the study received an mRNA vaccine.

“We found an increased risk of unexpected vaginal bleeding among women who are no longer menstruating due to menopause, as well as those who do not menstruate because they use hormones,” says Kristine Blix, physician and researcher at NIPH and first author of the study.

Specifically, Blix and colleagues found that 3.3 % of the postmenopausal women reported unexpected vaginal bleeding, with almost half of these women reporting that the bleed occurred in the first month after COVID-19 vaccination. In the perimenopausal group, 14.1% experienced unexpected vaginal bleeding. Similarly, half of these women reported that the bleeding occurred in the month after vaccination. For non-menstruating premenopausal women, of which 74% were using hormonal contraception in the form of intrauterine devices, 13.1% experienced unexpected bleeding.

“When we enter these figures into a statistical model that also takes into account that the time before vaccination is longer than the time after vaccination, we can estimate whether the risk is increased in the time after vaccination, and how much it is increased compared to the risk before the vaccine,” Blix describes. "Assuming that the women recalled all bleeding episodes equally well, that is, that they did not over-report bleeding after vaccination, or, more importantly perhaps, did not under-report bleeding before vaccination, the risk is increased 2-4 times in the first month after vaccination.” The risk figure varies for the three different groups, with postmenopausal women having a 2–3 fold increased risk in the first month after vaccination, menopausal 3–4 fold and premenopausal 4–fold.

“Among non-menstruating women who reported bleeding after vaccination, most reported having a single bleeding episode, that the bleeding lasted for a week or less, and that the bleeding was not heavy,” says Blix.

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The exact cause of unexpected vaginal bleeding post-vaccination in menstruating and non-menstruating individuals has not yet been determined. In a previous interview on this topic with Technology Networks, Victoria Male, a lecturer in reproductive immunology at Imperial College London, suggested two plausible mechanisms: “One is that a perturbation to the immune system, such as occurs after vaccination or infection, could affect sex hormones and that this in turn will affect the menstrual cycle,” she explains. “The other is that the immune cells that help control the build-up and break down of the lining of the uterus could be affected by the general activation of the immune response, and this could in turn affect the timing and heaviness of bleeding.”

Effects of medical interventions on menstruation cannot be an afterthought

Blix and colleagues believe their research contributes important information to this field of study. “In our sample of health-conscious women, only 31, 14 and 9% of the post-, peri-, and premenopausal women with reported bleeding also reported that they sought medical care, respectively,” they say. “This health-seeking behavior also differed by vaccination status. This illustrates the role of self-reported data in the investigation of certain end points. While bias may partly explain the association in this retrospective analysis, we do not believe that it accounts for all the increased risk we observed. Together with current knowledge, it seems probable that both pre- and postmenopausal women are at increased risk of unexpected vaginal bleeding after COVID-19 vaccination.”

The researchers encourage future clinical trials of vaccines to consider the data observed in this and other related studies. Male says that the effects of medical interventions on menstruation cannot be an afterthought. “In the trials, information was solicited about events that were expected but not serious, such as fever and fatigue, or serious,” she discusses. “Since changes to the menstrual cycle didn’t fit in either of these categories, it wasn’t solicited – and most people won’t volunteer information about their periods unless specifically asked. This is partly because we don’t talk about our periods as much as maybe we should. This lack of discussion not only means that people didn’t volunteer information, it also means that people designing trials don’t necessarily have this in the forefront of their minds.”

At this stage, it’s unclear whether pharmaceutical regulatory bodies will consider unexpected vaginal bleeding as a possible vaccination side effect for non-menstruating populations. There are limitations to consider with this study, including its self-report methodology and susceptibility to bias, which warrants further research being undertaken.

The NIPH team emphasize that women experiencing unexpected vaginal bleeding should assess whether to consult a physician, regardless of whether they have been vaccinated. For postmenopausal women, the team advocates seeking a physician’s advice in order to rule out other medical conditions.

Reference: Blix K, Laake I, Juvet L, et al. Unexpected vaginal bleeding and COVID-19 vaccination in nonmenstruating women. Sci Adv. 2023. doi:10.1126/sciadv.adg1391