Jerilynn C. Prior, MD, FRCPC

The question whether unexpected uterine bleeding relates to having recently been vaccinated for COVID-19 continues to be of intense interest. Early in 2020, as the first SARS-CoV-2 mRNA vaccines became available to more than older adults or the immunocompromised, social media and individual conversations exploded with women reporting changes in their periods. The COVID-19 vaccination association with unexpectedly early menstruation has now been further answered by this systematic review of data from the full-dimension outpatient and hospital Kaiser Permanente records in over 79,000 menstruating-aged women.

As a busy website with an “Ask Us” service, the Centre for Menstrual Cycle and Ovulation Research (www.cemcor.ubc.ca), received many posts in 2020. As the scientific director and an endocrinology clinician-scientist focusing on women’s reproduction, I responded to these many reports and urgent questions. Most women reported that, within 5 days following their first vaccination, they unexpectedly began spotting or bleeding. This was often a week or more before they expected their period. Those who were adolescents or in their 40s were also more likely to describe the unexpected flow as being heavy with clots, flooding and sometimes anemia development. As I reviewed all of these and explored the literature, I posted this on the Centre for Menstrual Cycle and Ovulation Research website: www.cemcor.ubc.ca/resources/menstrual-flow-and-timing-changes-following-covid-19-infection-or-vaccination.

I tried to reassure these women. Following the immediate flurry, I also wanted to get an idea from all these inquirers about whether they recovered their usual cycles after that episode. All of those from whom I got a further response reported that they did.

In trying to understand what was occurring, I sought literature evidence for previous vaccine associations with unexpected flow. I didn’t find any. Then I realized that all the reproductive-aged women tested in the vaccine trials would have been required to be using reliable hormonal contraception. Combined hormonal contraception or a progestin-releasing IUD would have prevented early flow; thus, vaccine trial data would be unhelpful.

In my search, I discovered something I had not previously realized — menstrual-type bleeding can be triggered by major stress. There are direct uterine-lining inputs from stress hormones (Cannon W, et al. Am J Physiol. 1914;doi:10.1152/ajplegacy.1914.34.2.225). The best clinical evidence came from a report of young women who, while demonstrating in the Black Lives Matter protests on the streets of Portland, had been tear-gassed or pepper-sprayed (Torgrimson-Ojerio B, et al. BMC Public Health. 2021;doi:10.1186/s12889-021-10859-w). The startling early bleeding they experienced occurred 3 to 5 days after that distressing experience — a striking resemblance to what women reported following receiving the new COVID-19 mRNA vaccines.

The recent Kaiser study reported unchanged menstrual flow. They found no increase in unexpected menstrual bleeding from the nine to 19 per 100,000 woman-days that had been reported before COVID or in more than 60 days after vaccination. However, other studies showed a 13% to 30% increase in unexpectedly early or heavy menstrual-like flow. The women who were menopausal in one Norwegian survey reported a doubling of menopausal bleeding (Blix K, et al. Sci Adv. 2023;doi:10.1126/sciadv.adg1391). When that was reported to me by one menopausal woman, I told her that she really needed to have an endometrial biopsy. She reported back to me with gratitude that her biopsy showed early endometrial cancer from which she was cured following hysterectomy. A Canadian study also reported that perimenopause or menopausal women reported an increase in vasomotor symptoms (Garcia de Leon R, et al. Womens Health (Lond) 2023;doi:10.1177/17455057231199051); that is consistent with the important role of elevated stress hormones in hot flash and night sweat experiences (Fan Y, et al. Drug Disc Today: Disease Models 2020;doi:10.1016/j.ddmod.2020.11.004 and Freedman RR, et al. J Steroid Biochem Mol Biol. 2014;doi:10.1016/j.jsbmb.2013.08.010).

I have no doubt that the Kaiser medical record study and the online or mobile phone surveys are accurate. I believe what women say. The Kaiser data did not show a significant increase because most women would not have gone to see a doctor with their unexpectedly early periods, especially during the pandemic when health care systems were overwhelmed, and an ED visit involved an increased COVID-19 risk. Only a few with very heavy flow would have visited a doctor or an ED.

But women reported an increase in early unexpected flow and often reported they felt it was associated with COVID-related stressors. The common etiology for unexpected early flow likely further depended on three things: a natural cycle without combined hormonal contraception or hormone-eluting IUD use; a menstrual cycle that was not normally ovulatory, thus the endometrium would be more fragile, which is plausible since 24% to 37% of normal-length cycles in the population are ovulation disturbed (Prior JC, et al. PLOS One. 2015;doi:10.1371/journal.pone.0134473); and an important increase in psychosocial or situational stress. I recall my first vaccination — I had to take time from work, figure out transit to a large building I’d never seen before, line up with masked people I didn’t know, follow all kinds of processes and procedures to eventually end up getting a somewhat mysterious and unknown injection that I really hoped would protect me from a deadly health threat.