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Women vaccinated against COVID-19 during the follicular phase of their period had their next cycle last 1 day longer than normal, according to a retrospective cohort analysis of menstrual cycle data.

That increase was 1.00 day (98.75% CI 0.88-1.13) when the first vaccine dose occurred in the follicular phase and 1.11 days (98.75% CI 0.93-1.29) for second doses that fell in that window leading up to ovulation, researchers led by Alison Edelman, MD, MPH, of the Oregon Health & Science University in Portland, reported in .

In this cohort of women not on hormonal contraception, there was no change in cycle length with doses given during the luteal phase, at -0.09 days for the first dose (98.75% CI -0.26 to 0.07) and 0.06 days for the second dose (98.75% CI -0.16 to 0.29), similar to a control group of unvaccinated people who also had no change in cycle length at the time either dose would have been suggested.

Additionally, people vaccinated in their follicular phase were more likely to have a clinically significant change of 8 days or more in their cycle length. This happened for 6.8% of the follicular group but only 3.3% of the luteal and 5% of the unvaccinated groups (P<0.001). Younger people from ages 18 through 29 were also more likely to have changes to their cycle (P<0.001 for both doses).

The follicular phase -- the first half of a menstrual cycle, lasting an average of 13 or 14 days until ovulation -- drives the cycle length and is "the most variable part of the cycle, whereas the luteal phase, which is post ovulation, is usually pretty set," Edelman told 番茄社区app.

Edelman said that this research aids understanding of what contributes to these menstrual cycle changes on a macro level, though more research is needed to understand the micro level of what is happening with the immune system and reproductive system.

"We have a little bit of a better understanding around why this is happening and can provide folks further reassurance about getting vaccinated," Edelman said. "And if they do experience small changes in their menstrual cycle, it's temporary and it'll get back to normal."

The group had previously shown a small increase in menstrual cycle length after COVID-19 vaccination that disappeared by the second cycle post-vaccination and was on par with the impact of COVID-19 infection.

Pamela Berens, MD, an ob/gyn at the McGovern Medical School at UTHealth Houston who was also part of the first wave of research investigating the impact of the COVID-19 vaccine on menstruation although not involved in Edelman's study, told 番茄社区app that the new findings were not surprising.

"It makes sense that a stressor of any particular type would impact [the follicular] phase of the cycle ... because the last 2 weeks of the cycle usually are pretty regulated," Berens said. "And so it makes sense that something that's going to impact the cycle would impact it in the follicular phase."

She noted that the clinical message is unchanged: physicians should encourage patients to get COVID vaccines whenever they are able.

Edelman said that future research could go in several directions, such as looking at the impact of other vaccines on menstrual cycles, long COVID's effect on menstruation, and specifically analyzing data from people with irregular cycles.

In total, 19,497 participants from ages 18 through 45 prospectively logged menstrual cycle data from October 2020 through November 2021 in the app Natural Cycles, which is used to track menstrual cycles to prevent or plan pregnancy without hormonal contraception. Most were younger than 35 (80.1%) and from North America (28.6%), the U.K. (31.7%), or continental Europe (33.5%).

Participants logged COVID-19 vaccines received from January through October 2021, with mRNA vaccines accounting for 63.8%. Analysis included 9,279 individuals who got the vaccine in their follicular phase and 5,532 who received their first dose in the luteal phase. An unvaccinated group of 4,686 women served as controls. To be included, individuals had to be at least three cycles post-pregnancy, post-positive pregnancy test, or post-hormonal contraception use during the whole study period. They also had to have a normal menstrual cycle length (24 to 38 days), have known geographic location, and not be menopausal.

The primary outcome was the adjusted within-individual change in days from their normal cycle, which was the average of three menstrual cycles before vaccination. For the unvaccinated control group, cycles 4 and 5 were considered the notional first and second dose vaccination cycles for comparison. The cycle length for this group was unchanged, at 0.08 days for the first dose (98.75% CI −0.10 to 0.27) and 0.17 days for the second dose (98.75% CI −0.04 to 0.38).

Many of the study's limitations were tied to the data source, authors noted. For instance, Natural Cycles users don't use hormonal contraception and are more likely to be white, living in North America or Europe, well-educated, and have lower BMIs. Plus, the data also couldn't answer the magnitude of an individual's immune response to vaccination. Additionally, the researchers couldn't use this data to account for how SARS-CoV-2 impacts menstruation.

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