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Women who were immunized against COVID-19 experienced a slight, but non-significant, change in the length of their menstrual cycle compared with those who were unvaccinated, according to a retrospective cohort analysis.

Patients experienced less than 1-day increases in cycle length after their first (0.71 day increase, 98.75% CI 0.47-0.94) and second (0.91-day increase, 98.75% CI 0.63-1.19) shots compared with the 3 months before they got the vaccine, reported Alison Edelman, MD, MPH, of Oregon Health & Science University in Portland.

Unvaccinated patients did not experience any significant change in cycle length over the course of the study. The length of menses was unchanged in both groups, the authors noted in .

In adjusted models, patients who received one vaccine dose had a 0.64-day increase in their menstrual cycles (98.75% CI 0.27-1.01) and those who received a second dose had a 0.79-day increase (98.75% CI 0.40-1.18) compared with unvaccinated patients.

Additionally, after adjustment, all women with a regular cycle experienced variations in the length of their menstrual cycle, despite vaccination status, Edelman and colleagues noted. While statistically significant differences existed between vaccinated and unvaccinated groups, they said the 1-day difference was "not clinically significant."

"Our findings are reassuring," they wrote. "We find no population-level clinically meaningful change in menstrual cycle length associated with COVID-19 vaccination."

Edelman and colleagues noted that the slight increase in cycle length among the vaccinated cohort appeared to be driven by patients who received two doses in a single menstrual cycle. This cohort experienced about a 2-day increase in the length of their cycles (2.32 days, 98.75% CI 1.59-3.04) compared with unvaccinated patients.

The proportion of people who experienced a clinically meaningful change in menstrual cycle length (8 days or more) did not significantly differ between the vaccinated and unvaccinated cohorts (4.3% for unvaccinated vs 5.2% for vaccinated, P=0.181).

Menstrual cycle changes are likely to occur throughout the life-course, explained Taraneh Shirazian, MD, of NYU Langone Health in New York City, who was not involved in this study. While there was a slight difference between the two groups, she told 麻豆传媒 that it was not surprising nor significant.

"Menstrual cycling can often be irregular," Shirazian noted. As women age, the length of their cycle, duration of menses, and changes in blood color or flow are all expected, she added.

Timing of the menstrual cycle is regulated by the hypothalamic-pituitary-ovarian axis, Edelman's group explained. Stressors such as undergoing a surgery, getting sick, or starting a new medication may all affect how periods are regulated, even if only for a short time. The COVID-19 mRNA vaccines, which induce an immune response, may throw off that axis.

For this study, the authors compared within-individual cycle changes between vaccinated and unvaccinated patients ages 18 to 45 who had a regular cycle, and had at least three cycles since being pregnant or using hormonal contraception. They analyzed data that were collected from Natural Cycles, a digital fertility tracker, from October 2020 to September 2021.

Each patient contributed information on six menstrual cycles. Among the patients who received a COVID-19 vaccine, three pre-vaccine and three post-vaccine cycles were analyzed. Patients who were in menopause or those who received a vaccine that was not approved in the U.S. were excluded from the analysis. The researchers also controlled for confounders including age, race/ethnicity, parity, BMI, education status, and relationship status.

Nearly 4,000 women were included in the study, 60% of whom were vaccinated; 55% received the Pfizer/BioNTech vaccine, 35% received Moderna, and 7% received Johnson & Johnson. The vaccinated cohort was more likely to be older, white, nulliparous, college-educated, and reside in the Northeast or the West.

Edelman and colleagues noted that these findings may not be generalizable to the broader U.S. population because the study exclusively included Natural Cycles users, who are more likely to be white and college-educated. Additionally, they chose only to analyze people who have a consistent, regular cycle length, and not all individuals fit into this category.

While people who received a two-dose vaccine regimen returned to a baseline cycle quickly, these data did not include enough subsequent cycles to investigate this fully, they noted.

Shirazian said the study data will be useful in patient counseling, as it can show patients that they might experience changes in their cycle after vaccination, but that those changes will be small and temporary.

"I think acknowledgment is key," Shirazian said.

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