Covid-19 vaccination and menstrual cycle length in the Apple Women’s Health Study

Abstract

Background: COVID-19 vaccination may be associated with change in menstrual cycle length following vaccination. Methods: We conducted a longitudinal analysis within a subgroup of 14,915 participants in the Apple Womens Health Study (AWHS) who enrolled between November 2019 and December 2021 and met the following eligibility criteria: were living in the U.S., met minimum age requirements for consent, were English speaking, actively tracked their menstrual cycles, and responded to the COVID-19 Vaccine Update survey. In the main analysis, we included tracked cycles recorded when premenopausal participants were not pregnant, lactating, or using hormonal contraceptives. We used conditional linear regression and multivariable linear mixed-effects models with random intercepts to estimate the covariate-adjusted difference in mean cycle length, measured in days, between pre-vaccination cycles, cycles in which a vaccine was administered, and post-vaccination cycles within vaccinated participants, and between vaccinated and unvaccinated participants. We further compared associations between vaccination and menstrual cycle length by the timing of vaccine dose within a menstrual cycle (i.e., in follicular or luteal phase). We present Bonferroni-adjusted 95% confidence intervals to account for multiple comparisons. Results: A total of 128,094 cycles (median = 10 cycles per participant; interquartile range: 4-22) from 9,652 participants (8,486 vaccinated; 1,166 unvaccinated) were included. The average within-individual standard deviation in cycle length was 4.2 days. Fifty-five percent of vaccinated participants received Pfizer-BioNTechs mRNA vaccine, 37% received Modernas mRNA vaccine, and 7% received the Johnson & Johnson/Janssen vaccine (J&J). We found no evidence of a difference between mean menstrual cycle length in the unvaccinated and vaccinated participants prior to vaccination (0.24 days, 95% CI: -0.34, 0.82). Among vaccinated participants, COVID-19 vaccination was associated with a small increase in mean cycle length (MCL) for cycles in which participants received the first dose (0.50 days, 95% CI: 0.22, 0.78) and cycles in which participants received the second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared with pre-vaccination cycles. Cycles in which the single dose of J&J was administered were, on average, 1.26 days longer (95% CI: 0.45, 2.07) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length. Estimates for pre vs post cycle lengths were 0.14 days (95% CI: -0.13, 0.40) in the first cycle following vaccination, 0.13 days (95% CI: -0.14, 0.40) in the second, -0.17 days (95% CI: -0.43, 0.10) in the third, and -0.25 days (95% CI: -0.52, 0.01) in the fourth cycle post-vaccination. Follicular phase vaccination was associated with an increase in MCL in cycles in which participants received the first dose (0.97 days, 95% CI: 0.53, 1.42) or the second dose (1.43 days, 95% CI: 1.06, 1.80) of mRNA vaccines or the J&J dose (2.27 days, 95% CI: 1.04, 3.50), compared with pre-vaccination cycles. Conclusions:COVID-19 vaccination was associated with an immediate short-term increase in menstrual cycle length overall, which appeared to be driven by doses received in the follicular phase. However, the magnitude of this increase was small and diminished in each cycle following vaccination. No association with cycle length persisted over time. The magnitude of change associated with vaccination was well within the natural variability in the study population. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated.

Covid-19 vaccines and menstrual changes

“…Other studies have shown that the mean cycle length was increased for women vaccinated during the follicular phase, whereas no change was found if women were vaccinated during the luteal phase. 16 These findings agree with the results of Edelman and colleagues' study because two vaccinations given during one cycle suggest that one was given during the follicular phase. Analyses of menses lengths showed a small but significant mean difference in change of 0.13 days (0.06 to 0.20) after the second dose, however, this result is mainly explained by shorter menses lengths of the women who were not vaccinated.…”

Uncommon Side Effects of COVID-19 Vaccination in the Pediatric Population

“…These changes in the menstrual cycle were noted to be transient. The changes in cycle length did not persist over time [ 22 ]. Historically, about 75% of adolescents were affected by menstruation disorders years before COVID-19 and its vaccines [ 23 ].…”

Does side effects of COVID-19 vaccination include changes in menstrual cycle or its associated pre- and post-menstrual symptoms in reproductive-age women: A Multi-centric Observational study in India.

“…It was concluded that COVID-19 vaccination was associated with an immediate short-term increase in menstrual cycle length. 22 Very few studies have been conducted to know the impact of COVID-19 vaccination on pre-and postmenstrual symptoms. A recent questionnaire-based study compared menstruation characteristics (regularity, volume, intermenstrual bleeding, and dysmenorrhea) before and after receiving the COVID-19 vaccine in Saudi Arabia and reported a significant impact of COVID-19 vaccination on menstrual disturbances.…”