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

The impact of COVID-19 vaccination on menstrual characteristics is a topic of emerging interest. While some studies have reported temporary increases in menstrual cycle length, heavier bleeding, and other irregularities following vaccination, the extent and duration of these effects remain unclear. Anecdotal reports from systems like VAERS (US) and the MHRA Yellow Card scheme (UK) showed numerous self-reported menstrual issues following vaccination. Although COVID-19 vaccination is largely considered safe and there’s no evidence of fertility impacts, understanding potential temporary menstrual changes is crucial for patient counseling. This study leverages the Apple Women’s Health Study (AWHS), a longitudinal cohort with manually logged menstrual cycles, to rigorously evaluate the relationship between COVID-19 vaccination and menstrual cycle length over time, comparing pre-vaccination, vaccination, and post-vaccination cycles.

Prior research on the effects of COVID-19 vaccination on menstrual cycles has yielded mixed results, with some studies reporting temporary changes such as increased cycle length, heavier bleeding, and irregularities. However, many of these studies have been limited by sample size or methodology. The existing literature includes both observational studies and anecdotal evidence from adverse event reporting systems, highlighting the need for larger, more robust studies to clarify the nature of these potential associations. There is also debate around potential mechanisms, including the inflammatory response to vaccination and its impact on the hypothalamic-pituitary-ovarian (HPO) axis.

This prospective cohort study used data from the Apple Women’s Health Study (AWHS), a large digital cohort of U.S. participants who self-reported menstrual cycles. The study included 9652 participants (8486 vaccinated), contributing 128,904 cycles. Participants logged their menstrual cycle data via the Apple Health app or compatible third-party apps. The study analyzed cycle length differences between pre-vaccination, vaccination (first and second mRNA doses, single J&J dose), and post-vaccination cycles. Statistical analyses, using conditional linear regression with subject-level fixed effects and logistic regression, accounted for participant characteristics, including age, BMI, race/ethnicity, parity, and seasonal variations. Sensitivity analyses were conducted to assess robustness, including restricting analysis to participants with three or more cycles and controlling for various confounding factors. Vaccination timing within the menstrual cycle (follicular vs. luteal phase) was also analyzed to investigate potential phase-specific effects.

COVID-19 vaccination was associated with a small increase in mean menstrual cycle length. The increase was observed in cycles where participants received the first dose (0.50 days, 95% CI: 0.21, 0.78) and second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared to pre-vaccination cycles. The effect was more pronounced for the J&J vaccine (1.26 days longer, 95% CI: 0.45, 2.07). Post-vaccination cycles returned to pre-vaccination lengths. Vaccination in the follicular phase was associated with a larger increase in cycle length compared to vaccination in the luteal phase. The study also found a significant increase in the probability of a long cycle (≥38 days) following vaccination, but this effect was not persistent. Sensitivity analyses generally supported the main findings, although some variations were observed when including cycles with two doses in a single cycle or focusing on cycles between doses.

The findings suggest a small, transient increase in menstrual cycle length following COVID-19 vaccination, particularly when the dose was administered during the follicular phase. This increase likely falls within the range of normal individual variability. The observed effects were relatively minor and temporary, suggesting that they are unlikely to be clinically significant. Potential mechanisms include the inflammatory response to vaccination influencing HPO axis function. The study’s results align with some prior findings of small increases in cycle length following vaccination. The study highlights the importance of considering vaccination timing within the menstrual cycle when investigating these associations.

This large-scale study provides evidence of a small and temporary increase in menstrual cycle length following COVID-19 vaccination. The effect appears to be driven by vaccination during the follicular phase and is within the range of normal individual variation. These findings support the safety and efficacy of COVID-19 vaccines and should not deter individuals from vaccination. Future studies could investigate underlying biological mechanisms and explore potential differences in response across diverse subpopulations.

The study relies on self-reported menstrual cycle data, which may be subject to recall bias or variations in tracking consistency. The study population is limited to iPhone users in the U.S., potentially limiting the generalizability of the results. The lack of hormonal measurements prevents a more detailed investigation of the underlying physiological mechanisms. The study did not account for potential interactions between COVID-19 infection and vaccination.