App-based research published in npj Women’s Health suggests that the timing of COVID-19 vaccination within the menstrual cycle may influence self-reported side effects, according to a study released on Jun. 8.
Researchers analyzed data from 1,474 users of Clue, a period-tracking application, matching logged menstrual data with participants’ self-reported vaccine experiences. The study found that individuals vaccinated during the estrogen-dominant follicular phase had 35% higher odds of reporting any side effects compared to those vaccinated during the progesterone-dominant luteal phase.
The findings also indicated a longer median time to breakthrough infection among those vaccinated in the follicular phase. However, this observation was considered exploratory due to limited statistical power and should be interpreted as hypothesis-generating rather than confirmatory.
Participants were classified into two groups based on their estimated menstrual phase at vaccination: follicular-phase (760 participants) and luteal-phase (714 participants). Multivariable regression models adjusted for age, body mass index, smoking status, and pre-existing medical conditions showed that 75.9% of follicular-phase recipients reported side effects versus 70.3% in the luteal group. Younger participants aged 18 to 24 exhibited an even stronger association between vaccination timing and reported side effects.
The study did not find statistically significant differences between phases regarding severity or total number of reported side effects. Limitations included reliance on calendar-based estimates rather than direct hormonal biomarkers, self-reported outcomes subject to recall bias, and a self-selected sample from app users.
Authors say these preliminary results highlight a need for further research into how cyclical hormonal fluctuations might affect vaccine reactogenicity and clinical protection.
