Period‑tracking data linked with vaccination records provided insight into how menstrual cycles influence COVID‑19 vaccine responses.
Image credit:© iStock.com, Bat Run
Shortly after COVID‑19 vaccines became available, women reported changes to their menstrual cycles through social media, including heavier bleeding, longer cycles, and increased pain. These anecdotal observations spurred several large‑scale studies and surveys that confirmed such effects.1,2
However, the reverse question—how the menstrual cycle might affect vaccine outcomes—remained unexplored.
Researchers addressed this gap by combining menstrual‑cycle data from a period‑tracking app with COVID‑19 vaccination surveys from 1,474 women. “We could align the dates they received the vaccine with where they were in their cycle,” said Poppy Cooper, a doctoral student in epidemiology and public health at the London School of Hygiene & Tropical Medicine and a co‑author of the study, which appeared in npj Women’s Health.3
Poppy Cooper warns that although the data is promising, it’s not quite time to base vaccine appointments on menstrual cycle phase.
LSHTM
The menstrual cycle lasts roughly 28 days. The investigators defined the luteal phase as the 14 days before menstruation began, with the remaining days constituting the follicular phase. They compared vaccination outcomes between individuals immunized during the follicular phase and those immunized during the luteal phase. Women vaccinated in the follicular phase experienced a 35 % higher odds of reporting common side effects such as injection‑site pain, fatigue, and musculoskeletal aches. Intriguingly, these participants also showed a median 35‑day longer time to infection, hinting at a potentially stronger immune response when vaccination coincides with the follicular phase.
Assessing infection rates after vaccination remains challenging because relatively few vaccinated individuals develop symptomatic infection, limiting statistical power. The researchers noted that only 82 participants experienced infection, which precludes definitive conclusions from that portion of the analysis. “It’s an interesting signal, and we would like to explore it further,” Cooper commented.
A plausible mechanism involves hormonal influences: rising estrogen levels during the follicular phase are known to enhance immune reactivity, whereas progesterone, which peaks in the luteal phase, tends to dampen immune activity. In contrast, progesterone’s immunosuppressive effects may reduce side‑effect frequency. Immunologist Sabra Klein of Johns Hopkins Bloomberg School of Public Health, who was not involved in the study, observed via email that the findings align with her own research indicating that estrogen is linked to stronger vaccine responses in females compared with males. “Their observation fits well with my own research showing that estrogens are associated with greater immune responses to vaccines in females compared with males.”
The team’s first analysis split the cycle into just two phases, a simplification that can mask subtle, day‑to‑day hormonal changes. To address this, Cooper transformed varied cycle lengths onto a common scale divided into 20 segments. This finer‑grained view revealed fluctuations in side‑effect probability within each phase. During the follicular phase, side‑effect likelihood peaked at menstrual onset, dipped near the midpoint, and rose again just before ovulation. After ovulation, side‑effect rates fell, then climbed toward the end of the luteal phase. Neuroscientist and physiologist Dóra Zelena of the University of Pécs, who was not part of the investigation, suggested that a more detailed analysis could improve predictions of side‑effects and immune response, especially with larger sample sizes to boost statistical power. “There are constant changes throughout the entire menstrual cycle that we should take into consideration,” she noted.
Future work aims to integrate hormone and immune biomarkers to pinpoint menstrual‑cycle phases more precisely and to correlate them with immunological outcomes. Cooper emphasized that the current findings are preliminary and that replication in diverse populations is essential. The study’s cohort was largely homogeneous—predominantly white, educated, and affluent U.S. residents—and the data were limited to app users, which may not fully represent the broader population. Nonetheless, Zelena believes these limitations are unlikely to overturn the main conclusions. “It’s still a solid proof of concept,” she added in an email.
Beyond the immediate implications for vaccination timing, Cooper views the research as part of a growing appreciation for hormonal effects on health. “The menstrual cycle has traditionally been ignored or treated as background noise,” she said. “This study demonstrates that it is an important variable to consider in biomedical research.”
