PROJECT SUMMARY Regular menstruation is considered an indicator of whole-body health, and subtle changes in health can lead to noticeable fluctuations in the regular cycle. The large roll-out of COVID-19 vaccine was accompanied by anecdotal evidence that suggested that those who menstruate experienced changes in the menstrual cycle with some reporting unexpected spotting or heavier and/or longer cycles. Unfortunately, the initial clinical trials for the Pfizer, Moderna, and Johnson and Johnson vaccines did not follow up on possible menstrual cycle changes. The first aim of our project is to assess the clinical effects of the COVID-19 vaccination on the menstrual cycle using data from participants in our ongoing clinical trial who document their menstrual cycle using a menstrual diary. We will expand recruitment through a national, digital campaign: www.covidmenses.org. Data reported in the popular Period-Tracking App “Clue” will also be used to assess the clinical effects. The second aim will focus on the mechanisms of COVID-19 vaccines' effects on the menstrual cycle through assessing endometrial changes associated with vaccination. This will be done by comparing the immune cell profile at the level of the endometrium before and after vaccination as well as evaluating the expression of cytokines, chemokines and extracellular degradation mediators. The successful completion of this project will provide evidence on the effect of COVID-19 vaccination on menstrual health. This can reduce vaccine anxiety and hesitancy among those who menstruate.