Project Summary/Abstract Menstrual characteristics can provide critical information about women’s overall health and well-being. Yet, recent clinical trials for the COVID-19 vaccine failed to gather this information. This is particularly relevant, as anecdotal reports have suggested that the COVID-19 vaccine may be affecting menstrual patterns and characteristics. Additionally, potential mechanisms underlying this relationship, such as inflammatory responses or stress, have not been identified. The overarching objective of this administrative supplement, “COVID19 Vaccination and Menstruation,” is to evaluate the relationship between administration of the COVID- 19 vaccine and menstrual health (i.e., cycle length, duration of bleeding, spotting between periods, menstrual flow, and menstrual pain) in a sample of 80 healthy adolescent girls (ages 14-18 years; estimated n=64 who will receive the vaccine, and n=16 who will not receive the vaccine and serve as the control group) with varying levels of menstrual pain who are not using any exogenous hormones. This objective will be achieved through the following specific aims: 1) characterize the relationship between the COVID-19 vaccine and inflammation, after adjusting for effects of potential confounders (e.g., levels of estradiol/progesterone and stress); 2) identify the impact of inflammatory markers on measures of menstrual health, after adjusting for effects of potential confounders (e.g., levels of estradiol/progesterone and stress); and 3) determine if the COVID-19 vaccine is associated with changes in menstrual health via changes in inflammation, after adjusting for effects of potential confounders (e.g., levels of estradiol/progesterone and stress). As part of the parent study, participants provide baseline levels of menstrual health data and are assessed monthly to characterize menstrual health (cycle length, menstrual pain, duration of menstruation, flow, and spotting between periods). Participation in this supplement will include obtaining measures of stress and saliva to assess for ovarian hormones, pro-inflammatory cytokines, and SARS-CoV-2 antibodies at 10 different time points (pre-vaccine, 24h post-vaccine, 48h post-vaccine, 14 days post-vaccine, and 28 days post-vaccine; repeated after 2nd dose of either Moderna or Pfizer-BioNTech vaccines, or repeated without a second dose if receiving the Johnson & Johnson vaccine). The control group will provide data on the identical timeline. These results are expected to determine whether a relationship between the COVID-19 vaccine and changes in menstrual health exist, and if so, elucidate possible inflammatory mechanisms underlying this relationship. Findings from the study will help characterize potential side effects of the COVID-19, thus reducing health disparities among reproductive-age girls and women.