PROJECT SUMMARY/ABSTRACT Despite prevalent anecdotal reports, the impact of SARS-CoV-2 infection or vaccination on menorrhagia and menstrual regularity remains largely undocumented and unstudied. COVID-19 disease has impacted millions, while stay-at-home orders and heightened stress have impacted billions. Menorrhagia, menstrual irregularity, and chronic pelvic pain (with or without endometriosis) are known to increase in severity when challenged with stress, unraveling of personal coping mechanisms, or diminished access to healthcare ? all of which occurred during the COVID-19 pandemic. To successfully assess changes in menstrual and gynecologic characteristics attributable to SARS-CoV-2 infection or vaccination, it is critical to compare post-infection or post-vaccination menstruation and pelvic symptoms to that person?s pre-exposure menstruation and also to compare menstruation among those who have been infected or vaccinated to those who have not, accounting for pandemic impacts that may vary by individual social or economic frailty and mental health. Answering these critical questions with scientific rigor in existing research cohort populations is responsive to Notice of Special Interest (NOSI) to Encourage Administrative Supplement Applications to Investigate COVID-19 Vaccination and Menstruation (NOT-HD-21-035). We will utilize an ongoing prospective study, the Women?s Health Study: from Adolescence to Adulthood (A2A, N=1569) - the core cohort included in the Parent R01 (HD094842). Cohort participants have completed annual questionnaires since enrollment began in 2012, which includes assessment of menstrual characteristics. Leveraging this cohort to compare and contrast prospectively collected pre-, peri-, and post-pandemic characteristics and inflammatory markers, we will test these hypotheses: a) SARS-CoV-2 infection is associated with incident or worsened menorrhagia, menstrual irregularity or pelvic pain compared to pre-pandemic and pre-infection menstrual characteristics within individual women, and compared to women who have not been infected; b) SARS-CoV-2 vaccination is associated with incident or worsened menorrhagia, menstrual irregularity or pelvic pain, as has been reported anecdotally, compared to pre-vaccination menstrual characteristics within individuals, and compared to unvaccinated women; and c) Increase in COVID-19 pandemic-related distress (e.g. depression, anxiety, social isolation, economic peril) and diminished healthy coping will be associated with incident or increased severity of menorrhagia, menstrual cycle irregularity, or chronic pelvic pain ? independent of SARS-CoV-2 infection or vaccination. While many are scrambling to assemble research teams and establish de novo human data and sample collection, which will yield uncertain deliverables, small samples sizes, and often reliance on fully de-identified samples from which confounding and modification cannot be validly assessed, the proposed study capitalizes on well-established resources providing cost and time efficiency as well as scientifically robust opportunity.