PROJECT SUMMARY/ABSTRACT The goal of this proposal is to expand and extend the ongoing longitudinal Study of Transition, Outcomes & Gender (STRONG), which is a cohort of transgender people identified from the electronic medical records of three large integrated health care systems: Kaiser Permanente Georgia, Kaiser Permanente Southern California, and Kaiser Permanente Northern California. The study now includes 6,459 members with an index date (first evidence of transgender status) from 2006 through 2014. The transgender cohort is matched on year of birth, race/ethnicity, site, and membership year at initial presentation (index date) with up to 10 male and 10 female non-transgender enrollees. To-date cohort follow up extends through the end of 2016. The STRONG cohort has already provided a number of new findings that will inform clinical practice. We found that estrogen use is associated with several-fold increase in risk for venous thromboembolism and ischemic stroke among transfeminine cohort members. We also found a much higher prevalence of psychiatric polypharmacy and higher incidence of suicide attempts among transgender participants compared to matched controls. Despite the importance of these results, many analyses were not feasible due to sparse treatment- specific strata and the need for longer follow up. It is unclear if the observed associations can be explained by a specific route of administration, dosage, or drug combinations. In addition, the STRONG cohort offers an opportunity to characterize the distributions of a wide range of clinical health indicators and laboratory measures among transgender people, which may help with the development of relevant reference ranges in these population. In this application, we propose 1) including additional subjects at existing sites identified through 2024, 2) adding a new site at Kaiser Permanente Mid-Atlantic States to increase geographic and demographic diversity of the cohort, and 3) extending follow up through 2025. The final cohort will include as many as 30,000 members matched to 600,000 referents. The methods of data collection described in the current application have been successfully implemented previously. The new project will address three areas of importance: 1) occurrence of acute cardiovascular events in relation to various aspects of hormone therapy; 2) changes in mental health status and incidence of suicide attempts among transgender people; and 3) metabolic and hematologic consequences of cross-sex hormone therapy. The project will be carried out by a team that includes experts in transgender health, electronic record-based data collection, s epidemiology and specifically pharmacoepidemiology methods, advanced longitudinal data analyses, mental health, cardiovascular disease, neuroscience and endocrinology.

PROJECT NARRATIVE The purpose of this study is to determine whether transgender people have higher or lower risk of certain diseases than men and women in the general population. Many transgender people require extensive treatment of hormones. The study will also compare results of different hormone treatments with regards to complications and other health problems.