Phase 1 clinical drug trials critically depend on the participation of
healthy volunteers to evaluate the safety and pharmacokinetics of new
medicinal products. Current selection criteria and health definitions
often overlook the unique health profiles of transgender and nonbinary
individuals, potentially excluding them from participating in these
essential early-stage studies. This review aims to identify and discuss
current knowledge gaps and considerations regarding the inclusion of
transgender and nonbinary participants in Phase 1 clinical drug trials.
We highlight the need for research on how gender-affirming hormone
therapy may affect drug pharmacokinetics and call for the development of
inclusive biological reference ranges that account for the physiological
effects of hormone therapies.