Pharmacokinetics of Metoprolol in Cisgender Males, Cisgender Females, and Transgender Women Receiving Gender-Affirming Hormone Therapy: An Exploratory Pilot Study

1. This exploratory pilot study aimed to characterize metoprolol pharmacokinetics and assess the feasibility of pharmacokinetic sampling among cisgender males, cisgender females, and transgender women receiving gender-affirming hormone therapy.2. Nine healthy volunteers (three per group) received a single 100 mg oral dose of metoprolol, and serial blood samples were collected over 12 hours. Plasma metoprolol concentrations were determined using HPLC and analyzed by a non-compartment model. CYP2D6 genotyping or phenotyping was not performed; therefore, the analysis was descriptive and hypothesis-generating.3. Descriptively, mean area under the concentration-time curve values were 2550 ± 126 ng·h/mL in cisgender males, 2142 ± 463 ng·h/mL in cisgender females, and 1522 ± 189 ng·h/mL in transgender participants. Mean peak plasma concentrations were 418 ± 43, 363 ± 58, and 269 ± 27 ng/mL, respectively. The corresponding elimination rates were 0.139, 0.140, and 0.268 h−1, and mean half-lives were 4.98, 4.92, and 2.58 h, respectively.4. The observed profiles suggest between-participant variability that warrants further investigation; however, three participants per group cannot represent the respective populations, and the findings cannot be attributed to sex, gender, or hormone therapy without CYP2D6 genotype data. Larger, genotype-stratified studies with detailed hormone and body-composition measurements are required.