Gender-Affirming Hormone Therapy: Pharmacokinetic Considerations for Oncology in Transgender Patients

Gender-Affirming Hormone Therapy (GAHT) is a cornerstone of transgender care which induces profound physiological changes and significantly impacts pharmacokinetics and drug dosing strategies. This narrative review examines the clinical implications of GAHT, with a particular focus on renal function parameters, biomarkers, and challenges in the oncological setting. Evidence shows that GAHT considerably alters body composition, muscle mass and serum creatinine levels, resulting in fluctuations of standard calculations of creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR). Unfortunately, standardized dosing formulas remain unvalidated in transgender populations, although gender identity should guide renal function estimates and advocate for cautious interpretation and case-by-case assessment. Recent studies underscore the relevance of emerging biomarkers, such as cystatin C, as possible solutions for assessing renal function in transgender patients, since they are less influenced by body mass. Moreover, direct effects of exogenous hormones on renal physiology have also been highlighted, stressing the importance of thorough evaluation of all these factors, in order to ensure the accuracy of dosing algorithms based on gender-affirming hormones. This issue becomes especially important in oncology, considering that improper use of antineoplastic agents may result in under or overdosing, especially for renally excreted or narrow therapeutic index drugs. Overall, this review aims to represent a resounding prompt to a multidisciplinary team of clinicians, pharmacists and pharmacologists that should play a crucial role in implementing safe, evidence-based, and respectful individualized care pathways, particularly in complex clinical scenarios such as oncology.