A scoping review of imatinib-induced testicular toxicity and male fertility impairment

• Published in: Frontiers in Endocrinology
• Main Authors: Xia Ji, Mohd Faizal Ahmad, Mohd Helmy Mokhtar, XiaoYing He, Abdul Kadir Abdul Karim
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2026-05-01
• Subjects: fertility preservation; imatinib mesylate; spermatogenesis; testicular diseases; testis/drug effects
• Online Access: https://www.frontiersin.org/articles/10.3389/fendo.2026.1811653/full

BackgroundImatinib, the first-generation tyrosine kinase inhibitor (TKI), has been widely adopted as frontline therapy for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Growing evidence indicates potential gonadotoxic effects, raising concerns about its long-term impact on male fertility.ObjectiveThis scoping review was undertaken to synthesize preclinical and clinical evidence on imatinib-induced reproductive toxicity in males, with emphasis on mechanisms, dose- and age-dependent susceptibility, and reversibility of testicular injury.MethodsA comprehensive literature search was conducted in PubMed, Scopus, and Web of Science following PRISMA-ScR guidelines. Twenty studies published between 2003 and 2025 were included.ResultsAcross animal and human studies, inhibition of Proto-oncogene c-KIT (c-KIT) and Platelet-Derived Growth Factor Receptor (PDGFR) signaling was consistently observed, leading to germ cell apoptosis, impaired spermatogonial proliferation, and disruption of the blood–testis barrier (BTB). Dose-dependent reductions in testosterone and sperm density were documented, with partial recovery after drug discontinuation in several models. However, neonatal exposure was more often associated with persistent or irreversible testicular damage.ConclusionImatinib exerts gonadotoxic effects through inhibition of c-KIT/PDGFR signaling, disruption of the BTB, and dysregulation of the hypothalamic–pituitary–gonadal axis in a dose- and age-dependent manner. Although partial recovery is possible after withdrawal, neonatal and prepubertal exposures carry a high risk of irreversible impairment. These findings highlight the need for systematic fertility counseling and preservation in adolescent and reproductive-age males, in line with the 2025 European LeukemiaNet (ELN) recommendations.