Scoping review examines imatinib gonadotoxicity in males with chronic myeloid leukemia or gastrointestinal stromal tumors

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Frontiers in Medicine Published May 15, 2026 Medically reviewed May 15, 2026 Study authors: Xia Ji, Mohd Faizal Ahmad, Mohd Helmy Mokhtar, XiaoYing He, Abdul Kadir Abdul Karim DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider fertility counseling for adolescent males receiving imatinib for chronic myeloid leukemia or gastrointestinal stromal tumors.

This scoping review evaluates the gonadotoxic potential of imatinib in males diagnosed with chronic myeloid leukemia or gastrointestinal stromal tumors. The analysis encompasses twenty studies that collectively describe the biological mechanisms and clinical consequences of the medication on male reproductive health. No specific numerical data or pooled effect sizes were reported in the source material.

The review details how imatinib inhibits Proto-oncogene c-KIT and Platelet-Derived Growth Factor Receptor signaling. This inhibition leads to germ cell apoptosis, impaired spermatogonial proliferation, and disruption of the blood-testis barrier. Consequently, dose-dependent reductions in testosterone and sperm density are observed. The authors also highlight that neonatal exposure can result in persistent or irreversible testicular damage.

Recovery of reproductive function after drug discontinuation is described as partial. The review underscores that these effects occur in a dose- and age-dependent manner. The authors conclude that systematic fertility counseling and preservation are necessary for adolescent and reproductive-age males. These recommendations align with the 2025 European LeukemiaNet guidelines. The review does not report specific adverse event rates or discontinuation frequencies.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Imatinib, 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. This 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. A 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. Across 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. Imatinib 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.