Endocrine Abstracts

Introduction: Tumors in adolescents and young adults are on the rise, and the number of young cancer patients undergoing chronic treatment with targeted therapy is growing. Although much is known about the toxicity of conventional anti-cancer therapies, evidence on tyrosine kinase inhibitor (TKI) effects on fertility is still lacking. This systematic review was undertaken to evaluate the effects of TKIs on male gonadal function to provide adequate counseling to patients undergoing these therapies.

Methods: A comprehensive search of PubMed and Scopus databases was conducted, focusing on the effects of TKIs on spermatogenesis and testicular endocrine function. We included animal studies, observational studies, and case reports published up to December 31, 2023. The identified articles were reviewed and analyzed to evaluate the impact of TKIs on the male gonad, their long-term effects, the reversibility of the observed changes, and the underlying molecular mechanisms involved.

Results: Imatinib, gefitinib, sorafenib, sunitinib, quizartinib, dasatinib, and nilotinib appear to damage spermatogenesis, decreasing sperm count and motility. Mechanisms involved include interference with the KIT system, PI3K, and ERK kinase, affecting spermatogonia maturation and survival. Furthermore, TKIs alter the function of the hypothalamic-pituitary-testicular axis, decreasing serum gonadotropins and testosterone levels. Finally, TKIs appear to have a direct impact on testicular tissue, compromising testicular function and therefore spermatogenesis. However, the extent and severity of these effects may vary between patients and within this class of drugs.

Conclusion: TKIs appear to damage spermatogenesis. Understanding the molecular mechanisms of TKI effects on male reproductive health is essential to providing adequate fertility counseling and managing hormonal imbalances. The paucity of available studies on this topic indicates the need for further research. However, based on these results, we suggest that healthcare providers should discuss the potential impact of this type of treatment on testicular hormone production and fertility and consider sperm cryopreservation to optimize the quality of life of patients recovering from cancer.