A systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility

Abstract

Long-term cancer treatment complications in men include testicular dysfunction and infertility. Although various chemotherapies have been studied, there is limited evidence on their effects, especially for bleomycin. Despite its known lung toxicity, bleomycin’s impact on male reproductive health is not well-researched. This systematic review aimed to evaluate bleomycin’s effects on testicular function and fertility. A search of PubMed and Web of Science identified seven relevant animal studies on bleomycin's gonadotoxicity. The research, limited to animal models, shows that bleomycin significantly disrupts male reproductive health, including DNA damage in sperm, analogous to its effects on cancer cells, and notable histopathological changes in rodent testes. It reduces sperm quality and testosterone levels, correlating with Leydig cell degeneration and inflammatory responses, which further aligns with the drug’s known capacity to induce lung inflammation. Due to the inherent limitations in extrapolating results from rodents to humans, further research, particularly in humans, is needed to confirm these findings, assess hormonal impacts, temporal patterns of effects (whether transient or permanent), and their impacts implications for offspring, as well explore potential mitigation strategies. These findings are a first step in raising awareness among clinicians about bleomycin's fertility risks and developing strategies for fertility preservation.