Beyond bleomycin-induced pulmonary toxicity, its male reproductive
toxicity remains unanswered 50 years after its approval
Aim: Cancer treatment long-term complications for men include testicular
dysfunction and possible infertility. Nonetheless, the evidence for this
risk for various chemotherapies is insufficient. This is the case with
bleomycin, which, aside from its well-studied lung toxicity, has
received little research attention for its effect on male reproduction.
This systematic review sought evidence for the effects of
bleomycin-cancer treatment on testicular function and fertility.
Methods: PubMed and Web of Science were searched using specific search
terms, and seven animal studies met all inclusion criteria and provided
an analysis of bleomycin gonadotoxicity. Results: Overall, the results
suggest that bleomycin is gonadotoxic. It has the same effect on the
nuclear DNA integrity of rodent sperm as it does on cancer cells.
Bleomycin-induced changes in rodent testis histopathology are most
noticeable at seminiferous tubule structure level. Bleomycin also
significantly decreases rodents´ seminal conventional parameters and
testosterone levels, the latter of which is consistent with increased
induced degeneration of Leydig cells. Seminiferous tubule necrosis and
alterations in tunica albuginea thickness in rodent testis are signs of
a bleomycin-induced inflammatory process similar to the pulmonary one.
Conclusion: More research, particularly human research, is required to
provide strong evidence on how bleomycin affects human testicular
function, including hormone function; and whether is gonadotoxic,
whether it has a transient or permanent effect; how it may affect
offspring; and how it can be reduced. Despite this, the current findings
have important implications for clinicians in counseling patients about
fertility risk and guiding requirements for fertility preservation