Cytotoxic Properties of Cyclophosphamide: A Focus on Its Mechanistic Impacts on Male Gonadal Functions

Abstract

Cyclophosphamide (CP) is a potent chemotherapeutic agent utilized in the treatment of various types of cancer. However, in addition to its efficacy in combating cancer, CP also has severe side effects, including damage to male gonadal functions. This paper aims to explore the cytotoxic properties of CP and its mechanistic impacts on male gonadal functions. The search strategy was conducted using several reviewed articles indexed in PubMed, Science Direct, EBSCO, Scopus, Cochrane Library, Sage Journals, and Google Scholar. CP is an alkylating agent that damages cancer cell DNA, inhibiting growth and division. It also affects healthy cells, leading to severe cytotoxicity. In male gonadal tissues, CP damages germ cells, Leydig cells, and Sertoli cells, causing decreased sperm count, testosterone levels, and disruption of the blood-testis barrier. The metabolism of CP in the liver generates reactive oxygen species, leading to oxidative damage and cell death. Moreover, CP also affects the hypothalamic-pituitary-gonadal axis, regulating male gonadal functions. CP disrupts the production and secretion of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, resulting in a decrease in testosterone levels and impaired spermatogenesis. Additionally, CP exerts its cytotoxic effects by inhibiting the proliferation and differentiation of germ cells, leading to a decrease in sperm production. It also affects Leydig cells, which are responsible for the production of testosterone, thus decreasing testosterone levels. In conclusion, CP exhibits potent cytotoxic properties that not only affect cancer cells but also severely damage male gonadal functions. The mechanisms involved in CP-induced gonadal toxicity include oxidative stress and disruption of the hypothalamic-pituitary-gonadal axis. Therefore, it is crucial to consider the potential gonadal toxicity of CP when prescribing it for cancer treatment and to closely monitor the gonadal functions of male patients