The effect of antioxidants on antineoplastic-induced male reproductive system damage: a systematic review of experimental studies.

Abstract

Antineoplastic agents exacerbate oxidative stress and trigger inflammatory responses in the testis. Numerous studies have proposed antioxidants as a therapeutic approach to ameliorate chemotherapy-induced damage and improve reproductive outcomes. This systematic review aims to evaluate the potential therapeutic value of antioxidants in mitigating chemotherapy-induced male reproductive damage and address knowledge gaps to guide future research efforts. A comprehensive literature search was conducted in accordance with the PRISMA guidelines using the Google Scholar and Web of Science databases to identify experimental studies published between 2012 and 2025. The search strategy employed the following keywords: "antioxidant" AND "oxidative stress" AND "spermatozoa" AND "testosterone" AND "histopathology" AND ("rat" OR "mice") AND ("chemotherapy" OR "chemotherapeutic" OR "antineoplastic"). The study design was guided by the PICO framework. Data extraction focused on reproductive histopathological changes, testosterone levels, and sperm parameters. A total of 28 studies were deemed eligible for inclusion. The methodological quality and risk of bias of the included studies were assessed using SYRCLE's Risk of Bias tool. The majority of findings suggest that antioxidant administration mitigated male reproductive toxicity by improving sperm parameters, testicular histopathology, and testosterone levels; however, a small number of studies reported no significant effects. Additionally, a number of the included studies also presented the beneficial effects of several antioxidants on other endocrine parameters and oxidative stress markers. Current preclinical evidence suggests that antioxidants may mitigate chemotherapy-induced reproductive toxicity; however, clinical studies are required to clarify their clinical applicability, optimal dosing, and long-term safety.