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The effect of antioxidants on antineoplastic-induced male reproductive system damage: a systematic review of
Hale Bayram1, Yaprak Dönmez Çakıl2, Mustafa Erinç Sitar3,4
1Department of Histology and Embryology, Faculty of Medicine, Maltepe University, İstanbul, Türkiye.
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.
Insights
Antioxidants show promise in protecting male reproductive health from chemotherapy damage by improving sperm quality and testosterone levels. Further clinical studies are needed to confirm their effectiveness and safety in humans.
Area of Science:
- Reproductive Toxicology
- Pharmacology
- Oncology
Background:
- Antineoplastic agents can cause male reproductive toxicity through oxidative stress and inflammation.
- Antioxidants are investigated as a potential countermeasure to mitigate chemotherapy-induced testicular damage.
- Existing research highlights the need for a systematic evaluation of antioxidant efficacy in this context.
Purpose of the Study:
- To systematically review the therapeutic potential of antioxidants in reducing chemotherapy-induced male reproductive damage.
- To identify knowledge gaps and guide future research directions in this field.
Main Methods:
- A comprehensive literature search was performed in Google Scholar and Web of Science (2012-2025) following PRISMA guidelines.
- Keywords included "antioxidant," "oxidative stress," "spermatozoa," "testosterone," "histopathology," "rat/mice," and "chemotherapy/antineoplastic."
- Data extraction focused on histopathology, testosterone, and sperm parameters; risk of bias was assessed using SYRCLE's tool.
Main Results:
- Most of the 28 included studies indicated that antioxidant administration ameliorated male reproductive toxicity.
- Improvements were observed in sperm parameters, testicular histopathology, and testosterone levels in antioxidant-treated groups.
- Some studies reported no significant effects, and beneficial impacts on other endocrine markers and oxidative stress were also noted.
Conclusions:
- Current preclinical evidence suggests antioxidants can mitigate chemotherapy-induced reproductive toxicity in males.
- Further clinical trials are essential to establish clinical applicability, optimal dosages, and long-term safety of antioxidants for this purpose.
