Protective role of lycopene against cyclophosphamide-induced endocrine dysfunction in rats

Aim: Infertility is the inability to conceive after one year of unprotected intercourse, influenced by various physiological and environmental factors, including chemical exposure. Cyclophosphamide, used for treating tumors and autoimmune diseases, is linked to reproductive toxicity and endocrine disruption via oxidative stress and cell damage in reproductive tissues. This study assesses the protective effect of lycopene, an antioxidant found in red fruits and vegetables, against cyclophosphamide-induced hormonal changes in rats.

Materials and methods: Material and methods: Forty adult Wistar rats were assigned to four groups: a control group, a group treated with cyclophosphamide, a group treated with cyclophosphamide and lycopene, and a group treated with lycopene alone. Cyclophosphamide was administered to induce reproductive toxicity, while lycopene was administered to assess its protective role. After 29 days of treatment, samples were collected, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (Pg) and estrogen (E2), were measured and statistically analysed.

Results: Administering cyclophosphamide resulted in marked changes in reproductive hormone levels compared to the control group, indicating a disruption of normal hormonal regulation. Lycopene treatment significantly improved hormonal status, maintaining follicle-stimulating hormone, luteinizing hormone, progesterone, and estrogen levels closer to physiological values compared to the cyclophosphamide-treated group.

Conclusions: The findings of this study demonstrate that lycopene significantly mitigates cyclophosphamide-induced hormonal disruption in female Wistar rats, indicating its potential as a potent protective agent against chemotherapy-associated ovarian endocrine dysfunction. Beyond its role as an antioxidant, the preservation of follicle-stimulating hormone, luteinizing hormone, progesterone, and estrogen levels suggests that lycopene may help maintain the integrity of the hypothalamic-pituitary-gonadal axis during toxic insults. These results highlight the potential of lycopene as a low-cost, non-invasive, and natural adjunctive strategy to safeguard the ovarian reserve and reduce the long-term burden of treatment-induced infertility in patients undergoing gonadotoxic therapy. This study provides a foundational basis for future clinical investigations into antioxidant-based interventions as a standard component of fertility preservation protocols in oncology.