Abstract
Background:
Cisplatin (CP) is an effective anticancer agent whose clinical use is limited by organ toxicity, including gonadotoxicity and accompanying male infertility. Letrozole (LTZ) is a nonsteroidal aromatase inhibitor that may improve spermatogenesis by stimulating endogenous testosterone synthesis.

Aim:
This study assessed the protective effect of LTZ against CP-induced testicular toxicity in a rat model.

Methods:
Twenty adult male Sprague-Dawley rats were randomly assigned to four groups (n = 5): NC, CP (7 mg/kg, single intraperitoneal dose), LTZ (1.5 mg/kg orally for 10 days), and CP + LTZ. The experimental period lasted for 28 days. Body weight, sperm count, sperm motility, sperm morphology, and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were assessed, and testicular tissues were histologically examined.

Results:
CP administration markedly reduced body weight gain, sperm count, and sperm motility and increased sperm morphological abnormalities. Serum levels of FSH, LH, and testosterone were also reduced in CP-treated rats. Histopathological examination revealed seminiferous tubular degeneration, germ cell necrosis, and interstitial damage. Coadministration of LTZ with CP improved sperm count, motility, and reproductive hormone concentrations and mitigated histopathological alterations. However, the morphological sperm abnormalities remained largely unchanged.

Conclusion:
CP causes critical structural and functional testicular damage. However, LTZ partially reduces CP-induced reproductive damage by restoring hormonal balance and improving spermatogenic activity. LTZ confers a promising adjunctive therapy to mitigate chemotherapy-induced infertility in males.

Key words: Cisplatin; Letrozole; Rat model; Spermatogenesis; Testicular toxicity.