Methimazole-induced reproductive endocrine system disruption and hepatotoxicity: insights from a Trichogaster trichopterus animal model.

Abstract

Background: Methimazole is commonly prescribed for managing hyperthyroidism, although concerns regarding its reproductive and hepatic adverse effects persist. This study aimed to evaluate the dose-dependent effects of methimazole on reproductive endocrine system function and hepatic integrity using an animal model.

Methods: Adult female three-spot gourami (Trichogaster trichopterus) were administered intramuscular injections of methimazole at doses of 0.025, 0.05, and 0.1 mg/kg body weight every other day for 20 days. Gonadosomatic Index (GSI), Hepatosomatic Index (HSI), sex steroid hormones (17β-estradiol, testosterone, 17-hydroxyprogesterone), liver enzymes (GOT, GPT), and histological alterations in ovarian and hepatic histology were assessed.

Results: Methimazole significantly reduced GSI in a dose-dependent manner, with the lowest value (3.33%, P < 0.05) observed at the highest dose. Although HSI increased slightly, differences among groups were not significant. Dose-dependent declines were observed in sex steroid hormones, with the most pronounced reduction at 0.1 mg/kg (P < 0.05), indicating significant disruption in steroidogenesis and ovarian function. Liver enzymes activity GOT and GPT were significantly elevated at doses of 0.05 and 0.1 mg/kg (P < 0.05), reflecting hepatic stress and potential hepatotoxicity. Histological analyses demonstrated significant disruption in ovarian follicle maturation, with oocytes arrested at early growth stages at higher methimazole doses. Furthermore, structural liver damage including hepatocyte hypertrophy, inflammation, and necrosis was observed at the highest methimazole dose.

Conclusion: Methimazole induces notable reproductive and hepatic disturbances, highlighting the importance of monitoring endocrine and hepatic parameters during clinical methimazole therapy, especially in reproductive-age populations. These findings underscore the potential risks associated with methimazole treatment and suggest careful clinical monitoring to mitigate possible reproductive and hepatic adverse effects.