Hormonal fluctuations in rodent models using 4-vinylcyclohexene diepoxide: A systematic review and meta-analysis

An animal model of 4-vinylcyclohexene diepoxide (VCD)-induced premature ovarian failure was developed to mimic menopause; this model has been used in various field studies. However, detailed reports on the rodent model using VCD are lacking, and the animal species used, administration methods, and hormonal fluctuations in the creation of the VCD model have not been comprehensively elucidated. The aim of this study was to systematically review these aspects of the rodent model using VCD and elucidate its characteristics. Thirty-two studies were extracted; rats and mice (66 %/44 %) are the most commonly used animal species. In most of the studies involving mice, a dose of 160 mg/kg was administered, whereas in most rat studies, doses of 80 mg/kg and 160 mg/kg were administered. On most mice studies (70 %), the most frequently applied dosage duration was 15 days. In most rat studies (63 %), the most frequently applied duration was 25 days, followed by 14 and 15 days in 30 % of the studies. Meta-analysis indicated that the mouse model using VCD simulates significant hormonal changes, such as estradiol (E2), anti-Müllerian hormone (AMH), and follicle stimulating hormone (FSH) changes. In conclusion, although the VCD model has demonstrated significant promise in replicating menopausal hormonal conditions, further systematic studies are required to fully understand its potential applications and refine its methodologies. This comprehensive review of existing literature highlights the need for continued research to expand the use of the VCD model in diverse medical fields.