Research questionCan atorvastatin with antioxidant, anti-inflammatory, and anti-apoptotic properties improve ovarian function and follicular reserve in a model of premature ovarian insufficiency induced by cyclophosphamide? DesignIn this experimental study, twenty-four adult female Wistar rats were divided into four groups: control, POI, POI + atorvastatin, and atorvastatin. After treatment with atorvastatin, the serum levels of glutathione, total antioxidant capacity, malondialdehyde, follicle-stimulating hormone, estradiol, anti-Müllerian hormone, tumor necrosis factor-alpha, and interleukin-6 were evaluated. Additionally, the mRNA and protein expression of Bax, Bcl-2, and VEGF-A, the number of follicles, and the volume of the ovary were examined. ResultsOur result showed that the serum levels of total antioxidant capacity (P < 0.001), glutathione, estradiol,and anti-Müllerian hormone (P < 0.05), the expression of Bcl-2 and VEGF-A (P < 0.05), the number of primordial and primary follicles (P < 0.001), preantral and antral follicles (P < 0.01), the total volume of the ovary, and the volume of the cortex (P < 0.05) in the POI + atorvastatin group compared to the POI group increased significantly, while the serum levels of malondialdehyde, tumor necrosis factor-alpha, and interleukin-6, and the expression of Bax were significantly decreased (P < 0.05) ConclusionsAtorvastatin can significantly reduce the detrimental effects of cyclophosphamide in the POI model by reducing oxidative stress and proinflammatory cytokines, as well as regulating the expression of Bax, Bcl-2, and VEGF-A and improves ovarian function and follicular reservation.