Reproductive effects of statin exposure in female rodents: a systematic review and meta-analysis

Statins are the main medications prescribed to improve lipid profiles and avoid cardiovascular risks in humans. Preclinical studies have shown that statins may impair male reproduction; however, their effects on female reproduction remain unclear. This study conducted a systematic review of the literature regarding preclinical primary studies that assessed female reproductive outcomes in rodent models after exposure to statins. The studies were searched in the databases PubMed, Scopus, Embase, Web of Science, LILACS, and SciELO, using distinct combinations of the search terms "statins", "ovary", "uterus", "female reproduction", "mice", "rats", followed by the Boolean operators AND or OR. Subsequently, duplicities and studies that did not meet the eligibility criteria were excluded from this review. Afterward, the risk of bias was evaluated through the 10 points of the SYRCLE's risk of bias tool. Extraction and qualitative analysis of the data were carried out, and whenever possible, a meta-analysis was applied to assess the data quantitatively. The results indicated that normocholesterolemic female rodents exposed to statins showed ovarian morphological changes, such as impaired follicular dynamics. Additionally, when rodents were induced with endometriosis or reproductive-related cancer, there was a reduction in the volume of endometriotic implants and a complementary action on the reduction of tumor proliferation, respectively. As a limitation, there were no studies assessing the effects of statins in hyperlipidemic rodents, which may make it difficult to translate the adverse effects of statins observed in normolipidemic rodents to humans.