A Preliminary study on the reproductive toxicity of statins in rats

Abstract

Statins are reported to have a negative impact on steroidogenesis affecting reproduction, especially pregnancy. The aim of the present study was to evaluate the adverse effects of statins on the maintenance of pregnancy in Sprague-Dawley rats. Sprague-Dawley rats were given vehicle, pravastatin, atorvastatin or simvastatin by oral gavage at dose levels 5, 10 and 20 mg/kg/day and simvastatin (20 mg/kg/day) alone, in supplementation with hydroxy progesterone caproate, 5 mg/day or mevalonic acid lactone, 100 mg/kg/day during pregnancy (2-18 days) and were sacrificed on day 20. Pre- and post implantation loss was noted by performing laparotomy. Hormone analysis and histological evaluation of the uterus was performed in another group of rats receiving the drug or vehicle upto day 11 and sacrificed on day 12. As compared to pravastatin and atorvastatin, simvastatin induced significant implantation loss at 20 mg/kg/day dose level. Co-administration of a progestin could not stop fetal wastage but mevalonic acid supplementation could reverse the effect of simvastatin. The results substantiate that simvastatin emerged as the most active statin towards inducing fetotoxicity and exhibited total interceptive effect leading to loss of all implantation sites producing no live or dead embryos. The process of interception may be through changes in the implantation site and altered hormone level.