Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats

•Simvastatin and its metabolite Simvastatin β-hydroxy acid were investigated in-vitro and in rats.•Simvastatin and its metabolite decrease progestagen production in-vitro.•Simvastatin decreased progestagens in gonads, brain and plasma from rats.•Simvastatin affected the HPG-axis by decreasing plasma FSH.

Endocrine modulating effects of Simvastatin (SV) and its metabolite, Simvastatin β-hydroxy acid (SVA), were investigated in H295R cells and in female Sprague-Dawley (SPRD) rats. H295R cells were exposed to SV and SVA concentrations from 0 to 10 μM for 48 h. Four groups of SPRD rats received 0 (CT), 1.3 (L), 5.0 (M), and 20.0 (H) mg SV/kg bw/day for 14 days. 10 Steroids were investigated in H295R growth media, and in tissues and plasma from rats using GC-MS/MS. Plasma LH and FSH were quantified by ELISA. In the H295R assay, SV and SVA particularly decreased progestagens with IC50-values from 0.10-0.13 μM for SV and from 0.019-0.055 μM for SVA. In rats, SV decreased progestagens in ovaries, brain and plasma, and plasma FSH in the M (72.4% decrease) and H group (76.6% decrease). Because progestagens and gonadotropins are major players in fertility, administration of SV might exert negative effects on female reproduction.

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